[Show abstract][Hide abstract] ABSTRACT: Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively.
Smear-positive samples (N = 253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001.
In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K 76 Y 86 I 51 R 59 N 108 G 437 E 540 , from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1.
Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers.
[Show abstract][Hide abstract] ABSTRACT: We measured the reproduction number before and after interventions were implemented to reduce Ebola transmission in 9 outbreaks in Liberia during 2014. We evaluated risk factors for secondary cases and the association between patient admission to an Ebola treatment unit (ETU) and survival. The reproduction number declined 94% from 1.7 (95% CI 1.1–2.6) to 0.1 (95% CI 0.02–0.6) after interventions began. The risk for secondary infections was 90% lower for patients admitted to an ETU (risk ratio 0.1, 95% CI 0.04–0.3) than for those who died in the community. The case-fatality rate was 68% (95% CI 60–74), and ETU admission was associated with a 50% reduction in death (hazard ratio 0.5, 95% CI 0.4–0.8). Isolation and treatment of Ebola patients had the dual benefit of interrupting community transmission and improving survival.
[Show abstract][Hide abstract] ABSTRACT: Background: Current available malaria diagnostic methods each have some limitations to meet the need for real-time and large-scale screening of asymptomatic and low density malaria infection at community level. It was proposed that malaria parasite-specific low molecular-weight metabolites could be used as biomarkers for the development of a malaria diagnostic tool aimed to address this diagnostic challenge. In this study, high resolution metabolomics (HRM) was employed to identify malaria parasite-specific metabolites in Plasmodium falciparum in vitro culture samples.
Methods: Supernatants were collected at 12 hours interval from 3% haematocrit in vitro 48-hour time-course asynchronized culture system of P. falciparum. Liquid chromatography coupled with high resolution mass spectrometry was applied to discover potential parasite-specific metabolites in the cell culture supernatant. A metabolome-wide association study was performed to extract metabolites using Manhattan plot with false discovery rate (FDR) and hierarchical cluster analysis. The significant metabolites based on FDR cutoff were annotated using Metlin database. Standard curves were created using corresponding chemical compounds to accurately quantify potential Plasmodium-specific metabolites in culture supernatants.
Results: The number of significant metabolite features was 1025 in the supernatant of the Plasmodium infected culture based on Manhattan plot with FDR q=0.05. A two way hierarchical cluster analysis showed a clear segregation of the metabolic profile of parasite infected supernatant from non-infected supernatant at four time points during the 48 hour
culture. Among the 1025 annotated metabolites, the intensities of four molecules were significantly increased with culture time suggesting a positive association between the quantity of these molecules and level of parasitaemia: i) 3-methylindole, a mosquito attractant, ii) succinylacetone, a haem biosynthesis inhibitor, iii) S-methyl-L-thiocitrulline, a nitric oxide synthase inhibitor, and iv) O-arachidonoyl glycidol, a fatty acid amide hydrolase inhibitor, The highest concentrations of 3-methylindole and succinylacetone were 178 ± 18.7 pmoles at 36 hours and 157±30.5 pmoles at 48 hours respectively in parasite infected supernatant.
Conclusion: HRM with bioinformatics identified four potential parasite-specific metabolite biomarkers using in vitro culture supernatants. Further study in malaria infected human is needed to determine presence of the molecules and its relationship with parasite densities.
[Show abstract][Hide abstract] ABSTRACT: West Africa is experiencing its first epidemic of Ebola virus disease (Ebola) (1). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16–November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfully reduce transmission and improve outcomes.
MMWR. Morbidity and mortality weekly report 02/2015; MMWR(64):188-192.
[Show abstract][Hide abstract] ABSTRACT: On October 16, 2014, a woman aged 48 years traveled from Monrovia, Liberia, to the Kayah region of Rivercess County, a remote, resource-poor, and sparsely populated region of Liberia, and died on October 21 with symptoms compatible with Ebola virus disease (Ebola). She was buried in accordance with local tradition, which included grooming, touching, and kissing the body by family and other community members while it was being prepared for burial. During October 24-November 12, eight persons with probable and 13 with confirmed Ebola epidemiologically linked to the deceased woman had onset of symptoms. Nineteen of the 21 persons lived in five nearby villages in Kayah region; two, both with probable cases, lived in neighboring Grand Bassa County (Figure). Four of the confirmed cases in Kayah were linked by time and location, although the source case could not be determined because the patients had more than one exposure.
MMWR. Morbidity and mortality weekly report 02/2015; 64(7):183-5.
[Show abstract][Hide abstract] ABSTRACT: West Africa is experiencing its first epidemic of Ebola virus disease (Ebola). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16-November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfullyreduce transmission and improve outcomes.
MMWR. Morbidity and mortality weekly report 02/2015; 64(7):188-92.
[Show abstract][Hide abstract] ABSTRACT: Continuous monitoring in health and demographic surveillance sites (HDSS) allows for collection of longitudinal demographic data, health related, and socio-economic indicators of the site population. We sought to use household survey data collected between 2002 and 2006 in the Kenya Medical Research Institute in collaboration with Centers for Disease Control and prevention (KEMRI/CDC) HDSS site in Asembo and Gem Western Kenya to estimate socio-economic status (SES) and assess changes of SES over time and space. Data on household assets and characteristics, mainly source of drinking water, cooking fuel, and occupation of household head was annually collected from 44,313 unique households during the study period. An SES index was calculated as a weighted average of assets using weights generated via Principal Component Analysis (PCA), Polychoric PCA, and Multiple Correspondence Analysis (MCA) methods applied to the pooled data. The index from the best method was used to rank households into SES quintiles and assess their transition over time across SES categories. Kriging was employed to produce SES maps at the start and the end of the study period. First component of PCA, Polychoric PCA, and MCA accounted for 13.7%, 31.8%, and 47.3%, respectively of the total variance of all variables. The gap between the poorest and the least poor increased from 1% at the start to 6% at the end of the study period. Spatial analysis revealed that the increase in least poor households was centered in the lower part of study area (Asembo) over time. No significant changes were observed in Gem. The HDSS sites can provide a platform to assess spatial–temporal changes in the SES status of the population. Evidence on how SES varied over time and space within the same geographical area may provide a useful tool to design interventions in health and other areas that have a close bearing to the SES of the population.
[Show abstract][Hide abstract] ABSTRACT: Non-communicable diseases (NCDs) result in more deaths globally than other causes. Monitoring systems require strengthening to attribute the NCD burden and deaths in low and middle-income countries (LMICs). Data from health and demographic surveillance systems (HDSS) can contribute towards this goal.
Between 2003 and 2010, 15,228 deaths in adults aged 15 years (y) and older were identified retrospectively using the HDSS census and verbal autopsy in rural western Kenya, attributed into broad categories using InterVA-4 computer algorithms; 37% were ascribed to NCDs, 60% to communicable diseases (CDs), 3% to injuries, and <1% maternal causes. Median age at death for NCDs was 66y and 71y for females and males, respectively, with 43% (39% male, 48% female) of NCD deaths occurring prematurely among adults aged below 65y. NCD deaths were mainly attributed to cancers (35%) and cardio-vascular diseases (CVDs; 29%). The proportionate mortality from NCDs rose from 35% in 2003 to 45% in 2010 (χ2 linear trend 93.4; p<0.001). While overall annual mortality rates (MRs) for NCDs fell, cancer-specific MRs rose from 200 to 262 per 100,000 population, mainly due to increasing deaths in adults aged 65y and older, and to respiratory neoplasms in all age groups. The substantial fall in CD MRs resulted in similar MRs for CDs and NCDs among all adult females by 2010. NCD MRs for adults aged 15y to <65y fell from 409 to 183 per 100,000 among females and from 517 to 283 per 100,000 population among males. NCD MRs were higher among males than females aged both below, and at or above, 65y.
NCDs constitute a significant proportion of deaths in rural western Kenya. Evidence of the increasing contribution of NCDs to overall mortality supports international recommendations to introduce or enhance prevention, screening, diagnosis and treatment programmes in LMICs.
PLoS ONE 11/2014; 9(11):e114010. DOI:10.1371/journal.pone.0114010 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues.
This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR.
Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial.
In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.
[Show abstract][Hide abstract] ABSTRACT: Background
Assessing the progress in achieving the United Nation's Millennium Development Goals in terms of population health requires consistent and reliable information on cause-specific mortality, which is often rare in resource-constrained countries. Health and demographic surveillance systems (HDSS) have largely used medical personnel to review and assign likely causes of death based on the information gathered from standardized verbal autopsy (VA) forms. However, this approach is expensive and time consuming, and it may lead to biased results based on the knowledge and experience of individual clinicians. We assessed the cause-specific mortality for children under 5 years old (under-5 deaths) in Siaya County, obtained from a computer-based probabilistic model (InterVA-4).
Successfully completed VA interviews for under-5 deaths conducted between January 2003 and December 2010 in the Kenya Medical Research Institute/US Centers for Disease Control and Prevention HDSS were extracted from the VA database and processed using the InterVA-4 (version 4.02) model for interpretation. Cause-specific mortality fractions were then generated from the causes of death produced by the model.
A total of 84.33% (6,621) childhood deaths had completed VA data during the study period. Children aged 1–4 years constituted 48.53% of all cases, and 42.50% were from infants. A single cause of death was assigned to 89.18% (5,940) of cases, 8.35% (556) of cases were assigned two causes, and 2.10% (140) were assigned ‘indeterminate’ as cause of death by the InterVA-4 model. Overall, malaria (28.20%) was the leading cause of death, followed by acute respiratory infection including pneumonia (25.10%), in under-5 children over the study period. But in the first 5 years of the study period, acute respiratory infection including pneumonia was the main cause of death, followed by malaria. Similar trends were also reported in infants (29 days–11 months) and children aged 1–4 years.
Under-5 cause-specific mortality obtained using the InterVA-4 model is consistent with existing knowledge on the burden of childhood diseases in rural western Kenya.
Global Health Action 10/2014; 7:25581. DOI:10.3402/gha.v7.25581 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.
Global Health Action 10/2014; 7:25369. DOI:10.3402/gha.v7.25369 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003-2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003-2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5-14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003-2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions.
PLoS ONE 09/2014; 9(9):e106197. DOI:10.1371/journal.pone.0106197 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).
Methods and findings:
A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.
An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.
PLoS Medicine 09/2014; 11(9):e1001735. DOI:10.1371/journal.pmed.1001735 · 14.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract
Background:A malaria vaccine could be an important addition to current control strategies. We report the safety and
vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria
Methods and Findings:6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three
doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3
(per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p,0.01 across all sites). VE during the 20 mo after
vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and
all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%),
respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%],
ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Postvaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and
from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residualsp,0.001).
The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365
and from21 to 49, respectively; corresponding ranges among infants were210 to 1,402 and213 to 37, respectively (ITT).
Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in
the RTS,S/AS01 and control groups, respectively.
Conclusions:RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the
highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest
levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current
malaria control in Africa.
Trial registration:http://www.ClinicalTrials.gov NCT00866619
Please see later in the article for the Editors’ Summary
PLoS Medicine 07/2014; 11(7). DOI:10.1371/journal.pmed.1001685 · 14.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study assesses full and timely vaccination coverage and factors associated with full vaccination in children ages 12-23 months in Gem, Nyanza Province, Kenya in 2003. A simple random sample of 1,769 households was selected, and guardians were invited to bring children under 5 years of age to participate in a survey. Full vaccination coverage was 31.1% among 244 children. Only 2.2% received all vaccinations in the target month for each vaccination. In multivariate logistic regression, children of mothers of higher parity (odds ratio [OR] = 0.27, 95% confidence interval [95% CI] = 0.13-0.65, P ≤ 0.01), children of mothers with lower maternal education (OR = 0.35, 95% CI = 0.13-0.97, P ≤ 0.05), or children in households with the spouse absent versus present (OR = 0.40, 95% CI = 0.17-0.91, P ≤ 0.05) were less likely to be fully vaccinated. These data serve as a baseline from which changes in vaccination coverage will be measured as interventions to improve vaccination timeliness are introduced.
The American journal of tropical medicine and hygiene 12/2013; 90(2). DOI:10.4269/ajtmh.13-0127 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission.
To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events.
We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings.
Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded.
Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach.
Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%)Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence).The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%)Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence).Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolinesWe found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium speciesIn studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax.
MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings.To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance.
[Show abstract][Hide abstract] ABSTRACT: Information on trauma-related deaths in low and middle income countries is limited but needed to target public health interventions. Data from a health and demographic surveillance system (HDSS) were examined to characterise such deaths in rural western Kenya.
Verbal autopsy data were analysed. Of 11,147 adult deaths between 2003 and 2008, 447 (4%) were attributed to trauma; 71% of these were in males. Trauma contributed 17% of all deaths in males 15 to 24 years; on a population basis mortality rates were greatest in persons over 65 years. Intentional causes accounted for a higher proportion of male than female deaths (RR 2.04, 1.37-3.04) and a higher proportion of deaths of those aged 15 to 65 than older people. Main causes in males were assaults (n=79, 25%) and road traffic injuries (n=47, 15%); and falls for females (n=17, 13%). A significantly greater proportion of deaths from poisoning (RR 5.0, 2.7-9.4) and assault (RR 1.8, 1.2-2.6) occurred among regular consumers of alcohol than among non-regular drinkers. In multivariate analysis, males had a 4-fold higher risk of death from trauma than females (Adjusted Relative Risk; ARR 4.0; 95% CI 1.7-9.4); risk of a trauma death rose with age, with the elderly at 7-fold higher risk (ARR 7.3, 1.1-49.2). Absence of care was the strongest predictor of trauma death (ARR 12.2, 9.4-15.8). Trauma-related deaths were higher among regular alcohol drinkers (ARR 1.5, 1.1-1.9) compared with non-regular drinkers.
While trauma accounts for a small proportion of deaths in this rural area with a high prevalence of HIV, TB and malaria, preventive interventions such as improved road safety, home safety strategies for the elderly, and curbing harmful use of alcohol, are available and could help diminish this burden. Improvements in systems to record underlying causes of death from trauma are required.
PLoS ONE 11/2013; 8(11):e79840. DOI:10.1371/journal.pone.0079840 · 3.23 Impact Factor