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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., (© 2024. The Author(s).)

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Acute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation., Methods: Our retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children's hospital in Cape Town, South Africa, from January 2015 to December 2020., Results: Of 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution., Conclusions: Childhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure., (© 2024. The Author(s).)

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., Competing Interests: R.J.L.’s contribution was nonrated researcher support from the South African 10.13039/501100001321National Research Foundation (grant 121278). J.P.’s contribution was supported by a 10.13039/100000002National Institutes of Health 10.13039/100000061Fogarty career development award (K43TW011178-04). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

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.

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AG: Member of National Essential Medicines List Committee, Ministerial Advisory Committee on COVID-19, and various South African Health and Product Regulatory Authority (SAHPRA) technical advisory committees, TK: Co-Director of Cochrane Africa regional network; trustee on the Cochrane Board; is a current member of the National Essential Medicines List Committee; was a member of the Ministerial Advisory Committee on COVID-19 and COVID-19 Vaccines; and Co-director of South African GRADE Network., (Copyright: © 2023 Ebrahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Introduction: Low- 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., Methods: A 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., Results: RSV 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 = <0.001. Most cases occurred in autumn and winter with 126 (89%) cases over this period. IS demonstrated greater sensitivity for RSV diagnosis with 135 cases (95.1%) detected on IS and 57 cases (40.1%) identified on NP; P<0.001. The median length of hospital stay was 3.3 (SD 4.2) days in the RSV positive group and 2.7 (SD 3.3) days in the RSV negative group; P<0.001. The median number of detected viral pathogens was 1 (IQR 0-2) in RSV-positive children (when RSV was excluded from the count) compared to 2 (IQR 2-3) in RSV negative children; P<0.001. The presence of RSV was independently associated with a reduction in the frequency of most viruses tested for on PCR., Conclusions: RSV 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Morgan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The reviewer VVN declared a past co-authorship with the author EA-D to the handling editor. The author BMK declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Manga, Amponsah-Dacosta, Hussey, Muloiwa and Kagina.)

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 < 0.001). Independent associations with mortality were observed with leucopenia, neutropenia and thrombocytopenia. Risk of mortality in HIV-uninfected children with thrombocytopenia at T1 and T2 was aRR 2.5 (95% CI: 1.34-4.64) and 3.18 (95% CI: 1.31-7.73) respectively, whereas the mortality risk in the HIV-infected group with thrombocytopaenia at T1 and T2 was aRR 1.99 (95% CI: 0.94-4.19) and 2.01 (95% CI: 0.65-5.99) respectively. Neutropenia in the HIV-uninfected group at T1 and T2, showed aRR 2.17 (95% CI: 1.22-3.88) and aRR 3.70 (95% CI 1.30-10.51) respectively, while in the HIV-infected group, they were aRR 1.18 (95% CI 0.69-2.03) and aRR 2.05 (95% CI 0.87-4.85) at similar time points. Leucopenia at T2 was associated with mortality in HIV-uninfected and HIV-infected patients, aRR 3.22 (95%CI 1.22-8.51) and aRR 2.34 (95% CI 1.09-5.04) respectively. Persistent high band cell percentage at T2 in HIV-infected children indicated a risk of mortality of aRR 2.91 (95% CI 1.20-7.06)., Conclusion: Abnormal neutrophil counts and thrombocytopenia are independently associated with mortality in children with KPBSI. In resource-limited countries haematological markers have the potential to predict KPBSI mortality., (© 2023. The Author(s).)

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Buys et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. The Author(s).)

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.

Adolescent-tailored antiretroviral therapy (ART) adherence interventions take place within the context of unique developmental stage. Suboptimal ART adherence among adolescents living with HIV in South Africa underscores that interventions are urgently needed to improve adherence. We conducted semistructured in-depth interviews with 35 adolescents aged 10-19 years living with HIV. In addition, 14 clinicians and 35 caregivers were interviewed to provide a diverse perspective on barriers and facilitators of medication adherence for adolescents living with HIV (ALWH). Thematic coding was utilized for this analysis. Our main findings were organized by following a priori themes: (1) acceptability of conditional economic incentives (CEIs) as an adherence intervention strategy for adolescents, (2) predicted behavioral impacts, and the (3) durability of CEIs to ensure medication adherence for adolescents in the long term. Subthemes that emerged included CEIs as tool to overcome competing demands, increasing intrinsic motivation and orientation toward the future, and optimal timing of the intervention. Exposure to a CEI intervention during early adolescence (ages 10-13) may be a particularly helpful intervention as CEIs may have long-lasting effects given that habit-formation behavior is developed during early adolescence. There is little consensus on effect duration from the perspective of adolescents, clinicians, and caregivers. Future studies should continue to explore the impact of CEIs for long-term ART adherence.

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Objectives: Increased risk of morbidity and hospitalization has been observed in children who are HIV-exposed uninfected (HEU) compared with HIV-unexposed uninfected (HUU). Studies in the era of universal maternal antiretroviral treatment (ART) are limited., Design: Prospective cohort., Methods: We investigated hospitalization between 29 days and 12 months of life in a South African cohort of infants born between February 2017 and January 2019 (HEU = 455; HUU = 458). All mothers known with HIV during pregnancy received ART. We reviewed hospital records and classified and graded infectious diagnoses using a standardized tool. We examined factors associated with infectious-cause hospitalization using mixed-effects Poisson regression., Results: Infants HEU vs. HUU had higher all-cause and infectious-cause hospitalization (13 vs. 7%, P = 0.004 and 10 vs. 6%, P = 0.014, respectively). Infectious causes accounted for most hospitalizations (77%). More infants HEU were hospitalized with severe or very severe infections than those HUU (9 vs. 6%; P = 0.031). Mortality (<1%) did not differ between groups. HIV exposure was a significant risk factor for infectious-cause hospitalization [adjusted incidence rate ratios (aIRRs) = 2.8; 95% confidence interval (CI) 1.5-5.4]. Although increased incidence of preterm birth (14 vs. 10%; P < 0.05) and shorter duration of breastfeeding (44 vs. 68% breastfed for ≥3 months, P < 0.001) among infants HEU vs. HUU contributed to increased hospitalization, they did not account for all the increased risk., Conclusion: Infectious-cause hospitalization incidence was higher among infants HEU vs. HUU, likely partly because of higher incidence of preterm birth and lower breastfeeding rates among infants HEU. The increased infectious disease burden in HEU infants has important implications for health services in sub-Saharan Africa., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations. Systematic reviews are recommended to be used in this process, but conducting them requires significant resources, which many NITAGs lack. Using existing systematic reviews could help address this problem. The Robert Koch Institute and collaborators set up the SYSVAC2 project to facilitate the retrieval of existing systematic reviews and offer guidance on using them. This will include an online registry of systematic reviews relevant to immunization policy and an online course on how to use existing reviews. This report describes an international expert workshop held in December 2019 to develop consensus on methods for using existing reviews and other relevant factors for the registry and course. Members from NITAGs representing different regions of the world presented their experiences of using systematic reviews and reflected on challenges inhibiting use. Three methodologists considered different aspects of using systematic reviews. Interactive sessions followed, where implications for SYSVAC2 were discussed. Participants supported having critical appraisal ratings, plain language summaries, keyword search, and data visualization functions in the registry. They suggested tailoring course content to different audiences and including overviews of reviews as a topic and examples of how NITAGs have used or could use existing reviews. Participants agreed that whether a review is out-of-date should be decided by those using the review rather than registry staff. The registry could help by highlighting the date of literature search or included primary studies. Participants recommended a visualization function to highlight overlap across reviews and guidance on handling challenges to using reviews, ideally, involving a practical element. No consensus was reached on which critical appraisal tool to use for reviews in the registry, but a majority of participants wanted registry staff to perform appraisals. Formative research is planned before the registry and online course are launched in 2020., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021.)

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., Competing Interests: The authors declare no competing interests., (Copyright: Edina Amponsah-Dacosta et al.)

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.

Introduction: Despite a resurgence of disease, risk factors for pertussis in children in low and middle-income countries are poorly understood. This study aimed to investigate risk factors for pertussis disease in African children hospitalized with severe LRTI., Methods: A prospective study of children hospitalized with severe LRTI in Cape Town, South Africa was conducted over a one-year period. Nasopharyngeal and induced sputum samples from child and nasopharyngeal sample from caregiver were tested for Bordetella pertussis using PCR (IS481+/hIS1001). History and clinical details were documented., Results: 460 children with a median age of 8 (IQR 4-18) months were enrolled. B. pertussis infection was confirmed in 32 (7.0%). The adjusted risk of confirmed pertussis was significantly increased if infants were younger than two months [aRR 2.37 (95% CI 1.03-5.42]), HIV exposed but uninfected (aRR 3.53 [95% CI 1.04-12.01]) or HIV infected (aRR 4.35 [95% CI 1.24-15.29]). Mild (aRR 2.27 [95% CI 1.01-5.09]) or moderate (aRR 2.70 [95% CI 1.13-6.45]) under-nutrition in the children were also associated with higher risk. The highest adjusted risk occurred in children whose caregivers had B. pertussis detected from nasopharyngeal swabs (aRR 13.82 [95% CI 7.76-24.62]). Completion of the primary vaccine schedule (three or more doses) was protective (aRR 0.28 [95% CI 0.10-0.75])., Conclusions: HIV exposure or infection, undernutrition as well as detection of maternal nasal B. pertussis were associated with increased risk of pertussis in African children, especially in young infants. Completed primary vaccination was protective. There is an urgent need to improve primary pertussis vaccine coverage in low and middle-income countries. Pertussis vaccination of pregnant women, especially those with HIV infection should be prioritized., Competing Interests: The authors acknowledge financial support to their institution by Sanofi Pasteur for the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Rudzani Muloiwa has received honoraria from both Sanofi Pasteur and Pfizer for speaking engagements.”

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

Background: Computed 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., Aims: The study primarily aimed to retrospectively describe indications for non-trauma head CT and the findings at a tertiary paediatric hospital., Methods: Records 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., Results: Inclusion 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%; P<0.001)., Conclusion: A 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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Diagnosis of pertussis is challenging especially in infants. Most low and middle-income countries (LMIC) lack resources for laboratory confirmation, relying largely on clinical diagnosis alone for both case management and surveillance. This necessitates robust clinical case definitions., Objectives: This study assesses the accuracy of clinical case definitions with and without lymphocytosis in diagnosing pertussis in children with severe lower respiratory tract infection (LRTI) in a LMIC setting., Methods: Children hospitalized with severe LRTI in a South African hospital were prospectively enrolled and evaluated for pertussis using PCR on respiratory samples. Clinical signs and differential white cell counts were recorded. Sensitivity and specificity of pertussis clinical diagnosis using WHO and Global Pertussis Initiative (GPI) criteria; and with addition of lymphocytosis were assessed with PCR as the reference standard., Results: 458 children <10 years were enrolled. Bordetella pertussis infection was confirmed in 32 (7.0%). For WHO criteria, sensitivity was 78.1% (95% CI 60.7-89.2%) and specificity 15.5% (95% CI 12.4-19.3%); for GPI sensitivity was 34.4% (95% CI 20.1-52.1) and specificity 64.8% (95% CI 60.1-69.2%). Area under the curve (AUC) on receiver operating character (ROC) analysis was 0.58 (95% CI 0.46-0.70 for WHO criteria, and 0.72 (95% CI 0.56-0.88) for GPI with highest likelihood ratios of 5.33 and 4.42 respectively. Diagnostic accuracy was highest between five and seven days of symptoms for both criteria. Lymphocytosis had sensitivity of 31.3% (95% CI 17.5-49.3%) and specificity of 70.7% (95% CI 66.1-74.8%) and showed a marginal impact on improving clinical criteria., Conclusion: Clinical criteria lack accuracy for diagnosis and surveillance of pertussis. Non-outbreak settings should consider shorter durations in clinical criteria. New recommendations still fall short of what is required for a viable clinical screening test which means the need to improve access to laboratory diagnostic support remains crucial., Competing Interests: The authors acknowledge financial support to their institution by Sanofi Pasteur for the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Rudzani Muloiwa has received honoraria from both Sanofi Pasteur and Pfizer for speaking engagements.

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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Paediatric antiretroviral programmes have been implemented globally for more than a decade, yet information on long-term treatment outcomes in perinatally HIV-infected adolescents is limited. Published literature on long-term treatment outcomes was reviewed, including virologic, immunologic and growth outcomes, as well as drug resistance and factors associated with drug resistance. Outcomes were compared between high-income countries and low- and middle-income countries (LMIC), with additional focus on South Africa, the country with the biggest HIV epidemic in the world and the largest treatment programme. Treatment outcomes varied but viral suppression results globally were generally concerning. No studies from LMIC have reported on outcomes after >10 years follow-up, demonstrating that further studies are needed.

Introduction: Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa., Methods: We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years. Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospital HIV Clinic for at least 24 months between 2002 and 2016. The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow-up period., Results and Discussion: Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow-up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens. Total follow-up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overall time with detectable VL was 370 PY. This comprised 22% of total follow-up time, and 42% of the follow-up time contributed by those who experienced detectable VL. The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001). There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL., Conclusions: Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre-empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Introduction: Globally, some studies show a resurgence of pertussis. The risks and benefits of using whole-cell pertussis (wP) or acellular pertussis (aP) vaccines in the control of the disease have been widely debated. Better control of pertussis will require improved understanding of the immune response to pertussis vaccines. Improved understanding and assessment of the immunity induced by pertussis vaccines is thus imperative. Several studies have documented different immunological outcomes to pertussis vaccination from an array of assays. We propose to conduct a systematic review of the different immunological assays and outcomes used in the assessment of the humoraland cell-mediated immune response following pertussis vaccination., Methods and Analysis: The primary outcomes for consideration are quality and quantity of immune responses (humoral and cell-mediated) post-pertussis vaccination. Of interest as secondary outcomes are types of immunoassays used in assessing immune responses post-pertussis vaccination, types of biological samples used in assessing immune responses post-pertussis vaccination, as well as the types of antigens used to stimulate these samples during post-pertussis vaccination immune response assessments. Different electronic databases (including PubMed, Cochrane, EBSCO Host, Scopus and Web of Science) will be accessed for peer-reviewed published and grey literature evaluating immune responses to pertussis vaccines between 1990 and 2019. The quality of included articles will be assessed using standardised risk and quality assessment tools specific to the study design used in each article. Data extraction will be done using a data extraction form. The extracted data will be analysed using STATA V.14.0 and RevMan V.5.3 software. A subgroup analysis will be conducted based on the study population, type of vaccine (wP or aP) and type of immune response (cell-mediated or humoral). Guidelines for reporting systematic reviews in the revised 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement will be used in this study., Ethics and Dissemination: Ethics approval is not required for this study as it is a systematic review. We will only make use of data already available in the public space. Findings will be reported via publication in a peer-reviewed journal and presented at scientific meetings and workshops., Trial Registration Number: CRD42018102455., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Two types of vaccines are currently licensed for use against pertussis: whole-cell (wP) and acellular pertussis (aP). There is evidence that wP confers more durable immunity than aP, however wP has been more frequently associated with adverse events following immunisation (AEFI). A comparison of the frequency of AEFI with the first doses of wP and aP has not yet been clearly documented. This must be done in light of recent considerations to move towards a wP prime-aP boost vaccination strategy in low and middle-income countries., Objectives: To compare the frequency of AEFI associated with the first dose of the wP and aP vaccines. We also compared the frequency of AEFI associated with subsequent doses of wP., Methods: This systematic review was carried out in strict accordance with the published protocol., Results: High heterogeneity amongst included one-armed studies did not allow for pooling of prevalence estimates. The prevalence estimates of AEFI at first vaccine dose of wP ranged from 0 to 75%, while the prevalence estimates of AEFI at first vaccine dose of aP ranges from 0 to 39%. The prevalence estimates of adverse events following second and third vaccine dose of wP ranged from 0 to 71% and 0 to 61%, respectively. Risk ratios among two-armed studies showed an increased risk of adverse events with first dose of wP compared to aP [local reaction RR 2.73 (2.33, 3.21), injection site pain RR 4.15 (3.24, 5.31), injection site swelling RR 4.38 (2.70, 7.12), fever over 38 °C RR 9.21 (5.39, 15.76), drowsiness RR 1.34 (1.18, 1.52) and vomiting RR 1.28 (0.91, 1.79)]., Conclusion: Our results confirm that, when comparing the first dose, wP is more reacotgenic than aP. The proposed wP prime followed by aP boost pertussis vaccine strategy should be approached with caution., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare no potential conflict of interest.