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The Sisonke 2 study provided a homologous boost at least 6 months after administration of the priming dose of Ad26.COV2.S for healthcare workers enrolled on the Sisonke phase 3b implementation study. Safety monitoring was via five reporting sources: (i.) self-report through a web-link; (ii.) paper-based case report forms; (iii.) a toll-free telephonic reporting line; (iv.) healthcare professionals-initiated reports; and (v.) active linkage with National Disease Databases. A total of 2350 adverse events were reported by 2117 of the 240 888 (0.88%) participants enrolled; 1625 of the 2350 reported events are reactogenicity events and 28 adverse events met seriousness criteria. No cases of thrombosis with thrombocytopaenia syndrome were reported; all adverse events including thromboembolic disorders occurred at a rate below the expected population rates apart from one case of Guillain Barre Syndrome and one case of portal vein thrombosis. The Sisonke 2 study demonstrates that two doses of Ad26.COV2.S is safe and well tolerated; and provides a feasible model for national pharmacovigilance strategies for low- and middle-income settings. [ABSTRACT FROM AUTHOR]

• Background rates of maternal foetal and neonatal adverse events in South Africa have been assessed to support safety assessment of vaccines. • Retrospective review of paper-based medical records is challenging and time-consuming. • Missing data hampered alignment between clinically-reported adverse events and adverse events confirmed with GAIA case definitions. • Brighton Collaboration GAIA case definitions are useful, but some require amendments to improve utilization in real world settings. Background epidemiologic population data from low- and middle-income countries (LMIC), on maternal, foetal and neonatal adverse outcomes are limited. We aimed to estimate the incidence of maternal, foetal and neonatal adverse outcomes at South African maternal vaccine trial sites as reported directly in the clinical notes as well as using the 'Global Alignment of Immunization Safety Assessment in Pregnancy' case definitions (GAIA-CDs). GAIA-CDs were utilized as a tool to standardise data collection and outcome assessment, and the applicability and utility of the GAIA-CDs was evaluated in a LMIC observational study. We conducted a retrospective record review of maternity and neonatal case records for births that occurred in Soweto, Inner City- Johannesburg and Metro-East Cape Town, South Africa, between 1st July 2017 and 30th June 2018. Study staff abstracted data from randomly selected medical charts onto standardized study-specific forms. Incidence (per 100,000 population) was calculated for adverse maternal, foetal and neonatal outcomes, which were identified as priority outcomes in vaccine safety studies by the Brighton Collaboration and World Health Organization. Outcomes reported directly in the clinical notes and outcomes which fulfilled GAIA-CDs were compared. Incidence of outcomes was calculated by combining cases which were either reported in clinical notes by attending physicians and/ or fulfilled GAIA-CDs. Of 9371 pregnant women enrolled, 27·6% were HIV-infected, 19·9% attended antenatal clinic in the 1st trimester of pregnancy and 55·3% had ≥1 ultrasound examination. Fourteen percent of women had hypertensive disease of pregnancy, 1·3% had gestational diabetes mellitus and 16% experienced preterm labour. There were 150 stillbirths (1·6%), 26·8% of infants were preterm and five percent had microcephaly. Data available in clinical notes for some adverse outcomes, including maternal- & neonatal death, severe pre-eclampsia/ eclampsia, were able to fulfil GAIA-CDs criteria for all of the clinically-reported cases, however, missing data required to fulfil other GAIA-CD criteria (including stillbirth, gestational diabetes mellitus and gestational hypertension) led to poor correlation between clinically-reported adverse outcomes and outcomes fulfilling GAIA-CDs. Challenges were also encountered in accurately ascertaining gestational age. This study contributes to the expanding body of data on background rates of adverse maternal and foetal/ neonatal outcomes in LMICs. Utilization of GAIA-CDs assists with alignment of data, however, some GAIA-CDs require amendment to improve the applicability in LMICs. This study was funded by Pfizer (Inc). [ABSTRACT FROM AUTHOR]

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies – conducted in general, non-pregnant populations – suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization. [ABSTRACT FROM AUTHOR]

Abstract: Advocacy, social mobilisation and communication are key components of the successful introduction of new vaccines into childhood immunisation schedules. The development of many new vaccines and the innovation of finance mechanisms, means more efficacious vaccines are becoming available to children in developing countries. At the same time, communication technology is developing at a rapid rate, and with the dramatic decrease in vaccine-preventable diseases over the past few decades, the public have become increasingly exposed to confusing and conflicting information about the need for vaccination. The science of vaccines has become more complex, making effective, clear and consistent communication for healthcare workers and caregivers critical to the uptake of and adherence to life-saving vaccination. The introduction of two new vaccines, the 7-valent pneumococcal conjugate vaccine and the rotavirus vaccine together with the new pentavalent vaccine, which includes inactivated polio vaccine and replaced the former combination vaccine with four antigens, into the South African Expanded Programme on Immunisation over a short period of time, has been met with a number of challenges, some of which led to a lowering of confidence in the Department of Health to deliver on its promises. Had consistent advocacy, social mobilisation and communication efforts not been in place, efforts to make an impact on the burden of disease may not have been as successful. This paper focuses on the lessons learned about effective advocacy with decision makers, social mobilisation, communication with parents and caregivers, and training healthcare workers regarding the introduction of the new vaccines. [Copyright &y& Elsevier]

Abstract: Vaccination is one of the most cost-effective and successful public health interventions in the history of mankind. Anecdotal evidence, the media, and South African-based anti-vaccination websites and blogs point to the existence of anti-vaccination lobbies in South Africa, although the part played by these lobbies in sub-optimal vaccination coverage is unknown at present. This article discusses some of the claims made by South African anti-vaccination groups, including some drawn from anti-vaccination lobbyists based in highly resourced countries. While research is underway to better understand the scope and influence of anti-vaccine groups, it is important to build capacity among healthcare workers within the Expanded Programme on Immunisation of South Africa to enable them to deal empathically and effectively with parents and caregivers who have been exposed to anti-vaccination messages and who question the need to vaccinate their children. Claims that vaccines cause adverse effects need to be supported by valid and reliable scientific evidence. However, evidence alone that vaccines are safe and effective does not always result in parents being convinced to vaccinate their children. In addition to providing important evidence of vaccine safety, this paper discusses the important role of communication – especially dialogue – in building public trust in vaccination with the ultimate goal of increasing vaccination coverage and preventing future outbreaks of vaccine-preventable diseases. [Copyright &y& Elsevier]

Abstract: Diarrhoeal diseases are ranked the third major cause of childhood mortality in South African children less than 5years, where the majority of deaths are among black children. Acute severe dehydrating rotavirus diarrhoea remains an important contributor towards childhood mortality and morbidity and has been well documented in South Africa. As the preventive strategy to control rotavirus diarrhoea, South Africa became the first country in the WHO African Region to adopt the rotavirus vaccine in the national childhood immunisation programme in August 2009. The rotavirus vaccine in use, Rotarix®, GSK Biologicals, is given at 6 and 14weeks of age, along with other vaccines as part of Expanded Programme on Immunisation (EPI). Studies which facilitated the introduction of rotavirus vaccine in South Africa included the burden of rotavirus disease and strain surveillance, economic burden of rotavirus infection and clinical trials to assess the safety and efficacy of vaccine candidates. This paper reviews the epidemiology of rotavirus in South Africa, outlines some of the steps followed to introduce rotavirus vaccine in the EPI, and highlights the early positive impact of vaccination in reducing the rotavirus burden of disease based on the post-marketing surveillance studies at Dr George Mukhari hospital, a sentinel site at University of Limpopo teaching hospital in Pretoria, South Africa, which has conducted rotavirus surveillance for >20years. [Copyright &y& Elsevier]

Background: COVID-19 vaccines were rolled out in South Africa beginning in February 2021. In this study we retrospectively assessed the cost-effectiveness of the vaccination programme in its first two years of implementation., Method: We modelled the costs, expressed in 2021 US$, and health outcomes of the COVID-19 vaccination programme compared to a no vaccination programme scenario. The study was conducted from a public payer's perspective over two time-horizons - nine months (February to November 2021) and twenty-four months (February 2021 to January 2023). Health outcomes were estimated from a disease transmission model parameterised with data on COVID-19-related hospitalisations and deaths and were converted to disability adjusted life years (DALYs). Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to assess parameter uncertainty., Results: Incremental cost-effectiveness ratio (ICER) was estimated at US$1600 per DALY averted during the first study time horizon. The corresponding ICER for the second study period was estimated at US$1300 per DALY averted. When 85% of all excess deaths during these periods were included in the analysis, ICERs in the first and second study periods were estimated at US$1070 and US$660 per DALY averted, respectively. In the PSA, almost 100% of simulations fell below the estimated opportunity cost-based cost-effectiveness threshold for South Africa (US$2300 DALYs averted). COVID-19 vaccination programme cost per dose had the greatest impact on the ICERs., Conclusion: Our findings suggest that South Africa's COVID-19 vaccination programme represented good value for money in the first two years of rollout., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses., Methods: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age., Results: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively., Conclusions: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes., Clinicaltrials: gov registration of parent studies: NCT02943902 and NCT03330171., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 vaccination rates in South Africa remain low at 51% of the adult population being fully vaccinated, defined as having two shorts of the COVID-19 vaccine with or without a booster. To improve vaccine uptake, a community-based intervention was tested in a high vaccine hesitancy community in South Africa. Trained community youths used social media, face to face interactions, door to door and neighbourhood outreach activities to deliver the intervention., Methods: To assess if the intervention had an impact, data was collected before the intervention and after the intervention in two districts, Wentworth an intervention site and Newlands East a control site. Both districts are in KwaZulu Natal Province, South Africa. The following outcomes, changes on perceptions and knowledge about COVID-19, intention to get vaccinated for those who were not fully vaccinated and vaccination uptake were assessed using difference-in-difference methods applied through Augmented Inverse-Probability Weighting and contrasts of Potential Outcome Means (POM)., Results: One thousand, one hundred and fifty (1 150) participants agreed to take part in the study at baseline, and 916 (80%) were followed up after the 9-week intervention period. Intention to get vaccinated for COVID-19 was higher (difference-in-difference, DID 20%, 95% CI 6% - 35% higher), more people were fully vaccinated (DID 10%, 95% CI 0% - 20%) or partially vaccinated (DID 16%, 95% CI 6% - 26%) in Wentworth the intervention site compared to Newlands East, the control site. There were noticeable increases on the percentage of study participants indicating trust on the Government's COVID 19 programme, from 24% at baseline to 48% after the intervention in the intervention group than in the control group, 26% baseline and 29% at follow-up. There was a 10% (absolute) increase on the percentage of participants' saying they believed health care workers provided reliable information, 58% at baseline and 68% at follow-up in the intervention group, but there was little change in the control group 56% and 57% for baseline and follow-up respectively., Conclusion: The youth-led intervention implemented in Wentworth, a community with a high rate of vaccine hesitancy, was effective in increasing vaccination uptake. Given the low COVID-19 vaccine coverage in South Africa and across the African region, as well as the new emerging variant of concern (XBB 1.5), there is an urgent need to scale up such intervention at the community level to address persistent misinformation and promote vaccine equality., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths in 2021. New tuberculosis vaccines could play an important role in reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01 E vaccine candidate and BCG-revaccination. The potential population impact of these vaccines is unknown., Methods: We used an age-stratified transmission model of tuberculosis, calibrated to epidemiological data from South Africa, to estimate the potential health and economic impact of M72/AS01 E vaccination and BCG-revaccination. We simulated M72/AS01 E vaccination scenarios over the period 2030-2050 and BCG-revaccination scenarios over the period 2025-2050. We explored a range of product characteristics and delivery strategies. We calculated reductions in tuberculosis cases and deaths and costs and cost-effectiveness from health-system and societal perspectives., Findings: M72/AS01 E vaccination may have a larger impact than BCG-revaccination, averting approximately 80% more cases and deaths by 2050. Both vaccines were found to be cost-effective or cost saving (compared to no new vaccine) across a range of vaccine characteristics and delivery strategies from both the health system and societal perspective. The impact of M72/AS01 E is dependent on the assumed efficacy of the vaccine in uninfected individuals. Extending BCG-revaccination to HIV-infected individuals on ART increased health impact by approximately 15%, but increased health system costs by approximately 70%., Interpretation: Our results show that M72/AS01 E vaccination or BCG-revaccination could be cost-effective in South Africa. However, there is considerable uncertainty in the estimated impact and costs due to uncertainty in vaccine characteristics and the choice of delivery strategy., Funding: This work was funded by the Bill & Melinda Gates Foundation (INV-001754). This work used the Cirrus UK National Tier-2 HPC Service at EPCC (https://www.cirrus.ac.uk) funded by the University of Edinburgh and EPSRC (EP/P020267/1)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Financial support for this project was provided by Bill & Melinda Gates Foundation. If there are other authors, they 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Subunit vaccines for the Hepatitis B virus (HBV) have greatly reduced the prevalence of infection and morbidity through HBV-related liver cirrhosis and cancer. However, strength of immune response to vaccination varies considerably. While it is known that ABO blood types may influence HBV infection risk, the role of ABO and related blood types in strength of immune response to HBV vaccine has not been investigated. We examined 16 polymorphisms in the ABO, FUT2, and FUT3 genes and their related phenotypes for associations with strength of antibody response to HBV vaccine in Black South African infants. Anti-HBc and anti-HBs antibody levels were measured by CMIA assay 1-3 months after the last dose of HBV vaccine. Prior infection occurred in 8/207 individuals (3.86%) who were removed from further study. Of the remaining 199 individuals, 83.4% individuals were strong responders (anti-HBs ≥ 100 mIU/ml, median 973 mIU/ml), another 15.6% were weak responders (anti-HBs < 100 mIU/ml, median 50 mIU/ml) and 1% were non-responders (anti-HBs < 10 mIU/ml). The frequency of weak responders to HBV vaccine was not significantly affected by sex, birthweight, use of an additional booster dose of vaccine or cohort of origin. We characterised patterns of genetic variation present at the ABO, FUT2 and FUT3 loci by use of MassArray genotyping and used these data to predict ABO, Secretor and Lewis phenotypes. We observed significant association of ABO blood type with strength of antibody response to HBV vaccine in a Black South African cohort (p = 0.002). In particular, presence of rs8176747G and expression of B antigen (whether in B blood type or AB blood type) was associated with decreased antibody response to HBV vaccine. Secretor and Lewis blood types were not associated with antibody response to HBV vaccine. This work increases our understanding of the impact that host genetic variation may have on vaccine immunogenicity., 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 Elsevier Ltd. All rights reserved.)

The outbreak of the SARS-CoV-2 global pandemic heightened the pace of vaccine development with various vaccines being approved for human use in a span of 24 months. The SARS-CoV-2 trimeric spike (S) surface glycoprotein, which mediates viral entry by binding to ACE2, is a key target for vaccines and therapeutic antibodies. Plant biopharming is recognized for its scalability, speed, versatility, and low production costs and is an increasingly promising molecular pharming vaccine platform for human health. We developed Nicotiana benthamiana-produced SARS-CoV-2 virus-like particle (VLP) vaccine candidates displaying the S-protein of the Beta (B.1.351) variant of concern (VOC), which triggered cross-reactive neutralising antibodies against Delta (B.1.617.2) and Omicron (B.1.1.529) VOCs. In this study, immunogenicity of the VLPs (5 µg per dose) adjuvanted with three independent adjuvants i.e. oil-in-water based adjuvants SEPIVAC SWE TM (Seppic, France) and "AS IS" (Afrigen, South Africa) as well as a slow-release synthetic oligodeoxynucleotide (ODN) adjuvant designated NADA (Disease Control Africa, South Africa) were evaluated in New Zealand white rabbits and resulted in robust neutralising antibody responses after booster vaccination, ranging from 1:5341 to as high as 1:18204. Serum neutralising antibodies elicited by the Beta variant VLP vaccine also showed cross-neutralisation against the Delta and Omicron variants with neutralising titres ranging from 1:1702 and 1:971, respectively. Collectively, these data provide support for the development of a plant-produced VLP based candidate vaccine against SARS-CoV-2 based on circulating variants of concern., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Immunity gaps caused by COVID-19-related disruptions highlight the importance of catch-up vaccination. Number of countries offering vaccines in second year of life (2YL) has increased, but use of 2YL for catch-up vaccination has been variable. We assessed pre-pandemic use of 2YL for catch-up vaccination in three countries (Pakistan, the Philippines, and South Africa), based on existence of a 2YL platform (demonstrated by offering second dose of measles-containing vaccine (MCV2) in 2YL), proportion of card availability, and geographical variety., Methods: We conducted a secondary data analysis of immunization data from Demographic and Health Surveys (DHS) in Pakistan (2017-2018), the Philippines (2017), and South Africa (2016). We conducted time-to-event analyses for pentavalent vaccine (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenzae type b [Hib]) and MCV and calculated use of 2YL and MCV visits for catch-up vaccination., Results: Among 24-35-month-olds with documented dates, coverage of third dose of pentavalent vaccine increased in 2YL by 2%, 3%, and 1% in Pakistan, Philippines, and South Africa, respectively. MCV1 coverage increased in 2YL by 5% in Pakistan, 10% in the Philippines, and 3% in South Africa. In Pakistan, among 124 children eligible for catch-up vaccination of pentavalent vaccine at time of a documented MCV visit, 45% received a catch-up dose. In the Philippines, among 381 eligible children, 38% received a pentavalent dose during an MCV visit. In South Africa, 50 children were eligible for a pentavalent vaccine dose before their MCV1 visit, but only 20% received it; none with MCV2., Conclusion: Small to modest vaccine coverage improvements occurred in all three countries through catch-up vaccination in 2YL but many missed opportunities for vaccination continue to occur. Using the 2YL platform can increase coverage and close immunity gaps, but immunization programmes need to change policies, practices, and monitor catch-up vaccination to maximize the potential., 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 © 2022. Published by Elsevier Ltd.)

Objective: South Africa's infant Bacille Calmette Guerin (BCG) vaccine policy changed from percutaneous (PC) BCG Japan to intradermal (ID) BCG Denmark in 2000. This study investigated whether this change in infant BCG vaccination had any durable impact on TB incidence rates (IR) into adolescence., Methods: The Cape Town electronic TB register provided data (from 2008 to 2018) on HIV-negative TB patients born in 1991-1999 (BCG Japan cohort) and 2001-2008 (BCG Denmark cohort). Statistics South Africa provided population estimates. Annual TB IR per 100,000 population were calculated stratified by age, gender and birth year. Interrupted time series analysis with a segmented Poisson regression and birth cohort analyses were used to compare incidence between the BCG cohorts and trends over time., Findings: TB IR increased throughout adolescence, with 17-year-olds having 7.34 [95% confidence interval (CI), 6.48-8.32] times higher TB IR than 10-year-olds. Females had 1.22 [95% CI 1.17-1.27] higher IR than males. Overall, adolescents who received ID BCG Denmark had a lower TB IR compared to PC BCG Japan (rate ratio 0.86, [95% CI 0.80-0.94]). No interaction between BCG and age, nor BCG and gender were identified. Birth cohort analyses showed the increase in TB IR started around one year earlier in females than in males., Conclusion: The change in infant BCG policy was associated with a modest decrease in TB incidence in 10- to 17-year-old HIV-negative adolescents. However, TB incidence rapidly increased with age in both adolescent cohorts and remained high despite BCG vaccination at birth., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccination coverage remains suboptimal in many parts of the world, especially in low-and middle-income countries (LMICs), including South Africa. Vaccine hesitancy, a recognized factor contributing to low vaccination uptake in many parts of the world, is suspect in the suboptimal vaccination coverage level in South Africa, particularly in the Western Cape Province. We aimed to investigate vaccine hesitancy and to describe point-of-care vaccinators' perceptions of the drivers of vaccine hesitancy in the Cape Metropolitan District, South Africa (Cape Metro). We conducted in-depth interviews with 19 point-of-care vaccinators in 16 purposively selected healthcare facilities in the Cape Metro between September and November 2019. Participants were sampled purposively as 'rich cases' who had been delivering vaccination services for at least five years post-qualification. We organized the data thematically in ATLAS.ti and report findings thematically by the types of reasons participants reported for vaccine hesitancy amongst clients., Findings: Of the 19 interviewees, 11 (59%) reported having encountered vaccine-hesitant clients at some point in their careers. Reasons reported for vaccine hesitancy by clients included: (a) religion, (b) internet misinformation, (c) concern over causing the child pain, (d) natural immunity development, and (e) concern about possible adverse effect following immunization. Vaccine hesitancy in the Cape Metro cuts across all socio-economic classes. Also, some communities perceived to be vaccine-hesitant were mentioned by the participants in this study., Conclusions: Attitude towards vaccination are generally positive in the Cape Metro. However, vaccine hesitancy is present. The issues of vaccine hesitancy at the reported levels can still be mitigated by continuous health education in the clinics and communities, as well as stakeholder engagement as suggested by the point-of-care vaccinators in the Cape Metro., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Serogroup Y Neisseria meningitidis (NmY) is rare in China, and only serogroup A and C meningococcal polysaccharide vaccines (MPVs) are included in the national vaccination schedule. We describe a case of fulminant meningococcemia caused by NmY, which occurred in a pediatric patient (2 years old) for the first time in China, confirmed by culture. Although the boy was treated in time, the dry gangrene in his toes and fingers left him with severe sequelae. An NmY isolate was cultured from the blood of the patient, and showed decreased susceptibility to penicillin (minimum inhibitory concentration of 0.125 μg/ml), with sequence type (ST) 1655 assigned to clonal complex (cc) 23. Genomic analysis showed it was clustered with isolates from Italy, UK, Finland, and South Africa, sharing designation of Y:P1.5-1,10-1:F4-1:ST-1655(cc23). The emergence of NmY invasive meningococcal disease cases challenges local immunization strategy and warrants wider usage of MPV-ACYW if there is sustained circulation of NmY., 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 Elsevier Ltd. All rights reserved.)

The African Rotavirus Network organised the 12 th African Rotavirus Symposium (ARS) from 30 July to 1 August 2019 in Johannesburg, South Africa. The symposium theme "A decade of rotavirus vaccination in Africa - Saving lives and changing the face of diarrhoeal diseases", included sessions aimed at sharing ideas and expertise on prevention and control of diarrhoeal disease in Africa. Inter alia, the delegates reviewed global and regional epidemiological trends on rotavirus diarrhoea, progress and experiences on rotavirus vaccine introduction, including vaccine safety monitoring and impact in Africa, scientific advances in developing newer rotavirus vaccines, surveillance and research on other diarrhoeal pathogens, and providing an enabling environment for networking. Importantly, the 12 th ARS served to commemorate the 20 th anniversary of the African Rotavirus Network (AfrRN) coinciding with the 50th anniversary of the South African Medical Research Council. Four oral, live-attenuated rotavirus vaccines are currently prequalified by the WHO (Rotarix, RotaTeq, Rotavac and RotaSiil). African countries utilising rotavirus vaccines in routine national immunisation programmes are realising their effectiveness and impact on diarrhoeal disease morbidity. An ~40% reduction in hospitalisations of <5-year-olds with acute gastroenteritis following rotavirus vaccine introduction, was reported between 2006 and 2018 in 92,000 children from the WHO-coordinated African Rotavirus Surveillance Network (AfrRSN) comprising 33 Member States. This was corroborated by a meta-analysis of published data, sourced from January 2000 to August 2018 that reported substantial reductions in rotavirus hospitalisations in countries using rotavirus vaccines. However, it was highlighted that the transition of some countries from Gavi-eligibility and vaccine supply shortfalls present significant challenges to achieving the full impact of rotavirus immunization in Africa. The wide diversity of rotavirus genotypes continues in Africa, with variation observed both geographically and temporally. There is currently no evidence to suggest that the emergence of rotavirus strains not included in the current vaccines do escape vaccine-induced immunity., 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.)

Two HIV-1 vaccines (SAAVI DNA-C2 and SAAVI MVA-C) were previously developed in South Africa and tested in preclinical studies and Phase 1 clinical trials. Here we report on improvements made to the SAAVI MVA-C vaccine design which include: the use of different promoters for both the Gag and Env genes, replacement of the native Gag gene with an in silico designed subtype C mosaic Gag antigen which forms virus-like particles and the modification of Env by sequence changes to improve stability and transport to the cell surface. A head-to-head comparison of the newly conceived MVAGD5 candidate vaccine with SAAVI MVA-C showed increased in vitro expression of both Env and Gag, and superior immunogenicity in rabbits. MVAGD5 induced high levels of binding antibodies to Env and Tier 1A and 1B neutralizing antibodies, neither of which were induced by SAAVI MVA-C., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The recombinant MVA described in this paper is covered by a provisional patent “Recombinant MVA with Modified HIV-1 Env”, Patent Application Number PCT/IB2018/057731, filed on 4th October 2018 (GB 1716181.1 filed on 4 October 2017). The inventors are Anna-Lise Williamson, Edward Peter Rybicki, Michiel van Diepen, Nicola Jennifer Douglass and Rosamund Eira Chapman]. SHIP MVAGD5 is covered by a patent as described above., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months., Method: We employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination., Results: The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden., Conclusion: South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme., 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 © 2020. Published by Elsevier Ltd.)

Histo-blood group antigens are recognized by rotaviruses in a P- genotype dependent manner and their frequency in a population can influence fecal virus shedding. This study investigated the rate of fecal shedding of Rotarix vaccine and its association with HBGA phenotype distribution in South Africa. Stool and saliva specimens were collected from 150 infants attending immunization on the day of both first and second doses and 7 days later. Virus shedding was detected by real-time qPCR while HBGA phenotypes in saliva were determined by enzyme linked immunosorbent assay. Vaccine virus shedding was higher (23.6%) after the first dose than the second dose (4.7%). About 77% of virus-shedding infants were secretors (OR = 129; 95% CI, 6.088 - 2733), compared with none of non-virus shedding infants. Non-secretor status was significantly associated with low vaccine virus shedding while the likelihood of shedding was significantly higher in secretors., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries., Methods: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index., Results: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death., Conclusion: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups., 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 © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Toward the Global Vaccine Action Plan 2020 goal, almost 90% of countries have established a National Immunization Technical Advisory Group (NITAG). However, little is known about NITAG's contributions to governance., Methods: In 2017-2018, a two-step, qualitative retrospective study was conducted. Jordan (JO), Argentina (AR), and South Africa (SA) were selected owing to government-financed NITAGs from middle-income countries (MICs), geographic diversity, and a vaccine introduction with NITAG support. Country case studies were developed, collecting data through desk review and face-to-face key informant interviews (KIIs) from Ministry of Health (MoH) and NITAG. Case studies were analyzed together, to assess governance applying the European Observatory on Health Systems and Policies framework focusing on transparency, accountability, participation, integrity, and policy capacity (TAPIC)., Results: Document review and 53 KII (22 AR, 20 SA, 11 JO) showed NITAGs played a pivotal role as advisors promoting a culture of evidence-informed policies. NITAGs strengthened governance, although practices varied among countries. Meetings were conducted behind-closed-doors, participation restricted to members, only in one country agendas, and recommendations were public (AR). To increase participation, policy capacity, and transparency, countries considered adding experts in communications, advocacy, and economics. AR and SA contemplated including community members. NITAGs functioned autonomously from the government, with no established internal or external monitoring or supervision. NITAG meeting minutes allowed the review of integrity, adherence to terms of reference, standard operating procedures, and conflict of interest (CoI). For the most part, NITAGs abided by their mandates. Significant issues were related to the level of MoH support and oversight of CoI declaration and documentation., Conclusions: Systematically implementing governance approaches could improve processes, better tailor policies, and implementation. The long-term survival and resilience of NITAGs in these countries showed they play a significant role in strengthening governance. Lessons learned could be useful to those promoting country-driven evidence-informed decision-making., 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., (Published by Elsevier Ltd.)

Objective: To understand the predominant topics of discussion, stance and associated language used on social media platforms relating to maternal vaccines in 15 countries over a six-month period., Background: In 2019, the World Health Organisation prioritised vaccine hesitancy as a top ten global health threat and recognized the role of viral misinformation on social media as propagating vaccine hesitancy. Maternal vaccination offers the potential to improve maternal and child health, and to reduce the risk of severe morbidity and mortality in pregnancy. Understanding the topics of discussion, stance and language used around maternal vaccines on social media can inform public health bodies on how to combat vaccine misinformation and vaccine hesitancy., Methods: Social media data was extracted (Twitter, forums, blogs and comments) for six months from 15 countries (Australia, Brazil, Canada, France, Germany, India, Italy, Korea, Mexico, Panama, South Africa, Spain, United Kingdom and United States). We used stance, discourse and topic analysis to provide insight into the most frequent and weighted keywords, hashtags and themes of conversation within and across countries., Results: We exported a total of 19,192 social media posts in 16 languages obtained between 1st November 2018 and 30th April 2019. After screening all posts, 16,000 were included in analyses, while excluding retweets, 2,722 were annotated for sentiment. Main topics of discussion were the safety of the maternal influenza and pertussis vaccines. Discouraging posts were most common in Italy (44.9%), and the USA (30.8%)., Conclusion: The content and stance of maternal vaccination posts from November 2018 to April 2019 differed across countries, however specific topics of discussion were not limited to geographical location. These discussions included the promotion of vaccination, involvement of pregnant women in vaccine research, and the trust and transparency of institutions. Future research should examine the relationship between stance (promotional, neutral, ambiguous, discouraging) online and maternal vaccination uptake in the respective regions., 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., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: A key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination., Methods: We pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection., Results: For all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls., Conclusions: Our results provide robust support for further expansion of maternal influenza vaccination recommendations., Clinical Trials Registration: NCT01430689 and NCT01306669., 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 © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The University of the Free State - Next Generation Sequencing (NGS) Unit, Bloemfontein, South Africa, hosted a data and bioinformatics workshop from 19 to 22 June 2018. The workshop was coordinated by the African Enteric Viruses Genome Initiative (AEVGI) with support from the Bill & Melinda Gates Foundation. The event introduced technologies in NGS and data analysis with focus on the rotavirus (RV) genome. The workshop fostered interactions and networking between professionals, scientific experts, technicians and students. The courses provided an overview of RV diarrhoea and its burden in Africa, while highlighting the key resources and methodologies in NGS and advanced bioinformatics in deciphering vaccine impact. It was concluded that, despite the reported significant decline in RV associated-diarrhoea mortality and morbidity in Africa due to RV vaccine impact, the need for continuous surveillance and genomic characterization to better understand the ever-changing dynamics of RV strains is imperative., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013-2015., Methods: We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013-2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6-59 months; (ii) individuals aged 5-64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population., Results: During 2013-2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6-59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness., Conclusion: Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: Poor stock management has been identified as one of the causes of vaccine stock-outs in health facilities. This study assessed the occurrence of vaccine stock-outs and vaccine stock management practices in primary health care facilities in OR Tambo district of the Eastern Cape province, South Africa., Methods: Descriptive cross-sectional study design was used in this study to assess both the stock management practices and the availability of vaccines in the facilities. The study was conducted in 64 primary health care facilities across all sub-districts in OR Tambo. Data were collected using a questionnaire administered by the researcher, record checks and through observation. The occurrence of stock-outs of six tracer vaccines on the day of the visit and in the preceding 24 months were assessed. The data were captured into REDCap tool and analysed using STATA version 14., Results: Most standard stock management procedures were not adhered to, as these procedures were mostly handled by health care workers who either required formal training or refresher training on vaccine management. Cold chain capacity was not adequate and some vaccines were exposed to freezing. Both stock cards and the stock visibility solution (SVS) device were used in all the facilities for vaccine stock management. Less than half of the facilities visited 27 (44%) filled their stock cards regularly. Delays in receiving supplies from the pharmaceutical depot were commonly reported by facilities, which contributed to stock-outs. A total of 49 (77%) health facilities had at least one stockout for at least one vaccine on the day of the visit. Furthermore, BCG and OPV were the most affected vaccines in 37 (58%) and 28 (44%) of facilities, respectively., Conclusion: Interventions for improving vaccine availability should be considered, especially those targeting human resources and the entire stock management system., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: HIV-exposed uninfected (HEU) children have increased risk of infectious morbidity during early childhood. We evaluated the short-term immunogenicity and safety of single dose inactivated hepatitis-A virus (HAV) vaccine and live attenuated varicella zoster virus (VZV) vaccine in South African children., Methods: 195 HIV-unexposed and 64 HEU children received either one dose of HAV or VZV vaccine at 18 months of age. Blood samples were tested for hepatitis-A or VZV antibodies before and one month after vaccination by chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay, respectively. All children were evaluated for solicited adverse events (AEs)., Results: One-month post-vaccination, a similar percentage of HIV-unexposed (91.8%) and HEU (82.9%) children were seropositive for hepatitis-A (p = 0.144). VZV antibody geometric mean fold-rise was also similar in HIV-unexposed (5.6; 95%CI: 4.6-6.7) and HEU children (5.1; 95%CI: 3.7-7.2); however, only 44% HIV-unexposed and HEU seroconverted (titers > 50 mIU/ml). AEs occurred with similar frequency and severity between groups, except for more systemic AEs after VZV vaccination in HEU than HIV-unexposed children., Conclusions: Single dose HAV and VZV vaccine was similarly immunogenic in HIV-unexposed and HEU children. We did not identify differences in short-term humoral immunity after administration of either a live attenuated or inactivated vaccine. Seroconversion rates after a single dose of VZV vaccine were, however, lower compared to reports from previous studies (85-89%)., Clinical Trials Registration: NCT03330171., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Weinberg receives research grants from Merck and GSK. Moneys go to the University of Colorado. All other 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 © 2020 Elsevier Ltd. All rights reserved.)

Childhood immunization is one of the most effective health interventions, making it a key indicator of progress towards universal health coverage. In the last decade, improvements in coverage have been made globally, however, slow progress has been documented in sub-Saharan Africa with considerable subnational variations. We explore potential drivers of equitable immunization services based on subnational DTP3 coverage estimates. Using vaccine coverage at the 5 by 5 km area from 2000 to 2016, we quantify inequality using three measures. We assess the shortfall inequality which is the average deviation across subnational units from that with the highest coverage for each country. Secondly we estimate the threshold index, the proportion of children below a globally set subnational coverage target, and lastly, a Gini coefficient representing the within-country distribution of coverage. We use time series analyses to quantify associations with immunization expenditures controlling for country socio-economic and population characteristics. Development assistance, maternal education and governance were associated with reductions in inequality. Furthermore, high quality governance was associated with a stronger relationship between development assistance and reductions in inequality. Results from this analysis also indicate that countries with the lowest coverage suffer the highest inequalities. We highlight growing inequalities among countries which have met national coverage targets such as South Africa and Kenya. In 2016, values for the shortfall inequality ranged from 1% to 43%, the threshold index from 0% to 100% and Gini coefficient from 0.01 to 0.37. Burundi, Comoros, Eswatini, Lesotho, Namibia, Rwanda, and Sao Tome and Principe had the least shortfall inequality (<5%) while Angola, Ethiopia and Nigeria had values greater than 40%. A similar picture was noted for the other dimensions of inequality among these particular countries. Immunization program investments offer promise in addressing inequality, however, domestic mechanisms for resource implementation and accountability should be strengthened to maximize gains in coverage., 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 © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Due to limitations in standard culture methods, the impact of pneumococcal conjugate vaccine (PCV) immunization on nasopharyngeal bacterial carriage density is unclear, including among HIV-infected children., Methods: The prevalence and density of serotype/serogroup-specific pneumococcal and other nasopharyngeal colonizing bacteria were investigated in archived swabs of HIV-infected and HIV-uninfected, PCV-7 immunized (at 6, 10 and 14 weeks of age) South African children collected at 9 and 16 months of age. During the course of the study, PCV-immunization of children in Soweto was limited to study-participants, as the vaccine had not been introduced into the public immunization program., Results: At 9 months of age, the prevalence of overall pneumococcal colonization was lower in HIV-infected (58.6%) than HIV-uninfected children (69.9%, p = 0.02), mainly due to lower prevalence of non-vaccine-serotype colonization (27.8% vs. 40%, respectively; p = 0.047). The mean-log 10 density of pneumococcal colonization was, however, higher in HIV-infected (4.81 CFU/ml) than HIV-uninfected pneumococcal colonized children (4.44 CFU/ml; p = 0.014); mainly due to higher mean-log 10 density of PCV7-serotype colonization (4.21 vs. 3.72 CFU/ml; p = 0.014). No difference in the prevalence or density of overall pneumococci was found at 16 months of age. The prevalence of non-vaccine serotype colonization remained 1.7 fold higher in HIV-uninfected (60.4%) than HIV-infected children (50.9%, p = 0.049). Other differences included a lower prevalence of H. influenzae colonization in HIV-infected (42.3% and 56%) than HIV-uninfected children (64.2% and 73.4%) at both 9 and 16 months of age respectively; however, the density of colonization was similar., Conclusion: Increased carriage density of residual PCV7-serotypes might cause HIV-infected children to have a higher risk of pneumococcal disease. The higher carriage density observed in HIV-infected children could be attributed to a combination of factors, including HIV treatment and impaired host immunity. Additional studies are needed., 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 © 2019 Elsevier Ltd. All rights reserved.)

Background: The African Rotavirus Surveillance Network has been detecting and documenting rotavirus genotypes in the African sub-continent since 1998 in anticipation of the rollout of rotavirus vaccination in routine Expanded Programme on Immunisation. This paper reports distribution of the rotavirus strains circulating in 15 Eastern and Southern African (ESA) countries from 2010-2015 as part of active World Health Organization (WHO) rotavirus surveillance, and investigates possibility of emergence of non-vaccine or unusual strains in six selected countries post-vaccine introduction., Material and Methods: Stool samples were collected from children <5 years of age presenting with acute gastroenteritis at sentinel hospitals pre- and post-rotavirus vaccine introduction. Samples were tested for group A rotavirus using an enzyme immunoassay by the national and sentinel laboratories. At the WHO Rotavirus Regional Reference Laboratory in South Africa, molecular characterisation was determined by PAGE (n = 4186), G and P genotyping (n = 6447) and DNA sequencing for both G and P types (n = 400)., Results: The six-year surveillance period demonstrated that 23.8% of the strains were G1P[8], followed by G2P[4] (11.8%), G9P[8] (10.4%), G12P[8] (4.9%), G2P[6] (4.2%) and G3P[6] (3.7%) in 15 ESA countries. There was no difference in circulating strains pre- and post-rotavirus vaccine introduction with yearly fluctuation of strains observed over time. Atypical rotavirus G and P combinations (such as G1P[4], G2P[8], G9P[4] and G12P[4]) that might have arisen through inter-genogroup or inter-genotypes reassortment were detected at low frequency (2%). Close genetic relationship of African strains were reflected on the phylogenetic analysis, strains segregated together to form an African cluster in the same lineages/sub-lineage or monophyletic branch., Conclusion: There has been considerable concern about strain replacement post-vaccine introduction, it was not clear at this early stage whether observed cyclical changes of rotavirus strains were due to vaccine pressure or this was just part of natural annual fluctuations in the six ESA countries, long-term surveillance is required., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Due to intensified measles immunization efforts, measles mortality has decreased substantially worldwide, particularly in Sub-Saharan Africa (SSA). The World Health Organization (WHO) estimated a 92% decrease in measles-related deaths in the WHO AFRO region for the period 2000-2008. Recently, the AFRO region established a measles pre-elimination goal and experts have suggested engaging in a measles eradication campaign at the global level. However, recent large-scale outbreaks in many Sub-Saharan African countries present a challenge to measles control efforts. This paper examines measles immunization and the impact of measles supplemental immunization activities (SIAs) on routine immunization coverage in South Africa (SA)., Methods: We reported on immunization coverage trends in SA for the period 2001-2010 at the province and district levels. The data included routine immunization for 1st and 2nd doses of measles vaccine (MCV1, MCV2), SIAs, 1st dose of Bacille Calmette-Guérin vaccine, 1st and 3rd doses of oral polio vaccine (OPV1, OPV3), 3rd dose of Diphtheria-Tetanus-Pertussis-Haemophilus-influenzae-B vaccine (DTP-Hib3), and the number of under-one-year-olds having completed a primary course of immunization (Imm1). A regression model looked at the SIA impact on routine coverage., Results: Over the past decade, MCV1 and MCV2 coverage have increased nationally from 68% and 57% in 2001 to 95% and 83% in 2010, respectively. SIA coverage has remained at high levels, around 90%, over the same period. Substantial heterogeneity in MCV1 and MCV2 coverage is present across SA districts, with differences in coverage of 56% (MCV1) and 51% (MCV2) in 2010. In any given year, occurrence of SIAs was associated with a decrease in routine immunization coverage of MCV1, MCV2, OPV1, OPV3, DTP-Hib3, and Imm1, at the district level., Conclusions: The heterogeneity in measles vaccination coverage across SA districts challenges the goal of measles elimination in SA and SSA. The reduction in routine immunization coverage associated with the occurrence of SIAs raises the legitimate concern that SIAs may negatively impact health systems' functioning., (Copyright © 2012 Elsevier Ltd. All rights reserved.)