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Temporal Association of Rotavirus Vaccine Introduction and Reduction in All-Cause Childhood Diarrheal Hospitalizations in South Africa
Abstract
Background:
The public health impact of rotavirus vaccination in African settings with a high human immunodeficiency virus (HIV) infection prevalence is yet to be established. We evaluated trends in all-cause diarrheal hospitalizations in Soweto, Johannesburg, before and after the introduction of rotavirus vaccine into South Africa's national immunization program in August 2009.
Methods:
Hospitalizations in children <5 years of age with a diagnosis of diarrhea, defined byInternational Classification of Diseases, Tenth Revisioncodes A00-A05, A06.0-A06.3, A06.9, A07.0-A07.2, A07.9, and A08-A09, were identified at the Chris Hani Baragwanath Academic Hospital from 1 January 2006 to 31 December 2014. The median annual prevaccine (2006-2008) hospitalization incidence was compared to that of the vaccine era (2010-2014), and stratified by age group and HIV infection status.
Results:
Incidence reductions (per 1000 population) were greatest in children aged <12 months: 54.4 in the prevaccine era vs 30.0, 23.6, 20.0, 18.8, and 18.9 in the postvaccine years 2010-2014, respectively (a 44.9%-65.4% reduction). Lower incidence reductions (39.8%-49.4%) were observed among children aged 12-24 months from the second year post-vaccine introduction onward. Reductions were observed in both HIV-infected and HIV-uninfected children. There was a change in the seasonal pattern of diarrheal hospitalizations post-vaccine introduction, with flattening of the autumn-winter peaks seen in the prevaccine years.
Conclusions:
An accelerated and sustained decline in all-cause diarrheal hospitalizations, temporally associated with rotavirus vaccine introduction, was observed in children <2 years of age. However, the impact of other interventions such as improved sanitation and changes in HIV management cannot be discounted.
... 10 Studies in South Africa have reported a 33%-57% reduction in allcause diarrhea. [11][12][13] Five years into the era of high rotavirus vaccine coverage (>85%), we determined whether the reductions in acute diarrheal disease burden were maintained in young children hospitalized with a diarrheal illness; additionally, we determined predictors of mortality in these children. ...
... The incidence estimates for 2016 (612 per 100,000) are, however, 58% lower than the 2006-2008 prevaccine rates (1470 per 100,000) and 37% lower than reported in 2010 (970 per 100,000), the year after rotavirus vaccine introduction. 13 Nonetheless, despite the declining trends, the incidence of diarrheal disease is 2-fold higher than in high-income countries. 13,19 In our setting, the overall case fatality ratio from acute *Weight and length values were available for 2260 and 1801 patients, respectively. ...
... 13 Nonetheless, despite the declining trends, the incidence of diarrheal disease is 2-fold higher than in high-income countries. 13,19 In our setting, the overall case fatality ratio from acute *Weight and length values were available for 2260 and 1801 patients, respectively. †HIV-exposed infants whose polymerase chain reaction result was unavailable/ unknown (n = 97). ...
Background:
Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide. Multiple interventions, including rotavirus vaccination to infants since 2009, have reduced the incidence of diarrheal disease in South African children. Our study aimed to determine the burden of diarrheal disease 5 years after rotavirus vaccine introduction at a tertiary-level hospital.
Methods:
A retrospective review of a discharge summary database of children less than 5 years of age hospitalized with acute diarrheal illness from 2015 to 2016 at the Chris Hani Baragwanath Academic Hospital.
Results:
Diarrheal disease accounted for 14.8% of hospital admissions. The incidence (per 100,000 population) was 675.8 (95% CI: 638.8-714.3) in 2015 and 612.2 (95% CI: 577.0-648.9) in 2016. The case fatality ratio was 2.9% over the study period. The median age at diagnosis was 12 months (interquartile range: 6.2-21.4) and 50.4% of cases occurred during infancy. One third of cases were underweight and/or stunted. In a multivariable analysis using logistic regression, the adjusted odds ratio (aOR) for death was higher in children with an associated acute lower respiratory tract infection (aOR: 3.7, 95% CI: 1.2-11.5; P = 0.021), HIV infection (aOR: 9.1, 95% CI: 2.6-31.6; P = 0.001), and an age of less than 6 months (aOR: 6.9, 95% CI: 2.1-22.9; P = 0.002).
Conclusions:
Sustained reductions in diarrheal disease incidence were observed 5 years post rotavirus vaccine implementation. In children hospitalized with an acute diarrheal illness, an increased risk of mortality occurs in young infants, children that are HIV infected, and those with an associated acute lower respiratory tract infection.
... Interestingly, vaccine effectiveness in South Africa, where Rotarix™ was administered at an alternative schedule of 6 and 14 weeks of age, was demonstrated to have significant impact against rotavirus gastroenteritis and all-cause diarrhea hospital admissions in both the first year of life and persisted through the second year of life 63 and was documented in both HIV-infected and HIV-uninfected infants. 64 Thus, these combined observations suggest that the vaccine, administered at a longer interval between doses, was protective against the most severe rotavirus disease in the first two years of life, which is arguably the most significant public health issue. Certainly, increasing evidence in multiple settings demonstrates that the vaccines prevent rotavirusassociated mortality and hospitalizations. ...
... Nevertheless, the vaccines still demonstrate good public health impact, and have described additional benefit through indirect herd effects. [64][65][66][67][68][69][70] Furthermore, immune responses can be improved by changes to the number and timing of doses of the vaccine, although enhanced clinical protection has yet to be documented. Effectiveness studies to assess the clinical protection of differing immunization schedules should be considered to enhance the observed benefits. ...
... 4 Currently, 36 of 54 countries in the continent have introduced rotavirus vaccines into the Expanded Program for Immunization (EPI), and many have documented the major impact of immunization on rotavirus hospitalizations and deaths. [34][35][36][37]63,64 The enormous benefits demonstrated by countries utilizing the vaccines, and the continued support of Gavi and UNICEF for vaccine procurement, will continue to drive vaccine introduction in more countries in the immediate future. This should show even greater impact on reductions in diarrheal mortality over time. ...
Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vaccines are also considered by WHO as “very cost effective” interventions for young children, particularly in countries with high diarrheal disease burden. Yet the full potential impact of rotavirus immunization is yet to be realized. Large countries with big birth cohorts and where disease burden is high in Africa and Asia have not yet implemented rotavirus vaccines at all or at scale. Significant advances have been made demonstrating the impact of the vaccines in low- and lower-middle income countries, yet the modest effectiveness of the vaccines in these settings is challenging. Current research highlights these challenges and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.
... In some of these countries, rotavirus vaccination has also resulted in declines in rotavirus disease among children who were not vaccine eligible, a phenomenon referred to as herd immunity [19,20]. Similarly, there is increasing evidence to suggest that rotavirus vaccines will have a significant impact on infant morbidity and mortality in developing countries in Africa [21][22][23][24][25][26][27][28][29][30]. ...
... Among the early introducing African countries, declines in RVA-associated AGE hospitalizations have been shown to range between 24% and 49% following the nationwide vaccine use [24][25][26][27][28]38]. In addition, reductions in all-cause AGE have been reported to range from 18% to 65% following routine rotavirus immunizations in these countries [21][22][23][25][26][27]29,39]. ...
... These observations are consistent with reports from other African countries that were among the early adopters of the rotavirus vaccine. The reports describe greater initial declines in the proportion of RVA cases among younger age groups that received vaccination in the initial years of the vaccination, followed by a progressive decline in older age groups in later years after its introduction, when vaccine coverage increased among these older children [21][22][23][24][25][26]. Furthermore, following the vaccine introduction, we observed greater declines in rotavirus and all-cause AGE hospitalizations, primarily during the peak months of RVA and all-cause AGE. ...
... South Africa was the first African country to introduce the rotavirus vaccine [35]. As observed globally, the introduction of the monovalent vaccine Rotarix had a great impact on the mortality and morbidity of rotavirus infection in South Africa [36,37]. During the period of this study, to examine the etiology of acute gastroenteritis disease in Northern Pretoria, South Africa post introduction (June 2015-December 2017), rotavirus accounted for 14.3% of diarrheal cases seeking medical attention or hospitalization. ...
... Our study had few limitations. Firstly, relatively few cases of rotavirus diarrhea were detected as a result of the impact of rotavirus vaccination in South Africa which has significantly reduced diarrheal hospitalization and death [36,37]. In addition, the HBGA binding profiles of recombinant VP4/VP8* proteins of corresponding rotaviruses to saliva samples and genotyping of FUT2 and FUT3 genes of the saliva samples were not conducted. ...
Objectives:
Recently, histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors of several viral pathogens. Among rotaviruses, HBGAs interact with the outer viral protein, VP4, which has been identified as a potential susceptibility factor, although the findings are inconsistent throughout populations due to HBGA polymorphisms. We investigated the association between HBGA phenotypes and rotavirus infection in children with acute gastroenteritis in northern Pretoria, South Africa.
Methods:
Paired diarrheal stool and saliva samples were collected from children aged ≤ 59 months (n = 342) with acute moderate to severe diarrhea, attending two health care facilities. Rotaviruses in the stool samples were detected by commercial EIA and the rotavirus strains were characterized by RT-PCR targeting the outer capsid VP7 (G-type) and VP4 (P-type) antigens for genotyping. Saliva-based ELISAs were performed to determine A, B, H, and Lewis antigens for blood group typing.
Results:
Blood type O was the most common blood group (62.5%) in this population, followed by groups A (26.0%), B (9.3%), and AB (2.2%). The H1-based secretors were common (82.7%) compared to the non-secretors (17.3%), and the Lewis antigen positive phenotypes (Le(a+b+)) were predominant (54.5%). Blood type A children were more likely to be infected by rotavirus (38.8%) than any other blood types. P[4] rotaviruses (21/49; 42.9%) infected only secretor individuals, whereas P[6] rotaviruses (3/49; 6.1%) only infected Le(a-b-), although the numbers were very low. On the contrary, P[8] rotaviruses infected children with a wide range of blood group phenotypes, including Le(a-b-) and non-secretors.
Conclusions:
Our findings demonstrated that Lewis antigens, or the lack thereof, may serve as susceptibility factors to rotaviral infection by specific VP4 genotypes as observed elsewhere. Potentially, the P[8] strains remain the predominant human VP4 genotype due to their ability to bind to a variety of HBGA phenotypes.
... These data may suggest the positive impact of Rotavirus A vaccine in the prevention of RVA diarrhea. The same tendency to drastically reduced RVA cases has also been reported in other countries such as Rwanda (51 to 55%), Malawi (48.2%) and South Africa (44.9 to 65.4%) one to four years after vaccine introduction [27,28,29]. Similarly, the reduction of 86%, 96%, and 92%, respectively in the age groups of 6-11, 12-23, and 24-35 was reported [30]. ...
... The mixed infections with the unconventional strain G1P[4]P[6] detected in the rst time in RoC was previously identi ed in Kenyan children with diarrhea[37]. Those unusual combinations of G and P type that are reported in several developing countries as a cause of diarrheal disease in young children were certainly due to reassortment between human and animal RVA strains circulating in population[38].In addition, the identi cation of RVA strains such as G1P[8], G1P[4]P[6], G8P[8] and G12P[8] in four vaccinated children with Rotarix can be explained by several factors such as the fact that Rotavirus vaccines do not completely protect children against RVA gastroenteritis, as shown by several postvaccination studies[27, 28,29]. ...
Background: Acute gastroenteritis due to Rotavirus A infection is common in both developing and developed countries and is responsible for approximately 215,000 annual deaths especially in developing countries. In 2014, the Republic of Congo joined the immunization program recommended by WHO and introduced Rotarix (GlaxoSmithKline Biologicals, Belgium) into its national immunization schedule. However, information on the genetic diversity of Rotavirus strains in Congo is derived from a single pre-vaccination study conducted in the southern Brazzaville area.
To determine RVA prevalence and genotype distribution in Brazzaville and Pointe-Noire before and after the Rotarix vaccine introduction.
Methods: From February to September 2013 and from August 2017 to February 2018, stool samples were collected from children under 5 years of age suffering from gastroenteritis in Congolese hospitals before and after vaccine introduction. RVA was detected using the ELISA and the VP7 and VP4 genes were genotyped by multiplex RT-PCR. All data analyses were performed using the R software, version 3.4.
Results: Of 154 stool samples analyzed, 45.4% were positive from 108 samples before vaccination introduction and the genotypes G1P [8] (77.5%), G9P [8] (2%), G1G2P [6] P [8] 6%) and G1G9P [8] (2%) were detected. In the post-vaccination period, cases of Rotavirus gastroenteritis were 16% and 4.7% in Brazzaville and Pointe-Noire, respectively representing 52.17% of 46 samples. The genotypes G1P [8] (40%), G1P [4] P [6] (20%), G8P [8] (20%) and G12P [8] (20%) were detected.
Conclusions: RVA is the most common cause of acute gastroenteritis in children under five years of age. In the Republic of Congo, we found a considerable genetic diversity of Rotavirus strains and a decrease in cases of gastroenteritis five years after vaccine introduction. Some cases of vaccinated patients who have developed Rotavirus diarrhea have been reported. As a result, it is still important to continue monitoring Rotavirus strains and evaluate the impact of Rotavirus vaccine in Congo.
... Despite international studies not demonstrating seasonal variability [4], presentation was significantly more in the Spring months of September-November. This parallels findings in previous regional studies [2,5] but does not correlate with the peak incidence of gastroenteritis admissions across the country [14,15]. Traditional teaching is that rates of intussusception parallel rates of acute gastroenteritis-with gastroenteritis-causing lymphoid hyperplasia that acts as the lead point. ...
... All complications as per the Clavien-Dindo classification and interventions[14] ...
Purpose
We assessed management and outcomes for intussusception at nine academic hospitals in South Africa.
Methods
Patients ≤ 3 years presenting with intussusception between September 2013 and December 2017 were prospectively enrolled at all sites. Additionally, patients presenting between July 2012 and August 2013 were retrospectively enrolled at one site. Demographics, clinical information, diagnostic modality, reduction methods, surgical intervention and outcomes were reviewed.
Results
Four hundred seventy-six patients were enrolled, [54% males, median age 6.5 months (IQR 2.6–32.6)]. Vomiting (92%), bloody stool (91%), abdominal mass (57%), fever (32%) and a rectal mass (29%) represented advanced disease: median symptom duration was 3 days (IQR 1–4).
Initial reduction attempts included pneumatic reduction (66%) and upfront surgery (32%). The overall non-surgical reduction rate was 28% and enema perforation rate was 4%. Surgery occurred in 334 (70%), 68 (20%) patients had perforated bowel, bowel resection was required in 61%.
Complications included recurrence (2%) and nosocomial sepsis (4%). Length of stay (LOS) was significantly longer in patients who developed complications. Six patients died—a mortality rate of 1%. There was a significant difference in reduction rates, upfront surgery, bowel resection, LOS and mortality between centres with shorter symptom duration compared longer symptom duration.
Conclusion
Delayed presentation was common and associated with low success for enema reduction, higher operative rates, higher rates of bowel resection and increased LOS. Improved primary health-care worker education and streamlining referral pathways might facilitate timely management.
... Previously, a study conducted at CHBAH looked at trends in hospitalisations for more severe diarrhoeal disease. [10] We report a significant temporal decline in incidence of 'milder' diarrhoeal disease that followed introduction of the rotavirus vaccine into the EPI in 2009 and persisted with vaccine coverage rates above 85%. Although other interventions, such as improved access to ART, PMTCT, WASH, IMCI, breastfeeding practices and vitamin A supplementation have probably contributed to this decline, the most marked change was observed after rotavirus vaccine implementation. ...
... Numerous studies have reported the effectiveness of rotavirus vaccination on rotavirus-associated and all-cause diarrhoea in both high-and low-income settings. [2,10] The effectiveness has reportedly been less for milder forms of diarrhoeal disease. [2] Despite the 27% decline in the number of diarrhoeal patients seeking medical care at this PMEAD, our study did not include community-managed diarrhoeal disease. ...
Globally, a decline in diarrhoeal disease has been observed over the last two decades. This may be attributable to several interventions, including rotavirus vaccination since 2009 in South Africa. From January 2002 to December 2016, we conducted a retrospective trend analysis of diarrhoeal hospitalisations with mild or moderate dehydration to a short-stay ward (SSW) in children <14 years of age. We found that diarrhoeal hospitalisation to the SSW accounted for 29.3% of the 53 717 children who presented with diarrhoea to the emergency department. A significant decline in disease incidence was noted after 2009/2010, coinciding with rotavirus vaccine implementation into the Expanded Programme on Immunisation. The yearly incidence (per 100 000) declined from 307 (95% confidence interval (CI) 277 - 337) over the 2002/2008 period to 141 (95% CI 120- 161) from 2011/2016; p<0.001. In conclusion, rotavirus vaccination was associated with a decline of diarrhoeal disease hospitalisations to the SSW at this hospital.
... The efficacy of RV vaccine universal immunization has been demonstrated in not only developed countries 15,16 but also in developing countries. 17,18 The number of RV gastroenteritis patients and associated hospital visits has been gradually declining after the introduction of universal RV vaccination in many countries. [14][15][16][17][18] Additionally, the estimated number of RV deaths in children <5 years of age declined from 528 000 in 2000 to 215 000 in 2013 due to reduction in fatal cases in developing countries. ...
... 17,18 The number of RV gastroenteritis patients and associated hospital visits has been gradually declining after the introduction of universal RV vaccination in many countries. [14][15][16][17][18] Additionally, the estimated number of RV deaths in children <5 years of age declined from 528 000 in 2000 to 215 000 in 2013 due to reduction in fatal cases in developing countries. 19 The efficacy of RV vaccine for reduction of severe complications such as RV encephalitis/encephalopathy and sudden death, however, remains unclear. ...
Background:
Rotavirus can rarely cause severe complications such as encephalopathy/encephalitis, myocarditis, sudden unexpected death, urinary stone, and gastrointestinal bleeding; indeed incidence of these severe complications remains unclear. Additionally, it has not been determined whether rotavirus vaccine could reduce the cases with the severe complications or not.
Method:
A two-part questionnaire was designed to determine the number and clinical features of the cases with the severe complications between September 1st 2008 and August 31st 2015 including the observation periods before and after rotavirus vaccine introduction in Aichi prefecture.
Result:
Twenty-four cases of encephalitis/encephalopathy, 8 cases of sudden unexpected death, 3 cases of urinary tract stone, and 3 cases of gastrointestinal bleeding were reported during 2008/2009 season and 2012/2013 seasons. Although 5 cases of encephalitis/encephalopathy were reported, no cases with other severe complications were reported during the 2013/2014 and 2014/2015 seasons. No age difference was demonstrated among the patients with the four different complications. Although onset of the encephalitis/encephalopathy and sudden unexpected death were around day 2 of the illness, that of urinary tract stone and gastrointestinal bleeding were slightly later (day 6 and day 4). In addition to the 8 sudden unexpected death cases, 4 (13.8%) encephalitis/encephalopathy cases and 1 gastrointestinal bleeding case had fatal outcome.
Conclusion:
Incidences of the four severe rotavirus-associated complications were elucidated based on the questionaries' survey in Aichi prefecture that appeared to be declined after increasing in vaccination rate. This article is protected by copyright. All rights reserved.
... The introduction of the monovalent rotavirus vaccine into the South African national immunization program coincided with a temporal decline in all-cause diarrhoeal hospitalizations [38]. Despite fluctuations in genotype distribution over the surveillance period, the overall reduction in both all-cause diarrhoea and rotavirus hospitalizations remains significant [11,12,38]. ...
... The introduction of the monovalent rotavirus vaccine into the South African national immunization program coincided with a temporal decline in all-cause diarrhoeal hospitalizations [38]. Despite fluctuations in genotype distribution over the surveillance period, the overall reduction in both all-cause diarrhoea and rotavirus hospitalizations remains significant [11,12,38]. These results support the continued use of rotavirus vaccines in Africa and continued monitoring of rotavirus strain diversity is encouraged. ...
Background:
Rotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction.
Materials and methods:
In addition to pre-vaccine era surveillance conducted from 2002 to 2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children <5 years hospitalized for acute diarrhoea was established at seven sentinel sites in SA from April 2009 to December 2014. Stool specimens were screened by enzyme immunoassay and rotavirus positive specimens genotyped using standardised methods.
Results:
At DGM, there was a significant decrease in G1 strains from pre-vaccine introduction (34%; 479/1418; 2002-2009) compared to post-vaccine introduction (22%; 37/170; 2010-2014; p for trend <.001). Similarly, there was a significant increase in non-G1P[8] strains at this site (p for trend <.001). In expanded sentinel surveillance, when adjusted for age and site, the odds of rotavirus detection in hospitalized children with diarrhoea declined significantly from 2009 (46%; 423/917) to 2014 (22%; 205/939; p<.001). The odds of G1 detection declined significantly from 2009 (53%; 224/421) to 2010-2011 (26%; 183/703; aOR=0.5; p<.001) and 2012-2014 (9%; 80/905; aOR=0.1; p<.001). Non-G1P[8] strains showed a significant increase from 2009 (33%; 139/421) to 2012-2014 (52%; 473/905; aOR=2.5; p<.001).
Conclusions:
Rotavirus vaccination of children was associated with temporal changes in circulating genotypes. Despite these temporal changes in circulating genotypes, the overall reduction in rotavirus disease in South Africa remains significant.
... The ongoing worldwide introduction of rotavirus vaccines is expected to have a substantial impact on the burden of rotavirus diarrhea [2]. Despite clinical trials and real-world effectiveness studies demonstrating reduced performance of these vaccines in sub-Saharan Africa [3][4][5][6][7][8], a profound impact of vaccine introduction has been observed, with the majority of the impact seen by the third year after introduction [9][10][11][12]. ...
... The attenuation and delay in seasonal diarrhea, as well as the reduction in all-cause diarrhea admissions, are consistent with a substantial impact of vaccine introduction. The reduction in all-cause diarrhea admissions was similar to that described in South Africa and Rwanda [10,12] and suggests that if rotavirus caused 25% of diarrhea requiring admission after vaccine introduction, it was likely responsible for 50%-60% prior to introduction. The striking delay in the rotavirus season is consistent with data from the United States [32], and is predicted by modeling studies [33], but has not been observed in other studies of vaccine introduction in Africa. ...
Background:
No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on January 1, 2013. We performed a vaccine impact and effectiveness study as well as a qPCR-based etiology study at a rural Tanzanian hospital.
Methods:
We obtained data on admissions among children under 5 years to Haydom Lutheran Hospital between January 1, 2010 and December 31, 2015, and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions.
Results:
Vaccine introduction was associated with a 44.9% (95% CI 17.6 - 97.4) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of two doses of vaccine was 74.8% (-8.2 - 94.1) using an enzyme immunoassay-based case definition and 85.1% (26.5 - 97.0) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF 25.8%, 95% CI: 24.4 - 26.7), followed by heat-stabile enterotoxin-producing E. coli (18.4%, 12.9 - 21.9), Shigella/enteroinvasive E. coli (14.5%, 10.2 - 22.8), and Cryptosporidium (7.9%, 6.2 - 9.3).
Conclusions:
Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted.
... For example, three years after vaccine introduction, rotavirus hospitalizations in children <5 years of age declined by 69% in Armenia and 64% in Ghana, compared with their respective prevaccine rates [23,24]. Five years after introduction in South Africa, diarrhea hospitalizations in children <5 years of age decreased by 53%, with the most significant reductions in children <12 months and, to a lesser extent, children 12-23 months of age [25]. ...
... Programmatically, a three-dose schedule corresponds to the existing polio, DTP, Haemophilus influenzae b (Hib), hepatitis B and PCV infant schedule in many countries. A three-dose schedule was not found to significantly improve immunogenicity compared with a 10-and 14-week two-dose schedule during prelicensure trials in Malawi and South Africa (Figure 3) [25,50]; however in Ghana, statistically significantly higher anti-rotavirus IgA levels were observed after a three dose schedule versus a 6-and 10-week two-dose schedule in a postlicensure evaluation [23]. A similarly designed analysis from Pakistan did not show a difference [51]. ...
As of May 2016, 81 countries have introduced Rotarix or RotaTeq rotavirus vaccines into their national immunization program. Despite initially slow uptake in some countries and differences in vaccine effectiveness (VE) between high-, low- and middle-income countries, impact of the vaccines has been swift and striking in all settings, with good VE against vaccine-type and nonvaccine-type strains. Newly published research indicates poor nutrition is associated with decreased VE and breastfeeding at the time of vaccination does not affect vaccine response. Vaccines in development and proposed alternate schedules also promise to address limitations of the current vaccines and optimize rotavirus disease prevention.
... However, assessing trends in disease before and after vaccine introduction requires cautious interpretation to account for secular trends and other possible factors (eg, changes in surveillance practices or healthcare-seeking behavior) that might be associated with the decline. Several articles in this supplement from African (Botswana, South Africa, Ghana, Togo, Zambia) and East European/Central Asian (Armenia and Moldova) countries show evidence of rapid and substantial declines in severe diarrhea and/or rotavirus disease following vaccine introduction [31][32][33][34][35][36][37]. In these evaluations, a role for vaccine in disease reduction is supported by observations such as (1) sharp declines coinciding temporally with the timing of vaccine introduction; (2) greater declines during the months of the year with seasonal peaks of rotavirus disease; and (3) greater initial declines in younger age groups that receive vaccination in the initial years of the vaccination, followed by a progressive decline in older age groups in later years after introduction. ...
... The reports from Armenia and Moldova in this supplement both demonstrate a decline in severe rotavirus disease among older age groups that were not vaccinated and also greater declines in vaccinated age groups than that expected based on vaccine coverage and effectiveness, indicating evidence of indirect protection [36,37]. However, data from Zambia and South Africa do not indicate any evidence of indirect protection, and thus further evidence is required to understand the extent of herd protection across a range of geographic and socioeconomically diverse settings [32,35]. ...
Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have
been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible
for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia
and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of
routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented.
Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation
in these settings only began after additional clinical trials were completed and the World Health Organization issued a global
recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing
countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should
provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus
vaccination to reduce the health burden of severe childhood gastroenteritis.
... Since Africa is an HIV-endemic region, South Africa included the rotavirus vaccine in its national immunization program in August 2009. The diarrhea hospitalization rate in HIV-infected and non-infected children of less than 12 months old significantly dropped from 54.4 to 18.9 (per 1000 population) in the following 5 years [38]. Another study of 76 HIV-positive infants and 126 HIV-exposed (uninfected) infants suggested that the attenuated live rotavirus vaccine was capable of eliciting immune responses in both infected and uninfected infants, and both groups represented similar occurrences of side effects [39]. ...
Human immunodeficiency virus (HIV)-infected individuals have an increased risk of various infections due to their impaired host immune system, resulting in higher morbidity and mortality rates. These patients severely suffered during the COVID-19 epidemic, the influenza epidemic and the spread of monkeypox. Reducing serious infections is one of the most important measures to improve HIV-infected individuals’ quality and length of life. Based on the preparation processes and their antigenic properties, vaccines are divided into several types, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, toxoid vaccines, polysaccharide vaccines, polysaccharide (protein) combined vaccines, nucleic acid vaccines, viral vector vaccines, etc. With the innovation of vaccine preparation technology in recent years and the acceleration of vaccine approval and market launch, more and more vaccine products suitable for HIV-infected individuals have become available. Because of their deficient immune systems, the type of vaccines and the schedule of vaccinations available to individuals living with HIV are sometimes different from those with healthy immune systems. This article reviewed the current status of vaccination in and shed light on the vaccination strategies for HIV-infected persons in terms of their safety and effectiveness.
... Evaluation of the rotavirus vaccine programme in Soweto found a temporal association, with a decrease between 34% and 57% in the overall incidence of all-cause diarrhoeal hospitalisations in children under 5 years of age. [31] Despite this, diarrhoeal disease accounted for 16% of child deaths in 2012, the second largest proportion after HIV/AIDS, [2] perhaps indicating little change in the underlying causal pathways. ...
Background:
The incidence of diarrhoeal disease is closely linked to socioeconomic and environmental factors, household practices and access to health services. South African (SA) district health information and national survey data report wide variation in the incidence and prevalence of diarrhoeal episodes in children under 5 years of age. These differentials indicate potential for reducing the disease burden through improvements in provision of water and sanitation services and changes in hygiene behaviour.
Objectives:
To estimate the burden of disease attributed to unsafe water, sanitation and hygiene (WASH) by province, sex and age group for SA in 2000, 2006 and 2012.
Methods:
Comparative risk assessment methodology was used to estimate the disease burden attributable to an exposure by comparing the observed risk factor distribution with a theoretical lowest possible population distribution. The study adapts the original World Health Organization scenario-based approach for estimating diarrhoeal disease burden from unsafe WASH, by assigning different standards of household water and sanitation-specific geographical classification to capture SA living conditions in rural, urban and informal settlements.
Results:
SA experienced an improvement in water and sanitation supply in eight of the nine provinces between 2001 and 2011, with the exception of Northern Cape Province. In 2011, 41% of South Africans lived with poor water and sanitation conditions; however, wide provincial inequalities exist. In 2012, it was estimated that 84.1% of all deaths due to diarrhoeal disease were attributable to unsafe WASH; this equates to 13 757 deaths (95% uncertainty interval (UI) 13 015 - 14 300). Of these diarrhoeal disease deaths, 48.2% occurred in children under 5 years of age, accounting for 13.9% of all deaths in this age group (95% UI 13.1 - 14.4). Between 2000 and 2012, the proportion of deaths attributable to diarrhoea reduced from 3.6% to 2.6%. Gauteng and Western Cape provinces experienced much lower WASHattributable death rates than the more rural, poorer provinces.
Conclusion:
Unsafe WASH remains an important risk factor for disease in SA, especially in children. High priority needs to be given to the provision of safe and sustainable sanitation and water facilities and promoting safe hygiene behaviours. The COVID-19 pandemic has reinforced the critical importance of clean water for preventing and containing disease.
... [9][10][11][12][13] Infectious diseases continue to represent a large proportion of the paediatric disease burden in southern Africa, and seasonal variations are described for the incidence of pneumonia/ lower respiratory tract infections (LRTIs) and diarrhoea. [14,15] Since March 2020, COVID-19 has placed additional burdens on the SA health system. By 21 November 2020, children and adolescents aged ≤19 years, despite comprising 37% of the population, represented 9% of COVID-19 infections and 4% of hospital admissions, with an incidence risk one-sixth of that in adults, and with few severe and fatal outcomes. ...
Background:
Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non-fatal disease burden are limited. Furthermore, COVID-19 has affected children's health and wellbeing, both directly and indirectly.
Objectives:
To describe the pattern of disease on admission of children at different levels of care, and assess whether this has been affected by COVID-19.
Methods:
Retrospective reviews of children's admission and discharge registers were conducted for all general hospitals in iLembe and uMgungundlovu districts in KwaZulu-Natal Province, SA, from January 2018 to September 2020. The Global Burden of Disease framework was adapted to create a data capture sheet with four broad diagnostic categories and 37 specific cause categories. Monthly admission numbers were recorded per cause category, and basic descriptive analysis was completed in Microsoft Excel.
Results:
Overall, 36 288 admissions were recorded across 18 hospital wards, 32.0% at district, 49.8% at regional and 18.2% at tertiary level. Communicable diseases, perinatal conditions and nutritional deficiencies (CPNs) accounted for 37.4% of admissions, non-communicable diseases (NCDs) for 43.5% and injuries for 17.1%. The distribution of broad diagnostic categories varied across levels of care, with CPNs being more common at district level and NCDs more common at regional and tertiary levels. Unintentional injuries represented the most common cause category (16.6%), ahead of lower respiratory tract infections (16.1%), neurological conditions (13.6%) and diarrhoeal disease (8.4%). The start of the local COVID-19 outbreak coincided with a 43.1% decline in the mean number of monthly admissions. Admissions due to neonatal conditions and intentional injuries remained constant during the COVID-19 outbreak, while those due to other disease groups (particularly respiratory infections) declined.
Conclusions:
Our study confirms previous concerns around a high burden of childhood injuries in our context. Continued efforts are needed to prevent and treat traditional neonatal and childhood illnesses. Concurrently, the management of NCDs should be prioritised, and evidence-based strategies are sorely needed to address the high injury burden in SA.
... There is mixed evidence of herd protection by RVs in lowincome countries. Whereas studies from Zambia and South Africa showed no evidence of RV indirect protection [16,17], studies conducted in Zimbabwe and Rwanda showed indirect protection by RV [18,19]. A study in Malawi also demonstrated some evidence of indirect protection in infants <12 months, but not in older children following RV introduction into routine immunization programs for infants [20]. ...
Background:
Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a 'fried-egg' approach whereby the analysis, restricted to the innermost households of clusters, 'yolk', creates an insulating 'egg-white' periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis.
Methods:
In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively.
Results:
During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size.
Conclusion:
Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study.
... This includes data in pre-term, low birth weight infants, and other at-risk populations such as human immunodeficiency-virus (HIV)-infected or malnourished children. 13,36,38,88,95,[113][114][115][116][117][118][119][120] In contrast, to date, many of the locally marketed or recently launched vaccines have a limited record of efficacy and/or effectiveness data in global settings. Some of these vaccines with limited global experience data, namely 116E and BRV-PV (both locally manufactured), have received WHO prequalification, allowing accelerated introduction of RV vaccination in high-mortality countries (with the additional support of GAVI, PATH, and UNICEF). ...
PLAIN LANGUAGE SUMMARY
The disease
Rotaviruses are a leading cause of acute diarrhea, also called gastroenterities, among young children. They can lead to servere dehydration, hospitilization, and even death.
Several vaccines against rotavirus disease have been developed. Their design is based on:
weakened human rotavirus that mimic natural infection without causing disease, such as Rotarix, Rotavin-M1, Rotavac and RV3-BB (not yet marketed)
non-infective animal viruses such as RotaTeq, Rotasiil or LLR.
new concepts, such as inactivated vaccines
What is new?
We reviewed the current, recently launched and soon-to-be-launched rotavirus vaccines and found that:
Rotarix and RotaTeq have been used globally for more than a decade with demonstrated impact and favourable safety profile
Limited data on the impact and safety profile are available to date for:
Rotavin-M1 and LLR vaccines, locally marketed in Vietnam and China, respectively
Rotavac and Rotasiil, licensed in india
New vaccine concepts have been mainly investigated animal models with encouraging results
What is the impact?
Despite their different designs, the current rotavirus vaccines demonstrate effectiveness in protecting against rotairus gastroenterits.
Data for most recent vacciness are currently limited, for which additional data are needed to demonstrate how they will perform on a larger scale, their added value in a real setting and ther safety profile.
... 43 Another study in Soweto, South Africa, showed that all-cause diarrhoea hospitalisations in children < 5 years temporally decreased by 34% -57% in the post-rotavirus vaccination era. 44 In addition, rotavirus vaccine effectiveness against rotavirus diarrhoea hospitalisation was estimated at 57% (95% confidence interval [CI], 40-68) for two doses. 19 A trend towards delayed rotavirus season onset because of the introduction of rotavirus vaccine in August 2009 has been observed. ...
Background: Suspected diarrhoeal-illness outbreaks affecting mostly children 5 years were investigated between May and July 2013 in Northern Cape province (NCP) and KwaZulu-Natal (KZN) province. This study describes the epidemiological, environmental and clinical characteristics and diarrhoeal-illnesses causative agent(s).
Methods: A descriptive cross-sectional study was conducted. Cases were patients presenting at healthcare facilities with diarrhoeal-illness between 09 April and 09 July 2013 in NCP and 01 May and 31 July 2013 in KZN. Laboratory investigations were performed on stools and water samples using microscopy, culture and sensitivity screening and molecular assays.
Results: A total of 953 cases including six deaths (case fatality rate [CFR]: 0.6%) were recorded in the Northern Cape province outbreak. Children 5 years accounted for 58% of cases. Enteric viruses were detected in 51% of stools, with rotavirus detected in 43%. The predominant rotavirus strains were G3P[8] (45%) and G9P[8] (42%). Other enteric viruses were detected, with rotavirus co-infections (63%). No enteric pathogens detected in water specimens. KwaZulu-Natal outbreak: A total of 1749 cases including 26 deaths (CFR: 1.5%) were recorded. Children 5 years accounted for 95% of cases. Rotavirus was detected in 55% of stools; other enteric viruses were detected, mostly as rotavirus co-infections. The predominant rotavirus strains were G2P[4] (54%) and G9P[8] (38%).
Conclusion: Although source(s) of the outbreaks were not identified, the diarrhoeal-illnesses were community-acquired. It is difficult to attribute the outbreaks to one causative agent(s) because of rotavirus co-infections with other enteric pathogens. While rotavirus was predominant, the outbreaks coincided with the annual rotavirus season.
... There is mixed evidence of herd protection by RVs in lowincome countries. Whereas studies from Zambia and South Africa showed no evidence of RV indirect protection [16,17], studies conducted in Zimbabwe and Rwanda showed indirect protection by RV [18,19]. A study in Malawi also demonstrated some evidence of indirect protection in infants <12 months, but not in older children following RV introduction into routine immunization programs for infants [20]. ...
Background: Rotavirus is one of the causes of severe diarrhea and death in children. Studies showed varying level of efficacies (20% to 85%) of the rotavirus vaccine. Since earlier cluster-randomized effectiveness trial (CRT) conducted in rural Bangladesh showed only 29% overall effectiveness, reflecting little to no herd protection, we reanalyzed the data using the fried-egg approach.
Methods: The study was conducted in rural Matlab, Bangladesh. In the CRT, among 142 villages, 71 in human rotavirus vaccine (HRV) villages and rests in non-HRV villages. The infants at 6 months age received HRV, Rotarix, over nearly three-year period (2008 through 2011). We analyzed HRV protection against acute rotavirus diarrhea (ARD) for the entire clusters, and in innermost areas of the clusters. We assume if the population level effectiveness and herd effects were attenuated by rotavirus transmissions into the clusters from the outside, the effectiveness may evident among population living in the innermost part of the clusters.
Results: Among 10,917 age-eligible (6-20 weeks) children; 5,759 (53%) were in the HRV villages, 80% received at least one dose of Rotarix . We had 156 ARD cases in the HRV and 193 cases in the non-HRV villages. Estimates of overall protection against ARD was 30% (95% CI: 13%, 44%; p=0.0012) in P100 group (entire cluster), 28% (95% CI: 8%, 43%; p=0.0078) in P75 group, 16% ( 95% CI: -6%, 34%; p=0.14) in P50 group, and 37% (95% CI: 8%, 56%; p=0.0157) in P25 group (innermost yolk). Estimates of total protection against ARD was 38% (95% CI: 19%, 52%; p =0.0004) in P100 group, similar estimates for P75 group (PE=35%, 95% CI: 14%, 51%; p=.0029). Total protection was not observed in the P50 group (PE=19%, 95% CI: -6%, 38%; p=0.13). The total protection rose to 43% (95% CI: 12%, 64%; p=0.0124) in the P25 group. No indirect vaccine protection was observed in any clusters.
Conclusion: The fried-egg approach did not reveal improvement of the population level effectiveness restricting the children living in the innermost cluster compared to the entire clusters. We think the failure to reveal herd protection in the innermost clusters was due to the high basic reproduction number of rotavirus, which may have negated the transmission buffering effect of the cluster residents outside the yolk. Further studies are warranted to confirm the evidence of this study.
... Generally, in Africa, RV appears to remain an important cause of diarrhoea that requires admission to hospital following RV introduction even when deploying molecular diagnostics, which have improved attribution of diarrhoea to a broad range of enteropathogens [40,46]. Therefore, continuous surveillance post-vaccine introduction which has proven evidence of remarkable impact, with consistent reductions in admissions to hospital due to diarrhoea, all-cause severe diarrhoea, and specifically RV diarrhoea [46][47][48], is imperative and encouraged. ...
The University of the Free State - Next Generation Sequencing (NGS) Unit, Bloemfontein, South Africa, hosted a data and bioinformatics workshop from 19 to 22 June 2018. The workshop was coordinated by the African Enteric Viruses Genome Initiative (AEVGI) with support from the Bill & Melinda Gates Foundation. The event introduced technologies in NGS and data analysis with focus on the rotavirus (RV) genome. The workshop fostered interactions and networking between professionals, scientific experts, technicians and students. The courses provided an overview of RV diarrhoea and its burden in Africa, while highlighting the key resources and methodologies in NGS and advanced bioinformatics in deciphering vaccine impact. It was concluded that, despite the reported significant decline in RV associated-diarrhoea mortality and morbidity in Africa due to RV vaccine impact, the need for continuous surveillance and genomic characterization to better understand the ever-changing dynamics of RV strains is imperative.
... These benefits are of lesser importance in areas with high vaccine effectiveness and uptake (developed countries), but could help swing the pendulum further in favor of rotavirus vaccination in areas where vaccine effectiveness and coverage may be lower [20,40]. Data on indirect protection in developing countries is less clear, and additional work is needed to better understand the extent of herd protection in these settings [40,71,72]. ...
Introduction
Rotavirus is the leading cause of acute diarrhea among children <5 years worldwide. As all children are equally susceptible to infection and disease development, rotavirus vaccination programs are the best upstream approach to preventing rotavirus disease, and the subsequent risk of hospitalization or death.
Areas covered
We provide an overview of global rotavirus vaccine policy, summarize the burden of rotavirus disease in developing countries, review data on the effectiveness, impact, safety, and the cost-effectiveness of rotavirus vaccination programs, and identify areas for further research and improvement.
Expert opinion
Rotavirus vaccines continue to be an effective, safe, and cost-effective solution to preventing rotavirus disease. As two new rotavirus vaccines enter the market (Rotasiil and Rotavac) and Asian countries continue to introduce rotavirus vaccines into their national immunization programs, documenting vaccine safety, effectiveness, and impact in these settings will be paramount.
... Inclusion of herd effects could make the benefit-risk ratios more favourable in some settings, but it would be challenging to obtain robust estimates of the scale and duration of these effects in each of the 135 LMICs. Transmission dynamic models calibrated to data from Niger 42 and India 43 have predicted a minimal contribution of indirect effects to overall vaccine effect, and although short-term herd effects have been observed in El Salvador, 44 Ghana, 1 Moldova, 1 and Rwanda, 45 no substantial herd effects were observed in Malawi, 46 South Africa, 47 Tanzania, 1 and Zambia. 48 In principle, transmission dynamic models could be used to anticipate the longer-term effect and relative advantages of different vaccination schedule options but these models will require access to good quality data on disease surveillance and social contact patterns in narrow age groups. ...
Background:
Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages.
Methods:
All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5·0 years, with and without restrictions on age at administration. Benefit-risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria-tetanus-pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1.
Findings:
A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000-100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77-550) excess intussusception deaths (1·4% increase) compared with no vaccination, resulting in a benefit-risk ratio of 369:1 (160:1-895:1). The benefit-risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit-risk ratios.
Interpretation:
Rotavirus vaccines have a favourable benefit-risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits.
Funding:
Bill & Melinda Gates Foundation.
... [27] Similarly, in Soweto, introduction of the rotavirus vaccine into the SA immunisation programme was temporally associated with a decrease of between 34% and 57% in the overall incidence of allcause hospitalisations for diarrhoea of children aged <5 years of age. [28] Estimates from the 2016 Rapid Mortality Surveillance Report, [29] however, suggest that there had been only a slight improvement in under5 mortality after 2012, indicating that the impact of the interventions to reduce diarrhoeal disease and pneumonia in children together with PMTCT of HIV may have reached a limit. However, based on the modelled impact of known costeffective interventions, Chola et al. [30] demonstrated that further investment in 15 interventions, including labour and delivery management, early HIV treatment in pregnancy, PMTCT and handwashing with soap, will enable SA to reduce child mortality considerably. ...
Background:
The Rapid Mortality Surveillance System has reported reductions in child mortality rates in recent years in South Africa (SA). In this article, we present information about levels of mortality and causes of death from the second SA National Burden of Disease Study (SA NBD) to inform the response required to reduce child mortality further.
Objectives:
To estimate trends in and causes of childhood mortality at national and provincial levels for the period 1997 - 2012, to highlight the importance of the SA NBD.
Methods:
Numbers of registered child deaths were adjusted for under-reporting. Adjustments were made for the misclassification of AIDS deaths and the proportion of ill-defined natural causes. Non-natural causes were estimated using results from the National Injury Mortality Surveillance System for 2000 and the National Injury Mortality Survey for 2009. Six neonatal conditions and 11 other causes were consolidated from the SA NBD and the Child Health Epidemiological Reference Group lists of causes of death for the analysis. The NBD cause-fractions were compared with those from Statistics South Africa, the United Nations Children's Fund (UNICEF) and the Institute for Health Metrics and Evaluation (IHME).
Results:
Under-5 mortality per 1 000 live births increased from 65 in 1997 to 79 in 2004 as a result of HIV/AIDS, before dropping to 40 by 2012. The neonatal mortality rate declined from 1997 to 2001, followed by small variations. The death rate from diarrhoeal diseases began to decrease in 2008 and the death rate from pneumonia from 2010. By 2012, neonatal deaths accounted for 27% of child deaths, with conditions associated with prematurity, birth asphyxia and severe infections being the main contributors. In 1997, KwaZulu-Natal, Free State, Mpumalanga and Eastern Cape provinces had the highest under-5 mortality, close to 80 per 1 000 live births. Mortality rates in North West were in the mid-range and then increased, placing this province in the highest group in the later years. The Western Cape had the lowest mortality rate, declining throughout the period apart from a slight increase in the early 2000s.
Conclusions:
The SA NBD identified the causes driving the trends, making it clear that prevention of mother-to-child transmission of HIV, the Expanded Programme on Immunisation and programmes aimed at preventing neonatal deaths need to be equitably implemented throughout the country to address persistent provincial inequalities in child deaths. The rapid reduction of childhood mortality since 2005 suggests that the 2030 Sustainable Development Goal target of 25 per 1 000 for under-5 mortality is achievable for SA. Comparison with alternative estimates highlights the need for cause-of-death data from civil registration to be adjusted using a burden-of-disease approach.
... In conclusion, the risk of intussusception in the 1-7 and 8-21 days after the first or second dose of the monovalent oral rotavirus vaccine was not found to be higher than the background risk of intussusception among infants in South Africa. Postlicensure impact studies in our country have shown significant decreases in rotavirus-specific hospitalizations, with a 61%-69% reduction in the first 2 years after vaccine introduction, and sustained reductions in all-cause diarrheal hospitalizations in children <2 years of age [29,30]. The absence of an increased risk of intussusception after rotavirus vaccination in an upper-middle-income African country is reassuring. ...
Background:
Post-licensure studies have shown an association between rotavirus vaccination and intussusception. We assessed the risk of intussusception associated with Rotarix® (RV1) administration, at six and 14 weeks of age, in an upper-middle income country, South Africa.
Methods:
Active prospective surveillance for intussusception was conducted in eight hospitals from September 2013-December 2017. Retrospective case enrolment was done at one hospital from July 2012-August 2013. Demographic characteristics, symptom onset and rotavirus vaccine status were ascertained. Using the self-controlled case-series method, we estimated age-adjusted incidence-rate ratios within 1-7, 8-21, and 1-21 days of rotavirus vaccination in children aged 28-275 days at onset of symptoms. In addition, age-matched controls were enrolled for a subset of cases (n=169), and a secondary analysis performed.
Results:
There were 346 cases included in the case-series analysis. Post-dose one, there were zero intussusception cases within 1-7 days, and five cases within 8-21 days of vaccination. Post-dose two, 15 cases occurred within 1-7 days, and 18 cases within 8-21 days of vaccination. There was no increased risk of intussusception 1-7 days after dose one (no cases observed) or dose two (relative incidence (RI): 1·71; 95% confidence interval (CI) 0·83-3·01). Similarly, there was no increased risk 8-21 days after the first (RI: 4·01; 95% CI 0·87-10·56) or second dose (RI: 0·96; 95% CI 0·52-1·60). Results were similar for the case-control analysis.
Conclusions:
The risk of intussusception in the 21 days after the first or second dose of RV1 was not higher than the background risk among South Africa infants.
... 3 From 2009, a decrease in the total number of diarrhoea cases presenting at the surveillance sites was observed. This has been attributed to the introduction of the RV vaccine into the SA immunization schedule in 2009 and the concomitant reduction in the number of RV-associated diarrhoeal infections detected thereafter.42 The effect of the RV vaccine on HAstV gastroenteritis was not investigated in this study. ...
Background
The epidemiology of human astroviruses (HAstVs) in hospitalised patients <5 years of age from selected sites in South Africa (SA) was investigated. Diarrheagenic stool specimens collected from April 2009 to May 2014 were screened retrospectively for selected viruses, bacteria and parasites.
Method
Patient data were analysed to identify epidemiologic factors most frequently detected with HAstV infections. The following case‐comparisons were investigated; HAstV‐positive and HAstV‐negative children, human immunodeficiency virus (HIV)‐infected and HIV‐uninfected (HAstV‐positive) children and HIV‐exposed and unexposed (HAstV‐positive HIV‐uninfected) children.
Results
Astrovirus was identified in 7.0% (234/3 340) of cases and most frequently in ages 7 to 12 months (9.2%, 90/975) compared with 5.8%‐6.6% in other 6‐month age groups. No seasonal trends were observed. More HAstVs were detected in children from homes that used outdoor water sources (7.6%) compared to indoor sources (5.7%, aOR1.5, 95% CI 1.1‐2.1, p=0.009). Astroviruses were detected in 8.4% (67/799) of HIV‐uninfected patients that were exposed to HIV compared with 5.9% (74/1 257) of HIV‐unexposed patients (p=0.032).
Conclusion
Astroviruses were most prevalent in children aged 7 to 12 months and were detected throughout the study period. The study was limited as only hospitalised patients were investigated and no comparisons were made to diarrhoea‐free control groups. Future HAstV surveillance should include community‐based studies and children presenting at outpatient facilities.
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... 4,8 Conversely, monitoring after introduction has suggested a greater impact, with reductions in rotavirus diarrhoea, all-cause severe diarrhoea, and admissions to hospital due to diarrhoea that have been clear and consistent. [8][9][10] However, demonstration of a reduction in diarrhoea mortality would clearly lend the strongest possible support to broad programmatic introduction. ...
... The absence of observed indirect effects in these groups is contrary to findings from higher income settings and from Rwanda [13,18], but supported by studies from Zambia and South Africa which found no evidence of a rotavirus vaccine indirect effect in children too old to receive vaccine [29,30]. The absence of identifiable indirect effects in infants with severe disease could potentially be explained by the larger vaccine efficacy estimate in this group. ...
Introduction:
Despite increased use of vaccine in routine immunisation, rotavirus remains a major cause of acute gastroenteritis (AGE) in low-income countries. We describe rotavirus prevalence and hospitalisation in Malawi pre and four years post vaccine introduction; provide updated vaccine effectiveness (VE) estimates; and assess rotavirus vaccine indirect effects.
Methods:
Children under five years of age presenting to a referral hospital in Blantyre with AGE were recruited. Stool samples were tested for rotavirus using Enzyme Immunoassay. The change in rotavirus prevalence was evaluated using Poisson regression. Time series analysis was used to further investigate trends in prevalence over time. VE against rotavirus diarrhoea of any severity was estimated using logistic regression. Indirect effects were estimated by evaluating rotavirus prevalence in unvaccinated children over time, and by comparing observed reductions in incidence of rotavirus hospitalisation to those expected based on vaccine coverage and trial efficacy estimates.
Results:
2320 children were included. Prevalence of rotavirus in hospitalised infants (<12 months) with AGE decreased from 69/139(49.64%) prior to vaccine introduction to 197/607(32.45%) post-vaccine introduction (adjusted RR 0.67[95% CI 0.55, 0.82]). Prevalence in children aged 12-23 months demonstrated a less substantial decline: 15/37(40.54%) pre- and 122/352(34.66%) post-vaccine introduction (adjusted RR 0.85, 95% CI 0.57, 1.28). Adjusted VE was 61.89%(95% CI 28.04-79.82), but lower in children aged 12-23 months (31.69% [95% CI -139.03 to 80.48]). In hospitalised infants with rotavirus disease, the observed overall effect of the vaccine was 9% greater than expected according to vaccine coverage and efficacy estimates. Rotavirus prevalence among unvaccinated infants declined post-vaccine introduction (RR 0.70[95% CI 0.55-0.80]).
Conclusions:
Following rotavirus vaccine introduction in Malawi, prevalence of rotavirus in hospitalised children with AGE has declined significantly, with some evidence of an indirect effect in infants. Despite this, rotavirus remains an important cause of severe diarrhoea in Malawian children, particularly in the second year of life.
... Rotavirus vaccine administration was timely and coverage was high with over 93% of age-eligible children fully vaccinated during this 31 month period [1]. These findings are in line with those from other early introducing countries in sub-Saharan Africa which also showed substantial reductions in diarrhea hospitalizations following rotavirus vaccine introduction [2][3][4][5][6][7][8][9]. However, several countries in the region also showed lower protection of the vaccine in the second year of life and a shifting of the disease burden to older ages [1,5,7]. ...
Introduction:
Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction.
Methods:
Active sentinel surveillance for acute gastroenteritis hospitalizations among children <5 years of age was conducted at two sites from July 2009 through June 2016. Stool specimens were collected from enrolled children and tested by enzyme immunoassay. Changes in the proportion of all-cause gastroenteritis hospitalizations due to rotavirus pre- (July 2009-June 2012) and post-vaccine introduction (July 2012-June 2016) were compared using chi-square test.
Results:
The proportion of acute gastroenteritis hospitalizations due to rotavirus among children <5 years of age significantly declined by 42% from a pre-vaccine median of 50% (343/684) to a post-vaccine median of 29% (118/396) (p < 0.001). The age distribution of rotavirus hospitalizations shifted toward older ages with 64% (759/1197) of rotavirus hospitalizations occurring in children <12 months of age pre-vaccine introduction to 47% (212/453) occurring in children <12 months of age post-vaccine introduction (p < 0.001).
Discussion:
The decline in rotavirus hospitalizations following rotavirus vaccine introduction have been sustained over the first 4 years of the vaccination program in Ghana. Continued vaccination against rotavirus will ensure that this burden remains low.
... The ideal goal would be to have the severe rotavirus burden reasonably measured before and after vaccine introduction to be able to quantitate the change in the true outcome that the vaccine addresses. Examining trends in overall diarrheal hospitalizations can be attempted when rotavirus-specific data are not available, as was done here at these particular hospitals and in others in the African region [8][9][10][11][12], in part because this ''syndromic"-type disease reduction can resonate more clearly with policy makers on the value of an intervention. However, there are inherent limitations in ecologic analyses with this non-specific outcome, particularly in resource-limited settings that have a high burden of diarrheal illness from pathogens other than rotavirus. ...
Background:
The Tanzania Ministry of Health introduced monovalent human rotavirus vaccine in January 2013, to be administered at ages 6 and 10 weeks. Data suggest there was high vaccine uptake. We used hospital ward registers from 3 hospitals to examine trends in diarrhea hospitalizations among infants before and after vaccine introduction.
Methods:
Ward registers from Dodoma Regional Referral Hospital (Central Tanzania), and two hospitals in Mbeya (Southwest area), Mbeya Zonal Referral Hospital and Mbalizi Hospital, were used to tally admissions for diarrhea among children by age group, month and year. Rotavirus surveillance had started at these hospitals in early 2013; the proportion of infants enrolled and rotavirus-EIA positive were examined by month to determine peak periods of rotavirus disease post-vaccine introduction.
Results:
Registers were available for 2-4 prevaccine years and 2-3 post introduction years. At Dodoma Regional Referral Hospital, compared with the mean of 2011 and 2012, diarrhea hospitalizations among infants were 26% lower in 2015 and 58% lower in 2016. The diarrhea peak shifted later in the year first by 1 and then by 2-3 months from prevaccine. At the Mbeya hospitals, the number of diarrhea admissions in prevaccine period varied substantially by year. At Mbeya Referral Hospital, diarrhea hospitalizations among infants were lower by 25-37% in 2014 and 11-26% in 2015, while at Mbalizi Hospital, these hospitalizations were 4% lower in 2014 and 14% higher in 2015. Rotavirus testing data demonstrated a lowering of the prevaccine peak, a shift in timing of the peak months and indicated that other diarrheal peaks in post-introduction years were not due to rotavirus.
Conclusions:
In this ecological evaluation, total diarrhea hospitalizations among infants were lower (≥25% lower in ≥1 year) following introduction in 2 of 3 hospitals. There are challenges in using ward registers to ascertain possible impact of rotavirus vaccine introduction on trends in hospitalizations for treatment of all diarrheal illness.
... Several programmatic strategies have also been evaluated to boost rotavirus VE, including improving nutrition status, recommending alternative ages of administration, timing of breastfeeding, and supplementation with zinc [53][54][55][56][57][58][59][60][61][62][63]. Findings from studies that considered alternate ages of administration have been mixed, with one study demonstrating improved immunogenicity with older administration of Rotarix and two others showing no impact [29,56,64,65]. There was concern that lower VE may be because rotavirus vaccine is neutralized by high maternal antibody in breastmilk in settings with high rotavirus burden. ...
Rotavirus is the leading cause of diarrheal death among children < 5 years old worldwide, estimated to have caused ~ 215,000 deaths in 2013. Prior to rotavirus vaccine implementation, > 65% of children had at least one rotavirus diarrhea illness by 5 years of age and rotavirus accounted for > 40% of all-cause diarrhea hospitalizations globally. Two live, oral rotavirus vaccines have been implemented nationally in > 100 countries since 2006 and their use has substantially reduced the burden of severe diarrheal illness in all settings. Vaccine efficacy and effectiveness estimates suggest there is a gradient in vaccine performance between low child-mortality countries (> 90%) and medium and high child-mortality countries (57–75%). Additionally, an increased risk of intussusception (~ 1–6 per 100,000 vaccinated infants) following vaccination has been documented in some countries, but this is outweighed by the large benefits of vaccination. Two additional live, oral rotavirus vaccines were recently licensed and these have improved on some programmatic limitations of earlier vaccines, such as heat stability, cost, and cold-chain footprint. Non-replicating rotavirus vaccines that are parenterally administered are in clinical testing, and these have the potential to reduce the performance differential and safety concerns associated with live oral rotavirus vaccines.
... In South-Africa, this was associated with a 65% reduction in all-cause diarrheal hospitalizations in the 2010-2015 period in both HIV-infected and uninfected children. 25 Following earlier, smaller studies of rotavirus vaccination among HIV infected children, results from a large randomized controlled trial conducted in HIV exposed and HIV infected children in South-Africa recently demonstrated safety and immunogenicity of RV5 in both populations. 26 Dr. Gianquinto emphasized this is an important and reassuring confirmation that vaccination of HIV infected and exposed populations should be promoted. ...
The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include:
Rotavirus vaccination programmes in Europe have resulted in reductions of 60–90% in rotavirus outpatient visits and hospitalizations. Long term trends indicate this impact is sustained over the years. Herd effects, protecting unvaccinated children and neonates too young to be vaccinated have been observed in many European countries. Early evidence now also suggests that rotavirus vaccination may be instrumental in the prevention of celiac disease. Special attention should be given to preterm infants, who may age out of the vaccination window before hospital discharge and to HIV infected children who are at increased risk of severe rotavirus AGE. There is a small but increased risk of IS following rotavirus vaccination and parents should therefore be informed about possible signs and symptoms of IS. New insights in rotavirus genetic susceptibility and interactions with microbiome may open opportunities for interventions to improve protection by vaccination, in particular in LMIC. The development of several novel rotavirus vaccines discussed at the meeting is also promising in this respect.
... However, in the corresponding period of the post vaccination year, this peak did not happen and moved to August and September. This result was also observed in South Africa [15] and other African countries being attributed to the introduction of rotavirus vaccination in the routine immunization [13,14]. ...
Background:
Mozambique introduced rotavirus vaccine (Rotarix, GSK Biologicals) in the National Immunization Program in September 2015 with the objective of reducing the burden of total diarrheal disease and specifically severe rotavirus disease. This study aimed to evaluate the early impact of rotavirus vaccine in reducing all-cause diarrhea and rotavirus-specific hospitalizations.
Methods:
We analysed stool specimens collected from children under five years old, between January 2014 and June 2017 within the National Surveillance for Acute Diarrhea. We compared annual changes in rotavirus positivity, median age of children hospitalized for rotavirus and the number of all-cause for diarrheal hospitalizations. Rotavirus detection was performed using enzyme immunoassay.
Results:
During this period, 1296 samples were collected and analyzed. Rotavirus positivity before vaccine introduction was 40.2% (39/97) in 2014 and 38.3% (225/588) in 2015, then after vaccine introduction reduced to 12.2% and 13.5% in 2016 and 2017, respectively. The median age of children hospitalized for rotavirus was 9 and 11 months in 2014 and 2015 and 10 months in 2016 and 2017. Rotavirus hospitalizations exhibited a seasonal peak prior to vaccine introduction, between June and September in 2014 and 2015, coinciding with winter period in Mozambique. After vaccine introduction, the peak was delayed until August to December in 2016 and was substantially diminished. There was a reduction in all-cause acute diarrhea hospitalizations in children aged 0-11 months after vaccine introduction.
Conclusion:
We observed a reduction in rotavirus positivity and in the number of all-cause diarrhea hospitalizations after vaccine introduction. The data suggest rotavirus vaccine is having a positive impact on the control of rotavirus diarrheal disease in Mozambique.
... Since their introduction in 2006, rotavirus vaccines have decreased the morbidity and mortality of diarrheal disease in many countries that have included them in their national immunization programs [1][2][3][4]. Evidence from post-licensure studies continues to demonstrate decreases in rotavirus-related morbidity and mortality in these countries, however a low-level risk of intussusception has also been described following rotavirus vaccination [5][6][7][8]. ...
Introduction:
Rotavirus vaccines have significantly decreased the burden of diarrheal diseases in countries that have introduced them into their immunization programs. In some studies, there has been a small association between rotavirus vaccines and intussusception in post-marketing surveillance, highlighting the importance of tracking incidence before and after vaccine introduction. The objective of this study was to describe the epidemiology of intussusception among Bangladeshi children pre-vaccine introduction.
Methods:
We conducted active, hospital-based surveillance for intussusception at 7 tertiary care hospitals with pediatric surgical facilities during July 2012 to September 2016. Hospitalized children under 2years of age were identified according to Brighton Collaboration level 1 criteria for intussusception. The frequency and proportion of intussusception among overall surgical admissions, as well as the demographic and clinical information of the cases is described.
Results:
Overall 153 cases of intussusception among children <2years-old were identified at participating sites over the enrolment period, confirmed by Level 1 Brighton criteria. These cases represented 2% of all surgical admissions under 2years of age. One hundred twelve cases (73%) were male; the median age was 7months; and the median duration of hospitalization was 7days. One hundred forty-six (95%) children with intussusception required surgery, and 11 (7%) died.
Conclusions:
Confirmed cases of intussusception represented nearly 2% of pediatric surgical admissions at tertiary referral centers in Bangladesh during the study period and 7% of children with intussusception died. Given the high burden of rotavirus disease in Bangladesh, vaccine introduction is warranted, however, further studies after introduction of rotavirus vaccine are necessary to determine any association between vaccine and intussusception in this setting.
... Experience with the two internationally licensed vaccines -Rotarix and Rotateq -in 36 low-income countries confirms the drop in effectiveness with increasing under-five mortality rate in a country [5]. This lower effectiveness is associated with diminished immunogenicity and potentially a more limited herd-effect [6][7][8]. Thus, although rotavirus vaccination results in substantial health benefits in low-income countries, reflecting the high burden of disease, these benefits are more limited than if the vaccine were to perform at the levels seen in high-income countries. In India, a newly licensed (since 2014) locally manufactured vaccine (Rotavac) is being introduced to the routine immunization schedule. ...
Background:
Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.
Methods:
Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (10(10)Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration.
Results:
The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions.
Conclusions:
Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation.
Trial registration:
The trial was registered in India (CTRI/2012/05/002677).
... The substantial reduction of hospitalization in children younger than 12 months after vaccine introduction further supports the hypothesis that the observed decline in rotavirus hospitalizations can be attributed to the introduction of rotavirus vaccination in the routine immunization program. Similar results were also observed in South Africa [19] and other African countries following the introduction of rotavirus vaccination in the routine immunization [20,21]. ...
Background:
Swaziland introduced rotavirus vaccine in the National Immunization Program, in May 2015, with the objective of reducing the burden of rotavirus diarrheal disease. We monitored the early impact of the vaccine in reducing rotavirus diarrhea.
Methods:
We conducted sentinel rotavirus surveillance from January 2013 to December 2016 in children under five years of age admitted due to diarrhea attending Mbabane Government Referral Hospital in the Hhohho Region and Raleigh Fitkin Memorial Hospital in the Manzini Region. All cases had stool samples collected and tested for rotavirus antigen by enzyme immunoassay.
Results:
Between 2013 and 2016, 596 samples were collected and tested. Rotavirus positivity reduced from average of 50.8% (172/338) (in 2013-2014 (pre vaccine period)) to 29% (24/82) in 2016, post-vaccine introduction. The median age of children with rotavirus infection increased from average of 10months in 2013-2014 to 13.7months in 2016. The peak season for all-cause diarrhea and rotavirus-specific hospitalizations among children under five years of age was June-August in all years with a blunting of the peak season in 2016. Rotavirus positivity among children 0-11months reduced from an average of 49% in 2013-2014 (116/236) to 33% (15/45) in 2016, a 33% reduction following rotavirus vaccine introduction.
Conclusion:
There has been a rapid reduction of all-cause diarrhea and rotavirus hospitalizations in Swaziland, particularly in young children and during the rotavirus season, after the introduction rotavirus vaccine. Continued surveillance is needed to monitor the long-term impact of rotavirus vaccine introduction.
... These results are similar to those reported by other countries, including recent data from other African countries. [7][8][9][10][11][12] Our findings were consistent across data sources of different acuity levels and geographic scope in Zimbabwe. Prospective, active surveillance from 3 sentinel hospitals, a retrospective log book review of hospitalizations from the 3 sentinel hospitals and national-level, diarrhea-related outpatient visits all showed annual peaks of diarrhea-related healthcare visits in May and June before vaccine introduction. ...
Background:
In Zimbabwe, rotavirus accounted for 41-56% of acute diarrhea hospitalizations prior to rotavirus vaccine introduction in 2014. We evaluated rotavirus vaccination impact on acute diarrhea and rotavirus-related healthcare visits in children.
Methods:
We examined monthly and annual acute diarrhea and rotavirus test-positive hospitalizations and A&E visits among children <60 months at three active surveillance hospitals during 2012-2016; we compared pre-vaccine introduction (2012-2013) with post-vaccine introduction (2015 and 2016) data for two of the hospitals. We examined monthly acute diarrhea hospitalizations by year and age group for 2013-2016 from surveillance hospital registers and monthly acute diarrhea outpatient visits reported to the Ministry of Health and Child Care during 2012-2016.
Results:
Active surveillance data showed winter seasonal peaks in diarrhea and rotavirus-related visits among children <60 months during 2012-2014 that were substantially blunted in 2015 and 2016 following vaccine introduction; the percentage of rotavirus test-positive visits followed a similar seasonal pattern and decrease. Hospital register data showed similar pre-introduction seasonal variation and post-introduction declines in diarrhea hospitalizations among children 0-11 and 12-23 months. Monthly variation in outpatient diarrhea-related visits mirrored active surveillance data patterns. At two surveillance hospitals, the percentage of rotavirus-positive visits declined by 40% and 43% among children 0-11 months and by 21% and 33% among children 12-23 months in 2015 and 2016, respectively.
Conclusion:
Initial reductions in diarrheal illness among children <60 months, particularly among those 0-11 months, following vaccine introduction are encouraging. These early results provide evidence to support continued rotavirus vaccination and rotavirus surveillance in Zimbabwe.
... Formal vaccine effectiveness studies are difficult to conduct in broad surveillance studies for which vaccine card confirmation of vaccination status is not available, but a comparison of RV age-eligible and age-ineligible children provided indirect evidence for a strong RV effect in Africa, with a 46% effectiveness of vaccine introduction. This estimate is, as expected, lower than estimates from clinical trials and vaccine effectiveness studies showing rotavirus vaccine effectiveness of approximately 50%-60% in African countries, for which individual-level vaccination histories were available [12][13][14][15]. Future testing will allow further assessment of vaccine effectiveness in diverse countries. ...
Background
The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.
Methods
We performed qPCR for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously-developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs).
Results
Rotavirus remained the leading etiology (overall weighted AF 40.3%; 95% CI 37.6 – 44.3), though the AF was substantially lower in the Americas (12.2; 8.9 – 15.6), based on samples from a country with universal rotavirus vaccination. Norovirus GII (6.2; 2.8 – 9.2), Cryptosporidium (5.8; 4.0 – 7.6), Shigella (4.7; 2.8 – 6.9), heat-stable enterotoxin-producing E. coli (ST-ETEC)(4.2; 2.0 – 6.1) and adenovirus 40/41 (4.2; 2.9 – 5.5) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% confidence interval: 48.3 – 61.5) in RV age-ineligible children to 20.0% (12.4 – 30.4) in age-eligible children.
Conclusions
Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of RV introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.
Infectious diarrhoea contributes to high morbidity and mortality in young children from sub-Saharan Africa. The aim of this study was to assess the prevalence of single and multiple diarrhoeal-causing pathogen combinations in children suffering from diarrhoea from rural and peri-urban communities in South Africa. A total of 275 diarrhoea stool specimens were collected between 2014 and 2016 from Hospitals and Primary Health Care clinics. The BioFire® FilmArray® Gastrointestinal panel was used to simultaneously detect 22 diarrhoea pathogens (viruses, bacteria, parasites) known to cause diarrhoea. A total of 82% (226/275) enteric pathogens were detected in the stool specimens. The two most detected bacterial, viral and parasitic pathogens each included: EAEC (42%), EPEC (32%), Adenovirus F40/41 (19%), Norovirus (15%), Giardia (8%) and Cryptosporidium (6%), respectively. Single enteric pathogen infections were recorded in 24% (65/275) specimens with EAEC, and Norovirus was found in 26% (17/65) and 14% (9/65) of the specimens, respectively. Multiple enteric pathogen combinations were recorded in 59% (161/275) of the stool specimens with 53% (85/161) containing two pathogens, 22% (35/161) containing three pathogens and 25% (41/161) containing four or more pathogens. The results from this study demonstrated the complex nature of pathogen co-infections in diarrhoeal episodes which could have an impact on treatment effectiveness.
Aichi virus 1 (AiV-1) has a worldwide distribution and is associated with gastroenteritis in humans. In this study, raw sewage and mussel samples were analyzed for the presence of AiV-1 using reverse transcription-PCR (RT-PCR). Amplification and sequencing of the 3CD and VP1 genomic regions followed by phylogenetic analysis using selected genome sequences revealed the presence of AiV-1, genotype B. The results highlight the importance of further screening to evaluate the prevalence and epidemiology of this clinically important virus in South Africa.
Acute infectious diarrhea is one of the leading causes of morbidity and mortality globally, resulting in an estimated 1.3 million deaths per year. While infectious diarrhea is caused by a variety of pathogens, most cases can be successfully managed with rehydration, typically oral rehydration therapy. Antimicrobial therapy is only needed in specific circumstances. Improved nutrition, sanitation and, more recently, vaccination have led to a dramatic reduction in diarrheal deaths over the last several decades.
Importance
Since 2000, the Lanzhou lamb rotavirus vaccine has been exclusively licensed in China for voluntary rotavirus gastroenteritis (RV-GE) prevention.
Objective
To evaluate the association of the Lanzhou lamb rotavirus vaccination with RV-GE among children in southern China.
Design, Setting, and Participants
This cross-sectional, ecological study was set in Guangzhou, China. Participants were infants possibly vaccinated (aged 2 months to 3 years) and the children ineligible for vaccination (aged ≥4 years). The study was conducted from May 1, 2007, to April 30, 2016, and the data analysis was conducted in July 2016.
Main Outcomes and Measures
Annual median age at onset of RV-GE and seasonal distribution of incidence. Cases of RV-GE in Guangzhou, China, diagnosed from May 1, 2007, to April 30, 2016, and reported to the National Information System for Disease Control and Prevention were examined. Poisson regression models were fitted among 32 452 children younger than 4 years and among 450 children who had been ineligible for vaccination, while controlling for secular trends, socioeconomic status, and meteorological factors. Logistic regression was used to assess the indirect effects provided by the vaccinated infants from 2009 to 2011 on unvaccinated infants aged 2 to 35 months based on a separate case-control data set.
Results
During 9 seasons, 119 705 patients with gastroenteritis were reported; 33 407 were confirmed for RV-GE (21 202 [63.5%] male, 32 022 [95.8%] aged <4 years, and 31 306 [93.8%] residing in urban districts). The median age at onset for all patients with RV-GE increased from 11 months during the 2007 season to 15 months during the 2015 season, and the onset, peak, and cessation of incidence were delayed. When citywide vaccination coverage in the prior 12 months was classified into high and low groups (≥8.36% vs <8.36%), the incidence rate ratio for the high coverage group decreased by 32.4% among children younger than 4 years (incidence rate ratio, 0.676; 95% CI, 0.659-0.693; P < .001). Among the children ineligible for vaccination, the incidence rate ratio in higher coverage periods was 0.790 (95% CI, 0.351-0.915; P < .001) compared with the lower coverage. Compared with districts with 14% or less vaccination coverage, the adjusted odds ratio for RV-GE among unvaccinated children younger than 3 years was 0.85 (95% CI, 0.73-0.99; P = .03) for districts with 15% to 19% of coverage, and 0.79 (95% CI, 0.67-0.93; P = .004) for districts with more than 20% of coverage.
Conclusions and Relevance
This study provides evidence of the population health benefits of the Lanzhou lamb rotavirus vaccination in preventing RV-GE among children in China younger than 4 years, including herd effects.
Background
Monovalent rotavirus vaccine (RV1) was introduced in Lusaka in February 2012 and rolled out countrywide in November 2013 in the routine Expanded Programme on Immunisation and administered at 6 and 10 weeks with no catch up dose. Reported here is the monitoring of rotavirus acute gastroenteritis hospitalisations at the University Teaching Hospital, Lusaka, Zambia as part of efforts to document the impact of rotavirus vaccine.
Methods
Children <5 years hospitalised for acute gastroenteritis (AGE) from January 2009 to December 2016 were recruited into the rotavirus disease burden active surveillance and had their stools tested for rotavirus by enzyme immunoassay. We compared rotavirus-associated AGE hospitalisations of the pre-vaccine era (2009–2011) with the post-rotavirus vaccine introduction period (2013–2016).
Results
With the increase in RV1 coverage in Lusaka, rotavirus AGE declined significantly from 40% of diarrhoea hospitalisation in the pre-vaccine era to 29% of diarrhoea hospitalisation in the post-vaccine era (p < 0.001) in children <5 years. After a decreasing trend in rotavirus positivity from 2013 to 2015, positivity increased to 37% in 2016. However, the post-vaccine years (2012–2016) saw substantial decline in the number tested (median decline: 34% (range: 20–43%)) and the number of positive results (median decline: 52% (range: 30–65%).
Conclusion
A sustained and significant decline in rotavirus AGE hospitalisations was observed in children <5 years since the introduction of RV1 in Lusaka, Zambia. Despite an increase in rotavirus positivity in 2016, the total number of children enrolled and the number of rotavirus positive children remained below baseline. The reason for the increase in rotavirus positivity in 2016 is unknown but could be due to an accumulation of susceptible children and the shifting of disease to children of older age groups. This finding underscores the need for continued monitoring of rotavirus vaccine impact.
Objectives:
A two-dose oral monovalent rotavirus vaccine (RV1) was introduced into the Kenyan National Immunization Program in July 2014. We assessed trends in hospitalisation for rotavirus-specific acute gastroenteritis (AGE) and strain distribution among children <5 years in a rural, resource-limited setting in Kenya before and after the nationwide implementation of the vaccine.
Methods:
Data on rotavirus AGE and strain distribution were derived from a 5-year hospital-based surveillance. We compared rotavirus-related hospitalisations and strain distribution in the 2-year post-vaccine period with the 3-year pre-vaccine baseline. Vaccine administrative data from the Unit of Vaccines and Immunization Services (UVIS) for Mbita sub-county were used to estimate rotavirus immunisation coverage in the study area.
Results:
We observed a 48% (95% CI: 27-64%) overall decline in rotavirus-related hospitalisations among children aged <5 years in the post-vaccine period. Coverage with the last dose of rotavirus vaccine increased from 51% in year 1% to 72% in year 2 of the vaccine implementation. Concurrently, reductions in rotavirus hospitalisations increased from 40% in the first year to 53% in the second year of vaccine use. The reductions were most pronounced among the vaccine-eligible group, with the proportion of cases in this age group dropping to 14% in post-vaccine years from a high of 51% in the pre-vaccine period. A diversity of rotavirus strains circulated before the introduction of the vaccine with G1P[8] being the most dominant strain. G2P[4] replaced G1P[8] as the dominant strain after the vaccine was introduced.
Conclusions:
Rotavirus vaccination has resulted in a notable decline in hospital admissions for rotavirus infections in a rural resource-limited population in Kenya. This provides early evidence for continued use of rotavirus vaccines in routine childhood immunisations in Kenya. Our data also underscore the need for expanding coverage on second dose so as to maximise the impact of the vaccine.
Background:
Monovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children.
Methods:
Sentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus.
Results:
During the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53-62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1-4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year.
Conclusions:
We report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.
The 9th African rotavirus symposium was held in Maputo, Mozambique from the 8th to 10th of December 2015, including a total of 101 delegates from 17 countries, 15 of which were African countries. This forum brought together participants with various expertise including scientists, clinicians, immunization program managers, public health officials and policymakers. By the time of the symposium, 29/47 (61%) of countries in the World Health Organization (WHO) African Region had introduced rotavirus vaccine into their routine immunization program. Countries that had started monitoring impact and effectiveness of the rotavirus vaccines as well as potential adverse events following immunization (AEFI) including intussusception) also participated. Seven Rotarix® vaccine-using countries and another four countries that are using the Rotateq® vaccine are conducting systematic surveillance on intussusception and report data to the WHO and partners. The symposium concluded that the regional rotavirus surveillance network has played a crucial role in pre-vaccine data through documenting burden and epidemiology of rotavirus diarrhea in Africa, seasonal trends and identifying common rotavirus genotypes. The sentinel surveillance platform is now being used to assess the impact of the vaccines and monitoring adverse events with a focus on intussusception.
Background. South Africa’s National Strategic Plan (NSP) for 2007 - 2011 aimed to achieve new antiretroviral treatment (ART) enrolment numbers equal to 80% of the number of newly eligible individuals in each year, by 2011. Objectives. To estimate ART coverage in South Africa and assess whether NSP targets have been met. Methods. ART data were collected from public and private providers of ART. Estimates of HIV incidence rates were obtained from independent demographic projection models. Adult ART data and incidence estimates were entered into a separate model that estimated rates of progression through CD4 stages, and the model was fitted to South African CD4 data and HIV prevalence data. Results. By the middle of 2011, the number of patients receiving ART in South Africa had increased to 1.79 million (95% CI 1.65 - 1.93 million). Adult ART coverage, at the previous ART eligibility criterion of CD4
Background. South Africa’s National Strategic Plan (NSP) for 2007 - 2011 aimed to achieve new antiretroviral treatment (ART) enrolment numbers equal to 80% of the number of newly eligible individuals in each year, by 2011.
Objectives. To estimate ART coverage in South Africa and assess whether NSP targets have been met.
Methods. ART data were collected from public and private providers of ART. Estimates of HIV incidence rates were obtained from independent demographic projection models. Adult ART data and incidence estimates were entered into a separate model that estimated rates of progression through CD4 stages, and the model was fitted to South African CD4 data and HIV prevalence data.
Results. By the middle of 2011, the number of patients receiving ART in South Africa had increased to 1.79 million (95% CI 1.65 - 1.93 million). Adult ART coverage, at the previous ART eligibility criterion of CD4
Rotavirus is the main cause of severe acute gastroenteritis in children in Africa. Monovalent human rotavirus vaccine (RV1) was added into Malawi's infant immunisation schedule on Oct 29, 2012. We aimed to assess the impact and effectiveness of RV1 on rotavirus gastroenteritis in the 2 years after introduction.
From Jan 1, 2012, to June 30, 2014, we recruited children younger than 5 years who were admitted into Queen Elizabeth Central Hospital, Blantyre, Malawi, with acute gastroenteritis. We assessed stool samples from these children for presence of rotavirus with use of ELISA and we genotyped rotaviruses with use of RT-PCR. We compared rotavirus detection rates in stool samples and incidence of hospital admittance for rotavirus in children from Jan 1 to June 30, in the year before vaccination (2012) with the same months in the 2 years after vaccination was introduced (2013 and 2014). In the case-control portion of our study, we recruited eligible rotavirus-positive children from the surveillance platform and calculated vaccine effectiveness (one minus the odds ratio of vaccination) by comparing infants with rotavirus gastroenteritis with infants who tested negative for rotavirus, and with community age-matched and neighbourhood-matched controls.
We enrolled 1431 children, from whom we obtained 1417 stool samples (99%). We detected rotavirus in 79 of 157 infants (50%) before the vaccine, compared with 57 of 219 (40%) and 52 of 170 (31%) in successive calendar years after vaccine introduction (p=0·0002). In the first half of 2012, incidence of rotavirus hospital admission was 269 per 100 000 infants compared with 284 in the same months of 2013 (rise of 5·8%, 95% CI -23·1 to 45·4; p=0·73) and 153 in these months in 2014 (a reduction from the prevaccine period of 43·2%, 18·0-60·7; p=0·003). We recruited 118 vaccine-eligible rotavirus cases (median age 8·9 months; IQR 6·6-11·1), 317 rotavirus-test-negative controls (9·4 months; 6·9-11·9), and 380 community controls (8·8 months; 6·5-11·1). Vaccine effectiveness for two doses of RV1 in rotavirus-negative individuals was 64% (95% CI 24-83) and community controls was 63% (23-83). The point estimate of effectiveness was higher against genotype G1 than against G2 and G12.
Routine use of RV1 reduced hospital admissions for several genotypes of rotavirus in children younger than 5 years, especially in infants younger than 1 year. Our data support introduction of rotavirus vaccination at the WHO recommended schedule, with continuing surveillance in high-mortality countries.
Wellcome Trust, GlaxoSmithKline Biologicals.
Copyright © 2015 Bar-Zeev, et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.
Background
Almost all diarrhea deaths in young children occur in developing countries. Immunization against rotavirus, the leading cause of childhood severe dehydrating acute diarrhea may reduce the burden of severe diarrhea in developing countries. Ghana introduced rotavirus and pneumococcal vaccination in the national expanded program on immunization in May 2012.
Methods
Review of all-cause diarrheal hospitalization data for children aged 59 months and younger at 2 pediatric referral hospitals in southern Ghana from 2008 to 2014. The proportion of acute diarrhea (defined as 3 or more watery, non-bloody stools within 24 hours that has lasted for less than 7 days) cases caused by rotavirus was determined. Temporal trend and age group distribution of all-cause diarrhea and rotavirus gastroenteritis before and after introduction of the new vaccines were compared.
Results
Of the 5847 children hospitalized with all-cause diarrhea during the 74 months (January 2008 – February 2014), 3963 (67.8%) children were recruited for rotavirus surveillance and stool specimens were tested for rotavirus in 3160/3963 (79.7%). Median monthly hospitalization for all-cause diarrhea reduced from 84 [interquartile range (IQR) 62 – 105] during the 52 months pre-vaccination introduction to 46 (IQR 42 - 57) in the 22 months after implementation of vaccination. Significant decline in all-cause diarrhea hospitalization occurred in children aged 0 - 11 months: 56.3% (2711/4817) vs. 47.2% 486/1030 [p = 0.0001, 95% confidence interval (CI) 0.77 – 0.88] and there was significant reduction of rotavirus gastroenteritis hospitalization: 49.7% (1246/2505) vs. 27.8% (182/655) [p = 0.0001, 95% CI 0.32 - 0.47] before and after vaccine introduction respectively.
Conclusions
Implementation of rotavirus vaccination program may have resulted in significant reduction of severe diarrhea hospitalization even though this observational study could not exclude the effect of other confounding factors. Continued surveillance is recommended to monitor the progress of this program.
Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection were introduced into the South African Expanded Programme on Immunization in April 2009. This article describes the rationale for and process of the introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus vaccine. It also aims to evaluate the success of and challenges related to their introduction, in terms of both achieving universal coverage and improving survival and health in South African children.
Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among US children <5 years of age. In the first 7 years of vaccine use, both recommended rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) have been shown to be highly effective in preventing outcomes of severe disease in US children in a variety of settings. In addition, substantial decreases in severe diarrheal disease in US children, exceeding the level expected based on vaccine coverage, as well as the extension of benefits to older age groups ineligible for vaccination have demonstrated both the direct and indirect impacts of vaccination in the USA.
(See the editorial commentary by Glass, on pages 975–7.)
Following the introduction of rotavirus vaccination in the United States, rotavirus and cause-unspecified gastroenteritis
discharges significantly decreased in 2008 in the 0–4, 5–14, and 15–24-year age groups, with significant reductions observed
in March, the historic peak rotavirus month, in all age groups. We estimate that 15% of the total 66 000 averted hospitalizations
and 20% of the $204 million in averted direct medical costs attributable to the vaccination program were among unvaccinated
5–24 year-olds. This study demonstrates a previously unrecognized burden of severe rotavirus in the population >5 years and
the primacy of very young children in the transmission of rotavirus.
Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.
We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.
A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.
Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.)
Rotavirus is a leading cause of childhood gastroenteritis and death worldwide.
We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events.
The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent).
This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)
The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.
We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).
The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).
Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)
Background:
Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.
Methods:
We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.
Results:
A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.
Conclusions:
Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.).
Rotavirus is the main cause of severe acute gastroenteritis in children in Africa. Monovalent human rotavirus vaccine (RV1) was added into Malawi's infant immunisation schedule on Oct 29, 2012. We aimed to assess the impact and effectiveness of RV1 on rotavirus gastroenteritis in the 2 years after introduction. From Jan 1, 2012, to June 30, 2014, we recruited children younger than 5 years who were admitted into Queen Elizabeth Central Hospital, Blantyre, Malawi, with acute gastroenteritis. We assessed stool samples from these children for presence of rotavirus with use of ELISA and we genotyped rotaviruses with use of RT-PCR. We compared rotavirus detection rates in stool samples and incidence of hospital admittance for rotavirus in children from Jan 1 to June 30, in the year before vaccination (2012) with the same months in the 2 years after vaccination was introduced (2013 and 2014). In the case-control portion of our study, we recruited eligible rotavirus-positive children from the surveillance platform and calculated vaccine effectiveness (one minus the odds ratio of vaccination) by comparing infants with rotavirus gastroenteritis with infants who tested negative for rotavirus, and with community age-matched and neighbourhood-matched controls. We enrolled 1431 children, from whom we obtained 1417 stool samples (99%). We detected rotavirus in 79 of 157 infants (50%) before the vaccine, compared with 57 of 219 (40%) and 52 of 170 (31%) in successive calendar years after vaccine introduction (p=0·0002). In the first half of 2012, incidence of rotavirus hospital admission was 269 per 100,000 infants compared with 284 in the same months of 2013 (rise of 5·8%, 95% CI -23·1 to 45·4; p=0·73) and 153 in these months in 2014 (a reduction from the prevaccine period of 43·2%, 18·0-60·7; p=0·003). We recruited 118 vaccine-eligible rotavirus cases (median age 8·9 months; IQR 6·6-11·1), 317 rotavirus-test-negative controls (9·4 months; 6·9-11·9), and 380 community controls (8·8 months; 6·5-11·1). Vaccine effectiveness for two doses of RV1 in rotavirus-negative individuals was 64% (95% CI 24-83) and community controls was 63% (23-83). The point estimate of effectiveness was higher against genotype G1 than against G2 and G12. Routine use of RV1 reduced hospital admissions for several genotypes of rotavirus in children younger than 5 years, especially in infants younger than 1 year. Our data support introduction of rotavirus vaccination at the WHO recommended schedule, with continuing surveillance in high-mortality countries. Wellcome Trust, GlaxoSmithKline Biologicals.
Background. South Africa's National Strategic Plan (NSP) for 2007-2011 aimed to achieve new antiretroviral treatment (ART) enrolment numbers equal to 80% of the number of newly eligible individuals in each year, by 2011. Objectives. To estimate ART coverage in South Africa and assess whether NSP targets have been met. Methods. ART data were collected from public and private providers of ART. Estimates of HIV incidence rates were obtained from independent demographic projection models. Adult ART data and incidence estimates were entered into a separate model that estimated rates of progression through CD4 stages, and the model was fitted to South African CD4 data and HIV prevalence data. Results. By the middle of 2011, the number of patients receiving ART in South Africa had increased to 1.79 million (95% CI 1.65-1.93 million). Adult ART coverage, at the previous ART eligibility criterion of CD4 <200/μl, was 79% (95% CI 70-85%), but reduced to 52% (95% CI 46-57%) when assessed according to the new South African ART eligibility criteria (CD4<350/μl). The number of adults starting ART in 2010/11 was 1.56 times (95% CI 1.08-1.97) the number of adults who became ART-eligible in 2010/11, well in excess of the 80% target. However, this ratio was substantially higher in women (1.96, 95% CI 1.33-2.51) than in men (1.23, 95% CI 0.83-1.58) and children (1.13, 95% CI 0.74-1.48). Conclusion. South Africa has exceeded the ART targets in its 2007-2011 NSP, but men and children appear to be accessing ART at a lower rate than women.
Background
The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme.
Methods
This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 – adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247.
Findings
Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40–68) for two doses and 40% (16–57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks–11 months (54%, 95% CI 32–68) and 12–23 months (61%, 35–77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34–80) and HIV-unexposed-uninfected children (54%, 31–69).
Interpretation
Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries.
Funding
GAVI Alliance (with support from PATH).
Oral rotavirus vaccine was introduced into the South African routine immunization program in August 2009 administered at 6 and 14 weeks with no catch up. We described the change in rotavirus-associated diarrheal hospitalizations among children <5 years at 3 sentinel sites from 2009 through 2011.
During 2009-2011, we compared the proportion of enrolled children aged <5 years hospitalized with acute gastroenteritis and testing rotavirus positive. We used hospital data to determine the change in diarrhea hospitalizations, and estimated total numbers of rotavirus hospitalizations by adjusting for non-enrolled patients. Stool samples were tested for rotavirus using EIA.
In 2009 (May- December), 46% (404/883) of samples amongst children <5 years tested rotavirus positive, decreasing to 33% (192/580) (p<0.001) in 2010 and 29% (113/396) (p<0.001) in 2011. Compared to May- December 2009, total diarrhea hospitalizations among children aged <5 years was one-third lower in May-December of 2010 and 2011. Among infants, adjusted rotavirus hospitalizations were 61% (n=267) and 69% (n=214) lower respectively in 2010 and 2011 when compared to 2009 (n=689), and 45 and 50 percentage points greater than the reduction in rotavirus-negative cases. Among children <5 years rotavirus hospitalizations were 54% and 58% lower in 2010 and 2011, compared to 2009 (40 and 44 percentage points greater than reduction in rotavirus-negative cases). Rotavirus reductions occurred in rural and urban settings.
Using published estimates of rotavirus hospitalization burden, we estimate that at least 13,000 to 20,000 hospitalizations in children <2 years were prevented in the two years following rotavirus vaccine introduction.
Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010-11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the first 2 years of life in both diseases-72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.
WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection.
We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates.
Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453,000 deaths (95% CI 420,000-494,000) in children younger than 5 years-37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98,621 deaths).
Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced.
Rotavirus vaccine for infants was introduced into the National Immunisation Program in Australia in July 2007. To determine the impact of rotavirus vaccination on gastroenteritis hospitalisations amongst children less than six years of age in South Australia, we conducted a retrospective analysis of hospital admissions over two time periods: 1 May 2005-30 April 2007 (prior to rotavirus vaccination introduction) and 1 May 2008-30 April 2010 (post rotavirus vaccination introduction). The introduction of rotavirus vaccination has been associated with a marked reduction in hospital admissions for serious rotavirus gastroenteritis (RVGE) and all-cause gastroenteritis (ACGE). Following the introduction of rotavirus vaccination in South Australia, there was an 83% reduction in RVGE coded admissions (955 vs 165) and a 48% reduction in ACGE coded admissions (4153 vs 2142) for children aged less than six years. Children less than two years demonstrated the greatest reduction (90%) in RVGE admissions and ACGE admissions (57%). Age-specific RVGE hospitalisation rates decreased from 933/100,000 prior to rotavirus vaccine introduction to 88/100,000 for children less than two years of age. In addition, for gastroenteritis hospitalisations for children aged five years at time of admission (unvaccinated cohort) there was a reduction in the number of RVGE cases (24 vs 4), a reduction in age-specific RVGE hospitalisation rates (65/100,000 vs 11/100,000) and a significant reduction in the proportion of overall gastroenteritis cases which were rotavirus positive (11.5% vs 3.5%), suggesting a positive impact on both unvaccinated and vaccinated children less than six years of age in South Australia.
Single-strain rotavirus vaccine was added to the national immunization program in Mexico in May 2007. We assessed the impact of vaccination on the number of diarrhea-related hospitalizations in Mexican children in 2008 and 2009.
We obtained data on all-cause diarrhea-related hospitalizations from January 2003 to June 2009 in Mexican children <5 years of age. We compared diarrhea-related hospitalizations during the 2008 and 2009 rotavirus seasons with the median number of diarrhea-related hospitalizations at baseline (2003-2006), before rotavirus vaccine introduction, at 306 Ministry of Health hospitals. We estimated vaccine coverage using administrative data.
A median number of 10,993 diarrhea-related hospitalizations (range: 9877-11958) occurred each prevaccine rotavirus season from 2003 to 2006 among children < 5 years of age. Diarrhea-related hospitalizations decreased by 11% (N = 9836) in 2008 and by 40% (N = 6597) in 2009. The greatest declines occurred in infants < 12 months of age during 2008 (25%) and 2009 (52%), with 1-dose rotavirus vaccination coverage of 74% and 89% during these years, respectively. A 43% decline was also noted among children 12 to 23 months of age during the 2009 season. No declines were noted during either 2008 or 2009 among unvaccinated children >24 months of age during the study period.
Marked declines in diarrhea-related hospitalizations among vaccine-eligible Mexican children < 24 months of age have occurred during the first 2 complete rotavirus seasons following rotavirus vaccination. Rotavirus-specific surveillance and epidemiologic studies are necessary for a better understanding of the changes in disease epidemiology and public health impact from rotavirus vaccination.
A recent postlicensure study from El Salvador showed that the monovalent rotavirus vaccine conferred 76% protection against rotavirus hospitalizations. We further examined the impact of rotavirus vaccination on the national burden of childhood diarrhea to help assess the total public health benefits of vaccination.
We compared all-cause diarrhea and rotavirus-specific hospitalization rates during prevaccine year 2006, with postvaccine years 2008 and 2009 in children < 5 years of age from 7 sentinel surveillance hospitals. We also compared annual rates of diarrhea-related healthcare events during prevaccine years 2005 and 2006 with postvaccine years 2008 and 2009 to examine the national burden of healthcare utilization for all-cause diarrhea.
Among sentinel surveillance hospitals, rotavirus hospitalization rates among children < 5 years of age declined by 81% (95% confidence interval [CI]: 78%-84%) in 2008 when 2-dose rotavirus vaccine coverage was 50% among infants < 1 year; the decline was 69% (95% CI: 65%-73%) in 2009 when 2-dose vaccine coverage was 61% among infants < 1 year, compared with 2006. The greatest declines were observed in children ≤ 1 year of age, although sizeable reductions were also observed among children ≥ 2 years in 2008. National diarrhea-related healthcare visits during rotavirus season decreased by 48% (95% CI: 47%-48%) in 2008 and by 35% (95% CI: 34%-35%) in 2009 compared with the mean rate from the 2005 and 2006 rotavirus seasons.
Rotavirus vaccination had a substantial public health impact on rotavirus disease and overall diarrhea events in El Salvador. Important age-related changes in diarrheal incidence emphasize the need for ongoing rotavirus surveillance after vaccine introduction.
rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants.
a total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off ≥ 20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes.
all symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34-78.2) in RIX4414 and 18.2% (95% CI: 5.2-40.3) in the placebo group. The mean absolute CD4 cell count, CD4 percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only.
: Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition.
Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009.
In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.
5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for efficacy >0%). Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given. 42 (1.5%) of 2723 infants assigned to receive vaccine and 45 (1.7%) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was gastroenteritis (vaccine 17 [0.6%]; placebo 17 [0.6%]).
Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years. We support WHO's recommendation for adoption of rotavirus vaccine into national expanded programmes on immunisation in Africa.
PATH (GAVI Alliance grant) and Merck.
A phased introduction of a monovalent rotavirus vaccine occurred in Mexico from February 2006 through May 2007. We assessed the effect of vaccination on deaths from diarrhea in Mexican children in 2008 and 2009.
We obtained data on deaths from diarrhea, regardless of cause, from January 2003 through May 2009 in Mexican children under 5 years of age. We compared diarrhea-related mortality in 2008 and during the 2008 and 2009 rotavirus seasons with the mortality at baseline (2003-2006), before the introduction of the rotavirus vaccine. Vaccine coverage was estimated from administrative data.
By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003-2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P<0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009).
After the introduction of a rotavirus vaccine, a significant decline in diarrhea-related deaths among Mexican children was observed, suggesting a potential benefit from rotavirus vaccination.
Rotavirus infection is associated with acute infantile gastroenteritis in infants and young children globally. In South Africa, rotavirus infection has been shown to be associated with approximately one-quarter of all diarrhoeal admissions to hospital. Rotavirus infection predominantly occurs in infants less than 12 months of age (75%) and has a peak of shedding during the cooler, drier months of the year. A secondary peak during the spring has been observed. Multiple infections with rotavirus and at least one other microbial agent are common. The circulating VP7 serotypes and VP4 genotypes have been determined in various regions of South Africa and show a geographic specific distribution. A decade previously, P[8]G1 or G4 strains predominated, and P[4]G2 strains occurred in an epidemic pattern in one region. More recently, rotavirus strains with P[6] genotype have become common and novel VP7/VP4 genotype combinations are occurring across the country. G9 strains have been reported from Cape Town to Vendaland. The circulating rotavirus types observed in this study add to the knowledge of the natural history of rotavirus infection and provide the groundwork to consider future vaccine strategies.
We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life.
3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247).
120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown.
In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.
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