Association between BCG-induced immunity and risk of TB disease

We tested the hypothesis that a lower frequency and profile of specific T cells induced by BCG vaccination at birth is associated with subsequent risk of developing tuberculosis

Measles outbreak investigation in a highly vaccinated community in the Centre region of Cameroon

Background: Measles remains a threat in many African settings due to sub-optimal routine immunisation and catchup campaigns. The Global Vaccine Action Plan goal to eliminate measles by 2020 remains unmet as several countries reported an increase in cases in 2019. In Cameroon, a measles-rubella vaccination campaign was organised in 2019 to reduce the cohort of susceptible children. However, in 2020, eleven suspected cases of measles were notified in the Sa’a Health District and five were confirmed. Objective: This report summarizes a measles outbreak investigation and contact tracing in a highly vaccinated community residing in the Sa’a Health District of Cameroon. Methods: Outbreak investigations were carried out in the Sa’a, Nlong-Onambele and Nkolmgbana health areas from 18 to 21 February 2020. A register review from December 2019 to February 2020 was carried out in all health facilities of the affected health areas. followed by contact tracing in the community. Results: Thirty households were visited in four neighbourhoods. Six missed Epidemiologically-linked cases were discovered in the community, bringing the total number of suspected and confirmed cases to 17. Thirty-five percent of the cases had not received any measles-containing vaccine; 35% of the cases were aged 5 years or older; 53% had history of travel. Community transmission only occurred in the Sa’a health area through a breakthrough case. Conclusions: This outbreak investigation portrayed the role that adequate vaccination coverage plays in preventing widespread outbreaks. Nonetheless, community sensitisation and routine immunisation require strengthening in order to erase pockets of susceptible children

a systematic review protocol

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. Trial registration number CRD4201502614

The burden of pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunization (EPI) in 1974: a systematic review protocol

Abstract Background Vaccine against pertussis has been in use for several decades. Despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. Pertussis surveillance data is largely missing from low- and middle-income countries (LMICs). Without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. We propose conducting a systematic review to evaluate the burden and trends of pertussis in LMICs since 1974. Methods/design Common and medical subject heading (MeSH) terms for pertussis and LMICs will be used to search electronic databases for the relevant literature published between 1974 and December 2014. Only studies from LMICs that fulfils World Health Organisation (WHO) or CDC pertussis case definitions will be included. The studies must have a clear numerator and denominator in a well-defined population. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a modified quality score assessment tool. Standardised data extraction will be carried out after which descriptions of trends in the prevalence, incidence, as well as mortality rate and case fatality rate, will be done. Where sufficient data is available, the results will be stratified by age group, geography, location, vaccination and HIV status. Discussion The systematic review proposed by this protocol seeks to address the knowledge gap in the epidemiology of pertussis in LMICs for the first time. It is anticipated that the background epidemiological trends of pertussis in LMICs that our study will provide could be used in the planning for the control of pertussis. Systematic review registration PROSPERO CRD4201501515

A systematic review of the epidemiology of hepatitis A in Africa

Abstract Background Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. Methods We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. Results The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. Conclusions Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks

The burden of laboratory-confirmed pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunisation (EPI) in 1974: a systematic review and meta-analysis

Abstract Background An effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global reduction in pertussis morbidity and mortality. In low- and middle-income countries (LMICs), however, the epidemiology of pertussis remains largely unknown. This impacts negatively on pertussis control strategies in these countries. This study aimed to systematically and comprehensively review published literature on the burden of laboratory-confirmed pertussis in LMICs over the 45 years of EPI. Methods Electronic databases were searched for relevant literature (1974 to December 2018) using common and MeSH terms for pertussis. Studies using PCR, culture or paired serology to confirm Bordetella pertussis and parapertussis in symptomatic individuals were included if they had clearly defined numerators and denominators to determine prevalence and mortality rates. Results Eighty-two studies (49,167 participants) made the inclusion criteria. All six WHO regions were represented with most of the studies published after 2010 and involving mainly upper middle-income countries (n = 63; 77%). PCR was the main diagnostic test after the year 2000. The overall median point prevalence of PCR-confirmed Bordetella pertussis was 11% (interquartile range (IQR), 5–27%), while culture-confirmed was 3% (IQR 1–9%) and paired serology a median of 17% (IQR 3–23%) over the period. On average, culture underestimated prevalence by 85% (RR = 0.15, 95% CI, 0.10–0.22) compared to PCR in the same studies. Risk of pertussis increased with HIV exposure [RR, 1.4 (95% CI, 1.0–2.0)] and infection [RR, 2.4 (95% CI, 1.1–5.1)]. HIV infection and exposure were also related to higher pertussis incidences, higher rates of hospitalisation and pertussis-related deaths. Pertussis mortality and case fatality rates were 0.8% (95% CI, 0.4–1.4%) and 6.5% (95% CI, 4.0–9.5%), respectively. Most deaths occurred in infants less than 6 months of age. Conclusions Despite the widespread use of pertussis vaccines, the prevalence of pertussis remains high in LMIC over the last three decades. There is a need to increase access to PCR-based diagnostic confirmation in order to improve surveillance. Disease control measures in LMICs must take into account the persistent significant infant mortality and increased disease burden associated with HIV infection and exposure

Safety of licensed vaccines in HIV-infected persons: a systematic review protocol

Abstract Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons. Systematic review registration PROSPERO CRD42014009794

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

Knowledge, attitudes and practices on adolescent vaccination among parents, teachers and adolescents in Africa: a systematic review protocol

Background: Vaccines are the most successful and cost-effective public health interventions available to avert vaccine-preventable diseases and deaths. Despite progress in the field of adolescent health, many young people in Africa still get sick and die from vaccine-preventable diseases due to lack of vaccination. Parents, adolescents and teachers are key players with regard to implementation of adolescent vaccination policies. Therefore, understanding their knowledge, attitudes and practices towards adolescent vaccination may provide clues on what can be done to improve vaccine uptake among adolescents. The aim of this study is to conduct a qualitative and quantitative systematic review on knowledge, attitudes and practices on adolescent vaccination among parents, teachers and adolescents in Africa. Methods: We will include both quantitative and qualitative primary studies. Eligible quantitative studies include both intervention and observational studies. Qualitative studies to be included are focus group discussions, direct observations, in-depth interviews and case ethnographic studies. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide and CINAHL for eligible studies with no time and language limits. We will also check reference lists of included studies for other eligible reports. Two authors will independently screen the search output, select studies and extract data, resolving discrepancies by consensus and discussion. We will analyse qualitative data using thematic analysis where applicable, and quantitative studies findings will be presented in a narrative synthesis form based on the outcomes. Discussion: The findings from this systematic review will guide the identification of gaps on knowledge, attitudes and practices among the key role players on adolescent vaccination. We anticipate that our findings will guide the development of adolescent-focused vaccination policy in Africa, which is virtually non-existent at present. Systematic review registration: This review is registered with PROSPERO, registration number CRD42014010395.