Creating a best practice template for participant communication plans in global health clinical studies.

BACKGROUND: Clinical trial participants have a right to be informed throughout the entire process of human subject research. As part of this pillar of research ethics, participants and other stakeholders should be made aware of research findings after a trial has been completed. Though participants have both a right, and a desire to be informed of research outcomes, studies show that they rarely receive communication about study findings. Our aim was (1) to understand what, if any, role communication plans play in current global health clinical research protocols and (2) to use our findings to develop a communication plan template tailored to clinical research carried out in low-and-middle-income countries (LMIC) while minimizing colonial assumptions. While the template was drafted in the LMIC context, the principles are universally applicable and should be considered best practices for all global health clinical trials. METHODS: We carried out a mixed-method study over a period of 6 months to understand the role of communication with study participants and other stakeholders in clinical trials. The semiquantitative analysis included mining publicly available clinical trial protocols for communication-related language. Qualitative interviews (n = 7) were used to gather knowledge and insight from clinical trial experts to inform the development of a communication plan template. RESULTS: None of the 48 mined clinical trial protocols included a communication plan. Of the 48, 21% (n = 21) protocols included communication-related language, and 10% (n = 5) described plans to share trial results with participants. CONCLUSION: The use of communication plans in global health clinical trials is lacking. To our knowledge, this is the first in-depth analysis of communication plans in clinical trials to date. We recommend that researchers utilize the developed communication plan template throughout the entire research process to ensure a human-centered approach to participant communication. This communication plan should apply to all phases of a research trial, with a particular emphasis on plans to share results in an accessible and engaging manner once the trial has been completed.

Adding rapid diagnostic tests to community-based programmes for treating malaria.

BACKGROUND: The World Health Organization (WHO) recommends parasitological testing of all suspected malaria cases using malaria rapid diagnostic tests (mRDTs) or microscopy prior to treatment. Some governments have extended this responsibility to community health workers (CHWs) to reduce malaria morbidity and mortality through prompt and appropriate treatment. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To evaluate community-based management strategies for treating malaria or fever that incorporate both a definitive diagnosis with an mRDT and appropriate antimalarial treatment. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases, and three trials registers up to 14 September 2021. SELECTION CRITERIA: We included individually randomized trials and cluster-randomized controlled trials (cRCTs), controlled before-after studies, and controlled interrupted time series studies in people living in malaria-endemic areas, comparing programmes that train CHWs and drug shop vendors to perform mRDTs and provide appropriate treatment versus similar programmes that do not use mRDTs, and versus routine health facility care. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. For each dichotomous outcome, we extracted the number of participants with the event and the total number of participants in each group, unless studies presented results at a population level only. Primary outcomes were all-cause mortality, hospitalizations, and number of people receiving an antimalarial within 24 hours. Secondary outcomes were malaria-specific mortality, severe malaria, outcomes related to antimalarial treatments, antibiotic prescribing to people with a negative microscopy or polymerase chain reaction (PCR) result, parasitaemia, anaemia, and all adverse events. MAIN RESULTS: We included eight studies from several African countries, Afghanistan, and Myanmar. Staff included CHWs and drug shop vendors.  Community use of malaria rapid diagnostic tests compared to clinical diagnosis Compared to clinical diagnosis, mRDT diagnosis results in reduced prescribing of antimalarials to people who are found to be malaria parasite-negative by microscopy or PCR testing (71 fewer per 100 people, 95% confidence interval (CI) 79 to 51 fewer; risk ratio (RR) 0.17, 95% CI 0.07 to 0.40; 3 cRCTs, 7877 participants; moderate-certainty evidence). This reduction may be greater among CHWs compared to drug shop vendors. People diagnosed by mRDT are more likely to receive appropriate treatment; that is, an antimalarial if they are microscopy- or PCR-positive and no antimalarial if they are microscopy- or PCR-negative (RR 3.04, 95% CI 2.46 to 3.74, 3 cRCTs, 9332 participants; high-certainty evidence). Three studies found that a small percentage of people with a negative mRDT result (as read by the CHW or drug shop vendors at the time of treatment) were nevertheless given an antimalarial: 38/1368 (2.8%), 44/724 (6.1%) and 124/950 (13.1%). Conversely, in two studies, a few mRDT-positive people did not receive an antimalarial (0.5% and 0.3%), and one small cross-over study found that 6/57 (10.5%) people classified as non-malaria in the clinical diagnosis arm received an antimalarial. Use of mRDTs probably increases antibiotic use compared to clinical diagnosis (13 more per 100 people, 95% CI 3 to 29 more; RR 2.02, 95% CI 1.21 to 3.37; 2 cRCTs, 5179 participants; moderate-certainty evidence). We were unable to demonstrate any effect on mortality. Community use of malaria rapid diagnostic tests compared to health facility care Results were insufficient to reach any conclusion. AUTHORS' CONCLUSIONS: Use of mRDTs by CHWs and drug shop vendors compared to clinical diagnosis reduces prescribing of antimalarials to people without malaria. Deaths were uncommon in both groups. Antibiotic prescribing was higher in those with a negative mRDT than in those with a negative clinical diagnosis.

Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis.

BACKGROUND: Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens. METHODS: We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity. RESULTS: A total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%-0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28-7.07] and rotavirus (OR = 0.23, 95% CI: 0.13-0.39), respectively. CONCLUSION: We provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development.

Drivers of COVID-19 Vaccine Uptake amongst Healthcare Workers (HCWs) in Nigeria.

This study applied a behavioral lens to understand drivers of COVID-19 vaccination uptake among healthcare workers (HCWs) in Nigeria. The study used data from an online survey of Nigerian HCWs ages 18 and older conducted in July 2021. Multivariate logistic regression analyses were conducted to examine predictors of getting two doses of a COVID-19 vaccine. One-third of HCWs in our sample reported that they had gotten two doses of a COVID-19 vaccine. Motivation and ability were powerful predictors of being fully vaccinated: HCWs with high motivation and high ability had a 15-times higher odds ratio of being fully vaccinated. However, only 27% of HCWs had high motivation and high ability. This was primarily because the ability to get vaccinated was quite low among HCWs: Only 32% of HCWs reported that it was very easy to get a COVID-19 vaccination. By comparison, motivation was relatively high: 69% of HCWs reported that a COVID-19 vaccine was very important for their health. Much of the recent literature coming out of Nigeria and other LMICs focuses on increasing motivation to get a COVID-19 vaccination. Our findings highlight the urgency of making it easier for HCWs to get COVID-19 vaccinations.

The burden of meningococcal meningitis in the African Meningitis Belt, from 2009 to 2014: a trend analysis.

INTRODUCTION: Neisseria meningitides is the leading cause of meningitis in the African Meningitis Belt. The objective of this study was to conduct a trend analysis of the burden of meningococcal meningitis in the African Meningitis Belt countries from 2009 to 2014. METHODS: secondary data on incidence and death cases were collected from the World Health Organization (WHO) and analyzed to determine the trends of meningitis in the African Meningitis Belt countries using Microsoft excel and Stata 14. RESULTS: these data show unstable meningococcal meningitis outbreaks in the Meningitis Belt before and after the introduction of meningococcal A vaccine (MenAfriVac). The vaccine was introduced at different times in the different countries. E.g. it was introduced in 2010 across Burkina Faso, Mali and Niger while it was introduced from 2011 to 2016 in other countries through mass campaigns. Ever since the vaccine was introduced, there has been a decrease in the number of cases in the countries hence a reduction in the burden of the disease. CONCLUSION: after the introduction of the MenAfriVac, there has been a decline in the meningitis cases in Benin, Burkina Faso, Chad, Ghana, Niger and Nigeria while Sudan shows a decrease only in 2014.

A Systematic Review of Interventions to Improve HPV Vaccination Coverage.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Although most HPV infections are transient and asymptomatic, persistent infection with high-risk HPV types may results in diseases. Although there are currently three effective and safe prophylactic HPV vaccines that are used across the world, HPV vaccination coverage remains low. This review evaluates the effects of the interventions to improve HPV vaccination coverage. We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Scopus, and the World Health Organization International Clinical Trials Registry Platform and checked the reference lists of relevant articles for eligible studies. Thirty-five studies met inclusion criteria. Our review found that various evaluated interventions have improved HPV vaccination coverage, including narrative education, outreach plus reminders, reminders, financial incentives plus reminders, brief motivational behavioral interventions, provider prompts, training, training plus assessment and feedback, consultation, funding, and multicomponent interventions. However, the evaluation of these intervention was conducted in high-income countries, mainly the United States of America. There is, therefore, a need for studies to evaluate the effect of these interventions in low-and middle-income countries, where there is a high burden of HPV and limited HPV vaccination programs.

A systematic review of vaccine availability at the national, district, and health facility level in the WHO African Region.

INTRODUCTION: To describe vaccine stock-outs at national, district, and health facility levels in the WHO African region. AREAS COVERED: We conducted a systematic review to identify studies reporting on vaccine stock-outs at national, district, and health facility levels in 47 African countries. We searched both published and unpublished literature, including the WHO/UNICEF Joint Reporting Form (JRF), for eligible studies. EXPERT OPINION: Countries within the WHO African region continue to face the challenge of vaccine stock-outs at national, district, and health facility levels and this impacts on the delivery of immunization services. The frequency and the proportion of stock-outs vary between countries and between regions within a country. Countries need to put more efforts toward finding lasting solutions to vaccine shortages. We look forward to having more countries reporting vaccine stock-outs especially at the health facility level. Furthermore, countries are currently exploring different approaches for improving vaccine stock management. It is expected that in half a decade from now, more well-designed studies will be available that will inform decision-making.

Informing the measurement of wellbeing among young people living with HIV in sub-Saharan Africa for policy evaluations: a mixed-methods systematic review.

Young people living with HIV (YPLHIV) in sub-Saharan Africa (SSA) are at high risk of having a poor quality of life. Addressing wellbeing explicitly within HIV/AIDS policies could assist mitigation efforts. However, guidance on wellbeing measures to evaluate policies for YPLHIV is scarce. The aims of this mixed-methods review were to identify: i) key dimensions of wellbeing and ii) wellbeing measures that align to these dimensions among YPLHIV (15-24 years) in SSA. We searched six social science and medical databases, including grey literature. We included studies that examined correlates and lived experiences of wellbeing, among YPLHIV in SSA, from January 2000 to May 2019. Two reviewers independently screened abstracts and full texts and assessed methodological quality of included articles. We analysed quantitative and qualitative data using descriptive and meta-ethnographic approaches, respectively. Thereafter, we integrated findings using a framework approach. We identified 6527 citations. Of these, 10 quantitative and 30 qualitative studies were included. Being male, higher educational status, less stigma and more social support were likely correlates of wellbeing. Themes that shaped experiences suggestive of wellbeing were: 1) acceptance and belonging- stigma, social support; 2) coping; 3) standard of living. Our final synthesis found that the following dimensions potentially characterise wellbeing: self-acceptance, belonging, autonomy; positive relations, environmental mastery, purpose in life. Wellbeing for YPLHIV is multi-dimensional and relational. Relevant measures include the Personal Wellbeing Index, Ryff's Psychological Wellbeing Scale and Mental Health Continuum Short Form. However, psychometric evaluations of these scales among YPLHIV in SSA are needed.

HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: a systematic review and meta-analysis protocol.

BACKGROUND: Sub-Saharan Africa carries the greatest burden of HIV-infection with increasing drug resistance burden, which requires improved patient management and monitoring. Current WHO recommendations suggest transitioning to dolutegravir-based (adults) or raltegravir-based-regimens (neonates) for initial antiretroviral therapy (ART) and as a suitable alternative in cases of multi-resistance in resource-limited settings. This review aims at synthesizing the current knowledge on dolutegravir use and integrase resistance-associated mutations found before the wide use of dolutegravir-based regimens. METHODS: This systematic review will include randomized and non-randomized trials, cohort, and cross-sectional studies published on dolutegravir use or integrase resistance-associated mutations in Sub-Saharan Africa. Searches will be conducted (from 2007 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. We will include studies of adults and/or children exposed to integrase inhibitors-based therapies; especially dolutegravir or raltegravir (which is our intervention of interest as compared to other antiretroviral regimens). We will exclude studies of patients with specific co-morbidities such as tuberculosis or opportunistic infections. Primary outcomes will be "the rate of viral suppression" and "the level of drug resistance" on integrase inhibitor-based regimens among patients in Sub-Saharan Africa. Secondary outcomes will be "the effect of baseline viremia on viral suppression," "the effect of treatment duration on viral suppression," "the proportion of patients with immune recovery," "the rate of non-adherence," "rate of adverse events;" "drug resistance according to different integrase inhibitor-based regimens," and "drug resistance according to viral subtypes/recombinants." Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, sex, baseline viremia, CD4 following treatment, treatment duration, and adherence level). DISCUSSION: This review will help to strengthen evidence on the effectiveness of integrase strand transfer inhibitors by contributing to current knowledge on the use of dolutegravir and/or raltegravir (especially for neonates) in Sub-Saharan Africa. Results will therefore help in setting-up baseline data for an optimal management of people living with HIV as Sub-Saharan African countries are transitioning to dolutegravir-based regimens. Evidence will also support HIV/AIDS programs in identifying gaps and actions to be undertaken for improved long-term care and treatment of people living with HIV in Sub-Saharan Africa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122424.

Effectiveness of the female condom in preventing HIV and sexually transmitted infections: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of female condoms for preventing HIV and sexually transmitted infections (STIs) remains inconclusive. We examined the effects of female condoms on the acquisition of HIV and STIs. METHODS: We searched four databases, two trial registries, and reference lists of relevant publications in October 2018 and updated our search in February 2020. We screened search output, evaluated study eligibility, and extracted data in duplicate; resolving differences through discussion. We calculated the effective sample size of cluster randomised trials using an intra-cluster correlation coefficient of 0·03. Data from similar studies were combined in a meta-analysis. We performed a non-inferiority analysis of new condoms relative to marketed ones using a non-inferiority margin of 3%. We assessed the certainty of evidence using GRADE. RESULTS: We included fifteen studies of 6921 women. We found that polyurethane female condoms (FC1) plus male condoms may be as effective as male condoms only in reducing HIV acquisition (1 trial, n = 149 women, RR 0.07, 95%CI 0.00-1.38; low-certainty evidence). However, the use of FC1 plus male condoms is superior to male condoms alone in reducing the acquisition of gonorrhoea (2 trials, n = 790, RR 0.59, 95%CI 0.41-0.86; high-certainty evidence) and chlamydia (2 trials, n = 790, RR 0.67, 95%CI 0.47-0.94; high-certainty evidence). Adverse events and failure rates of FC1 were very low and decreased during follow up. Although the functionality of newer female condoms (Woman's, Cupid, Pheonurse, Velvet, and Reddy) may be non-inferior to FC2, there were no available studies assessing their efficacy in preventing HIV and STIs. CONCLUSION: The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV. There is a need for well conducted studies assessing the effects of newer female condoms on HIV and STIs. PROSPERO REGISTRATION NUMBER: CRD42018090710.

Cochrane corner: factors that influence compliance by healthcare workers with infection prevention and control guidelines for COVID-19 and other respiratory infections.

As rates of novel coronavirus disease 2019 (COVID-19) continue rising in Africa, usage of infection prevention and control (IPC) strategies by healthcare workers (HCW) is critical. We highlight a Cochrane review of qualitative evidence that explored barriers and facilitators to HCW compliance with IPC recommendations for COVID-19 and other respiratory infectious diseases. The review found various individual- and organizational- level barriers and facilitators. The findings suggest that healthcare system constraints that make it difficult for healthcare workers to implement IPC guidelines require urgent prioritisation. This will help lay the foundation for addressing the more individual-level barriers potentially discouraging HCW from implementing IPC guidelines. We draw attention to pan-African initiatives for enhancing healthcare workers' capacity to undertake IPC measures at such a critical time.

A scoping review on research agendas to enhance prevention of epidemics and pandemics in Africa.

INTRODUCTION: research is not only needed to prioritise the best possible response during an epidemic and pandemic, it is also understood to be a core pillar of outbreak response. However, few African countries are equipped to perform the needed surveillance and research activities during an outbreak. Therefore, we mapped out research agendas aimed at increased research preparedness towards epidemics or pandemics in Africa. METHODS: eligible studies were searched for in in PubMed, Scopus, and Google Scholar. Additionally, grey literature was sought in Google, citation searches, as well as targeted sites such as the World Health Organization (WHO), Africa Centres for Disease Control and Prevention, African Union, and the Wellcome Trust. Searches were done in March 2020. RESULTS: the electronic searches yielded 7344 records, of which 34 articles were included in the study. The studies identified around 18 factors highlighted through various research agendas. Majority of the research agendas spoke to general epidemic preparedness and focused largely on understanding virus transmission such as its characteristics and dynamics, and the infrastructure needed to carry out vital research activities. CONCLUSION: the review highlights the research needs in order to carry out vital research work but to also bridge knowledge gaps and harmonize outbreak response from key stakeholders. However, Africa needs to create its own health research agendas and capacitate itself to conduct and lead these studies. African health research decisions must center on Africa, with African researchers taking the lead not only on the science produced but ensuring inclusive and equitable involvement from fellow researchers, and in engaging national health ministries as well as the communities.

A systematic review of immunogenicity, clinical efficacy and safety of human papillomavirus vaccines in people living with the human immunodeficiency virus.

The human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide. People living with the human immunodeficiency virus (HIV) are at high risk of HPV infection. This systematic review evaluates the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in people living with HIV. We registered the protocol for this review in the International Prospective Register of Systematic Reviews (CRD42018109898) and prepared the review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Five randomized trials with 1042 participants are included in this review. One trial with 120 participants compared the bivalent HPV vaccine to placebo, three trials with 830 participants compared the quadrivalent vaccine to placebo, and another trial with 92 participants compared the quadrivalent to the bivalent vaccine. There was low to moderate certainty evidence suggesting that seroconversion was higher among participants in the vaccine arms compared to the placebo arms for both vaccines. In one study with very low certainty evidence, participants who received the bivalent vaccine had higher anti-HPV-18 geometric mean titers (GMTs) compared to those who received the quadrivalent vaccine, despite little difference in anti-HPV-16 GMTs between the two vaccines. There were no differences in the incident and persistent HPV infections in both groups. None of the studies reported data on the incidence of precancerous lesions, or cancer. There were no reports of serious adverse events following vaccination in any of the trials. None of the included studies assessed the effects of HPV vaccines in adolescents living with HIV. Very limited evidence suggests lower immunogenicity of HPV vaccines in HIV positive compared to HIV-negative people. Finally, the long-term effect of the HPV vaccine in the incidence of cervical precancerous lesions and cervical cancer needs to be monitored. There is an urgent need for more high-quality randomized controlled trials that can address these gaps.

Social media and HPV vaccination: Unsolicited public comments on a Facebook post by the Western Cape Department of Health provide insights into determinants of vaccine hesitancy in South Africa.

On the 4 February 2019, the Western Cape Department of Health's Facebook page announced the implementation of a school-based vaccination campaign aimed to administer the first doses of human papillomavirus (HPV) vaccine in public schools to Grade 4 girls who are nine years old. This announcement was met with a flurry of social media responses posted on the campaign's Facebook page. This study identifies determinants of vaccine hesitancy amongst responses provided by social media users to this post. On 8 March 2019, we conducted a qualitative study including all 157 comments to the Facebook post. The post had 659 'emotion' reactions: 574 "likes", 62 "loves", 21 "angry faces", 2 "laughs", 2 "wows" and 1 "sad face". An overwhelming majority (636/659 i.e. 97%) of reactions were favourable to the HPV vaccination campaign. Out of the 157 comments, we judged 52 (33%) of them to be 'hesitant', suggesting that people with negative reactions though few in number, were more likely to be vocal deniers. Concern around the safety of HPV vaccines including effects on reproductive health was the most common theme identified. Other emerging themes included: risk of cervical cancer perceived as being low, issues around consent, concerns that girls are being used for research, questionable vaccine effectiveness, use of the school-based strategy for the campaign, risk-benefits calculations of HPV vaccination and constraints such as stock-outs. Knowing someone who had been affected or being at risk of cervical cancer, having knowledge about the causes of cervical cancer, confidence in the effectiveness and safety of the vaccine, knowing the vaccine was being used in high income settings, and having strong recommendations from the World Health Organisation and key actors seemed to increase the willingness to accept the vaccine. The magnitude and causes of HPV vaccine hesitancy need to be investigated to ensure the success of this programme.

A global review of seasonal influenza vaccine introduction: analysis of the WHO/UNICEF Joint Reporting Form.

Background: Influenza is a highly contagious disease that affects the upper and lower respiratory tract caused by several subtypes of influenza viruses. While vaccination remains the mainstay strategy to protect populations against influenza, there is a global shortage and inequitable access to influenza vaccines. Although influenza vaccine production capacity increased from 500 million doses in 2006 to 1.5 billion doses in 2013, little is known about the global distribution of these vaccines albeit its introduction. We assessed the global status of influenza vaccine introduction. Research design and methods: We analyzed data from the World Health Organization (WHO) Joint Reporting Form, a publicly available source of immunization data from 194 countries of all six WHO regions. We used 2017 data, available as of July 2018. Results: By December 2017, 117 of 194 (60%) WHO Member States had introduced the seasonal influenza vaccine. European and American regions accounted for 70% (82/117) of the total number of countries that had introduced influenza vaccine. The other four regions account for only 30%. Ninety-four percent (50/53) of countries in the European region and 91% (32/35) in the American region had introduced influenza vaccine. In the Eastern Mediterranean and Western Pacific regions, 67% (14/21) and 52% (14/27), respectively, had introduced the vaccine. Yet only 27% (3/11) and 9% (4/47) in the Southeast Asian and African regions, respectively, had introduced the vaccine. Among countries (n = 117) that had introduced the vaccine, children (56%), older adults (87%), and risk groups (99%) were prioritized and given the vaccines. Conclusions: Introduction of influenza vaccine in the African and Southeast Asian regions remains suboptimal. This critically underscores the need for financing mechanisms and having countries in the regions that are lagging behind to prioritize seasonal influenza vaccine.

New vaccine introductions in Africa before and during the decade of vaccines - Are we making progress?

Vaccines are excellent investments with far-reaching rewards beyond individual and population health, but their introduction into national programs has been historically slow in Africa. We provide an overview of the introduction of new and underutilized vaccines in countries of the WHO African Region by 2017, using data from the WHO-UNICEF Joint Reporting Form. By 2017, all 47 countries had introduced vaccines containing hepatitis B (compared to 11% in 2000 and 98% in 2010) and Haemophilus influenzae type b (Hib) (compared to 4% in 2000 and 91% in 2010). The proportion of countries that had introduced other vaccines by 2017 was 83% for pneumococcal conjugate vaccine (PCV) from 7% in 2010, 72% for rotavirus vaccine from 2% in 2010, 55% for the second dose of a measles-containing vaccine (MCV2) (compared to 11% in 2000 and 17% in 2010), and 45% for rubella-containing vaccines (RCV) (compared to 4% in 2000 and 7% in 2010). From 2000 to 2010, there was no significant difference between countries eligible (N = 36) and those not eligible (N = 10) for Gavi support in the introduction of hepatitis B and PCV. However, Gavi eligible countries were more likely to introduce Hib and non-Gavi eligible countries were more likely to introduce MCV2 and RCV. From 2010 to 2017, the only significant differences that remained between the two groups of countries were with mumps, inactivated polio and seasonal influenza vaccines; which non-Gavi eligible countries were more likely to have introduced. There has been significant progress in the introduction of new childhood vaccines in Africa, mostly driven by Gavi support. As many countries are expected to transition out of Gavi support soon, there is need for countries in the region to identify predictable, reliable and sustainable immunization funding mechanisms. This requires commitments and actions that go beyond the purchase of vaccines.

Prevalence and dynamics of missed opportunities for vaccination among children in Africa: applying systems thinking in a systematic review and meta-analysis of observational studies.

OBJECTIVE: To estimate the prevalence of missed opportunities for vaccination (MOV) among children aged 0-23 months attending health-care facilities in Africa and explore the factors responsible for MOV using systems thinking. RESEARCH DESIGN AND METHODS: We conducted a systematic review and meta-analysis of studies reporting the proportion MOVs. Five electronic databases were searched. A random effects model was fitted to obtain pooled estimates of MOV and a causal loop diagram (CLD) was constructed to explore the dynamics of the causes of MOV. MOV was defined as any contact with health services in Africa, by an unvaccinated or under-vaccinated child, aged 0-23 months, who is eligible for vaccination and free of any contraindication, which does not result in vaccination. RESULTS: Four hundred and twenty-one publications were found, of which 20 studies from 14 countries were included. The pooled prevalence of MOV was estimated to be 27.26% (95%CI: 18.80-36.62). A CLD with seven reinforcing and two balancing loops were constructed. CONCLUSION: Our findings suggest that about one in every four children under the age of two years who visited health facilities in 14 African countries missed the vaccination they were eligible to receive. To enable continent-wide estimates, more MOV assessments are required.

Rural-urban disparities in missed opportunities for vaccination in sub-Saharan Africa: a multi-country decomposition analyses.

BACKGROUND: In this study, we aimed to explore the rural-urban disparities in the magnitude and determinants of missed opportunities for vaccination (MOV) in sub-Saharan Africa. METHODS: This was a cross-sectional study using nationally representative household surveys conducted between 2007 and 2017 in 35 countries across sub-Saharan Africa. The risk difference in MOV between rural or urban dwellers were calculated. Logistic regression method was used to investigate the urban-rural disparities in multivariable analyses. Then Blinder-Oaxaca method was used to decompose differences in MOV between rural and urban dwellers. RESULTS: The median number of children aged 12 to 23 months was 2113 (Min: 370, Max: 5896). There was wide variation in the the magnitude of MOV among children in rural and urban areas across the 35 countries. The magnitude of MOV in rural areas varied from 18.0% (95% CI 14.7 to 21.4) in the Gambia to 85.2% (81.2 to 88.9) in Gabon. Out of the 35 countries included in this analysis, pro-rural inequality was observed in 16 countries (i.e. MOV is prevalent among children living in rural areas) and pro-urban inequality in five countries (i.e. MOV is prevalent among children living in urban areas). The contributions of the compositional 'explained' and structural 'unexplained' components varied across the countries. However, household wealth index was the most frequently identified factor. CONCLUSIONS: Variation exists in the level of missed opportunities for vaccination between rural and urban areas, with widespread pro-rural inequalities across Africa. Although several factors account for these rural-urban disparities in various countries, household wealth was the most common.

Vaccine hesitancy 'outbreaks': using epidemiological modeling of the spread of ideas to understand the effects of vaccine related events on vaccine hesitancy.

INTRODUCTION: Vaccine hesitancy, a growing global problem which is aggravated by vaccine related rumors and (mis)information, has the potential to reverse the gains from vaccination. Areas covered: We describe a selection of vaccine-related events that have made headlines and highlight the effects that these have had on vaccine acceptance. Drawing on these cases, and an adaptation of an epidemiological modeling of the spread of ideas, we propose that vaccine hesitancy can be grouped into two categories: 'baseline' and 'reactive' vaccine hesitancy. 'Baseline' vaccine hesitancy refers to the level of refusal or delay in acceptance of vaccinations that is constantly present in the population. Though it may vary, changes are unlikely to be sudden or dramatic. 'Reactive' hesitancy, which often occurs because of vaccine-related events, is characterized by a rapid spike in levels of hesitancy, usually subsiding at a slow rate. Expert commentary: Different kinds of interventions are needed to address different forms of vaccine hesitancy. Modeling the diffusion of (mis)information during vaccine hesitancy 'outbreaks' is essential for designing interventions that will ensure appropriate management of 'reactive' hesitancy, and control of 'baseline' levels of vaccine hesitancy. More empirical research is needed to test and better understand this hypothesis.