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Abstract Background Pregnant women, fetuses, and neonates are particularly vulnerable to vaccine-preventable diseases (VPDs). These VPDs are associated with high morbidity and mortality among expectant mothers and their fetuses and neonates. Vaccination during pregnancy can protect the expectant mother from VPDs to which she may be especially vulnerable while pregnant. In addition, the passive transfer of maternal neutralizing immunoglobulin G (IgG) and secretory immunoglobulin A (IgA) also protects the fetus against congenital infections and may further protect the neonate from infection during the first few months of life. Despite this, coverage of recommended maternal vaccines remains suboptimal globally, especially in resource-constrained settings. Determinants of vaccine acceptance and uptake are frequently understudied in low- and middle-income countries (LMICs) and among specific groups such as pregnant and postpartum women. This proposed systematic review will assess the acceptance and uptake of vaccines against tetanus, influenza, pertussis, and COVID-19 among pregnant and postpartum women in LMICs. Methods A Boolean search strategy employing common and medical subject heading (MeSH) terms for tetanus, influenza, pertussis, and COVID-19 vaccines, as well as vaccine acceptance, hesitancy, together with uptake, pregnancy, and postpartum, will be used to search electronic databases for relevant literature published between 2009 and 2024. Only studies conducted in LMICs that investigated determinants of acceptance, hesitancy, and uptake of tetanus, influenza, pertussis, and COVID-19 vaccines among pregnant and postpartum women will be eligible for inclusion in the review. The quality and the risk of bias of all eligible full-text articles will be assessed using the Joanna Briggs Institute’s (JBI) critical appraisal tools. Discussion This protocol proposes a systematic review and meta-analysis that aims to assess the uptake of maternal vaccines and to systematically appraise and quantify determinants of the acceptance and uptake of recommended vaccines during pregnancy and postpartum in LMICs. A better understanding of these factors and how they influence maternal vaccine decision-making will enable public health practitioners as well as global and national policymakers to design more effective interventions as we look towards expanding the scope and reach of maternal immunization programs.

Background: RegiSCAR validation criteria for drug reaction with eosinophilia and systemic symptoms (DRESS) includes lymphadenopathy, a frequent feature of both tuberculosis (TB) and human immunodeficiency virus (HIV). TB is the most common HIV-associated coinfection. Advanced HIV is associated with lymph node (LN) fibrosis. It is not clear if this negatively affects case validation in HIV-associated DRESS. To answer this question, we designed a prospective descriptive study to assess lymphadenopathy in various combinations of comorbid HIV, TB, and DRESS. Objectives: We sought to describe the prevalence of DRESS-associated lymphadenopathy and characterize LN quality, size, and distribution in a high HIV-TB burden setting over time. Methods: We prospectively and systematically examined LN in 25 consecutive acute DRESS cases hospitalized at a South African tertiary-care center and 10 hospitalized non-DRESS HIV-TB coinfected controls. Results: Fourteen (56%) of 25 patients were HIV infected, with a median (interquartile range) CD4 count of 254 (66-478) cells/mm³, and 7 of 14 were coinfected with TB. Using RegiSCAR criteria, 12 (46%) of 25 were definite DRESS cases, 8 (31%) of 25 probable, and 5 (23%) of 25 possible. Possible cases were excluded in the analysis. Fifteen (75%) of 20 subjects had LN in ≥2 anatomic sites, including all 7 patients with HIV-TB coinfection. In contrast, 1 (20%) of 5 hospitalized non-DRESS HIV-TB coinfected controls had LN. Cervical LN, in 15 (88%) of 17, was most common, followed by axillary (76%) and inguinal (59%). Cervical LN ranged between 1 and 2 cm in size. Among the 8 (32%) of 25 subjects with follow-up data, LN had regressed in all within 6 weeks of stopping the offending drug and initiating TB treatment. There was no correlation with CD4 cell count and LN. Conclusion: Lymphadenopathy is a common feature of acute DRESS, even among HIV-TB–coinfected patients with advanced immunosuppression.

Abstract Background Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), is a leading cause of hospital-associated childhood mortality. There are limited data on how poor outcomes of KPBSI can be predicted in poorly resourced areas. This study aimed to assess if the profile of differential counts from full blood counts (FBC) taken at two time points in children with KPBSI could be used to predict the risk of death. Methods We conducted a retrospective study of a cohort of children admitted to hospital between 2006 and 2011 with KPBSI. FBC collected within 48 h (T1) of blood culture and 5–14 days later (T2), were reviewed. Differential counts were classified as abnormal if they were higher or lower than laboratory ranges for normal results. The risk of death was assessed for each category of differential counts. Risk ratios adjusted (aRR) for potential confounders were used to estimate the effect of cell counts on risk of death using multivariable analysis. Data were stratified by HIV status. Results Of 296 children, median age 5 (IQR:2–13) months, 82 were HIV -infected. Ninety-five (32%) children with KPBSI died. Mortality in HIV-infected and uninfected children was 39/82 (48%) and 56/214 (26%), respectively (p

Abstract Background Candida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa. Methods A retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa. Demographic and clinical details, antifungal management and patient outcome data were obtained by medical record review. Candida species distribution and antifungal susceptibility testing results were obtained from the National Health Laboratory Service database. Results Of the 97 Candida BSI episodes identified during a five-year period, 48/97 (49%) were Candida albicans (C. albicans), and 49/97 (51%) were non-C. albicans species. The overall incidence risk was 0.8 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children’s Hospital. Of the 77/97 (79%) Candida BSI episodes with available clinical information, the median age (interquartile range) at the time of BSI was 7 (1–25) months, 36/77 (47%) were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22/77 (29%) study participants. Most of the Candida BSI episodes were healthcare-associated infections, 63/77 (82%). Fluconazole resistance was documented among 17%, 0% and 0% of C. parapsilosis, C. tropicalis and C. albicans isolates, respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of Candida BSI diagnosis was 13/75 (17%). On multivariable analysis, factors associated with mortality within 30 days of Candida BSI diagnosis included vasopressor therapy requirement during Candida BSI, adjusted Odds ratio (aOR) 53 (95% confidence interval 2–1029); hepatic dysfunction, aOR 13 (95% CI 1–146); and concomitant bacterial BSI, aOR 10 (95% CI 2–60). Conclusion The study adds to the limited number of studies describing paediatric Candida BSI in sub-Saharan Africa. Non-C. Albicans BSI episodes occurred more frequently than C. albicans episodes, and vasopressor therapy requirement, hepatic dysfunction and concomitant bacterial BSI were associated with an increase in 30-day mortality.

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination. We used the calibrated model to evaluate the impact and costs of several childhood hepatitis A vaccination scenarios from 2023 to 2030. We assessed how each scenario impacted the burden of hepatitis A (symptomatic hepatitis A cases and mortality) as well as calculated the incremental cost per DALY averted as compared to the South African cost-effectiveness threshold. All costs and outcomes were discounted at 5%. For the modelled scenarios, the median estimated cost of the different vaccination strategies ranged from USD 1.71 billion to USD 2.85 billion over the period of 2023 to 2030, with the cost increasing for each successive scenario and approximately 39–52% of costs being due to vaccination. Scenario 1, which represented the administration of one dose of the hepatitis A vaccine in children < 2 years old, requires approximately 5.3 million vaccine doses over 2023–2030 and is projected to avert a total of 136,042 symptomatic cases [IQR: 88,842–221,483] and 31,106 [IQR: 22,975–36,742] deaths due to hepatitis A over the period of 2023 to 2030. The model projects that Scenario 1 would avert 8741 DALYs over the period of 2023 to 2030; however, it is not cost-effective against the South African cost-effectiveness threshold with an ICER per DALY averted of USD 21,006. While Scenario 3 and 4 included the administration of more vaccine doses and averted more symptomatic cases of hepatitis A, these scenarios were absolutely dominated owing to the population being infected before vaccination through the mass campaigns at older ages. The model was highly sensitive to variation of access to liver transplant in South Africa. When increasing the access to liver transplant to 100% for the baseline and Scenario 1, the ICER for Scenario 1 becomes cost-effective against the CET (ICER = USD 2425). Given these findings, we recommend further research is conducted to understand the access to liver transplants in South Africa and better estimate the cost of liver transplant care for hepatitis A patients. The modelling presented in this paper has been used to develop a user-friendly application for vaccine policy makers to further interrogate the model outcomes and consider the costs and benefits of introducing routine hepatitis A vaccination in South Africa.

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.

Abstract Background The aim of this study was to investigate the quality of immunization data and monitoring systems in the Dara Malo District (Woreda) of the Gamo Administrative Zone, within the Southern Nations, Nationalities, and Peoples’ Region (SNNPR) of Ethiopia. Methods A cross-sectional study was conducted from August 4 to September 27, 2019, in Dara Malo District. The district was purposively selected during the management of a pertussis outbreak, based on a hypothesis of ‘there is no difference in reported and recounted immunization status of children 7 to 23 months in Dara Malo District of Ethiopia’. The study used the World Health Organization (WHO) recommended Data Quality Self-Assessment (DQS) tools. The accuracy ratio was determined using data from routine Expanded Program of Immunization (EPI) and household surveys. Facility data spanning the course of 336 months were abstracted from EPI registers, tally sheets, and monthly routine reports. In addition, household surveys collected data from caretakers, immunization cards, or oral reports. Trained DQS assessors collected the data to explore the quality of monitoring systems at health posts, health centers, and at the district health office level. A quality index (QI) and proportions of completeness, timeliness, and accuracy ratio of the first and third doses of pentavalent vaccines and the first dose of measles-containing vaccines (MCV) were formulated. Results In this study, facility data spanning 336 months were extracted. In addition, 595 children aged 7 to 23 months, with a response rate of 94.3% were assessed and compared for immunization status, using register and immunization cards or caretakers’ oral reports through the household survey. At the district level, the proportion of the re-counted vaccination data on EPI registers for first dose pentavalent was 95.20%, three doses of pentavalent were 104.2% and the first dose of measles was 98.6%. However, the ratio of vaccination data compared using tallies against the reports showed evidence of overreporting with 50.8%, 45.1%, and 46.5% for first pentavalent, third pentavalent, and the first dose of measles vaccinations, respectively. The completeness of the third dose of pentavalent vaccinations was 95.3%, 95.6%, and 100.0% at health posts, health centers, and the district health office, respectively. The timeliness of the immunization reports was 56.5% and 64.6% at health posts and health centers, respectively, while the district health office does not have timely submitted on time to the next higher level for twelve months. The QI scores ranged between 61.0% and 80.5% for all five categories, namely, 73.0% for recording, 71.4% for archiving and reporting, 70.4% for demographic information, 69.7% for core outputs, and 70.4% for data use and were assessed as suboptimal at all levels. The district health office had an emergency preparedness plan. However, pertussis was not on the list of anticipated outbreaks. Conclusion Immunization data completeness was found to be optimal. However, in the study area, the accuracy, consistency, timeliness, and quality of the monitoring system were found to be suboptimal. Therefore, poor data quality has led to incorrect decision making during the reported pertussis outbreak management. Availing essential supplies, including tally sheets, monitoring charts, and stock management tools, should be prioritized in Daro Malo District. Enhancing the capacity of healthcare providers on planning, recording, archiving, and reporting, analyzing, and using immunization data for evidence-based decision making is recommended. Improving the availability of recording and reporting tools is also likely to enhance the data accuracy and completeness of the community health information system. Adapting pertussis outbreak management guidelines and conducting regular data quality assessments with knowledge sharing events to all stakeholders is recommended.

Abstract 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

A rapid systematic review, based on Cochrane rapid review methodology was conducted to assess the effectiveness of two 10μg doses of BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years. We searched the Cochrane Library COVID-19 study register, the COVID-NMA living review database and the McMaster University Living Evidence Synthesis for pre-appraised trials and observational studies up to 7 December 2022. Records were screened independently in duplicate. Where appraisal was not available, these were done in duplicate. Meta-analysis was conducted using RevMan 5.3 presenting risk ratios/odds ratios/inverse vaccine efficacy with 95% confidence intervals (CI). GRADE for assessing the overall certainty of the evidence was done in Gradepro. We screened 403 records and assessed 52 full-text articles for eligibility. One randomised controlled trial (RCT) and 24 observational studies were included. The RCT reported that BNT162b2 was likely safe and 91% efficacious, RR 0.09 (95% CI 0.03 to 0.32) against incident COVID-19 infection (moderate certainty evidence). In absolute terms, this is 19 fewer cases per 1,000 vaccines delivered (ranging from 15 to 21 fewer cases). Observational studies reported vaccine effectiveness (VE) against incident COVID-19 infection of 65% (OR 0.35, 95% CI 0.26 to 0.47) and 76% against hospitalisation (OR 0.24, 95% CI 0.13 to 0.42) (moderate certainty evidence). The absolute effect is 167 fewer cases per 1,000 vaccines given (ranging from 130 fewer to 196 fewer cases) and 4 fewer hospitalisations per 10,000 children (from 3 fewer to 5 fewer hospitalisations). Adverse events following vaccination with BNT162b2 were mild or moderate and transient. The evidence demonstrated a reduction in incident COVID-19 cases and small absolute reduction in hospitalisation if a two-dose BNT162b2 vaccine regimen is offered to children aged 5 to 11 years, compared to placebo. PROSPERO registration: CRD42021286710.

IntroductionLow- and middle-income countries carry the largest burden of Respiratory syncytial virus (RSV) disease, with most deaths occurring in these settings. This study aimed to investigate the burden of RSV disease in South African children hospitalised with lower respiratory tract infection (LRTI), with specific reference to incidence, risk factors, and co-infections.MethodsA database from a previous prospective study containing demographic, laboratory and clinical data on children hospitalised with LRTIs in Cape Town, South Africa, was used. A nasopharyngeal swab (NP) and induced sputum (IS) were tested for RSV PCR. Descriptive statistics were used to characterise the study population, and a multivariable analysis of risk factors and co-infections was done.ResultsRSV was detected in 142 (30.9%; 95% CI 26.7-35.3) of the included 460 study children with LRTI. The median age of RSV-positive children was 4.6 (IQR 2.4-9.7) months compared to RSV-negative children of 10.5 (IQR 4.4-21.3) months, P = ConclusionsRSV is common in children hospitalised with LRTI and mainly affects younger children. There is an urgent need to find an effective vaccine to prevent RSV pneumonia in children worldwide, especially in LMICs that carry the greatest burden of disease.

Objectives Bubble CPAP (bCPAP), a non-invasive ventilation modality, has emerged as an intervention that is able to reduce pneumonia-related mortality in children in low resourced settings. Our study primarily aimed to describe a cohort of children who were started on CPAP in the Medical Emergency Unit (MEU) of Red Cross War Memorial Children’s Hospital 2016–2018. Methods A retrospective review of a randomly selected sample of paper-based folders was conducted. Children started on bCPAP at MEU were eligible for inclusion. Demographic and clinical data, management, and outcomes regarding admission to PICU, need for invasive ventilation and mortality were documented. Descriptive statistical data were generated for all relevant variables. Percentages depicted frequencies of categorical data while medians with interquartile ranges (IQR) were used to summarise continuous data. Results Of 500 children started on bCPAP, 266 (53%) were male; their median age was 3.7 (IQR 1.7–11.3) months and 169 (34%) were moderately to severely underweight-for-age. There were 12 (2%) HIV-infected children; 403 (81%) had received appropriate immunisations for their age; and 119 (24%) were exposed to tobacco smoke at home. The five most common primary reasons for admission were acute respiratory illness, acute gastroenteritis, congestive cardiac failure, sepsis and seizures. Most children, 409 (82%), had no underlying medical condition. Most children, 411 (82%), were managed in high care areas of the general medical wards while 126 (25%) went to PICU. The median time on CPAP was 1.7 (IQR 0.9–2.8) days. The median hospitalisation time was 6 (IQR 4–9) days. Overall, 38 (8%) children required invasive ventilatory support. Overall, 12 (2%) children with a median age of 7.5 (IQR 0.7–14.5) months died, six of whom had an underlying medical condition. Conclusions Seventy-five percent of children initiated on bCPAP did not require PICU admission. This form of non-invasive ventilatory support should be considered more widely in the context of limited access to paediatric intensive care units in other African settings.

Abstract Background Paediatric poisoning is a common presentation to emergency departments worldwide. There is a paucity of data on the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS), in the management of paediatric poisoning in low-and middle-income countries (LMICs). In high-income countries, most studies are retrospective, and few include children. Objective The study describes the prevalence of liquid chromatography-tandem mass spectrometry confirmed paediatric poisoning at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Methods Children admitted with suspected poisoning between 1 January 2017 and 31 December 2017, were recruited. All patients had a urine and/or blood sample sent for LC-MS/MS toxicology. Data collected included demographic data, clinical features, investigations, management, outcome and social interventions. Results One hundred fifty-two children, with median age of 39 (IQR 25–61) months were enrolled of which 128 (84%) were poisoning cases. Of the 128 poisoning cases, 88 (69%) presented with a history of ingesting a known substance, 16 (12%) an unknown substance and 24 (19%) were cases of occult poisoning. LC-MS/MS was able to identify a substance in 92% of the cases of occult poisoning. In those who had presented with a seemingly known substance, LC-MS/MS found a different substance in 15 cases. LC-MS/MS was also able to detect multiple drugs in 40 patients. Of the poisoning cases, six (5%) cases were attempted homicide cases and 5 (4%) cases were attempted suicide cases. No children died. Individualized social interventions were instituted in poisoning cases. Emergency placement safety reasons was required in 6 children. Conclusion When the limitations are known, LC-MS/MS is useful in identifying cases of occult poisoning, identifying patients who have ingested multiple substances and/or an unknown substance and when targeted towards child protection. As LC-MS/MS is an expensive test, it should be used judiciously in LMICs.

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.

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

Abstract Background Despite the availability of effective vaccines, pertussis remains endemic with high fatality rates in low and middle-income countries (LMIC). This study aims to describe an outbreak of pertussis in a health district of Ethiopia. The study highlights the challenges faced by the health system in identifying pertussis cases and appropriately responding to the outbreak at the district level. Methods A descriptive cross-sectional study was conducted using data sourced from the District Public Health Emergency and Management (PHEM) surveillance service and outbreak management field reports. Stratified attack rates and fatality rates for pertussis are described. Systemic problems leading to the outbreak are explored and narrated. A modified CDC pertussis case definition was employed with a polymerase chain reaction used to confirm cases. Results From September 2018 to January 2019, 1840 suspected, probable, and confirmed pertussis cases and six deaths were identified. Pertussis cases ranged from 1 month to 51 years in age. An outbreak occurred in 14 out of the 24 villages of Dara Malo district. The overall attack rate was 1708 per 100,000 population with a fatality rate of 3.3 per 1000 pertussis cases. The highest attack rate of 12,689/100,000 was seen in infants. Among confirmed, probable and suspected pertussis cases, only 41.1% had completed the three-dose pertussis vaccine’s primary schedule. The household survey revealed a population coverage of 73.4 and 40.8% for Pentavalent vaccine dose one and three respectively. Investigations suggested the existence of a poor cold chain management system in the study area. Conclusions There is an urgent need to build capacity to strengthen routine vaccination services and improve the maintenance of the vaccine cold chain. Other LMICs are urged to take lessons learned from this outbreak to strengthen their own vaccination programs and capacitate health workers to manage local outbreaks.

The Global Pertussis Initiative is an expert scientific forum that publishes consensus recommendations concerning pertussis for many regions of the world. Here, we give recommendations for the primary vaccination of infants in those countries where whole-cell pertussis (wP)- and acellular pertussis (aP)-containing combination vaccines are used in parallel. A selective literature review was performed concerning the influence on safety, immunogenicity, and effectiveness of mixing wP- and aP-containing vaccines for primary immunization of infants. In addition, local data were collected from various countries and the results discussed in a face-to-face meeting. Very few data addressing issues of mixing combination vaccines were identified, and no data were available concerning the effectiveness or duration of protection. It was also found that pharmacovigilance data are scarce or lacking in those countries where they would be needed the most. We then identified frequent problems occurring in low- and middle-income countries (LMICs) where both vaccine types are used. Relying on local knowledge, we give practical recommendations for a variety of situations in different settings. Specific needs for additional data addressing these issues were also identified. International bodies, such as the World Health Organization (WHO), as well as vaccine producers should try to find ways to highlight the problems of mixing wP- and aP-containing combination vaccines with robust data. Countries are urged to improve on their pharmacovigilance for vaccines. For practicing physicians, our recommendations offer guidance when wP- and aP-containing vaccines are used in parallel during primary immunization.

Infants are at high risk for severe morbidity and mortality from pertussis disease during early infancy. Vaccination against pertussis in pregnancy has emerged as the ideal strategy to protect infants during these early, vulnerable, first months of life. On 30 November and 1 December 2021, the Global Pertussis Initiative held a meeting that aimed to discuss and review the most up-to-date scientific literature supporting vaccination against pertussis in pregnancy and outstanding scientific questions. Herein, we review the current and historically published literature and summarize the findings as consensus statements on vaccination against pertussis in pregnancy on behalf of the Global Pertussis Initiative.

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

For 15 years, the Annual African Vaccinology Course (AAVC) hosted by the Vaccines for Africa Initiative, has been at the forefront of vaccinology training in Africa. The AAVC was developed in 2005 in response to the growing demand for vaccinology training in Africa. To date, 958 policy makers, immunization managers, public and private health practitioners, scientists, postgraduate and postdoctoral students have been trained. These participants are from 44 of the 54 African countries. The course content covers diverse topics such as considerations for new vaccine introduction, mathematical modelling, and emerging and re-emerging vaccine preventable diseases. As the landscape of vaccinology continues to evolve, the AAVC aims to expand the reach of vaccinology training using blended learning approaches which will incorporate online and face-to-face formats, while expanding access to this popular course. Ultimately, the AAVC endeavours to develop a big pool of vaccinology expertise in Africa and to strengthen regional ownership for immunization programmes.

IntroductionDespite 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.MethodsA 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.Results460 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]).ConclusionsHIV 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.

BackgroundComputed tomography (CT) imaging is an indispensable tool in the management of acute paediatric neurological illness providing rapid answers that facilitate timely decisions and interventions that may be lifesaving. While clear guidelines exist for use of CT in trauma to maximise individual benefits against the risk of radiation exposure and the cost to the healthcare system, the same is not the case for medical emergency.AimsThe study primarily aimed to retrospectively describe indications for non-trauma head CT and the findings at a tertiary paediatric hospital.MethodsRecords of children presenting with acute illness to the medical emergency unit of Red Cross War Children's Hospital, Cape Town, over one year (2013) were retrospectively reviewed. Participants were included if they underwent head CT scan within 24 hours of presentation with a non-trauma event. Clinical data and reports of CT findings were extracted.ResultsInclusion criteria were met by 311 patients; 188 (60.5%) were boys. The median age was 39.2 (IQR 12.6-84.0) months. Most common indications for head CT were seizures (n = 169; 54.3%), reduced level of consciousness (n = 140;45.0%), headache (n = 74;23.8%) and suspected ventriculoperitoneal shunt (VPS) malfunction (n = 61;19.7%). In 217 (69.8%) patients CT showed no abnormal findings. In the 94 (30.2%) with abnormal CT results the predominant findings were hydrocephalus (n = 54;57.4%) and cerebral oedema (n = 29;30.9%). Papilloedema was more common in patients with abnormal CT (3/56; 5.4%) compared with none in those with normal CT; P = 0.015; while long tract signs were found in 42/169 (24.9%) and 23/56 (41.1%) of patients with normal and abnormal CT findings, respectively; P = 0.020. Post-CT surgery was required by 47(15.1%) of which 40 (85.1%) needed a ventricular drainage. A larger proportion of patients with VPS (25/62; 40.3%) required surgery compared to patients without VPS (22/249; 8.8%; PConclusionA majority of head CT scans in children with medical emergency with acute neurological illness were normal. Patients with VPS constituted the majority of patients with abnormal CT scans that required subsequent neurosurgical intervention. Evidence-based guidelines are required to guide the best use of head CT in the management of children without head trauma.

IntroductionDiagnosis 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.ObjectivesThis 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.MethodsChildren 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.Results458 children ConclusionClinical 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.

Abstract Background Varicella zoster virus (VZV) causes varicella and herpes zoster. These vaccine preventable diseases are common globally. Most available data on VZV epidemiology are from industrialised temperate countries and cannot be used to guide decisions on the immunization policy against VZV in Africa. This systematic review aims to review the published data on VZV morbidity and mortality in Africa. Methods All published studies conducted in Africa from 1974 to 2015 were eligible. Eligible studies must have reported any VZV epidemiological measure (incidence, prevalence, hospitalization rate and mortality rate). For inclusion in the review, studies must have used a defined VZV case definition, be it clinical or laboratory-based. Results Twenty articles from 13 African countries were included in the review. Most included studies were cross-sectional, conducted on hospitalized patients, and half of the studies used varying serological methods for diagnosis. VZV seroprevalence was very high among adults. Limited data on VZV seroprevalence in children showed very low seropositivity to anti-VZV antibodies. Co-morbidity with VZV was common. Conclusion There is lack of quality data that could be used to develop VZV control programmes, including vaccination, in Africa. Trial registration PROSPERO 2015: CRD42015026144 .

Background: Klebsiella pneumoniae bloodstream infection (KPBSI) is strongly linked to hospitalisation and can lead to significant morbidity and mortality. There is little data describing the autopsy findings of KPBSI in children. Methods: We conducted a retrospective review of clinicopathologic findings of children who died during the course of KPBSI at a children's hospital in Cape Town, South Africa. Results: Fifteen hospitalised children who died and had autopsies were included in this analysis. Their median age (interquartile range, IQR) was 4 (1–22) months, 2 (20%) were HIV-infected, and 10 (67%) were moderately or severely underweight. The median time to death from the time of positive blood culture was 1 (IQR 0–5) day. Notable autopsy findings were sepsis-induced multiorgan failure in many cases including thymic involution, oesophageal erosions, adrenal haemorrhage, acute tubular necrosis and lung parenchymal destruction. Other histologic findings included disseminated intravascular coagulopathy, necrotising inflammation in many organs; and in four of five children biofilm formation. Conclusion: KPBSI may cause widespread necrotic tissue.

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

No abstract available.

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.

INTRODUCTION:Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. METHODS:We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. RESULTS:From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. DISCUSSION:In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation.

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa.Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals.Trial registration number CRD42015026144.

A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir. We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population.We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes.We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73%) had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95%) cases. All 22 of the mothers survived with 3/22 (14%) developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50%) babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine.TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug reactions with a higher incidence in HIV-infected persons. SJS/TEN are associated with skin and mucosal failure, predisposing to systemic bacterial infection (BSI), a major cause of death. There are limited data on risk factors associated with BSI and and mortality in HIV-infected people with SJS/TEN.We conducted a retrospective study of patients admitted to a university hospital with SJS/TEN over a 3 year period. We evaluated their underlying illnesses, eliciting drugs, predictive value of bacterial skin cultures and other factors associated with mortality and BSI in a predominantly HIV-infected population by comparing characteristics of the patients who demised and those who survived.We admitted 86 cases during the study period and 67/86(78%) were HIV-infected. Tuberculosis was the commonest co-morbidity, diagnosed in 12/86(14%) cases. Skin cultures correlated with BSI by the same organism in 7/64(11%) cases and 6/7 were Gram-negative. Two of the 8 cases of Gram-negative BSI had an associated Gram-negative skin culture, although not always the same organism. All 8 fatalities had >30% epidermal detachment, 7 were HIV-infected, 6 died of BSI and 6 had tuberculosis.Having >30% epidermal detachment in SJS/TEN carries an increased risk of BSI and mortality. Tuberculosis and BSI are associated with higher risk of death in SJS/TEN. Our data suggests there may be an association between Gram-negative BSI and Gram-negative skin infection.