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In Kilifi (Kenya), a pneumococcal conjugate vaccine (PCV10) was introduced in 2011 in infants (aged <1 year, 3 + 0 schedule) with a catch-up campaign in children aged 1–4 years. We aimed to measure the effect of PCV10 on population immunity. In this observational study, repeated cross-sectional serosurveys were conducted in independent random samples of 500 children younger than 15 years every 2 years between 2009 and 2017. During these surveys, blood samples were collected by venesection. Concentrations of anti-capsular IgGs against vaccine serotypes (VTs) 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F, and against serotypes 6A and 19A, were assayed by ELISA. We plotted the geometric mean concentrations (GMCs) by birth year to visualise age-specific antibody profiles. In infants, IgG concentrations of 0·35 μg/mL or higher were considered protective. Of 3673 volunteers approached, 2152 submitted samples for analysis across the five surveys. Vaccine introduction resulted in an increase in the proportion of young children with protective IgG concentrations, compared with before vaccine introduction (from 0–33% of infants with VT-specific levels over the correlate of protection in 2009, to 60–94% of infants in 2011). However, among those vaccinated in infancy, GMCs of all ten VTs had waned rapidly by the age of 1, but rose again later in childhood. GMCs among children aged 10–14 years were consistently high over time (eg, the range of GMCs across survey rounds were between 0·45 μg/mL and 1·00 μg/mL for VT 23F and between 2·00 μg/mL and 3·11 μg/mL for VT 19F). PCV10 in a 3 + 0 schedule elicited protective IgG levels during infancy, when disease risk is high. The high antibody levels in children aged 10–14 years might indicate continued exposure to vaccine serotypes due to residual carriage or to memory responses to cross-reactive antigens. Despite rapid waning of IgG after vaccination, disease incidence among young children in this setting remains low, suggesting that lower thresholds of antibody, or other markers of immunity (eg, memory B cells), may be needed to assess population protection among children who have aged past infancy. Gavi, the Vaccine Alliance; Wellcome Trust. [ABSTRACT FROM AUTHOR]

Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in parts of Africa. In May, 2022, the world was alerted to circulation of monkeypox virus in many high-income countries outside of Africa. Continued spread resulted in a WHO declaration of a Public Health Emergency of International Concern. Although there has been much attention on the global outbreak, most of the focus has been on high-income countries outside of Africa, despite the fact that monkeypox virus has been causing disease in parts of Africa for at least 50 years. Furthermore, the long-term consequences of this event, especially the risk that mpox fills the niche vacated through smallpox eradication, have not been sufficiently considered. The heart of the problem is the historical neglect of mpox in Africa where the disease is endemic, and the actual and potential consequences if this neglect is left uncorrected. [ABSTRACT FROM AUTHOR]

We propose a novel, non-discriminatory classification of monkeypox virus. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within IIb, the cause the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomics surveillance. The current nomenclature for monkeypox virus is stigmatising and misleading. This Perspective article proposes a practical and neutral system of nomenclature that will allow efficient communication without the risk of further misconceptions, discrimination and stigmatisation. [ABSTRACT FROM AUTHOR]

World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respiratory syncytial virus (RSV) vaccines, WHO recently published preferred product characteristics for monoclonal antibodies to prevent severe RSV disease in infants. This article summarizes the key attributes from the preferred product characteristics and discusses key considerations for future access and use of preventive RSV monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Background: The global Immunisation Agenda 2030 highlights coverage and equity as a strategic priority goal to reach high equitable immunisation coverage at national levels and in all districts. We estimated inequities in full immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics among children aged 12-23 months in Kenya.Methods: We analysed full immunisation coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, 1-dose measles, and 3-dose pneumococcal vaccines) of 3943 children aged 12-23 months from the 2014 Kenya Demographic and Health Survey. We disaggregated mean coverage by socioeconomic (household wealth, religion, ethnicity), geographic (place of residence, province), maternal (maternal age at birth, maternal education, maternal marital status, maternal household head status), child (sex of child, birth order), and place of birth characteristics, and estimated inequities in full immunisation coverage using bivariate and multivariate logistic regression.Results: Immunisation coverage ranged from 82% [81-84] for the third dose of polio to 97.4% [96.7-98.2] for the first dose of DTP-HepB-Hib, while full immunisation coverage was 68% [66-71] in 2014. After controlling for other background characteristics through multivariate logistic regression, children of mothers with primary school education or higher have at least 54% higher odds of being fully immunised compared to children of mothers with no education. Children born in clinical settings had 41% higher odds of being fully immunised compared to children born in home settings. Children in the Coast, Western, Central, and Eastern regions had at least 74% higher odds of being fully immunised compared to children in the North Eastern region, while children in urban areas had 26% lower odds of full immunisation compared to children in rural areas. Children in the middle and richer wealth quintile households were 43-57% more likely to have full immunisation coverage compared to children in the poorest wealth quintile households. Children who were sixth born or higher had 37% lower odds of full immunisation compared to first-born children.Conclusions: Children of mothers with no education, born in home settings, in regions with limited health infrastructure, living in poorer households, and of higher birth order are associated with lower rates of full immunisation. Targeted programmes to reach under-immunised children in these subpopulations will lower the inequities in childhood immunisation coverage in Kenya. [ABSTRACT FROM AUTHOR]

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa is poorly described. The first case of SARS-CoV-2 in Kenya was reported on 12 March 2020, and an overwhelming number of cases and deaths were expected, but by 31 July 2020, there were only 20,636 cases and 341 deaths. However, the extent of SARS-CoV-2 exposure in the community remains unknown. We determined the prevalence of anti–SARS-CoV-2 immunoglobulin G among blood donors in Kenya in April–June 2020. Crude seroprevalence was 5.6% (174 of 3098). Population-weighted, testperformance-adjusted national seroprevalence was 4.3% (95% confidence interval, 2.9 to 5.8%) and was highest in urban counties Mombasa (8.0%), Nairobi (7.3%), and Kisumu (5.5%). SARS-CoV-2 exposure is more extensive than indicated by case-based surveillance, and these results will help guide the pandemic response in Kenya and across Africa. [ABSTRACT FROM AUTHOR]

This study examines the prevalence of SARS-CoV-2 antibodies among blood donors aged 16 to 64 years in Kenya from January to March 2021. [ABSTRACT FROM AUTHOR]

Highlights • A high coverage is essential if the full benefits of vaccines are to be enjoyed. • A vaccine registry can help quantify the errors in coverage estimates from surveys. • Vaccination coverage obtained using a survey approach overestimates coverage by 2%. • Survey and administrative methods underestimate fully immunised children by ≥10%. • Non-hospital delivery and stock-outs were associated with failure to vaccinate. Abstract Background The benefits of childhood vaccines are critically dependent on vaccination coverage. We used a vaccine registry (as gold standard) in Kenya to quantify errors in routine coverage methods (surveys and administrative reports), to estimate the magnitude of survivor bias, contrast coverage with timeliness and use both measures to estimate population immunity. Methods Vaccination records of children in the Kilifi Health and Demographic Surveillance System (KHDSS), Kenya were combined with births, deaths, migration and residence data from 2010 to 17. Using inverse survival curves, we estimated up-to-date and age-appropriate vaccination coverage, calculated mean vaccination coverage in infancy as the area under the inverse survival curves, and estimated the proportion of fully immunised children (FIC). Results were compared with published coverage estimates. Risk factors for vaccination were assessed using Cox regression models. Results We analysed data for 49,090 infants and 48,025 children aged 12–23 months in 6 birth cohorts and 6 cross-sectional surveys respectively, and found 2nd year of life surveys overestimated coverage by 2% compared to birth cohorts. Compared to mean coverage in infants, static coverage at 12 months was exaggerated by 7–8% for third doses of oral polio, pentavalent (Penta3) and pneumococcal conjugate vaccines, and by 24% for the measles vaccine. Surveys and administrative coverage also underestimated the proportion of the fully immunised child by 10–14%. For BCG, Penta3 and measles, timeliness was 23–44% higher in children born in a health facility but 20–37% lower in those who first attended during vaccine stock outs. Conclusions Standard coverage surveys in 12–23 month old children overestimate protection by ignoring timeliness, and survivor and recall biases. Where delayed vaccination is common, up-to-date coverage will give biased estimates of population immunity. Surveys and administrative methods also underestimate FIC prevalence. Better measurement of coverage and more sophisticated analyses are required to control vaccine preventable diseases. [ABSTRACT FROM AUTHOR]

Objective: Paragonimiasis is a foodborne trematode infection of the lungs caused by Paragonimus spp., presenting clinically with similar symptoms to active tuberculosis (TB). Worldwide, an estimated 20.7 million people are infected with paragonimiasis, but relatively little epidemiological data exists for Africa. Given a recently reported case, we sought to establish whether paragonimiasis should be considered as an important differential diagnosis for human TB in The Gambia, West Africa. Results: We developed a novel PCR-based diagnostic test for Paragonimus species known to be found in West Africa, which we used to examine archived TB negative sputum samples from a cross-sectional study of volunteers with tuberculosis-like symptoms from communities in the Western coastal region of The Gambia. Based on a "zero patient" design for detection of rare diseases, 300 anonymised AFB smear negative sputum samples, randomly selected from 25 villages, were screened for active paragonimiasis by molecular detection of Paragonimus spp. DNA. No parasite DNA was found in any of the sputa of our patient group. Despite the recent case report, we found no evidence of active paragonimiasis infection masking as TB in the Western region of The Gambia. [ABSTRACT FROM AUTHOR]

Objective To estimate the population prevalence of active pulmonary tuberculosis in Gambia. Methods Between December 2011 and January 2013, people aged ≥ 15 years participating in a nationwide, multistage cluster survey were screened for active pulmonary tuberculosis with chest radiography and for tuberculosis symptoms. For diagnostic confirmation, sputum samples were collected from those whose screening were positive and subjected to fluorescence microscopy and liquid tuberculosis cultures. Multiple imputation and inverse probability weighting were used to estimate tuberculosis prevalence. Findings Of 100 678 people enumerated, 55 832 were eligible to participate and 43 100 (77.2%) of those participated. A majority of participants (42 942; 99.6%) were successfully screened for symptoms and by chest X-ray. Only 5948 (13.8%) were eligible for sputum examination, yielding 43 bacteriologically confirmed, 28 definite smear-positive and six probable smear-positive tuberculosis cases. Chest X-ray identified more tuberculosis cases (58/69) than did symptoms alone (43/71). The estimated prevalence of smear-positive and bacteriologically confirmed pulmonary tuberculosis were 90 (95% confidence interval, CI: 53-127) and 212 (95% CI: 152-272) per 100 000 population, respectively. Tuberculosis prevalence was higher in males (333; 95% CI: 233-433) and in the 35-54 year age group (355; 95% CI: 219-490). Conclusion The burden of tuberculosis remains high in Gambia but lower than earlier estimates of 490 per 100 000 population in 2010. Less than half of all cases would have been identified based on smear microscopy results alone. Successful control efforts will require interventions targeting men, increased access to radiography and more accurate, rapid diagnostic tests. [ABSTRACT FROM AUTHOR]

Background: A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia. Methods: This was a nationwide, multi-cluster survey in children aged 6–11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods. Results: TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8–10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47–7.37] and the ARTI was 0.75% [95%CI 0.60–0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence. Conclusions: This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: The identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–γ may help to define markers of early Mtb infection. Methods: We assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST−). We assessed their short- and long-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages. Results: After 1 and 6 days stimulation with EC, 12 cytokines (IFN–γ, IL–2, IP–10, TNF–α, IL–13, IL–17, IL–10, GMCSF, MIP–1β, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–γ ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection. Conclusion: We describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at-risk’ populations beyond TST and IGRA. [ABSTRACT FROM AUTHOR]

Background: Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. Methods: This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). Results: The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged ,9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Conclusions: Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria. [ABSTRACT FROM AUTHOR]

Background: Qualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy. Methods: Newly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models. Results: A total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found. Conclusions: TB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: T cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. Subjects with active disease had a greater proportion of polyfunctional cells responding to ESAT-6/CFP-10 stimulation than their infected but non-diseased household contacts (HHC). We therefore wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy. Methods: We performed a cross-sectional study using PBMC from TB cases (pre- and post-treatment) and HHC. Samples were stimulated overnight with TB antigens (ESAT-6/CFP-10 and PPD) and their CD4+ and CD8+ T cells were assessed for production of CD107a, IFN-γ, IL-2 and TNF-α and the complexity of the responses was determined using SPICE and PESTLE software. Results and Conclusions: We found that an increase in complexity (i.e., production of more than 1 factor simultaneously) of the T cell profile was associated with TB disease and that this was significantly reduced following TB treatment. This implies that T cells are able to respond adequately to TB antigens with active disease (at least initially) but the ability of this response to protect the host from disease progression is hampered, presumably due to immune evasion strategies by the bacteria. These findings have implications for the development of new diagnostics and vaccine strategies. [ABSTRACT FROM AUTHOR]

Mycobacterium africanum (MAF) is a common cause of human pulmonary tuberculosis in West Africa. We previously described phenotypic differences between MAF and Mycobacterium tuberculosis (MTB) among 290 patients. In the present analysis, we compared 692 tuberculosis patients infected with the two most common lineages within the (MTB) complex found in the Gambia, namely MAF West African type 2 (39% prevalence) and Euro-American MTB (55% prevalence). We identified additional phenotypic differences between infections with these two organisms. MAF patients were more likely to be older and HIV infected. In addition, they had worse disease on chest X-ray, despite complaining of cough for an equal duration, and were more likely severely malnourished. In this cohort, the prevalence of MAF did not change significantly over a 7-year period. [ABSTRACT FROM AUTHOR]

Interferon gamma remains a key effector molecule that is still widely used as the most informative biomarker for screening human immune responses against tuberculosis, particularly in ELISPOT assays. We investigated the participation of CD4+ and CD8+ T lymphocytes in the PBMC responses to Mycobacterium tuberculosis (Mtb) specific antigens in 33 TB cases and 49 contacts. Responses to ESAT-6 were higher than CFP-10. There was no significant difference in responses to both Mtb antigens between cases and contacts. PBMCs response to ESAT-6 but not CFP-10 in cases was significantly reduced by depletion of CD4+ cells whereas CD8+ cell depletion had no impact. In conclusion, ESAT-6 is a more recognized antigen in this population, and CD4+ lymphocytes are the main participants in IFN-γ response by ELISPOT. Thus, a decline of CD4+ T lymphocytes below a critical level might affect the sensitivity of IFN-γ release assays for detecting Mtb infection. [ABSTRACT FROM AUTHOR]

Background: IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Their performance may depend on assay format and may vary across populations and settings. We compared the diagnostic performance of an in-house T -cell and commercial whole blood-based IGRAs for the diagnosis of LTBI and TB disease in The Gambia. Methods: Newly diagnosed sputum smear positive cases and their household contacts were recruited. Cases and contacts were bled for IGRA and contacts had a Mantoux skin test. We assessed agreement and discordance between the tests and categorized a contact's level of M. tuberculosis exposure according to where s/he slept relative to a case: the same room, same house or a different house. We assessed the relationship between exposure and test results by multiple logistic regression. Results: In 80 newly diagnosed TB cases, the sensitivity of ELISPOT was 78.7% and for QFT-GIT was 64.0% (p = 0.047). Of 194 household contacts 57.1% and 58.8% were positive for ELISPOT and QFT-GIT respectively. The overall agreement between both IGRAs for LTBI in contacts was 71.4% and there was no significant discordance (p = 0.29). There was significant discordance between the IGRAs and TST. Neither IGRA nor TST had evidence of false positive results because of Bacille Calmette Gu&erin;rin (BCG) vaccination. However, agreement between QFT-GIT and TST as well as discordance between both IGRAs and TST were associated with BCG vaccination. Both IGRAs responded to the M. tuberculosis exposure gradient and were positively associated with increasing TST induration (p = 0.003 for ELISPOT and p = 0.001 for QFT-GIT). Conclusion: The ELISPOT test is more sensitive than the QFT-GIT for diagnosing TB disease. The two tests perform similarly in the diagnosis of LTBI in TB contacts. Significant discordance between the two IGRAs and between each and the TST remain largely unexplained. [ABSTRACT FROM AUTHOR]

Tungiasis is a highly neglected tropical skin disease caused by the sand flea, Tunga penetrans. The flea burrows into the skin inducing a strong inflammatory response, leading to pain and mobility restrictions with potential impacts on quality of life. Few countries implement control efforts and there are few data on the impact of the disease to support policy decisions. We conducted a survey to determine the impact of tungiasis among primary school children across nine counties of Kenya. A total of 10,600 pupils aged 8 to 14 years were randomly selected from 97 primary schools and examined for tungiasis. For 81 cases and 578 randomly selected controls, anthropometric measurements were made, and school attendance and exam scores were collected from school records. Of those with tungiasis, 73 were interviewed regarding their quality of life using a tungiasis-specific instrument. Mixed effect ordered logistic and linear models were used to assess associations between disease status and impact variables. Compared to uninfected pupils, those with tungiasis had lower weight-for-age z-scores (adjusted β -0.41, 95% CI: -0.75–0.06, p = 0.020), missed more days of school the previous term (adjusted Incidence Rate Ratio: 1.49, 95% CI: 1.01–2.21, p = 0.046) and were less likely to receive a high score in mathematics (aOR 0.18, 95% CI: 0.08–0.40, p<0.001) and other subjects. Pupils with severe disease (clinical score >10) were four times more likely to experience severe pain than those with mild disease (OR 3.96, 95% CI: 1.35–11.64, p = 0.012) and a higher impact on their quality of life than those with mild disease (aOR 3.57, 95% CI: 1.17–10.8, p = 0.025) when adjusted for covariates. This study has demonstrated tungiasis has a considerable impact on children's lives and academic achievement. This indicates the need for integrated disease management for school-aged children to protect their physical and cognitive development and their future prospects. Author summary: Tungiasis is one of the most neglected tropical diseases (NTDs). It is caused by a flea which burrows into the skin, usually of the feet. The neglect has resulted in large gaps in our knowledge of the disease, how to treat and prevent infection. This is partly due to a lack of appreciation for the impact the disease has on patients' lives by health officials, policymakers and the research community. In this study we aimed to determine the impact on school children in nine counties of Kenya. We found evidence that children experience considerable pain and itching which affects their ability to attend school and to concentrate on their classes. They had lower exam scores in mathematics, English and science than uninfected children. This study has provided evidence that tungiasis is a disease that has a considerable impact on children and urgently needs more attention from researchers, donors, and policy makers. Integrating tungiasis into comprehensive disease management for school-aged children will protect their physical and cognitive development and their future prospects. [ABSTRACT FROM AUTHOR]

Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2–66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0–9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9–6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1–3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7–2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. The Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that—inferring a rate of ~6 APOBEC3 mutations per year—estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control. [ABSTRACT FROM AUTHOR]

Background: Tungiasis is a highly neglected tropical skin disease caused by the sand flea, Tunga penetrans, the female of which burrows into the skin, causing pain and itching. The disease occurs throughout South America and sub-Saharan Africa but there are few systematic data on national disease burdens. The tungiasis research community is keen to develop survey methods to fill this gap. Here we used a school-based, thorough examination method to determine the prevalence and risk factors for tungiasis in Kenya. Methods: We conducted the first nationally representative survey of tungiasis, including nine counties covering the major ecological zones of Kenya. A stratified multistage random sampling was used to select 22 primary schools from each of the nine counties and to select up to 114 pupils aged 8 to 14 years in each school. Pupils were examined thoroughly for tungiasis. Two surveys were conducted, the first between May and July 2021 and the second between October 2021 and April 2023 when pupils were also interviewed for risk factors. Mixed effect logistic regression models were used to test associations of independent variables with tungiasis using the school as a random effect. Results: The overall prevalence of tungiasis in the first survey was 1.35% [95% confidence interval (CI): 1.15–1.59%], and 0.89% in the second survey. The prevalence ranged from 0.08% (95% CI: 0.01–0.59%) in Taita Taveta county to 3.24% (95% CI: 2.35–4.44%) in Kajiado county. Tungiasis infection was associated with county of residence, male sex [adjusted odds ratio (aOR) = 2.01, 95% CI: 1.52–2.67], and lower age (aOR = 0.81, 95% CI: 0.75–0.88). For the first time we demonstrate an association with attending public schools rather than private schools (aOR = 5.62, 95% CI: 1.20–26.22) and lower socioeconomic status (aOR = 0.10, 95% CI: 0.03–0.33). Using a rapid screening method of the top of feet only, would have missed 62.9% of all cases, 78.9% of mild cases and 20.0% of severe cases. Conclusions: Tungiasis is widely but heterogeneously distributed across Kenya. School-based surveys offer an efficient strategy for mapping tungiasis distribution. [ABSTRACT FROM AUTHOR]

Background Vaccination against coronavirus disease 2019 (COVID-19) is a cost-effective mitigation strategy against the pandemic. As the COVID-19 vaccine becomes more available, low uptake is now a global threat and understanding the underpinnings in local contexts is a priority for intervention development. We aimed to evaluate behavioural determinants of COVID-19 vaccine acceptance that could inform engagement strategies to improve vaccine uptake in Makoko, an urban slum in Lagos, Nigeria. Methods A population-based case–control study utilized the barrier analysis (BA) approach to evaluate the beliefs and behaviours of 45 'doers' and 45 'non-doers'. The standardized BA tabulation sheet was used to assess differences in the proportions between the two groups to identify significant factors that could be addressed through a behaviour change strategy. Results Perceived social norms (family, friend, healthcare workers) that approve the vaccine and expected vaccine protection against diseases among doers were determinants of behaviour. Perceived poor accessibility, safety concerns, lack of trust, low vaccine efficacy and low susceptibility to the infection were the most important determinants of behaviour among non-doers. Conclusions Measures to improve COVID-19 vaccine acceptance in Makoko should include improvement in accessibility and exposing myths and misinformation through clear, concise and evidence-based community education delivered by trusted persons such as healthcare workers and religious leaders. [ABSTRACT FROM AUTHOR]

Introduction: Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. Methods: All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. Results: Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6–12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. Conclusion: There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication. Author summary: The nature of disease caused by snakebite amongst children in rural Africa is poorly understood. All children presenting to Kilifi County Hospital, Kenya with snakebite between 2003 and 2021 were recruited into a study that was nested in an ongoing hospital and community surveillance study. 584 children presented following snakebite and the incidence was 29.1/100,000 person-years amongst children aged 6–12 years. The incidence remained consistent over the course of the study despite the population increasing by over 50%, highlighting that the burden of disease is increasing in-line with population growth. Many children initially sought traditional therapies, which was associated with delayed presentation to hospital. The mortality rate was low, and most children had local, rather than systemic, envenoming. Predictors of severe local envenoming at the time of admission included a high white blood cell count, low haemoglobin, and an upper limb bite site. The findings of this study highlight the need to strengthen strategies to prevent snakebite in children, to overcome barriers to attending hospital, and to develop therapeutics that better treat local envenoming. [ABSTRACT FROM AUTHOR]

Lassa fever (LF) remains endemic in Nigeria with the country reporting the highest incidence and mortality globally. Recent national data suggests increasing incidence and expanding geographic spread. Predictors of LF case positivity in Nigeria have been sparsely studied. We thus sought to determine the sociodemographic and clinical determinants of LF positivity amongst suspected cases presenting to health facilities from 2018 to 2021. A secondary analysis of the national LF surveillance data between January 2018 and December 2021. Socio-demographic and clinical data of 20,027 suspected LF cases were analysed using frequencies and Chi-square statistics with significant p-value set at p < 0.05. The outcome variable was LF case status (positive or negative). Predictors of LF case positivity were assessed using multiple logistic regression models with 95% confidence intervals (CI). Case positivity rate (CPR) for the four years was 15.8% with higher odds of positivity among age group 40–49 years (aOR = 1.40; 95% CI 1.21–1.62), males (aOR = 1.11; 95% CI 1.03–1.20), those with formal education (aOR = 1.33; 95% CI 1.13–1.56), artisans (aOR = 1.70; 95% CI 1.28–2.27), religious leaders (aOR = 1.62; 95% CI 1.04–2.52), farmers (aOR = 1.48; 95% CI 1.21–1.81), and symptomatic individuals (aOR = 2.36; 95% CI 2.09–2.68). Being a health worker (aOR = 0.69; 95% CI 0.53–0.91), a teacher (aOR = 0.69; 95% CI 0.53–0.89) and cases reporting in the 3rd quarter (aOR = 0.79; 95% CI 0.69–0.92) had lower odds. In a sex-disaggregated analysis, female farmers had higher odds of positivity (aOR = 2.43; 95% CI 1.76–3.38; p < 0.001) than male farmers (aOR = 1.52; 95% CI 1.19–1.96; p < 0.01). Fever (aOR = 2.39; 95% CI 2.00–2.84) and gastrointestinal (GI) symptoms (aOR = 2.15; 95% CI 1.94–2.37) had the highest odds among symptoms. Combination of fever and GI symptoms (aOR = 2.15; 95% CI 1.50–3.10), fever and neurological symptoms (aOR = 6.37; 95% CI 1.49–27.16), fever and musculo-skeletal symptoms (aOR = 2.95; 95% CI 1.37–6.33), fever and cardiopulmonary symptoms (aOR = 1.81; 95% CI 1.24–2.64), and cardiopulmonary and general symptoms (aOR = 1.50; 95% CI 1.19–1.89) were also predictive. Cumulative LF CPR appears high with clearly identified predictors. Targeted interventions with heightened index of suspicion for sociodemographic categories predictive of LF in suspected cases are recommended. Ethnographic and further epidemiological studies could aid better understanding of these associations. [ABSTRACT FROM AUTHOR]

Background: Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. Method: We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Discussion: Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates. [ABSTRACT FROM AUTHOR]

Background: Lassa fever is a viral haemorrhagic fever endemic in Nigeria. Improved surveillance and testing capacity have revealed in an increased number of reported cases and apparent geographic spread of Lassa fever in Nigeria. We described the recent four-year trend of Lassa fever in Nigeria to improve understanding of its epidemiology and inform the design of appropriate interventions. Methods: We analysed the national surveillance data on Lassa fever maintained by the Nigeria Centre for Diseases Control (NCDC) and described trends, sociodemographic, geographic distribution, and clinical outcomes. We compared cases, positivity, and clinical outcomes in the period January 2018 to December 2021. Results: We found Lassa fever to be reported throughout the year with more than half the cases reported within the first quarter of the year, a recent increase in numbers and geographic spread of the virus, and male and adult (>18 years) preponderance. Case fatality rates were worse in males, the under-five and elderly, during off-peak periods, and among low reporting states. Conclusion: Lassa fever is endemic in Nigeria with a recent increase in numbers and geographical distribution. Sustaining improved surveillance, enhanced laboratory diagnosis and improved case management capacity during off-peak periods should remain a priority. Attention should be paid to the very young and elderly during outbreaks. Further research efforts should identify and address specific factors that determine poor clinical outcomes. [ABSTRACT FROM AUTHOR]

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease. [ABSTRACT FROM AUTHOR]

Introduction: The high proportion of SARS-CoV-2 infections that have remained undetected presents a challenge to tracking the progress of the pandemic and estimating the extent of population immunity. Methods: We used residual blood samples from women attending antenatal care services at three hospitals in Kenya between August 2020 and October 2021and a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. We fitted a two-component mixture model as an alternative to the threshold analysis to estimate of the proportion of individuals with past SARS-CoV-2 infection. Results: We estimated seroprevalence in 2,981 women; 706 in Nairobi, 567 in Busia and 1,708 in Kilifi. By October 2021, 13% of participants were vaccinated (at least one dose) in Nairobi, 2% in Busia. Adjusted seroprevalence rose in all sites; from 50% (95%CI 42–58) in August 2020, to 85% (95%CI 78–92) in October 2021 in Nairobi; from 31% (95%CI 25–37) in May 2021 to 71% (95%CI 64–77) in October 2021 in Busia; and from 1% (95% CI 0–3) in September 2020 to 63% (95% CI 56–69) in October 2021 in Kilifi. Mixture modelling, suggests adjusted cross-sectional prevalence estimates are underestimates; seroprevalence in October 2021 could be 74% in Busia and 72% in Kilifi. Conclusions: There has been substantial, unobserved transmission of SARS-CoV-2 in Nairobi, Busia and Kilifi Counties. Due to the length of time since the beginning of the pandemic, repeated cross-sectional surveys are now difficult to interpret without the use of models to account for antibody waning. [ABSTRACT FROM AUTHOR]

The burden of severe Covid-19 has been relatively low in sib-Saharan Africa compared to Europe and the Americas. However, SARS-CoV-2 sero-prevalence data has demonstrated that there has been more widespread transmission than can be deduced from reported cases. This could be attributed to under reporting due to low testing capacity or high numbers of asymptomatic SARS-CoV-2 infection in communities. Recent data indicates that prior SARS-CoV-2 exposure is protective against reinfection and that vaccination of previously SARS-CoV-2 infected individuals induces robust cross-reactive antibody responses. Considering these data, calls for a need for a re-think of the COVID-19 vaccination strategy in sub-Saharan African settings with high SARSCoV-2 population exposure but limited available vaccine doses. A potential recommendation would be to prioritize rapid and widespread vaccination of the first dose, while waiting for more vaccines to become available. [ABSTRACT FROM AUTHOR]

Policy decisions on COVID-19 interventions should be informed by a local, regional and national understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Epidemic waves may result when restrictions are lifted or poorly adhered to, variants with new phenotypic properties successfully invade, or infection spreads to susceptible subpopulations. Three COVID-19 epidemic waves have been observed in Kenya. Using a mechanistic mathematical model, we explain the first two distinct waves by differences in contact rates in high and low social-economic groups, and the third wave by the introduction of higher-transmissibility variants. Reopening schools led to a minor increase in transmission between the second and third waves. Socioeconomic and urbanÐrural population structure are critical determinants of viral transmission in Kenya. [ABSTRACT FROM AUTHOR]

CD4+ T cells are required for protection against tuberculosis (TB) disease progression, but interest in the role of antibodies in early protection, as biomarkers for disease status, and use in diagnostic tests has recently increased. In this study we analyzed plasma antibody levels in TB cases before and after treatment in both HIV-positive and -negative individuals and compared them with tuberculin skin test (TST+) (latently infected) household contacts (HHC). We also analyzed HHC that subsequently progressed to active disease within 2 years in order to see if antibodies play a role in protection against disease progression. We used a commercially available kit to 38 kDa antigen and lipoarabinomannan (LAM) and found that immunoglobulin (Ig)G levels were 4-fold higher in subjects with disease compared to latently infected controls (P < 0.001) and were 2-fold higher than pretreatment levels following successful TB treatment (P < 0.001 compared to both pretreated cases and latently infected controls). HIV infection resulted in low antibody levels regardless of disease status or treatment outcome. Furthermore, levels in disease progressors (incident cases) were similar to nonprogressors and were not elevated until just prior to disease progression confirming previous reports that IgG antibodies, at least in the periphery, do not confer protection against TB disease progression. [ABSTRACT FROM AUTHOR]

Determining what constitutes protective immunity to TB is critical for the development of improved diagnostics and vaccines. The comparison of the immune system between contacts of TB patients, who later develop TB disease (progressors), versus contacts who remain healthy (non-progressors), allows for identification of predictive markers of TB disease. This study provides the first comprehensive analysis of the immune system of progressors and non-progressors using a well-characterised TB case-contact (TBCC) platform in The Gambia, West Africa. 22 progressors and 31 nonprogressors were analysed at recruitment, 3 months and 18 months (time to progression: median[IQR] of 507[187-714] days). Immunophenotyping of PBMC, plasma cytokine levels and RT-MLPA analysis of whole blood-derived RNA was performed to capture key immune system parameters. At recruitment, progressors had lower PBMC proportions of CD4+ T cells, NKT cells and B cells relative to non-progressors. Analysis of the plasma showed higher levels of IL-18 in progressors compared to non-progressors and analysis of the RNA showed significantly lower gene expression of Bcl2 but higher CCR7 in progressors compared to non-progressors. This study shows several markers that may predict the onset of active TB at a very early stage after infection. Once these markers have been validated in larger studies, they provide avenues to prospectively identify people at risk of developing TB, a key issue in the testing of new TB vaccines. [ABSTRACT FROM AUTHOR]

OBJECTIVE. To compare the enzyme-linked immunospot (ELISPOT) assay with the tuberculin skin test (TST) in children for the diagnosis of Mycobacterium tuberculosis infection in the Gambia. METHODS. We divided child contacts of sputum smear-positive tuberculosis cases into 3 age categories (<5, 5-9, and 10-14 years) and assessed agreement between the 2 tests plus their relationship to prior Bacille Calmette-Guerin (BCG) vaccination. We categorized a child's level of M tuberculosis exposure according to where he/she slept relative to a case: the same room, same house, or a different house. The relationship between exposure and test result was assessed by multiple logistic regression. RESULTS. In child contacts of 287 cases, 225 (32.5%) of 693 were positive by TST and 232 (32.3%) of 718 by ELISPOT. The overall agreement between tests was 83% and the discordance was not significant. Both tests responded to the M tuberculosis exposure gradient in each age category. The percentage of those who were TST positive/ELISPOT negative increased with increasing exposure. At the lowest exposure level, the percentage of ELISPOT-positive children who were TST negative was increased compared with the highest exposure level. Neither test had evidence of false positive results because of BCG. CONCLUSIONS. In Gambian children, the ELISPOT is slightly less sensitive than the TST in the diagnosis of M tuberculosis infection from recent exposure, and neither test is confounded by prior BCG vaccination. Evidence of reduced TST sensitivity in subjects with the lowest known recent M tuberculosis exposure suggests that, when maximal sensitivity is important, the 2 tests may lie best used together. [ABSTRACT FROM AUTHOR]

Objective and methods: Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent. In many countries, national TB prevalence surveys are the only way to reliably measure the burden of TB disease and can also provide other evidence to inform national efforts to improve TB detection and treatment. Our objective was to synthesise the results and lessons learned from national surveys completed in Africa between 2008 and 2016, to complement a previous review for Asia. Results: Twelve surveys completed in Africa were identified: Ethiopia (2010–2011), Gambia (2011–2013), Ghana (2013), Kenya (2015–2016), Malawi (2013–2014), Nigeria (2012), Rwanda (2012), Sudan (2013–2014), Tanzania (2011–2012), Uganda (2014–2015), Zambia (2013–2014) and Zimbabwe (2014). The eligible population in all surveys was people aged ≥15 years who met residency criteria. In total 588 105 individuals participated, equivalent to 82% (range 57–96%) of those eligible. The prevalence of bacteriologically confirmed pulmonary TB disease in those ≥15 years varied from 119 (95% CI 79–160) per 100 000 population in Rwanda and 638 (95% CI 502–774) per 100 000 population in Zambia. The male:female ratio was 2.0 overall, ranging from 1.2 (Ethiopia) to 4.1 (Uganda). Prevalence per 100 000 population generally increased with age, but the absolute number of cases was usually highest among those aged 35–44 years. Of identified TB cases, 44% (95% CI 40–49) did not report TB symptoms during screening and were only identified as eligible for diagnostic testing due to an abnormal chest X‐ray. The overall ratio of prevalence to case notifications was 2.5 (95% CI 1.8–3.2) and was consistently higher for men than women. Many participants who did report TB symptoms had not sought care; those that had were more likely to seek care in a public health facility. HIV prevalence was systematically lower among prevalent cases than officially notified TB patients with an overall ratio of 0.5 (95% CI 0.3–0.7). The two main study limitations were that none of the surveys included people <15 years, and 5 of 12 surveys did not have data on HIV status. Conclusions: National TB prevalence surveys implemented in Africa between 2010 and 2016 have contributed substantial new evidence about the burden of TB disease, its distribution by age and sex, and gaps in TB detection and treatment. Policies and practices to improve access to health services and reduce under‐reporting of detected TB cases are needed, especially among men. All surveys provide a valuable baseline for future assessment of trends in TB disease burden. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment of tuberculosis (TB) are the mainstay of global and national TB control efforts. However, the gap between expected and reported cases persists for various reasons attributable to the TB services and care-seeking sides of the TB care cascade. Understanding individual and collective perspectives of knowledge, attitudes, beliefs and other social circumstances around TB can inform an evidence-based approach in engaging communities and enhance their participation in TB case detection and treatment.Methods: The study was conducted during the Gambian survey of TB prevalence. This was a nationwide cross-sectional multistage cluster survey with 43,100 participants aged ≥15 years in 80 clusters. The study sample, a random selection of 10% of the survey population within each cluster responded to a semi-structured questionnaire administered by trained fieldworkers to assess the knowledge, attitudes and practice of the participants towards TB. Overall knowledge, attitude and practice scores were dichotomised using the computed mean scores and analysed using descriptive, univariable and multivariable logistic regression.Results: All targeted participants (4309) were interviewed. Majority were females 2553 (59.2%), married 2614 (60.7%), had some form of education 2457 (57%), and were unemployed 2368 (55%). Although 3617 (83.9%) of the participants had heard about TB, only 2883 (66.9%) were considered to have good knowledge of TB. Overall 3320 (77%) had unfavourable attitudes towards TB, including 1896 (44%) who indicated a preference for staying away from persons with TB rather than helping them. However, 3607(83.7%) appeared to have the appropriate health-seeking behaviours with regard to TB as 4157 (96.5%) of them were willing to go to the health facility if they had symptoms suggestive of TB.Conclusions: About 3 in 10 Gambians had poor knowledge on TB, and significant stigma towards TB and persons with TB persists. Interventions to improve TB knowledge and address stigma are required as part of efforts to reduce the burden of undiagnosed TB in the country. [ABSTRACT FROM AUTHOR]

Background Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs). Methods Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre– and post–vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post–vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes). Results Between January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8–80%) reduction in RVHs observed in the first year post–vaccine introduction in Kilifi and a 59% (95% CI, 20–79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46–93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61–92%); this reduction was sustained at both sites into the third year. Conclusions A substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction. [ABSTRACT FROM AUTHOR]

Background: Ten-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2-11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12-59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.Methods: This study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999-Dec 31, 2010) and postvaccine (Jan 1, 2012-Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016.Findings: Surveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03-0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17-0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5-14 years [adjusted IRR 0·26, 95% CI 0·11-0·59], and ≥15 years [0·19, 0·07-0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19-0·35) and non-PCV10-type carriage increased (1·71, 1·47-1·99).Interpretation: Introduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa.Funding: Gavi, The Vaccine Alliance and The Wellcome Trust of Great Britain. [ABSTRACT FROM AUTHOR]

Background In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5 years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off. Methods We developed a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non-vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction. Results The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1–5 year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination. Conclusion We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign. [ABSTRACT FROM AUTHOR]

Background: In West Africa, penicillin, macrolide and lincosamide resistance among beta-haemolytic streptococci (BHS) isolates has rarely been described. However, such data are critical to detect and track the emergence of antibiotic resistance. Methods: Beta-haemolytic streptococci were cultured from clinical specimens from patients attending the clinic at the Medical Research Council Unit The Gambia (n = 217) and kept at -70 °C. Of these, 186 were revived and tested for penicillin susceptibility by disc diffusion and E-test methods, and the D-test for determination of constitutive and inducible macrolide-lincosamide (MLSB) resistance phenotypes. Results: The majority of BHS isolates from infections were group A streptococci (GAS) (126/186, 67.7%). Of these, 16% were from invasive disease (30/186). Other BHS isolated included lancefield groups B (19, 10.2%); C (9/186, 4.8%), D (3/186, 1.6%), F (5/186, 2.7%), G (16/186, 8.6%) and non-typeable (8/186, 4.3%). Prevalence of BHS isolated from blood cultures ranges from 0% (2005) to 0.5% (2010). Most (85, 45.7%) of the isolates were from wound infections. Of the 186 BHS isolates, none was resistant to penicillin and 14 (6.1%) were resistant to erythromycin. Of these, 8 (4.3%) demonstrated constitutive MLSB resistance, and 5 (2.7%) were inducible MLSB resistant. All the inducible MLSB isolates were GAS, and majority of the constitutive MLSB isolates (6/8, 75.0%) were non-GAS. Conclusions: Beta-haemolytic streptococci, predominantly GAS are associated with a wide range of infections in The Gambia. It is reassuring that macrolide and lincosamide resistance is relatively low. However, monitoring of MLSB resistance is necessary with the global spread of resistant BHS strains. [ABSTRACT FROM AUTHOR]

Background: MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. Methodology/Principal Findings: We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37°C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. Conclusions/Significance: In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs. [ABSTRACT FROM AUTHOR]

Background: In West Africa, the carriage of Group B Streptococcus (GBS), among infants is poorly characterised. We investigated co-carriage of GBS with other respiratory pathogens in the infants' nasopharynx in The Gambia. Methods: We assessed the carriage, serotypes and antibiotic susceptibility of Beta-haemolytic Streptococci (BHS) groups A-G; along with the carriage of Streptococcus pneumoniae; Haemophilus influenzae; Staphylococcus aureus and Moraxella catarrhalis in 1200 two-month old infants. Results: The BHS prevalence was 20.0 % and GBS dominated (13.8 %), particularly serotypes V and II; serotype V being negatively associated with H. Influenzae carriage (OR 0.41 [95 % CI: 0.18-0.93], p = 0.033). Although co-colonization of GBS and other BHS was not seen, colonization with GBS was positively associated with S. aureus (OR 1.89 [95 % CI: 1. 33-2.69], P < 0.001) and negatively associated with S. pneumoniae (OR 0.47 [95 % CI: 0.33-0.67], p < 0.001) and M. catarrhalis (OR 0.61 [95 % CI: 0.40-0.92], p = 0.017). ≥ 89 % of GBS isolates were susceptible to most antibiotics tested, except for tetracycline resistance, which was 89 %. Conclusion: This study provides baseline data on the carriage of GBS in two month old infants from West Africa. The dominant serotypes of GBS in this setting are serotypes V and II. This may be important for future GBS vaccine development for the West African sub-region. [ABSTRACT FROM AUTHOR]

Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility. [ABSTRACT FROM AUTHOR]

To reach performance levels comparable to human experts, computer-aided detection (CAD) systems are typically optimized following a supervised learning approach that relies on large training databases comprising manually annotated lesions. However, manually outlining those lesions constitutes a difficult and time-consuming process that renders detailedly annotated data difficult to obtain. In this paper, we investigate an alternative approach, namely multiple-instance learning (MIL), that does not require detailed information for optimization. We have applied MIL to a CAD system for tuberculosis detection. Only the case condition (normal or abnormal) was required during training. Based upon the well-known miSVM technique, we propose an improved algorithm that overcomes miSVM’s drawbacks related to positive instance underestimation and costly iteration. To show the advantages of our MIL-based approach as compared with a traditional supervised one, experiments with three X-ray databases were conducted. The area under the receiver operating characteristic curve was utilized as a performance measure. With the first database, for which training lesion annotations were available, our MIL-based method was comparable to the supervised system (0.86 versus 0.88). When evaluating the remaining databases, given their large difference with the previous image set, the most appealing strategy was to retrain the CAD systems. However, since only the case condition was available, only the MIL-based system could be retrained. This scenario, which is common in real-world applications, demonstrates the better adaptation capabilities of the proposed approach. After retraining, our MIL-based system significantly outperformed the supervised one (0.86 versus 0.79 and 0.91 versus 0.85, p<0.0001 and p=0.0002, respectively). [ABSTRACT FROM AUTHOR]

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative-induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia. [ABSTRACT FROM AUTHOR]

• Both assays discriminate SARS-CoV-2 seropositive and seronegative individuals. • Both assays correctly estimate seroprevalence in a wide range of seroprevalences. • WANTAI has slightly higher sensitivity than KWTRP. • KWTRP has slightly higher specificity than WANTAI. Many SARS-CoV-2 antibody detection assays have been developed but their differential performance is not well described. In this study we compared an in-house (KWTRP) ELISA which has been used extensively to estimate seroprevalence in the Kenyan population with WANTAI, an ELISA which has been approved for widespread use by the WHO. Using a wide variety of sample sets including pre-pandemic samples (negative gold standard), SARS-CoV-2 PCR positive samples (positive gold standard) and COVID-19 test samples from different periods (unknowns), we compared performance characteristics of the two assays. The overall concordance between WANTAI and KWTRP was 0.97 (95% CI, 0.95–0.98). For WANTAI and KWTRP, sensitivity was 0.95 (95% CI 0.90–0.98) and 0.93 (95% CI 0.87–0.96), respectively. Specificity for WANTAI was 0.98 (95% CI, 0.96–0.99) and 0.99 (95% CI 0.96–1.00) while KWTRP specificity was 0.99 (95% CI, 0.98–1.00) and 1.00 using pre-pandemic blood donors and pre-pandemic malaria cross-sectional survey samples respectively. Both assays show excellent characteristics to detect SARS-CoV-2 antibodies. [ABSTRACT FROM AUTHOR]

Summary: Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium tuberculosis (MTb) infects approximately 2 billion people world-wide resulting in almost 2 million deaths per year. Determining biomarkers that distinguish different stages of tuberculosis (TB) infection and disease will provide tools for more effective diagnosis and ultimately aid in the development of new vaccine candidates. The current diagnostic kits utilising production of IFN-γ in response to TB antigens can detect MTb infection but are unable to distinguish between infection and disease. The aim of this study was to assess if the use of a longer term assay and the analysis of multiple cytokines would enhance diagnosis of active TB in a TB-endemic population. Methods: We compared production of multiple cytokines (TNF-α, IFN-γ, IL-10, IL-12(p40), IL-13, IL-17 and IL-18) following long-term (7 days) stimulation of whole-blood with TB antigens (ESAT-6/CFP-10 (EC), PPD or TB10.4) from TB cases (n = 36) and their Mycobacterium-infected (TST+; n = 20) or uninfected (TST2; n = 19) household contacts (HHC). Results and Conclusions: We found that TNF-α production following EC stimulation and TNF-α and IL-12(p40) following TB10.4 stimulation were significantly higher from TB cases compared to TST+ HHC, while production of IFN-γ and IL-13 were significantly higher from TST+ compared to TST- HHC following PPD or EC stimulation. Combined analysis of TNF-α, IL- 12(p40) and IL-17 following TB10.4 stimulation resulted in 85% correct classification into TB cases or TST+ HHC. 74% correct classification into TST+ or TST2 HHC was achieved with IFN-γ alone following TB10.4 stimulation (69% following EC) and little enhancement was seen with additional cytokines. We also saw a tendency for TB cases infected with M. africanum to have increased TNF-α and IL-10 production compared to those infected with M. tuberculosis. Our results provide further insight into the pathogenesis of tuberculosis and may enhance the specificity of the currently available diagnostic tests, particularly for diagnosis of active TB. [ABSTRACT FROM AUTHOR]