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Low paediatric tuberculosis case detection rate in Southern Mozambique

Low paediatric tuberculosis case
detection rate in Southern Mozambique
To the Editor:
Two core indicators adopted for evaluating tuberculosis (TB) control programmes are treatment outcome
and case detection rate (CDR). While the former is easy to report, the CDR can only be estimated (calculated
as notifications of new and relapse cases divided by estimated incidence). According to the World Health
Organization (WHO), Mozambique has one of the lowest CDRs among the high TB burden countries
(HBCs), with 37% in 2013 [1]. In children, calculating CDR is even more challenging, given the difficulty in
diagnosing TB and the lack of accurate estimates for paediatric incidence [2]. Several paediatric TB incidence
estimates have been published recently [35], showing higher figures than those provided by WHO. The
large variation in estimates and the lack of population-based data from HBCs (particularly from
Sub-Saharan Africa) highlights the urgent need for new data to inform predictive models necessary to
implement the End TB Strategy and achieve elimination [6]. The objective of this study was to calculate
the paediatric CDR in Mozambique and to provide reference methodology and evidence for other countries.
The study was conducted in the Manhiça District, a high TB-HIV burden district in southern
Mozambique [7], where the Manhiça Health Research Centre runs a health and demographic surveillance
system (HDSS) [8]. It was a retrospective, population-based analysis, which estimated the TB CDR by
comparing the routine TB incidence rate in children aged <3 years reported in the district between 2006
and 2010 with the incidence rate in the study area computed during a prospective study (the ITACA study:
determination of the minimum incidence rate of tuberculosis in infants and children in the Manhiça
District, Mozambique; October 2011October 2012) [9]. The latter was considered as the most accurate
incidence rate estimate available. Prior to the ITACA study, no routine active case finding was performed
and bacteriological confirmation was mostly based on smear microscopy. During the ITACA period, all
presumptive TB cases were identified through an active and passive case detection system. Children with
TB-related symptoms and close contact with a sputum smear-positive TB patient were evaluated through
physical and radiological examination, HIV and tuberculin skin testing, as well as smear microscopy and
culture of both induced sputum and gastric aspirate samples [9, 10]. For the purpose of this analysis, TB
cases were defined as those who started anti-TB treatment. Relapse patients were included.
We calculated the TB incidence rate during the ITACA period as the number of cases in the HDSS area
divided by the mid-year population at risk. Pre-ITACA incidence rates were calculated yearly using the
number of TB cases in the whole district divided by the district mid-year population, using the
Mozambican National Statistics Institute (INE) latest official census data (2007) and taking into account
the estimated age-specific population growth for the whole period. Yearly confidence intervals were
calculated assuming a Poisson distribution. A pooled incidence rate was calculated for the pre-ITACA
period using a weighting scheme through a Poisson regression with random effects and jackknife 95% CI.
According to the 20002013 WHO data, there has been a slight increase in incidence during this
time-frame in Mozambique (figure 1) [1]. Using a log-linear regression and WHO data, we estimated an
overall 0.6% yearly increasing trend in TB incidence rate and applied this correction factor to the final
CDR to mitigate overestimation.
A total of 217 TB cases aged <3 years were diagnosed in the pre-ITACA period (20062010), with a pooled
incidence rate of 251 per 100 000 people (95% CI 227276 per 100 000). During ITACA, 57 TB cases aged
<3 years initiated anti-TB treatment in the HDSS area, equivalent to an incidence rate of 615 per 100 000
people (95% CI 466797 per 100000 people) (figure 1). The estimated CDR was 40.8% (95% CI 36.6
45.1%), and 41.8% (95% CI 37.246.4%) after correction. In the hypothetical case of a 5% increase in the
national incidence, sensitivity analysis showed that the CDR would increase to (49.1%; 95% CI 41.357.0%).
The HIV prevalence among the study population was 47% and 46% during the pre-ITACA and ITACA
periods, respectively. During the ITACA period, fewer patients aged <1 year initiated anti-TB treatment
(8.8% versus 35.9%), more TB cases were extrapulmonary (12.3% versus 7.4%) and the treatment success
rate was significantly better (82.5% versus 67.3%; p=0.025).
To our knowledge, this is the first study providing estimates of TB under-detection using population-based
data in the paediatric population in Africa and one of the few worldwide. We found a low CDR regardless
. Published on December 23, 2015 as doi: 10.1183/13993003.01454-2015ERJ Express
Copyright 2015 by the European Respiratory Society.
of age and sex, which underscores the urgent need to close the gap in case detection and reporting, in
order to better assess new control interventions [6, 11].
Our findings are in line with the low CDR for Mozambique reported by WHO [1]; however, the rate we
report is probably a maximum, given that the ITACA incidence rate is a conservative estimate (single-day
samples were obtained in contrast to the recommended 3-day consecutive sampling; contact tracing could
not be fully implemented mainly due to difficulties in patient identification; and some TB cases could have
been missed due to mortality prior to treatment initiation or transfers of severely ill patients to the tertiary
reference hospital) [9].
The CDR higher than the 35% estimated by D
ODD et al. [5] for children aged <15 years in all HBCs (based
on mathematical modelling of 2010 data) could be due to several reasons.
Given that Mozambique has one of the lowest CDRs among all HBCs and that under-estimation is more
frequent in children aged <5 years, the difference observed between our CDR and the one reported by
ODD et al. [5] could support the hypothesis that the true CDR in Manhiça is probably lower than 40.8%.
Besides, TB incidence and CDR vary greatly across countries and regions (depending on the local
epidemiology of TB/HIV and healthcare system characteristics, among others) and Manhiça could show an
improved CDR compared with other settings.
Although under-ascertainment, under-reporting and under-diagnosis can all contribute to TB
under-estima tion [12], the la tter is the most probable in Mozambique, where broad paediatric TB case
definitions, lack of clear clinical algorithms, low referral rates and difficulties in obtaining samples all contribute
to under-diagnosis. Under-reporting is not common, as the private sector has a small role in TB diagnosis and
management. Under-ascertainment alone, although common in Manhiça, cannot explain the low CDR, given
the small impact of the active case-finding component of this study.
This study has several limitations. First, the use of a historical control for the calculation of CDR may be
imperfect as the incidence rate and CDR vary over time. Although we expected that the 0.6% yearly
correction could compensate, we acknowledge that the extent of increase in incidence reported for adults
may not be the same for children aged <3 years. Furthermore, we compared incidence rates calculated with
different denominators (the intervention HDSS population, based on real annual census data for a smaller
urban-shaped area versus the whole district population, based on projections from the INE 2007 census
and considering age-specific annual population growth). We did, however, verify that the CDR did not
vary substantially when we calculated the ITACA incidence based on INE district data (and using as
denominator the percentage of the INE population belonging to HDSS).
This study provides a novel population-based CDR for paediatric TB in a HBC. Although this estimate is
probably a maximum, differences in local detection rates can explain a higher CDR than those reported by
others [1, 5]. Given the multiple downstream ramifications of inaccurate estimates [13] and the high
Incidence rate per 100 000 persons
Case detection rate %
2006 2007 2008
2009 2010 2011 2012
Case detection rate for all ages (WHO estimates)
Incidence rate for all ages (WHO estimates)
Manhiça District incidence rate for age <3 years (pre-ITACA)
Manhiça District incidence rate for age <3 years (ITACA)
FIGURE 1 Yearly tuberculosis incidence rate in the population aged <3 years in the Ma nhiça Dis trict. World Heal th
Organization (WHO) estimates for all-age incidence rate and case detection rate for Mozambique are shown for
the pre-ITACA period. ITACA: study for determination of the minimum incidence rate of tuberculosis in infants and
children in the Manhiça District, Moza mbique; October 2011October 2012.
mortality of undiagnosed TB in younger children [14], this finding calls for urgent public health
interventions to ensure that all TB cases are promptly identified and treated.
In this study, the case detection rate of TB in children <3 years in Manhiça, Mozambique was
estimated to be 40.8%
Elisa López-Varela
, Orvalho Joaquim Augusto
, Luis Guerra
, Durval Respeito
, Charfudin Sacoor
Jahit Sacarlal
, Giovanni Battista Migliori
, Giovanni Sotgiu
, Pedro L. Alonso
and Alberto L. García-Basteiro
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
Instituto de Salud Global de Barcelona
(ISGLOBAL), Barcelona, Spain.
WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care
and Research Institute, Tradate, Italy.
Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences,
University of Sassari Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
Correspondence: Elisa López-Varela, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
Received: Sept 01 2015 | Accepted after revision: Nov 09 2015
Conflict of interest: None declared.
Acknowledgements: The authors thank the participants and their families. The authors are grateful to the National TB
Program (Maputo, Mozambique), Denise Naniche (ISGLOBAL, Barcelona, Spain), Alberto Bila Junior (CISM, Manhiça,
Mozambique), health staff at the Manhiça District Hospital (Manhiça, Mozambique) and peripheral health centers for
their contribution.
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Eur Respir J 2015; In press | DOI: 10.1183/13993003.01454-2015 | Copyright ©ERS 2015
... Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1% [3][4][5] and 21% (95%CI 15-28) of new and previously treated patients, respectively, were MDR-TB/R R -TB. 1 Different risk factors for the development of MDR-TB have been described, including poor DOTS implementation, high cost of treatment, poor quality drugs, inadequate drug regimens (that may or may not be associated with drug shortages) or other factors that make patients vulnerable to infection by MDR-TB strains (i.e., living in areas with high MDR-TB prevalence or contact with an MDR-TB case). 2,3 The emergence of drug resistance reflects poor implementation of TB control programme interventions. ...
... Mozambique is a high TB burden country with an estimated TB incidence rate of 551 cases per 100 000 population 1 and a low case detection rate in 2015. 1,4 Few studies have evaluated anti-tuberculosis drug resistance patterns in Mozambique. In 1998-2000, it was estimated that 3.5% of patients co-infected with TB and the human immunodeficiency virus (HIV) had MDR-TB. ...
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Setting: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. Objective: To determine the drug resistance patterns of laboratory-confirmed TB cases. Design: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. Results: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). Conclusion: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.
... Those differences were even higher among paediatric cases (NNS HCs 89.9 in HCs vs NNS 1102 in CCs). Since TB disease among children results from persistent close contact with an infectious IC, this finding would support the benefit of intensive household screening and confirm the low paediatric TB case detection in our setting , as previously described (30). Reported data on childhood TB is an important indicator when evaluating NTPs. ...
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Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We aimed to determine the impact of the scale-up of Xpert Ultra as frontline test for TB diagnosis, and an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi quantitative results and spatial parameters) on new TB cases diagnosed in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited all incident TB-cases (index cases, ICs) and their household contacts (HCs). Community contacts (CCs) recruitment depended on the semi-quantitative results of Xpert Ultra of the IC and the population density of the area where the IC lived in. TB-contacts, either symptomatic or people living with HIV (regardless of symptoms), were asked for providing a spot sputum for lab-testing. Trends on TB case notification in the intervention area were compared to the previous years and to those of two districts in the south of the Maputo province (control area) using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.2% laboratory-confirmed) were recruited; 3165 HC and 4730 CC were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The ACF intervention increased by 8.2% all forms of TB cases detected in 2018. CITS model showed an increase of laboratory confirmed TB cases in the intervention district, compared to the control area. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). Number needed to screen (NNS) to find a TB case differed widely among HCs (NNS:55) and CCs (153). The intervention resulted in an overall increase in TB diagnoses and higher proportion of laboratory confirmation.
... Therefore, the currently reported prevalence of pediatric TB may be underestimating the true dimension of the epidemic in this age group. [2][3][4] In resourcelimited settings, TB in children can be difficult to diagnose and treat caused by the high frequency of atypical forms of the disease; difficulty with obtaining diagnostic specimens and the severity of presentation when associated with multidrug resistance, HIV infection and/or the presence of malnutrition. 1,5,6 Mozambique is classified as one of the 30 high TB and TB/HIV burden countries. ...
Background: Globally, tuberculosis (TB) remains a serious cause of morbidity and mortality for children. Mozambique is 1 of 30 high TB and TB/HIV burden countries. This study aimed to assess treatment outcomes of childhood TB in Chókwè District, Mozambique. Methods: A retrospective cohort study of children <15-years-old treated for TB from 2006 to 2017 was conducted at Carmelo Hospital of Chókwè. Descriptive statistics were used to summarize patient characteristics. Treatment outcomes stratified by HIV status were compared with χ. Multivariable logistic regression was used to estimate the odds of a favorable TB treatment outcome. Kaplan-Meier curves were used to estimate the cumulative incidence of death. Results: Nine hundred thirty-three cases of childhood TB were enrolled, 45.9% of which were female and 49.6% were <5-years-old. Five hundred sixty-five (62%) children were HIV positive. Seven hundred sixty-two (83.6%) cases had a favorable TB treatment outcome. In comparison to children 0-4 years, the 5-14 age group had a higher odds of a favorable outcome [odds ratio: 2.02, 95% confidence interval: 1.42-3.05]. Being 5-14 years was associated with lower risk of death (hazard ratio: 0.435; 95% confidence interval: 0.299-0.632). Those starting anti-TB treatment ≤3 months after antiretroviral therapy initiation had a survival probability of approximately 75% at 1 year compared with 95% for those who were HIV negative. Conclusions: Most children in this cohort had favorable TB treatment outcomes. Worse outcomes were observed for younger children and if anti-TB treatment started ≤3 months after initiation of antiretroviral therapy. Rigorous screening for TB and isoniazid preventative therapy may reduce the burden of TB in this population and lead to better outcomes.
... The minimum community-based incidence rate of TB (laboratory confirmed plus probable cases) in children under 3 years of age was 470 of 100,000 person-years in 2012 [32•]. HIV coinfection was present in 44% of the TB cases, and the case detection rate was estimated to be around 40% in this age group [33]. The high prevalence of non tuberculous mycobacteria could hinder TB diagnosis in young children investigated for TB, although these findings do not seem to have clinical relevance [34,35]. ...
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Purpose of Review Tuberculosis (TB) is a global health concern, and Mozambique is one of the few high burden tuberculosis countries where the estimated TB incidence has not improved in recent years. The objective of this review is to provide a snapshot of the current situation of the TB epidemic in Mozambique, highlighting the main epidemiological features and particularities of TB care and control in the country. Recent Findings Despite several efforts aimed at improving diagnosis and treatment success, the overall burden of TB, HIV-TB, and multidrug-resistant (MDR)-TB is enormous, with high TB-associated mortality. Improving surveillance is a key step for understanding the TB epidemic in the country, and the first TB prevalence survey is underway. Overall, drug-sensitive and MDR-TB notifications have increased markedly over the last 5 years, likely due in part to a more active case finding approaches, but the diagnosis gap is still substantial. The roll-out of Xpert technology to decentralized settings is improving TB diagnosis in the country, particularly for MDR-TB. Summary Although some progress has been made in TB control in Mozambique, the challenges for TB control and elimination are enormous. More actively finding cases at health facilities and in communities via contact tracing, improving national surveillance/monitoring and evaluation systems, expanding TB molecular diagnosis, implementing shorter MDR-TB treatments, and improving HIV-TB case management (including rigorous TB screening and higher coverage of preventive therapies in people living with HIV) are considered key priorities for the National TB Control Program.
... Lastly, the pathogenesis and clinical presentation of TB in children are different from that in adults, reducing the sensitivity and specificity of adjunctive diagnostic tools, such as conventional radiology, which, on the other hand, is often unavailable or of poor quality in low income countries [8,9]. Child TB cases are therefore often missed and microbiological confirmation is low [10], leading to some uncertainty about the quality of TB diagnosis in notified children. Furthermore, reporting of child TB cases to national TB programmes has been suboptimal [11,12]. ...
... In Mozambique, where high pediatric TB rates and low case detection rates have been reported [35,36], children receive a national health card (also called "vaccination card") at birth or in their first contact with the health system, where immunization, anthropometric and basic health data are registered. All children born in the district of Manhiça participate in the HDSS. ...
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Background Over the past four decades, the World Health Organization established the Expanded Programme on Immunization (EPI) to foster universal access to all relevant vaccines for all children at risk. The success of this program has been undeniable, but requires periodic monitoring to ensure that coverage rates remain high. The aim of this study was to measure the BCG vaccination coverage in Manhiça district, a high TB burden rural area of Southern Mozambique and to investigate factors that may be associated with BCG vaccination. Methods We used data from the Health and Demographic Surveillance System (HDSS) run by the Manhiça Health Research Centre (CISM) in the district of Manhiça. A questionnaire was added in the annual HDSS round visits to retrospectively collect the vaccination history of children under the age of 3 years. Vaccinations are registered in the National Health Cards which are universally distributed at birth. This information was collected for children born from 2011 to 2014. Data on whether a child was vaccinated for BCG were collected from these National Health Cards and/or BCG scar assessment. ResultsA total of 10,875 number of children were eligible for the study and 7903 presented the health card. BCG coverage was 97.4% for children holding a health card. A BCG-compatible scar was observed in 99.0% of all children and in 99.6% of children with recorded BCG in the card. A total of 93.4% of children had been vaccinated with BCG within their first 28 days of life. None of the factors analysed were found to be associated with lack of BCG vaccination except for living in the municipality of Maluana compared to living in the municipality of Manhiça; (OR = 1.89, 95% CI: 1.18-3.00). Coverage for other EPI vaccines during the first year of life was similarly high, but decreased for subsequent doses. ConclusionsBCG coverage is high and timely administered. Almost all vaccinated infants develop scar, which is a useful proxy for monitoring BCG vaccine implementation.
... 25 This estimate was confirmed in a recent study Journal of Pediatric Infectious Diseases Vol. 13 No. 2/2018 conducted in Southern Mozambique where the TB case detection rate in children < 3 years of age was considered to be 40.8%. 36 The greatest case detection failure occurs in young children, and in a setting with poor epidemic control and little use of preventive therapy, children < 5 years are expected to account for at least half of all pediatric cases. The potential reporting gap of child TB cases is also emphasized by post-mortem examinations and by the yield of intensified case-finding (ICF) initiatives. ...
The epidemiology of tuberculosis, particularly in children, is highly intertwined with socio-political factors, such as poverty, access to healthcare, and migration. Growing evidence around the world shows that more children have tuberculosis (TB) than was previously thought, most of whom are undiagnosed and untreated, and that TB is a significant cause of morbidity and mortality in children in TB endemic areas. Since TB in young children results from recent transmission, the incidence of pediatric TB is a marker of epidemic control in a community and an indirect indicator of the effectiveness of TB control programs. It is estimated that pediatric TB represents between 4 and 21% of all TB cases, depending on the background prevalence in the country, and at least 10 to 20% of the total cases in areas with poor epidemic control. However, a precise estimate of the global burden of TB in children is difficult due to challenges in case ascertainment, diagnosis, and weak surveillance systems in many countries with a high burden of disease. Several recent estimates highlight these difficulties and provide a starting point to motivate further study. In addition, since drug-resistant TB in young children reflects transmission of resistant strains in the community and occurs with the same frequency as in treatment-naïve adults, accurate monitoring of drug-susceptibility patterns in pediatric TB cases will inform optimal empiric treatment regimens in both adults and children, in the context of increasing rates of drug-resistant TB globally.
... Introduction Tuberculosis (TB) is an under-recognized but important cause of morbidity and mortality among children from high TB burden countries [1,2]. Estimates indicate that the National TB Control Programs (NTP) only capture one-third of paediatric TB cases in these settings [3,4]. This is mostly due to the difficulties in diagnosing paediatric TB, in turn leading to underdiagnosis, misdiagnosis or delayed diagnosis. ...
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Background Tuberculosis (TB) remains an important public health concern, especially in poorly resourced settings. TB diagnosis is challenging, particularly for children, who are the most vulnerable to its′ impacts. Lack of knowledge and awareness of the disease compromises prompt diagnosis and treatment compliance. Objective To gain insights regarding caretakers′ knowledge of the aetiology and prevention of paediatric TB in southern Mozambique, to describe their care-seeking behaviours and to assess the acceptability of diagnostic procedures. Methods A total of 35 caretakers were interviewed, all of which had children with TB compatible symptoms. Eleven were caretakers of children diagnosed with TB at the health facility, 11 of children for whom TB was excluded as a diagnosis at the health facility and 13 of children with TB compatible symptoms identified in the community. The first two groups took part in a TB incidence study, while the third group did not. All underwent the same semi-structured interviews, the results of which were analysed and compared using content analysis. Results Even when confronted with signs suggestive of TB, most caretakers never suspected it or misinterpreted the signs, even among caretakers with TB and TB contacts. There was limited knowledge of TB, except among those undergoing treatment. The transgression of social norms was often presented as an explanation for TB in parallel to medically sound causes. The use of traditional care for prevention is widespread, but it varied for treatment purposes. TB diagnostic procedures were considered painful but were unanimously tolerated. Conclusions and significance Misconceptions of paediatric TB, associated complex care-seeking itineraries and negative feelings of the diagnostic procedures may result in delays, low adherence and lost to follow-up, which needs to be addressed by adequately framed health promotion approaches.
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Objectives: The contact investigation of tuberculosis (TB) index case is one of the critical elements pointed by the WHO to reach the end of the TB epidemic. The scoping review aimed to map out the recommended and the adopted processes applied to active contact investigation of TB index case in African Portuguese-speaking countries (PALOP). Design: Scoping review. Data sources: We searched B-on, Cochrane Library, PubMed, Web of Science, Scopus, WHOLIS, IRIS, OKR, each country's Ministry of Health websites, WHO, Global Fund, World Bank and bibliographic reference lists from February to May 2020. Eligibility criteria: All available literature on TB contact investigation in each country part of PALOP (Angola, Cape Verde, Guinea-Bissau, Mozambique and Sao Tome and Principe) published from 1 January 2010 to 31 January2020. Data extraction and synthesis: A data-charting form was developed to extract data on documents' characteristics and variables pertinent to the TB contact investigation process. Before qualitative analysis, we thematically synthesised findings and converted them into appropriate text units. Results: Fifteen documents were included in the scoping review. The recommended processes for TB contact investigation were identified only for Cape Verde and Mozambique. It included clinical evaluation, counselling and testing for HIV, chest radiography, tuberculin skin test, sputum smear microscopy or Xpert MTB/RIF. The adopted processes were detected only in research studies from Angola, Guinea-Bissau and Mozambique. Therefore, they cannot be assumed as adopted within the scope of the national programmes of the respective countries. Conclusion: This review highlights the scarcity of references on TB contact investigation in PALOP at the End TB Strategy era. Furthermore, it is well clear the importance of an information system that provides actual data for assessing the real impact of such interventions in controlling the disease in African Portuguese-speaking countries.
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Simple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological status at diagnosis among 127 HIV-infected patients starting TB treatment. All participants were then classified as responding or not responding to treatment blindly using a previously described IP-10 kinetic algorithm. There were 77 bacteriologically confirmed cases and 41 Xpert MTB/RIF® and culture negative cases. Most participants had a measurable decline in IP-10 during the first 7 days of therapy. Bacteriologically confirmed cases were more likely to have high IP-10 levels at D0 and had a steeper decline than clinically diagnosed cases (mean decline difference 2231 pg/dl, 95% CI: 897-3566, p = 0.0013). Bacteriologically confirmed cases were more likely to have a measurable decline in IP-10 at day 7 than clinically diagnosed cases (48/77 (62.3%) vs 13/41 (31.7%), p < 0.001). This study confirms the association between a decrease in IP-10 levels during the first week of treatment and a bacteriological confirmation at diagnosis in a large cohort of HIV positive patients.
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Introduction Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhiça, southern Mozambique, an area with a high prevalence of TB and HIV. Methods Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied. Results A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children. Conclusion Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms.
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Tuberculosis (TB) contributes significantly to child morbidity and mortality. This study aimed to estimate the minimum community-based incidence rate of TB among children <3 years of age in Southern Mozambique. Between October 2011 and October 2012, in the Manhiça District Health and Demographic Surveillance System, we enrolled prospectively all presumptive TB cases younger than 3 years of age through passive and active case finding. Participants included all children who were either symptomatic or were close contacts of a notified adult smear-positive pulmonary TB. Children were clinically evaluated at baseline and follow-up visits. Investigation for TB disease included chest radiography, HIV and tuberculin skin testing as well as gastric aspirate and induced sputum sampling, which were processed for smear, culture and mycobacterial molecular identification. During the study period, 13,764 children <3 years contributed to a total of 9575 person-year. Out of the 789 presumptive TB cases enrolled, 13 had TB culture confirmation and 32 were probable TB cases. The minimum community-based incidence rate of TB (confirmed plus probable cases) was 470 of 100,000 person-year (95% confidence interval: 343-629 of 100,000). HIV co-infection was present in 44% of the TB cases. These data highlight the huge burden of pediatric TB. This study provides one of the first prospective population-based incidence data of childhood tuberculosis and adds valuable information to the global effort of producing better estimates, a critical step to inform public health policy.
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This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
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Extract Tuberculosis (TB) remains an important public health concern, and a leading cause of disease and death worldwide. Mozambique is one of the few high TB burden countries where TB figures have not improved in recent years, with an estimated TB incidence in 2013 of 552 cases per 100 000 population [1]. With 58% of all notified TB cases being HIV-positive, Mozambique also has one of the highest TB/HIV co-infection rates. Published data on the burden of TB or HIV disease in the country are scarce, and improving epidemiological surveillance has been identified as an urgent step to improve TB control [2].
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Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010—13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Findings: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Interpretation: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
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Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease. Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude. Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15,319,701 (IQR 13,766,297-17,061,821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7,591,759 (5,800,053-9,969,780), and 650,977 children (424,871-983,118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53,234,854 (41,111,669-68,959,804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%. Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment. Funding: UNITAID and the US Agency for International Development.
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Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true' incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence.
Multidrug-resistant tuberculosis threatens to reverse recent reductions in global tuberculosis incidence. Although children younger than 15 years constitute more than 25% of the worldwide population, the global incidence of multidrug-resistant tuberculosis disease in children has never been quantified. We aimed to estimate the regional and global annual incidence of multidrug-resistant tuberculosis in children. We developed two models: one to estimate the setting-specific risk of multidrug-resistant tuberculosis among child cases of tuberculosis, and a second to estimate the setting-specific incidence of tuberculosis disease in children. The model for risk of multidrug-resistant tuberculosis among children with tuberculosis needed a systematic literature review. We multiplied the setting-specific estimates of multidrug-resistant tuberculosis risk and tuberculosis incidence to estimate regional and global incidence of multidrug-resistant tuberculosis disease in children in 2010. We identified 3403 papers, of which 97 studies met inclusion criteria for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies reported the risk of multidrug-resistant tuberculosis in both children and treatment-naive adults with tuberculosis and were used for evaluation of the linear association between multidrug-resistant disease risk in these two patient groups. We identified that the setting-specific risk of multidrug-resistant tuberculosis was nearly identical in children and treatment-naive adults with tuberculosis, consistent with the assertion that multidrug-resistant disease in both groups reflects the local risk of transmitted multidrug-resistant tuberculosis. After application of these calculated risks, we estimated that around 999 792 (95% CI 937 877-1 055 414) children developed tuberculosis disease in 2010, of whom 31 948 (25 594-38 663) had multidrug-resistant disease. Our estimates underscore that many cases of tuberculosis and multidrug-resistant tuberculosis disease are not being detected in children. Future estimates can be refined as more and better tuberculosis data and new diagnostic instruments become available. US National Institutes of Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and the Doris and Howard Hiatt Residency in Global Health Equity and Internal Medicine at the Brigham and Women's Hospital.