Crude childhood vaccination coverage in West Africa: Trends and predictors of completeness.

Background: Africa has the lowest childhood vaccination coverage worldwide. If the full benefits of childhood vaccination programmes are to be enjoyed in sub-Saharan Africa, all countries need to improve on vaccine delivery to achieve and sustain high coverage. In this paper, we review trends in vaccination coverage, dropouts between vaccine doses and explored the country-specific predictors of complete vaccination in West Africa.  Methods: We utilized datasets from the Demographic and Health Surveys Program, available for Benin, Burkina Faso, The Gambia, Ghana, Guinea, Cote d'Ivoire, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone and Togo, to obtain coverage for Bacillus Calmette-Guerin, polio, measles, and diphtheria, pertussis and tetanus (DPT) vaccines in children aged 12 - 23 months. We also calculated the DPT1-to-DPT3 and DPT1-to-measles dropouts, and proportions of the fully immunised child (FIC). Factors predictive of FIC were explored using Chi-squared tests and multivariable logistic regression.  Results: Overall, there was a trend of increasing vaccination coverage. The proportion of FIC varied significantly by country (range 24.1-81.4%, mean 49%). DPT1-to-DPT3 dropout was high (range 5.1% -33.9%, mean 16.3%). Similarly, DPT1-measles dropout exceeded 10% in all but four countries. Although no single risk factor was consistently associated with FIC across these countries, maternal education, delivery in a health facility, possessing a vaccine card and a recent post delivery visit to a health facility were the key predictors of complete vaccination.  Conclusions: The low numbers of fully immunised children and high dropout between vaccine doses highlights weaknesses and the need to strengthen the healthcare and routine immunization delivery systems in this region. Country-specific correlates of complete vaccination should be explored further to identify interventions required to increase vaccination coverage. Despite the promise of an increasing trend in vaccination coverage in West African countries, more effort is required to attain and maintain global vaccination coverage targets

Serological Surveys for complementing assessments of vaccination coverage in sub-Saharan Africa: A systematic review

Background: Serosurveys of biomarkers of infection/vaccination are widely used for evaluating vaccine-induced immunity and monitoring the effectiveness of immunisation programmes in developed countries. In sub-Saharan Africa (sSA) where vaccination coverage (VC) estimates are often incomplete, inaccurate and overestimate effective population immunity, the use of serosurveys is limited. Methods: We conducted a review of the use of serosurveys to assess/complement assessments of VC in sSA by searching electronic databases (PubMed, Embase, Web of Science, Popline, Ovid and Africa Wide Information) for English language articles published from 1 January 1940 to 31 January 2017. We also searched the references of retrieved articles. SSA was defined as all of Africa excluding the countries in North Africa. We included only articles that measured VC and assessed the quality of these studies using the Newcastle-Ottawa Scale. Results: We found 1056 unique records, reviewed 20 eligible studies of which just 12 met our inclusion criteria. These 12 studies were serosurveys of measles, tetanus, polio and yellow fever. Antibodies induced by natural infection confounded serological test results and there was significant discordance between vaccination history and the presence of antibodies in all except for tetanus vaccine. No study looked at Hepatitis B. Conclusions: Serosurveys for tetanus or tetanus containing vaccines may be directly useful for ascertainment of vaccination exposure or reliably complement current survey methods that measure VC. Given the limited experience in using serosurveys for this purpose in sSA, well-designed serosurveys of tetanus and possibly hepatitis B are required to further validate/evaluate their performance

Inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics in Kenya.

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

Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment.

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-gamma, IL-2 and TNF-alpha 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

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children.

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

Population immunity to pneumococcal serotypes in Kilifi, Kenya, before and 6 years after the introduction of PCV10 with a catch-up campaign: an observational study of cross-sectional serosurveys

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Gavi, the Vaccine Alliance; Wellcome Trust

A tuberculosis nationwide prevalence survey in Gambia, 2012.

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

Population immunity to pneumococcal serotypes in Kilifi, Kenya, before and 6 years after the introduction of PCV10 with a catch-up campaign: an observational study of cross-sectional serosurveys

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Gavi, the Vaccine Alliance; Wellcome Trust

Comparison of two interferon gamma release assays in the diagnosis of Mycobacterium tuberculosis infection and disease in The Gambia

<p>Abstract</p> <p>Background</p> <p>IFN-γ Release Assays (IGRAs) have been licensed for the diagnosis of latent <it>Mycobacterium tuberculosis </it>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.</p> <p>Methods</p> <p>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 <it>M. tuberculosis </it>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.</p> <p>Results</p> <p>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 Guérin (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 <it>M. tuberculosis </it>exposure gradient and were positively associated with increasing TST induration (p = 0.003 for ELISPOT and p = 0.001 for QFT-GIT).</p> <p>Conclusion</p> <p>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.</p

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors.

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, test-performance-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