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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.
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Hepatite A , Adolescente , Adulto , Criança , Análise Custo-Benefício , Hepatite A/epidemiologia , Humanos , Estudos Retrospectivos , África do Sul/epidemiologia , VacinaçãoRESUMO
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.
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Bordetella pertussis/patogenicidade , Programas de Imunização/métodos , Coqueluche/epidemiologia , Países em Desenvolvimento , Feminino , História do Século XX , Humanos , MasculinoRESUMO
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.
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Educação em Saúde/métodos , Vacinação/estatística & dados numéricos , Adolescente , Criança , Estudos Controlados Antes e Depois , Pessoal de Saúde/educação , Humanos , Pais/educação , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação/tendênciasRESUMO
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.
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Hepatite A/epidemiologia , África/epidemiologia , Surtos de Doenças , Hepatite A/mortalidade , Anticorpos Anti-Hepatite A/sangue , Hospitalização/estatística & dados numéricos , Humanos , Imunoglobulina M/sangue , Pobreza , Fatores de Risco , Saneamento , Estudos Soroepidemiológicos , África do Sul/epidemiologiaRESUMO
RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. CONCLUSIONS: Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).
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Vacinas contra a Tuberculose/uso terapêutico , Tuberculose Pulmonar/terapia , Adenoviridae , Adulto , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Oximetria , Radiografia Torácica , Tomografia Computadorizada por Raios X , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas de DNA , Vacinas Sintéticas , Adulto JovemRESUMO
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.
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Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Tuberculose/prevenção & controle , Vacinação/efeitos adversos , Adjuvantes Imunológicos/administração & dosagem , Vacina BCG/administração & dosagem , Estudos de Casos e Controles , Feminino , Regulação Bacteriana da Expressão Gênica/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Tuberculose/imunologiaRESUMO
Absolute cell counts are typically measured in fresh samples, but this is impractical in large field studies. We compared quantification of leukocyte proportions and absolute counts using reference real-time methods (stain and lyse/no-wash (LNW) or hematology analyser) with a novel assay that allows long-term cryopreservation of fixed leukocytes for later counting (DLC-ICE: differential leukocyte count and immunophenotype in cryopreserved ex vivo whole blood). For the LNW method, whole blood (WB) was stained with fluorescent antibodies, then erythrocytes were lysed, and leukocytes fixed prior to flow cytometry. Alternatively, our novel DLC-ICE method entailed erythrocyte lysis and leukocyte fixation, cryopreservation and later staining of permeabilized cells prior to flow cytometry. Outcomes were proportions and absolute counts of granulocytes, lymphocytes, monocytes, T cells, B cells, and activated T cells within the leukocyte population. We also compared leukocyte subset counts in fresh WB from 51 healthy infants measured by hematology analyser at a rural clinical site or by DLC-ICE method after 2 years of cryopreservation. We observed excellent agreement and strong correlations between absolute counts or cell proportions measured by the LNW and DLC-ICE methods on fresh WB from 10 healthy adults. Compared to LNW, DLC-ICE yielded similar or brighter staining even after cryopreservation. Duration of cryopreservation, assessed monthly for 1 year, had little effect on cell enumeration: median coefficients of variation were below 15% for all outcomes. Under field site conditions, we observed strong correlations between infant leukocyte numbers measured in fresh samples by hematology analyser and those measured by DLC-ICE up to 2 years of cryopreservation. Our novel DLC-ICE method allows accurate flow cytometric quantification of cell subsets from fixed WB even after long-term cryopreservation. This method is ideal for batched, retrospective analysis of samples from large field studies, or when advanced flow cytometry equipment is not available for clinical research purposes. © 2014 International Society for Advancement of Cytometry.
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Preservação de Sangue/métodos , Criopreservação , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Contagem de Leucócitos/métodos , Adulto , Linfócitos B/citologia , Imunofluorescência , Granulócitos/citologia , Humanos , Ativação Linfocitária , Monócitos/citologia , Linfócitos T/citologiaRESUMO
National Immunization Technical Advisory Groups (NITAGs) are independent bodies that help improve national immunization programmes in decision making on immunization policy. The new NITAG Maturity Assessment Tool (NMAT) provided an opportunity to conduct a region-wide assessment to improve NITAG capacity and foster institutional growth. We share experience of the Eastern Mediterranean Region (EMR) of the World Health Organization (WHO) in using NMAT and the use of findings to develop improvement plans. NITAG chairs and secretariats from 22 EMR countries attended a virtual NMAT training in 2023. They self-assessed their NITAGs using the tool and developed improvement plans. An algorithm used the data to determine maturity levels for seven indicators. We consolidated results for the region by income groups. Of 22 countries (or NITAGs), 20 (91%) submitted NITAG assessment findings and 19 an improvement plan. The proportion of criteria met per indicator varied from 36% for independence and non-bias to 74% for establishment and composition. Maturity level varied by indicator. Of 20 NITAGs, less than half had an intermediate or higher-level maturity for the indicators of independence and non-bias 1 (5%), operations 3 (15%), making recommendations 4 (20%), stakeholder recognition 6 (30%), and resources and secretariat support 7 (35%). Meanwhile 11 (55%) NITAGs had an intermediate or higher maturity level for the indicators of establishment and composition and for integration into policy making process. Participants described NMAT as a concise, useful, user-friendly tool. NMAT is a practical tool that can be used by NITAGs to provide insights and strategic direction for individual countries and regionally. Prevention and management of conflict of interest is the domain that requires the most improvement in EMR. Planned activities should be implemented, monitored and a follow up assessment conducted in 2025.
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Comitês Consultivos , Política de Saúde , Humanos , Programas de Imunização , Imunização , Organização Mundial da SaúdeRESUMO
Introduction: It is estimated that one in five African children lack access to recommended life-saving vaccines. This situation has been exacerbated by the COVID-19 pandemic which disrupted routine immunization services in several parts of the region. To better support recovery efforts and get immunization programmes back on track, policy makers, programme managers, immunization providers and academics need continuous upskilling. Unfortunately, the vaccinology training needed by these cadres remains limited and oftentimes inaccessible within our context. In addition, cadres should be continuously updated on advances in vaccinology so as to keep abreast with this rapidly evolving field. This calls for new and accessible approaches to training vaccinologists in Africa where the demand is high. Methods: The aim of this proof-of-concept study was to ascertain the training needs of alumni of the Annual African Vaccinology Course and assess the effectiveness of an online webinar series in meeting those needs. Results: We found that alumni from across Africa required refresher training to gain up-to-date information about new developments in vaccinology, leverage opportunities to reinforce and consolidate their knowledge, and exchange country-specific experiences with their counterparts. A prominent motivation for refresher training was the rapid developments and challenges brought on by the COVID-19 pandemic. Drawing on the expressed needs of our alumni, we developed a webinar training series. This series aimed to provide participants with training on current and emerging trends in vaccinology with a focus on the regional context. Online participation in the webinar series was found to be comparable to previous in-person training, reaching a diverse group of cadres, and allowing for participation of a richer global faculty due to fewer cost constraints. Further to this, a post-training survey indicated that generally, alumni training needs were successfully met. Discussion: The findings suggest that an online approach can be used to expand the reach of vaccinology training in Africa.
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Tetanus, pertussis, influenza, and COVID-19 vaccines are recommended for the prevention of related morbidity and mortality during pregnancy and postpartum. Despite the established benefits of vaccination for prenatal and postnatal women, maternal vaccination is not universally included in routine antenatal programs, especially in low- and middle-income countries. Furthermore, the uptake of recommended vaccines among pregnant and postpartum women remains below optimum globally. This review aimed to map the evidence on interventions to improve knowledge, attitudes, and uptake of recommended vaccines among pregnant and postpartum women. We conducted a comprehensive and systematic search for relevant literature in PubMed, Scopus, Web of Science, EBSCOhost, and Google Scholar. Overall, 29 studies published between 2010 and 2023 were included in this review. The majority (n = 27) of these studies were from high-income countries. A total of 14 studies focused on the influenza vaccine, 6 on the Tdap vaccine, 8 on both influenza and Tdap vaccines, and only one study on the COVID-19 vaccine. Patient-centered interventions predominated the evidence base (66%), followed by provider-focused (7%), health system-focused (10%), and multilevel interventions (17%). Overall, the effect of these interventions on knowledge, attitudes, and uptake of maternal vaccines was variable.
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Tuberculosis (TB) is a global health emergency. Across the globe, approximately 2 billion people are currently infected with Mycobacterium tuberculosis (Mtb), and of those, 5-10% may progress to become ill and potentially transmit the bacterium. In 2021, nearly 10.6 million people developed TB disease and 1.6 million died. There is an urgent need for accelerated development of new TB-focused interventions, in particular, improved TB vaccines. However, progress in developing highly effective TB vaccines has been slow and is chronically under-resourced. The mRNA vaccine platform may offer an opportunity to accelerate development of new TB vaccines. In April 2023, the World Health Organization convened global experts to discuss the feasibility and potential value of mRNA-based vaccines for TB. Here we report on meeting deliberations related to the current TB vaccine pipeline and potential novel antigens, the status of efforts to identify correlates of protection, potential clinical development strategies and considerations for community acceptance of new TB vaccines based on this relatively new platform. The role of industry collaborations, ethics, social science, and responsibility to the global community regarding transparency and manufacturing capacity building were discussed through expert presentations and panel sessions. The overall conclusion of the meeting is that mRNA-based vaccines constitute a potentially powerful new tool for reducing the global burden of TB.
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Mycobacterium tuberculosis , Vacinas contra a Tuberculose , Tuberculose , Humanos , Vacinas contra a Tuberculose/genética , Mycobacterium tuberculosis/genética , Organização Mundial da Saúde , RNA Mensageiro/genéticaRESUMO
BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2. METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively. DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.
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COVID-19 , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Eficácia de Vacinas , Viés , Metanálise como AssuntoRESUMO
Adherence to recommended age-specific immunisation schedules is critical in ensuring vaccine effectiveness against vaccine preventable diseases (VPDs). There is limited data on immunisation timeliness in sub-Saharan Africa. Therefore, this study assessed the timeliness of age-specific routine childhood immunisation within the Western Cape Province of South Africa. Participant records (N = 709) from a prospective health-facility based study conducted in Cape Town, SA in 2012-2016 were analysed. The outcome measure was receiving age-specific immunisations ≥4 weeks of that recommended for age as per the South African Expanded Programme on Immunisation (EPI-SA) schedule. Proportions, medians, inter-quartile ranges (IQR) and regression were used to obtain the prevalence, time-at-risk, and risk factors for delayed immunisation. A total of 652 /709 (91.9%) participants were eligible. Immunisation coverage declined with age from 94.9% (95% CI 92.9-96.4) at birth to 72.0% (95% CI 65.7-77.6) at 18 months. The highest delay in the uptake of vaccine doses was observed among the 3 rd dose of the DTP vaccine [163 (34.6% (95% CI 30.3-39.1)], while the lowest was seen among BCG [40 (6.5% (95% CI 4.7-8.8)]. The longest median time-at-risk of VPDs was among the 2 nd dose of the measles vaccine [12.9 (IQR 6.7-38.6) weeks] and the lowest was OPV birth dose [IQR 6.3 (5.3-9.1) weeks]. Low and upper-middle socio-economic quartiles were associated with delayed uptake of vaccine doses. Delayed vaccination increases the time of susceptibility to VPDs during infancy and childhood. There is a need to develop strategies aimed at mitigating factors associated with delay in uptake of routine childhood vaccines in the Western Cape. Mitigation strategies should provide vaccine education and mobile reminder systems. Education about timely vaccine uptake will aid in the provision of informed council from healthcare providers to caregivers. Multiple reminder systems could cater for low network coverage areas and caregivers with busy schedules.
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RATIONALE: Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells. OBJECTIVES: We tested whether this outcome correlates with protection against childhood TB disease after newborn vaccination with bacillus Calmette-Guérin (BCG). METHODS: Whole blood from 10-week-old infants, routinely vaccinated with BCG at birth, was incubated with BCG for 12 hours, followed by cryopreservation for intracellular cytokine analysis. Infants were followed for 2 years to identify those who developed culture-positive TB-these infants were regarded as not protected against TB. Infants who did not develop TB disease despite exposure to TB in the household, and another group of randomly selected infants who were never evaluated for TB, were also identified-these groups were regarded as protected against TB. Cells from these groups were thawed, and CD4, CD8, and γδ T cell-specific expression of IFN-γ, TNF-α, IL-2, and IL-17 measured by flow cytometry. MEASUREMENTS AND MAIN RESULTS: A total of 5,662 infants were enrolled; 29 unprotected and two groups of 55 protected infants were identified. There was no difference in frequencies of BCG-specific CD4, CD8, and γδ T cells between the three groups of infants. Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants. CONCLUSIONS: The frequency and cytokine profile of mycobacteria-specific T cells did not correlate with protection against TB. Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-γ production, may not necessarily translate into immune correlates of protection against TB disease.
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Vacina BCG/imunologia , Tuberculose/prevenção & controle , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/imunologia , Humanos , Imunofenotipagem , Recém-Nascido , Interferon gama/sangue , Estudos Prospectivos , África do Sul , Tuberculose/imunologiaRESUMO
Given the vast investments made in national immunization programmes (NIPs) and the significance of NIPs to public health, it is important to understand what influences the optimal performance of NIPs. It has been established that well-performing NIPs require enabling health systems. However, systematic evidence on how the performance of health systems impacts on NIPs is lacking, especially from sub-Saharan Africa. We conducted a qualitative systematic review to synthesize the available evidence on health systems constraints and facilitators of NIPs in sub-Saharan Africa, using human papillomavirus immunization programmes as a proxy. Fifty-four articles published between 2008 and 2018 were found to be eligible. Data extraction was guided by an analytical model on the interface between NIPs and health systems. A cross-cutting thematic analysis of the extracted data was performed. This systematic review provides evidence necessary for informing ongoing health systems strengthening initiatives in sub-Saharan Africa. There is evidence to suggest that NIPs in sub-Saharan Africa have surmounted significant health systems constraints and have achieved notable public health success. This success can be attributed to strong political endorsement for vaccines, clear governance structures and effective collaboration with global partners. Despite this, significant health systems constraints persist in service delivery, vaccine communication, community engagement, the capacity of the health workforce and sustainable financing. These constraints could derail further progress if not addressed through health systems strengthening efforts. There is a need to expand the research agenda to include the comprehensive evaluation of health systems constraints and facilitators of NIPs within sub-Saharan Africa.
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Administração de Serviços de Saúde , Programas de Imunização , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , África Subsaariana , Programas Governamentais , Humanos , Vacinação/métodosRESUMO
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.
Assuntos
Países em Desenvolvimento , Vírus da Hepatite A , Estudos Transversais , Humanos , Índia , Quênia , Marrocos , Moçambique , Paquistão , Filipinas , África do Sul , Tunísia , UgandaRESUMO
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.
Assuntos
Infecções por Vírus Epstein-Barr , Falência Hepática Aguda , Viroses , Citomegalovirus , Herpesvirus Humano 4 , Humanos , Falência Hepática Aguda/epidemiologia , Falência Hepática Aguda/etiologiaRESUMO
BACKGROUND: There is limited evidence on whether screening for type 2 diabetes mellitus affects health outcomes. A recent systematic review of randomised clinical trials found only one trial that met their inclusion criteria; therefore, current guidelines for screening interventions for type 2 diabetes mellitus are based on expert opinions and best practice rather than synthesised evidence. This systematic review seeks to collate evidence from non-randomised studies to investigate the effect of screening for adults with type 2 diabetes on outcomes including diabetes-related morbidity, mortality (all-cause and diabetes-related) and harms. METHODS: This systematic review will follow Effective Practice and Organisation of Care (EPOC) guidelines for the synthesis of non-randomised studies. We will search PubMed/MEDLINE, Scopus, Web of Science, CINAHL, Academic Search Premier and Health Source Nursing Academic (from inception onwards). We will include non-randomised trials, controlled before-after studies, interrupted time-series studies, repeated measures studies and concurrently controlled prospective cohort studies. The primary outcome will be diabetes-related morbidity (microvascular complications of diabetic retinopathy, nephropathy or neuropathy or macrovascular complications of non-fatal myocardial infarction, peripheral arterial disease or non-fatal stroke). The secondary outcomes will be mortality (all-cause and diabetes-related) and harms of screening strategies to patients (including psychological harms or adverse events following treatments) or to health care system (including resource allocation for false-positives or overdiagnosis). Two reviewers will independently screen all citations and full-text articles. Data will be abstracted by one reviewer and checked by a second. The risk of bias of individual studies will be appraised using the ROBINS-I tool. GRADE will be used to determine the quality of the scientific evidence. If feasible, we will conduct random effects meta-analysis where appropriate. If necessary, analyses will be conducted to explore the potential sources of heterogeneity (e.g. age, sex, socio-economic status, rural versus urban or low-middle income versus high-income country). We will disseminate the findings via publications and through relevant networks. DISCUSSION: The protocol outlines the methods for systematically reviewing and synthesising evidence of screening strategies for type 2 diabetes mellitus and their effect on health outcomes associated with the disease. The potential impact of this systematic review is improved evidence-informed decision-making for policies and practice for screening of type-2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020147439.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Adulto , Atenção à Saúde , Diabetes Mellitus Tipo 2/complicações , Humanos , Programas de Rastreamento , Metanálise como Assunto , Estudos Prospectivos , Revisões Sistemáticas como AssuntoRESUMO
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.