The COVID-19 experience in Africa and the Middle East.

AIMS: The experience of Africa and the Middle East with the COVID-19 pandemic has been unique, which can be attributed, in part, to disparities within these regions. METHODS: This review describes COVID-19 emergence, epidemiology, vaccination strategies and uptake, and lessons learned within Africa and the Middle East. RESULTS: For vaccines to be effective in curtailing COVID-19, a global approach to vaccination is required. However, vaccine inequities exist in Africa and the Middle East, with countries with better healthcare infrastructure having advantages in acquiring and delivering vaccines. Currently, the greatest challenges to the effective rollout of COVID-19 vaccination in Africa and the Middle East are funding, healthcare resources, infrastructure, and vaccine access and hesitancy. While mechanisms to support vaccine access in low- and middle-income countries are initiated, their success has been limited and vaccine inequity is arguably the biggest hurdle to a successful response. The collection of surveillance data at both regional and global levels is also critical in response to the pandemic and provides the necessary tools and data to drive vaccine development. CONCLUSION: These considerations of the learnings can help refine the pandemic response and inform countries to better prepare for similar public health emergencies.

Learnings from previous epidemics enabled African nations to respond rapidly and cohesively to the emergence of the COVID-19 pandemic; similarly, nations in the Middle East also drew on previous outbreaks of other viruses to respond robustly, although perhaps less cohesively than the African nations.The populations of Africa and the Middle East share many of the same comorbidities (with the exception of HIV in Africa) and risk factors as other regions of the world, and both have experienced multiple waves of COVID-19 infections as new genetic variants of SARS-CoV-2 have evolved.African and Middle Eastern nations have had a wide range of success in vaccine rollout and uptake due to several factors including national wealth/income, populations with varying levels of vaccine hesitancy, and a range of access to private and/or public healthcare.Current challenges, some of which are being addressed by governmental and international entities, include a lack of vaccine- and surveillance-related infrastructure, needed improvement in regulatory standards, and persistent financial strains on healthcare systems that hinder improvements in vaccine delivery.

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa.

BACKGROUND: While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. OBJECTIVES: To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. METHODS: We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. RESULTS: In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients [Formula: see text] 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. CONCLUSION: More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.

Co-detection of Bordetella pertussis and other respiratory organisms in children hospitalised with lower respiratory tract infection.

Multiple potential pathogens are frequently co-detected among children with lower respiratory tract infection (LRTI). Evidence indicates that Bordetella pertussis has an important role in the aetiology of LRTI. We aimed to study the association between B. pertussis and other respiratory pathogens in children hospitalised with severe LRTI, and to assess clinical relevance of co-detection. Nasopharyngeal (NP) swabs and induced sputa (IS) were tested with a B. pertussis specific PCR; additionally, IS was tested for other pathogens using a multiplex PCR. We included 454 children, median age 8 months (IQR 4-18), 31 (7%) of whom tested positive for B. pertussis. Children with B. pertussis had more bacterial pathogens detected (3 versus 2; P < 0.001). While B. pertussis showed no association with most pathogens, it was independently associated with Chlamydia pneumoniae, Mycoplasma pneumoniae and parainfluenza viruses with adjusted risk ratios of 4.01 (1.03-15.64), 4.17 (1.42-12.27) and 2.13 (1.03-4.55), respectively. There was a consistent increased risk of severe disease with B. pertussis. Patterns indicated even higher risks when B. pertussis was co-detected with any of the three organisms although not statistically significant. Improving vaccine coverage against B. pertussis would impact not only the incidence of pertussis but also that of severe LRTI generally.

Risk factors for Bordetella pertussis disease in hospitalized children.

INTRODUCTION: Despite a resurgence of disease, risk factors for pertussis in children in low and middle-income countries are poorly understood. This study aimed to investigate risk factors for pertussis disease in African children hospitalized with severe LRTI. METHODS: A prospective study of children hospitalized with severe LRTI in Cape Town, South Africa was conducted over a one-year period. Nasopharyngeal and induced sputum samples from child and nasopharyngeal sample from caregiver were tested for Bordetella pertussis using PCR (IS481+/hIS1001). History and clinical details were documented. RESULTS: 460 children with a median age of 8 (IQR 4-18) months were enrolled. B. pertussis infection was confirmed in 32 (7.0%). The adjusted risk of confirmed pertussis was significantly increased if infants were younger than two months [aRR 2.37 (95% CI 1.03-5.42]), HIV exposed but uninfected (aRR 3.53 [95% CI 1.04-12.01]) or HIV infected (aRR 4.35 [95% CI 1.24-15.29]). Mild (aRR 2.27 [95% CI 1.01-5.09]) or moderate (aRR 2.70 [95% CI 1.13-6.45]) under-nutrition in the children were also associated with higher risk. The highest adjusted risk occurred in children whose caregivers had B. pertussis detected from nasopharyngeal swabs (aRR 13.82 [95% CI 7.76-24.62]). Completion of the primary vaccine schedule (three or more doses) was protective (aRR 0.28 [95% CI 0.10-0.75]). CONCLUSIONS: HIV exposure or infection, undernutrition as well as detection of maternal nasal B. pertussis were associated with increased risk of pertussis in African children, especially in young infants. Completed primary vaccination was protective. There is an urgent need to improve primary pertussis vaccine coverage in low and middle-income countries. Pertussis vaccination of pregnant women, especially those with HIV infection should be prioritized.

Characterisation of the environmental presence of hepatitis A virus in low-income and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To characterise the environmental presence of hepatitis A virus (HAV) in low- and middle-income countries (LMICs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: EBSCOhost, PubMed, Scopus, ScienceDirect, Clinical Key and Web of Science were searched. Grey literature was sourced by searching the following electronic databases: Open Grey, National Health Research Database and Mednar. ELIGIBILITY CRITERIA FOR INCLUDING STUDIES: Cross-sectional and ecological studies reporting HAV environmental presence and conducted in LMICs between January 2005 and May 2019, irrespective of language of publication. DATA EXTRACTION AND DATA SYNTHESIS: Relevant data were extracted from articles meeting the inclusion criteria, and two reviewers independently assessed the studies for risk of bias. High heterogeneity of the extracted data led to the results being reported narratively. RESULTS: A total of 2092 records were retrieved, of which 33 met the inclusion criteria. 21 studies were conducted in Tunisia, India and South Africa, and the rest were from Philippines, Pakistan, Morocco, Chad, Mozambique, Kenya and Uganda. In Tunisian raw sewage samples, the prevalence of HAV ranged from 12% to 68%, with an estimated average detection rate of 50% (95% CI 25 to 75), whereas HAV detection in treated sewage in Tunisia ranged from 23% to 65%, with an estimated average detection rate of 38% (95% CI 20 to 57). The prevalence of HAV detection in South African treated sewage and surface water samples ranged from 4% to 37% and from 16% to 76%, with an estimated average detection rates of 15% (95% CI 1 to 29) and 51% (95% CI 21 to 80), respectively. Over the review period, the estimated average detection rate of environmental HAV presence appeared to have declined by 10%. CONCLUSION: The quality of included studies was fair, but sampling issues and paucity of data limited the strength of the review findings. PROSPERO REGISTRATION NUMBER: CRD42019119592.

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.

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.

Systematic review of the global epidemiology of viral-induced acute liver failure.

OBJECTIVES: The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention. PARTICIPANTS: This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review. RESULTS: This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries. CONCLUSIONS: Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure. REGISTRATION: PROSPERO registration number: CRD42017079730.

Diagnostic limitations of clinical case definitions of pertussis in infants and children with severe lower respiratory tract infection.

INTRODUCTION: Diagnosis of pertussis is challenging especially in infants. Most low and middle-income countries (LMIC) lack resources for laboratory confirmation, relying largely on clinical diagnosis alone for both case management and surveillance. This necessitates robust clinical case definitions. OBJECTIVES: This study assesses the accuracy of clinical case definitions with and without lymphocytosis in diagnosing pertussis in children with severe lower respiratory tract infection (LRTI) in a LMIC setting. METHODS: Children hospitalized with severe LRTI in a South African hospital were prospectively enrolled and evaluated for pertussis using PCR on respiratory samples. Clinical signs and differential white cell counts were recorded. Sensitivity and specificity of pertussis clinical diagnosis using WHO and Global Pertussis Initiative (GPI) criteria; and with addition of lymphocytosis were assessed with PCR as the reference standard. RESULTS: 458 children <10 years were enrolled. Bordetella pertussis infection was confirmed in 32 (7.0%). For WHO criteria, sensitivity was 78.1% (95% CI 60.7-89.2%) and specificity 15.5% (95% CI 12.4-19.3%); for GPI sensitivity was 34.4% (95% CI 20.1-52.1) and specificity 64.8% (95% CI 60.1-69.2%). Area under the curve (AUC) on receiver operating character (ROC) analysis was 0.58 (95% CI 0.46-0.70 for WHO criteria, and 0.72 (95% CI 0.56-0.88) for GPI with highest likelihood ratios of 5.33 and 4.42 respectively. Diagnostic accuracy was highest between five and seven days of symptoms for both criteria. Lymphocytosis had sensitivity of 31.3% (95% CI 17.5-49.3%) and specificity of 70.7% (95% CI 66.1-74.8%) and showed a marginal impact on improving clinical criteria. CONCLUSION: Clinical criteria lack accuracy for diagnosis and surveillance of pertussis. Non-outbreak settings should consider shorter durations in clinical criteria. New recommendations still fall short of what is required for a viable clinical screening test which means the need to improve access to laboratory diagnostic support remains crucial.

Improving vaccination uptake among adolescents.

BACKGROUND: Adolescent vaccination has received increased attention since the Global Vaccine Action Plan's call to extend the benefits of immunisation more equitably beyond childhood. In recent years, many programmes have been launched to increase the uptake of different vaccines in adolescent populations; however, vaccination coverage among adolescents remains suboptimal. Therefore, understanding and evaluating the various interventions that can be used to improve adolescent vaccination is crucial. OBJECTIVES: To evaluate the effects of interventions to improve vaccine uptake among adolescents. SEARCH METHODS: In October 2018, we searched the following databases: CENTRAL, MEDLINE Ovid, Embase Ovid, and eight other databases. In addition, we searched two clinical trials platforms, electronic databases of grey literature, and reference lists of relevant articles. For related systematic reviews, we searched four databases. Furthermore, in May 2019, we performed a citation search of five other websites. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series studies of adolescents (girls or boys aged 10 to 19 years) eligible for World Health Organization-recommended vaccines and their parents or healthcare providers. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, reviewed full-text articles to identify potentially eligible studies, extracted data, and assessed risk of bias, resolving discrepancies by consensus. For each included study, we calculated risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) where appropriate. We pooled study results using random-effects meta-analyses and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 16 studies (eight individually randomised trials, four cluster randomised trials, three non-randomised trials, and one controlled before-after study). Twelve studies were conducted in the USA, while there was one study each from: Australia, Sweden, Tanzania, and the UK. Ten studies had unclear or high risk of bias. We categorised interventions as recipient-oriented, provider-oriented, or health systems-oriented. The interventions targeted adolescent boys or girls or both (seven studies), parents (four studies), and providers (two studies). Five studies had mixed participants that included adolescents and parents, adolescents and healthcare providers, and parents and healthcare providers. The outcomes included uptake of human papillomavirus (HPV) (11 studies); hepatitis B (three studies); and tetanus-diphtheria-acellular-pertussis (Tdap), meningococcal, HPV, and influenza (three studies) vaccines among adolescents. Health education improves HPV vaccine uptake compared to usual practice (RR 1.43, 95% CI 1.16 to 1.76; I² = 0%; 3 studies, 1054 participants; high-certainty evidence). In addition, one large study provided evidence that a complex multi-component health education intervention probably results in little to no difference in hepatitis B vaccine uptake compared to simplified information leaflets on the vaccine (RR 0.98, 95% CI 0.97 to 0.99; 17,411 participants; moderate-certainty evidence). Financial incentives may improve HPV vaccine uptake compared to usual practice (RR 1.45, 95% CI 1.05 to 1.99; 1 study, 500 participants; low-certainty evidence). However, we are uncertain whether combining health education and financial incentives has an effect on hepatitis B vaccine uptake, compared to usual practice (RR 1.38, 95% CI 0.96 to 2.00; 1 study, 104 participants; very low certainty evidence). Mandatory vaccination probably leads to a large increase in hepatitis B vaccine uptake compared to usual practice (RR 3.92, 95% CI 3.65 to 4.20; 1 study, 6462 participants; moderate-certainty evidence). Provider prompts probably make little or no difference compared to usual practice, on completion of Tdap (OR 1.28, 95% CI 0.59 to 2.80; 2 studies, 3296 participants), meningococcal (OR 1.09, 95% CI 0.67 to 1.79; 2 studies, 3219 participants), HPV (OR 0.99, 95% CI 0.55 to 1.81; 2 studies, 859 participants), and influenza (OR 0.91, 95% CI 0.61 to 1.34; 2 studies, 1439 participants) vaccination schedules (moderate-certainty evidence). Provider education with performance feedback may increase the proportion of adolescents who are offered and accept HPV vaccination by clinicians, compared to usual practice. Compared to adolescents visiting non-participating clinicians (in the usual practice group), the adolescents visiting clinicians in the intervention group were more likely to receive the first dose of HPV during preventive visits (5.7 percentage points increase) and during acute visits (0.7 percentage points for the first and 5.6 percentage points for the second doses of HPV) (227 clinicians and more than 200,000 children; low-certainty evidence). A class-based school vaccination strategy probably leads to slightly higher HPV vaccine uptake than an age-based school vaccination strategy (RR 1.09, 95% CI 1.06 to 1.13; 1 study, 5537 participants; moderate-certainty evidence). A multi-component provider intervention (including an education session, repeated contacts, individualised feedback, and incentives) probably improves uptake of HPV vaccine compared to usual practice (moderate-certainty evidence). A multi-component intervention targeting providers and parents involving social marketing and health education may improve HPV vaccine uptake compared to usual practice (RR 1.41, 95% CI 1.25 to 1.59; 1 study, 25,869 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Various strategies have been evaluated to improve adolescent vaccination including health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. However, most of the evidence is of low to moderate certainty. This implies that while this research provides some indication of the likely effect of these interventions, the likelihood that the effects will be substantially different is high. Therefore, additional research is needed to further enhance adolescent immunisation strategies, especially in low- and middle-income countries where there are limited adolescent vaccination programmes. In addition, it is critical to understand the factors that influence hesitancy, acceptance, and demand for adolescent vaccination in different settings. This is the topic of an ongoing Cochrane qualitative evidence synthesis, which may help to explain why and how some interventions were more effective than others in increasing adolescent HPV vaccination coverage.

The global epidemiology of viral-induced acute liver failure: a systematic review protocol.

INTRODUCTION: The burden of viral-induced acute liver failure (ALF) around the world still remains unclear, with little to no data collected regarding the disease incidence in general and synthesised data on the relative contribution of different viruses to the aetiology of ALF is missing in the field. The aim of this review is to estimate the burden (prevalence, incidence, mortality, hospitalisation) of ALF following infection HAV, HBV, HCV, HDV, HEV, EBV), HSV1, HSV2, VZV, parvo-virus B19, HPIVs, YFV, HVV-6, CMV, CA16 and/or HAdVs. Establishing the common aetiologies of viral-induced ALF, which vary geographically, is important so that: (1) treatment can be initiated quickly, (2) contraindications to liver transplant can be identified, (3) prognoses can be deterined more accurately, and most importantly, (4) vaccination against viral ALF aetiologies can be prioritised especially in under-resourced regions with public health risks associated with the relevant attributable diseases. METHODS AND ANALYSIS: EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science databases will be searched for relevant literature published and grey literature from 2009 up to 2019. Published cross-sectional and cohort studies will be eligible for inclusion in this review. Qualifying studies will be formally assessed for quality and risk of bias using a standardised scoring tool. Following standardised data extraction, meta-analyses will be carried out using STATA. Depending on characteristics of included studies, subgroup analyses and meta-regression analyses will be performed. This review will be reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018110309.

A systematic review of the epidemiology of hepatitis A in Africa.

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.

Assessment of humoral and cell-mediated immune responses to pertussis vaccination: a systematic review protocol.

INTRODUCTION: Globally, some studies show a resurgence of pertussis. The risks and benefits of using whole-cell pertussis (wP) or acellular pertussis (aP) vaccines in the control of the disease have been widely debated. Better control of pertussis will require improved understanding of the immune response to pertussis vaccines. Improved understanding and assessment of the immunity induced by pertussis vaccines is thus imperative. Several studies have documented different immunological outcomes to pertussis vaccination from an array of assays. We propose to conduct a systematic review of the different immunological assays and outcomes used in the assessment of the humoraland cell-mediated immune response following pertussis vaccination. METHODS AND ANALYSIS: The primary outcomes for consideration are quality and quantity of immune responses (humoral and cell-mediated) post-pertussis vaccination. Of interest as secondary outcomes are types of immunoassays used in assessing immune responses post-pertussis vaccination, types of biological samples used in assessing immune responses post-pertussis vaccination, as well as the types of antigens used to stimulate these samples during post-pertussis vaccination immune response assessments. Different electronic databases (including PubMed, Cochrane, EBSCO Host, Scopus and Web of Science) will be accessed for peer-reviewed published and grey literature evaluating immune responses to pertussis vaccines between 1990 and 2019. The quality of included articles will be assessed using standardised risk and quality assessment tools specific to the study design used in each article. Data extraction will be done using a data extraction form. The extracted data will be analysed using STATA V.14.0 and RevMan V.5.3 software. A subgroup analysis will be conducted based on the study population, type of vaccine (wP or aP) and type of immune response (cell-mediated or humoral). Guidelines for reporting systematic reviews in the revised 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement will be used in this study. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as it is a systematic review. We will only make use of data already available in the public space. Findings will be reported via publication in a peer-reviewed journal and presented at scientific meetings and workshops. TRIAL REGISTRATION NUMBER: CRD42018102455.

An update on trends in the types and quality of childhood immunization research outputs from Africa 2011-2017: Mapping the evidence base.

BACKGROUND: Strengthening immunisation programmes in Africa remains a key strategy of improving vaccine coverage. Research plays a vital role in the design and implementation of strategic immunisation plans for improving vaccination coverage, in turn providing context specific evidence to inform policy and practice. We therefore updated an evidence map describing the types and quality of available literature on childhood immunisation in Africa from 2011 to 2017. METHODS: PubMed and Africa Wide databases were searched for English studies on childhood immunisation in Africa published from January 2011 to September 2017. Studies had to be conducted in humans and the reported information needed to be on either: vaccines; immunisation programmes; immunisation policies; or epidemiology of vaccine preventable diseases targeted by Expanded Programme on Immunisation vaccines. RESULTS: Out of 5567 studies retrieved, 797 studies from 165 journals met the inclusion criteria. During 2011-2017, 42 African countries contributed to research on childhood immunisation. Most studies were carried out in multiple countries (15.1%). Five countries contributed 41% of the total research output. Nigeria and South Africa contributed the highest proportion of studies at 12% and 11.4% respectively. The quantity of research output increased progressively from 2011 to 2015 after which there was a significant decline. CONCLUSION: There was a remarkable increase in childhood immunisation research in the period 2011 to 2017 when compared to the initial assessment. However, the reason for decline in research output from 2015 requires further investigation. Most childhood immunisation research was still generated by five countries as previously observed, highlighting the critical need for strategic investment in research capacities and improved collaboration between countries in Africa.

Comparison of adverse events following immunisation with acellular and whole-cell pertussis vaccines: A systematic review.

INTRODUCTION: Two types of vaccines are currently licensed for use against pertussis: whole-cell (wP) and acellular pertussis (aP). There is evidence that wP confers more durable immunity than aP, however wP has been more frequently associated with adverse events following immunisation (AEFI). A comparison of the frequency of AEFI with the first doses of wP and aP has not yet been clearly documented. This must be done in light of recent considerations to move towards a wP prime-aP boost vaccination strategy in low and middle-income countries. OBJECTIVES: To compare the frequency of AEFI associated with the first dose of the wP and aP vaccines. We also compared the frequency of AEFI associated with subsequent doses of wP. METHODS: This systematic review was carried out in strict accordance with the published protocol. RESULTS: High heterogeneity amongst included one-armed studies did not allow for pooling of prevalence estimates. The prevalence estimates of AEFI at first vaccine dose of wP ranged from 0 to 75%, while the prevalence estimates of AEFI at first vaccine dose of aP ranges from 0 to 39%. The prevalence estimates of adverse events following second and third vaccine dose of wP ranged from 0 to 71% and 0 to 61%, respectively. Risk ratios among two-armed studies showed an increased risk of adverse events with first dose of wP compared to aP [local reaction RR 2.73 (2.33, 3.21), injection site pain RR 4.15 (3.24, 5.31), injection site swelling RR 4.38 (2.70, 7.12), fever over 38 °C RR 9.21 (5.39, 15.76), drowsiness RR 1.34 (1.18, 1.52) and vomiting RR 1.28 (0.91, 1.79)]. CONCLUSION: Our results confirm that, when comparing the first dose, wP is more reacotgenic than aP. The proposed wP prime followed by aP boost pertussis vaccine strategy should be approached with caution.

Adverse events following primary and secondary immunisation with whole-cell pertussis: a systematic review protocol.

INTRODUCTION: Pertussis is a contagious respiratory illness caused by the bacterium Bordetella pertussis. Two types of vaccines are currently available against the disease: whole-cell pertussis (wP) and acellular pertussis (aP). With the shift of high-income countries from wP to aP as a result of adverse events following immunisation (AEFI), an upsurge in reported cases of pertussis has been noticed. Owing to this, it is proposed to use wP as a prime and aP for boost vaccination strategy. However, a comparison of the AEFI with the first doses of wP and aP are not clearly documented. METHODS AND ANALYSIS: The primary outcomes of interest are AEFI with dose 1 of wP, subsequent doses of wP and dose 1 of aP. As a secondary outcome frequency of AEFI with wP will be compared with the AEFI of doses 2 and 3 of wP and dose 1 of aP. Electronic databases will be searched and two authors will screen the titles and abstracts of the output. Full texts will then be independently reviewed by the first author and two other authors. Qualifying studies will then be formally assessed for quality and risk of bias using a scoring tool. Following standardised data extraction, statistical analysis will be carried out using STATA. Where data are available, subgroup analyses will be performed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed in reporting the findings of the systematic review and meta-analysis. ETHICS AND DISSEMINATION: No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42016035809.

Comparison of school based and supplemental vaccination strategies in the delivery of vaccines to 5-19 year olds in Africa - a systematic review.

BACKGROUND: Some vaccine preventable diseases (VPDs) still remain a public health burden in many African countries. The occurrence of VPDs in all age groups has led to the realization of the need to extend routine immunisation services to school age children, adolescents and adults. Supplemental immunisation activities (SIAs) and school based vaccinations (SBVs) are common strategies used to complement the expanded programme on immunisation (EPI). This review aimed to assess the effectiveness of SIAs compared to SBVs in the administration of vaccines to 5-19 year olds in Africa. METHODS: Systematic review methods were used to address our study aim. Several electronic databases were searched up to March 30, 2017 for primary studies investigating the delivery of vaccines via SIAs or SBVs to 5-19 year olds. This search was complemented by browsing reference lists of potential studies obtained from search outputs. Outcomes considered for inclusion were: vaccination coverage, costs of the strategy or its effect on routine immunisation services. RESULTS: Out of the 4938 studies identified, 31 studies met the review inclusion criteria. Both SIAs and SBVs showed high vaccination coverage. However, the SIAs reported higher coverage than SBVs: 91% (95% CI: 84%, 98%) versus 75% (95% CI: 67%, 83%). In most settings, SBVs were reported to be more expensive than SIAs. The SIAs were found to negatively affect routine immunisation services. CONCLUSIONS: Both SIAs and SBVs are routinely used to complement the EPI in the delivery of vaccines in Africa. In settings where school enrolment is suboptimal, as is the case in many African countries, our results show SIAs may be more effective in reaching school age children and adolescents than SBVs. Our results re-iterate the importance of evaluating systematic evidence to best inform African authorities on the optimal vaccine delivery strategies targeting school age children and adolescents.

Public stewardship of private for-profit healthcare providers in low- and middle-income countries.

BACKGROUND: Governments use different approaches to ensure that private for-profit healthcare services meet certain quality standards. Such government guidance, referred to as public stewardship, encompasses government policies, regulatory mechanisms, and implementation strategies for ensuring accountability in the delivery of services. However, the effectiveness of these strategies in low- and middle-income countries (LMICs) have not been the subject of a systematic review. OBJECTIVES: To assess the effects of public sector regulation, training, or co-ordination of the private for-profit health sector in low- and middle-income countries. SEARCH METHODS: For related systematic reviews, we searched the Cochrane Database of Systematic Reviews (CDSR) 2015, Issue 4; Database of Abstracts of Reviews of Effectiveness (DARE) 2015, Issue 1; Health Technology Assessment Database (HTA) 2015, Issue 1; all part of The Cochrane Library, and searched 28 April 2015. For primary studies, we searched MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 16 June 2016); Science Citation Index and Social Sciences Citation Index 1987 to present, and Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 3 May 2016 for papers citing included studies); Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 3, part of The Cochrane Library (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register) (searched 28 April 2015); Embase 1980 to 2015 Week 17, OvidSP (searched 28 April 2015); Global Health 1973 to 2015 Week 16, OvidSP (searched 30 April 2015); WHOLIS, WHO (searched 30 April 2015); Science Citation Index and Social Sciences Citation Index 1975 to present, ISI Web of Science (searched 30 April 2015); Health Management, ProQuest (searched 22 November 2013). In addition, in April 2016, we searched the reference lists of relevant articles, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and various electronic databases of grey literature. SELECTION CRITERIA: Randomised trials, non-randomised trials, interrupted time series studies, or controlled before-after studies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and extracted data, comparing their results and resolving discrepancies by consensus. We expressed study results as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI), where appropriate, and assessed the certainty of the evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). We did not conduct meta-analysis because of heterogeneity of interventions and study designs. MAIN RESULTS: We identified 20,177 records, 50 of them potentially eligible. We excluded 39 potentially eligible studies because they did not involve a rigorous evaluation of training, regulation, or co-ordination of private for-profit healthcare providers in LMICs; five studies identified after the review was submitted are awaiting assessment; and six studies met our inclusion criteria. Two included studies assessed training alone; one assessed regulation alone; three assessed a multifaceted intervention involving training and regulation; and none assessed co-ordination. All six included studies targeted private for-profit pharmacy workers in Africa and Asia.Three studies found that training probably increases sale of oral rehydration solution (one trial in Kenya, 106 pharmacies: RR 3.04, 95% CI 1.37 to 6.75; and one trial in Indonesia, 87 pharmacies: RR 1.41, 95% CI 1.03 to 1.93) and dispensing of anti-malarial drugs (one trial in Kenya, 293 pharmacies: RR 8.76, 95% CI 0.94 to 81.81); moderate-certainty evidence.One study conducted in the Lao People's Democratic Republic shows that regulation of the distribution and sale of registered pharmaceutical products may improve composite pharmacy indicators (one trial, 115 pharmacies: improvements in four of six pharmacy indicators; low-certainty evidence).The outcome in three multifaceted intervention studies was the quality of pharmacy practice; including the ability to ask questions, give advice, and provide appropriate treatment. The trials applied regulation, training, and peer influence in sequence; and the study design does not permit separation of the effects of the different interventions. Two trials conducted among 136 pharmacies in Vietnam found that the multifaceted intervention may improve the quality of pharmacy practice; but the third study, involving 146 pharmacies in Vietnam and Thailand, found that the intervention may have little or no effects on the quality of pharmacy practice (low-certainty evidence).Only two studies (both conducted in Vietnam) reported cost data, with no rigorous assessment of the economic implications of implementing the interventions in resource-constrained settings. No study reported data on equity, mortality, morbidity, adverse effects, satisfaction, or attitudes. AUTHORS' CONCLUSIONS: Training probably improves quality of care (i.e. adherence to recommended practice), regulation may improve quality of care, and we are uncertain about the effects of co-ordination on quality of private for-profit healthcare services in LMICs. The likelihood that further research will find the effect of training to be substantially different from the results of this review is moderate; implying that monitoring of the impact is likely to be needed if training is implemented. The low certainty of the evidence for regulation implies that the likelihood of further research finding the effect of regulation to be substantially different from the results of this review is high. Therefore, an impact evaluation is warranted if government regulation of private for-profit providers is implemented in LMICs. Rigorous evaluations of these interventions should also assess other outcomes such as impacts on equity, cost implications, mortality, morbidity, and adverse effects.

The Cape Town Declaration on Vaccines 2012: Unlocking the full potential of vaccines in Africa.

Delegates at the first International African Vaccinology Conference noted, with dismay, that many African children have limited access to existing and new vaccines as a consequence of weak immunisation programmes, lack of political will, and high vaccine prices. This inequality is a denial of the African child her basic right to a healthy life, and jeopardises long term economic growth on the continent. In addition, there is insufficient emphasis in Africa on adolescent and adult immunisation. The delegates documented various concerns and made various commitments; contained in this Cape Town Declaration on Vaccines, adopted on 11 November 2012. Finally, delegates confirmed their agreement with the goals and strategic objectives of the Global Vaccine Action Plan, and committed to hold African leaders accountable for its implementation during the Decade of Vaccines. The full list of registered conference delegates is provided as supplementary data to this manuscript.

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

INTRODUCTION: Vaccines are the most successful and cost-effective public health interventions available to avert vaccine-preventable diseases and deaths. Despite global progress in adolescent health, many adolescents in Africa still get sick and die from vaccine-preventable diseases due to lack of vaccination. Adolescents, parents and teachers are key players in the development and implementation of adolescent vaccination policies. Optimal knowledge, attitudes and practices towards adolescent vaccination among these key players may improve vaccine uptake among adolescents. We conducted a qualitative and quantitative systematic review on knowledge, attitudes and practices of adolescent vaccination among adolescents, parents and teachers in Africa. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide and CINAHL for eligible quantitative and qualitative primary studies with no time limits. We also checked reference lists of included studies for eligible studies and searched grey literature. Two authors independently screened the search outputs, selected studies and extracted data; resolving discrepancies by consensus and discussion. Qualitative data were analysed using thematic analyses where applicable, while analyses from quantitative studies used different methods based on the type of outcomes. RESULTS: We included 18 cross-sectional studies in this review. The included studies were conducted in 10 out of the 54 countries in Africa. The 18 studies focused on a wide range of adolescent vaccines. Thirteen studies evaluated vaccines against Human Papilloma Virus, while each of the remaining 5 studies, evaluated vaccines against rabies, HIV, tetanus toxoid, tuberculosis and adolescent vaccines in general. Among the key players, we found low to moderate levels of knowledge about adolescent vaccination. Positive attitudes and practices towards adolescent vaccination, especially against Human Papilloma Virus were reported. Despite the low knowledge, our results showed high levels of acceptability to adolescent vaccination among adolescents, parents and teachers. CONCLUSIONS: It was evident in our review that all key demographics (parents, adolescents and teachers) were receptive towards adolescent vaccines. We propose relevant policy makers in Africa to consider continuous education programs such as those aimed to inform the parents, adolescents and teachers on adolescent vaccination.

Human newborn bacille Calmette-Guérin vaccination and risk of tuberculosis disease: a case-control study.

BACKGROUND: An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette-Guérin (BCG) vaccination. METHODS: In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls). RESULTS: Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays. CONCLUSIONS: Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.