Vaccine In South Africa Research Articles

Modeling the potential public health impact of different vaccination strategies with an adapted vaccine in South Africa

ABSTRACT Background COVID-19 vaccines adapted to newly emerging circulating variants are necessary to better protect the population due to the evolving nature of the SARS-CoV-2 virus. Research Design and Methods The South African population was stratified by age and risk (defined by comorbidities such as diabetes, obesity, smoking, cancer, and asthma), and HIV status. The outcomes of different vaccination strategies based on age, risk, and HIV status were estimated using a Markov-decision tree model based on age-specific inputs derived from the literature and South African surveillance data. Results Vaccinating older adults and those with comorbidities was estimated to avert 111,179 infections 18,281 hospitalizations, and 3,868 deaths, resulting in savings of ZAR 1,260 million (USD 67 million) and ZAR 3,205 million (USD 170 million) in direct and indirect costs, respectively. Similar results were obtained when considering strategies targeting older adults and the HIV population. Expanding vaccination to 75% of the standard-risk population prevented more infections (401%), hospitalizations (167%), and deaths (67%) and increased the direct (232%) and indirect (455%) cost savings compared to the base case. Conclusions Implementing widespread vaccination strategies that utilize a vaccine adapted to the prevailing circulating variant in South Africa would result in significant public health and economic gains.

Mandatory Vaccinations at the Workplace during Covid-19 Times in South Africa: Lessons Learnt for Future Pandemics

The purpose of the study was to analyse mandatory vaccinations at the workplace during COVID-19 times in South Africa. COVID-19 was first identified in March 2020 in South Africa. The National State of Disaster was ended by the President on 4 April 2022. However, while economic activities were gradually opening to revive the economy, some employers had issued mandatory vaccinations to all their employees at their workplaces. This was regarded in some quarters as a violation of the rights of workers. This paper however argues that there was a misunderstanding on whether any law authorised these mandatory vaccinations. The study found that forcing employees to vaccinate against their will, despite World Health Organisation (WHO) ethical considerations against mandatory vaccinations, was a violation of their constitutional right to security in and control over their bodies. Furthermore, it found that this violation was not justifiable under the limitation clause. The paper concluded that no law clearly authorised employers to apply mandatory vaccinations at the workplace. The authors hope that employers learnt some lessons from the implementation of COVID-19 mandatory vaccinations. The paper recommends that mandatory vaccinations should not be applied for future pandemics at the workplace without basis or authority of law. The study further recommends that government must develop clear laws and guidelines to regulate mandatory vaccinations for future pandemics in the workplace. The paper exposes the weaknesses of mandatory vaccinations which were applied by employers to employees at their workplaces during COVID-19 times in South Africa. The paper contributes to the growing constitutional and legal discontent of mandatory vaccines in South Africa and beyond to guide governmental intervention in future pandemics as individual rights interface with general health safety. Keywords: COVID-19, Mandatory Vaccinations, Employees’ rights, Employers, National State of Disaster, Workplace, Lockdown.

The role of new hepatitis B vaccines in South Africa.

Vaccination is key to eliminating hepatitis B virus infection in South Africa (SA). Despite introducing immunisation in 1995, as part of the expanded programme of immunisation (EPI), hepatitis B virus infection remains endemic, and EPI vaccine coverage is incomplete. In addition to infants, non-immune adults at risk of infection through their occupation or with behavioural risk factors should receive vaccination. SA has many individuals with diabetes mellitus (a prevalence of almost 13%), obesity, HIV (8.45 million) or older age (5 million >60 years old), associated with a poorer vaccine response. Recently two new hepatitis B vaccines have been licensed: HEPLISAV-B includes an adjuvant that improves immunogenicity and has shown improved vaccine response in individuals with HIV, old age or diabetes mellitus. PreHevbrio, which includes three hepatitis B surface protein domains, instead of one, may also be more immunogenic, although clinical study data are still limited. These two novel vaccines have not yet been investigated in children and licensed in SA. Should HEPLISAV-B become available in SA, it may be particularly valuable to target high-risk groups in the country, such as people living with HIV, who show a poor response to the currently licensed vaccine.

Modelling the Cost-Effectiveness of Hepatitis A in South Africa.

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.

Examining healthcare worker willingness to promote COVID-19 vaccines in South Africa: the importance of a clear evidence base

Background Studies have shown that healthcare workers (HCWs) are considered trusted sources of coronavirus disease 2019 (COVID-19) information in their communities, ideally placing them as effective vaccine advocates. However, limited data exist on the role of HCWs in the promotion of vaccines, and whether they feel adequately equipped to fulfil this role. This study therefore aimed to determine the willingness of HCWs in promoting COVID-19 vaccines, how this correlated with their own vaccination behaviour and attitudes to alternative therapies, and whether they felt they had adequate knowledge and skills to communicate effectively with patients. Methods A mixed-methods design was adopted, involving an online web-based survey and in-depth interviews (IDIs). HCWs were recruited for the online survey from an integrated health system database in South Africa using voluntary response sampling, with follow-up qualitative interviews conducted with HCWs who indicated interest in participating in an interview. Univariate and multivariate logistical regression models were used to understand how demographic characteristics, HCW roles, vaccination status, attitudes and practices around alternative medications, and information on COVID-19 vaccines were related to the willingness of HCWs to recommend vaccination to their patients. Results Most of the survey sample were vaccinated (90.7%) and indicated that they would recommend vaccination (81.7%). However, a significant proportion of the sample (58.6%) felt that they did not have enough information on COVID-19 vaccines, while 59.8% felt that they required additional guidance on how to educate their patients on COVID-19 vaccines. Vaccinated HCWs were more likely to recommend vaccination (OR=10.63 [95% CI: 6.53-17.31]) than their unvaccinated counterparts. The qualitative results provide further insights into why HCWs were willing or unwilling to administer and promote vaccines, with three themes emerging: (i) HCWs’ belief in the value of vaccines and their promotion strategies; (ii) challenges facing HCWs in fulfilling their mandate of administering and promoting COVID-19 vaccination; and (iii) the rationale for HCWs discouraging vaccination and promoting alternative medicines for COVID-19 prevention and treatment. Conclusions This study posits that if HCWs are key to the success of national vaccination programmes, then they will need to be provided with clear, contextual, up-to-date information in order to enhance patient communication and vaccine uptake.

The Impact of SARS-CoV-2 Lineages (Variants) and COVID-19 Vaccination on the COVID-19 Epidemic in South Africa: Regression Study.

Emerging SARS-CoV-2 variants have been attributed to the occurrence of secondary, tertiary, quaternary, and quinary COVID-19 epidemic waves threatening vaccine efforts owing to their immune invasiveness. Since the importation of SARS-CoV-2 in South Africa, with the first reported COVID-19 case on March 5, 2020, South Africa has observed 5 consecutive COVID-19 epidemic waves. The evolution of SARS-CoV-2 has played a major role in the resurgence of COVID-19 epidemic waves in South Africa and across the globe. We aimed to conduct descriptive and inferential statistical analysis on South African COVID-19 epidemiological data to investigate the impact of SARS-CoV-2 lineages and COVID-19 vaccinations in South African COVID-19 epidemiology. The general methodology involved the collation and stratification, covariance, regression analysis, normalization, and comparative inferential statistical analysis through null hypothesis testing (paired 2-tailed t tests) of South African COVID-19 epidemiological data. The mean daily positive COVID-19 tests in South Africa's first, second, third, fourth, and fifth COVID-19 epidemic wave periods were 11.5% (SD 8.58%), 11.5% (SD 8.45%), 13.3% (SD 9.72%), 13.1% (SD 9.91%), and 14.3% (SD 8.49%), respectively. The COVID-19 transmission rate in the first and second COVID-19 epidemic waves in South Africa was similar, while the COVID-19 transmission rate was higher in the third, fourth, and fifth COVID-19 epidemic waves than in the aforementioned waves. Most COVID-19 hospitalized cases in South Africa were in the general ward (60%-79.1%). Patients with COVID-19 on oxygen were the second-largest admission status (11.2%-16.8%), followed by patients with COVID-19 in the intensive care unit (8.07%-16.7%). Most patients hospitalized owing to COVID-19 in South Africa's first, second, third, and fourth COVID-19 epidemic waves were aged between 40 and 49 years (16.8%-20.4%) and 50 and 59 years (19.8%-25.3%). Patients admitted to the hospital owing to COVID-19 in the age groups of 0 to 19 years were relatively low (1.98%-4.59%). In general, COVID-19 hospital admissions in South Africa for the age groups between 0 and 29 years increased after each consecutive COVID-19 epidemic wave, while for age groups between 30 and 79 years, hospital admissions decreased. Most COVID-19 hospitalization deaths in South Africa in the first, second, third, fourth, and fifth COVID-19 epidemic waves were in the ages of 50 to 59 years (15.8%-24.8%), 60 to 69 years (15.9%-29.5%), and 70 to 79 years (16.6%-20.7%). The relaxation of COVID-19 nonpharmaceutical intervention health policies in South Africa and the evolution of SARS-CoV-2 were associated with increased COVID-19 transmission and severity in the South African population. COVID-19 vaccination in South Africa was strongly associated with a decrease in COVID-19 hospitalization and severity in South Africa.

Hepatitis B Virus Immunity Gap: A Six-Year Laboratory Data Review of Hepatitis B Serological Profiles in Gauteng Province, South Africa.

In 1995, the hepatitis B vaccine in South Africa was incorporated into the childhood expanded programme of immunization. We report on immunity gaps of laboratory-based hepatitis B virus (HBV) among patients in public facilities in Gauteng Province from 1st January 2014 to 31st December 2019. Methodology. We analyzed HBV serological data extracted from the National Health Laboratory Services Central Data Warehouse (NHLS CDW). A descriptive analysis was performed for hepatitis B surface antigen (HBsAg), antibodies to HBV core (anti-HBc) total, anti-HBc IgM, and antibodies to HBV surface antigen (anti-HBs) according to annual distribution, age groups, and sex. The HBsAg positivity rate was 7.0% (75,596/1,095,561; p=0.001): 7.4% (96,532/944,077) in the 25 years and over age group and 4.0% (358/9,268 and 325/10,864) in the under 5 and 13-24 year age groups. The positivity rates of the other HBV serological markers were as follows: anti-HBc total was 37.0% (34,377/93,711; p < 0.001), anti-HBc IgM was 2.4% (5,661/239,237; p=0.05), and anti-HBs was 37.0% (76,302/206,138; p ≤ 0.001). Naturally acquired HBV immunity was detected in 25.7% (11,188/43,536) of patients in the 25 years and over age group, and 9.7% and 8.2% (113/1,158 and 541/6,522) among those under 5 years and 13-24 year age group, respectively (p < 0.001). Vaccine-induced immunity was 56.6% (656/1,158) in children under 5 years and 10.2% (4,425/43,536) among those 25 years and above (p < 0.001). Fifty-six percent (29,404/52,581) of patients were HBV seronegative; predominantly among patients in the 13-24 year age group (60.6%; (3,952/6,522)) and 25 years and over (56.3% (24,524/43,536)) (p=<0.001). The HBV infection seroprevalence remains high in South Africa, with Gauteng province having high intermediate endemicity. However, the HBV immunity gap has shifted from younger children to older children and adults.

The population impact of herpes simplex virus type 2 (HSV-2) vaccination on the incidence of HSV-2, HIV and genital ulcer disease in South Africa: a mathematical modelling study

Evidence suggests HSV-2 infection increases HIV acquisition risk and HIV/HSV-2 coinfection increases transmission risk of both infections. We analysed the potential impact of HSV-2 vaccination in South Africa, a high HIV/HSV-2 prevalence setting. We adapted a dynamic HIV transmission model for South Africa to incorporate HSV-2, including synergistic effects with HIV, to evaluate the impact of: (i) cohort vaccination of 9-year-olds with a prophylactic vaccine that reduces HSV-2 susceptibility; (ii) vaccination of symptomatically HSV-2-infected individuals with a therapeutic vaccine that reduces HSV shedding. An 80% efficacious prophylactic vaccine offering lifetime protection with 80% uptake could reduce HSV-2 and HIV incidence by 84.1% (95% Credibility Interval: 81.2-86.0) and 65.4% (56.5-71.6) after 40 years, respectively. This reduces to 57.4% (53.6-60.7) and 42.1% (34.1-48.1) if efficacy is 50%, 56.1% (53.4-58.3) and 41.5% (34.2-46.9) if uptake is 40%, and 29.4% (26.0-31.9) and 24.4% (19.0-28.7) if protection lasts 10 years. An 80% efficacious therapeutic vaccine offering lifetime protection with 40% coverage among symptomatic individuals could reduce HSV-2 and HIV incidence by 29.6% (21.8-40.9) and 26.4% (18.5-23.2) after 40 years, respectively. This reduces to 18.8% (13.7-26.4) and 16.9% (11.7-25.3) if efficacy is 50%, 9.7% (7.0-14.0) and 8.6% (5.8-13.4) if coverage is 20%, and 5.4% (3.8-8.0) and 5.5% (3.7-8.6) if protection lasts 2 years. Prophylactic and therapeutic vaccines offer promising approaches for reducing HSV-2 burden and could have important impact on HIV in South Africa and other high prevalence settings. WHO, NIAID.

Understanding COVID-19 Vaccine Hesitancy among Healthcare Workers in South Africa.

Healthcare workers (HCWs) were the first population group offered coronavirus disease 2019 (COVID-19) vaccines in South Africa because they were considered to be at higher risk of infection and required protecting as they were a critical resource to the health system. In some contexts, vaccine uptake among HCWs has been slow, with several studies citing persistent concerns about vaccine safety and effectiveness. This study aimed to determine vaccine uptake among HCWs in South Africa whilst identifying what drives vaccine hesitancy among HCWs. We adopted a multimethod approach, utilising both a survey and in-depth interviews amongst a sample of HCWs in South Africa. In a sample of 7763 HCWS, 89% were vaccinated, with hesitancy highest among younger HCWs, males, and those working in the private sector. Among those who were hesitant, consistent with the literature, HCWs raised concerns about the safety and effectiveness of the vaccine. Examining this further, our data revealed that safety and effectiveness concerns were formed due to first-hand witnessing of patients presenting with side-effects, concern over perceived lack of scientific rigor in developing the vaccine, confidence in the body's immune system to stave off serious illness, and both a general lack of information and distrust in the available sources of information. This study, through discursive narratives, provides evidence elucidating what drives safety and effectiveness concerns raised by HCWs. These concerns will need to be addressed if HCWs are to effectively communicate and influence public behaviour. HCWs are key role players in the national COVID-19 vaccination programme, making it critical for this workforce to be well trained, knowledgeable, and confident if they are going to improve the uptake of vaccines among the general population in South Africa, which currently remains suboptimal.

Re-emergence of Rift Valley fever: an update and preventive measures.

Re-emergence of Rift Valley fever: an update and preventive measures.

Feasibility of novel adult tuberculosis vaccination in South Africa: a cost-effectiveness and budget impact analysis

Early trials of novel vaccines against tuberculosis (TB) in adults have suggested substantial protection against TB. However, little is known about the feasibility and affordability of rolling out such vaccines in practice. We conducted expert interviews to identify plausible vaccination implementation strategies for the novel M72/AS01E vaccine candidate. The strategies were defined in terms of target population, coverage, vaccination schedule and delivery mode. We modelled these strategies to estimate long-term resource requirements and health benefits arising from vaccination over 2025–2050. We presented these to experts who excluded strategies that were deemed infeasible, and estimated cost-effectiveness and budget impact for each remaining strategy. The four strategies modelled combined target populations: either everyone aged 18–50, or all adults living with HIV, with delivery strategies: either a mass campaign followed by routine vaccination of 18-year olds, or two mass campaigns 10 years apart. Delivering two mass campaigns to all 18–50-year olds was found to be the most cost-effective strategy conferring the greatest net health benefit of 1.2 million DALYs averted having a probability of being cost-effective of 65–70%. This strategy required 38 million vaccine courses to be delivered at a cost of USD 507 million, reducing TB-related costs by USD 184 million while increasing ART costs by USD 79 million. A suitably designed adult TB vaccination programme built around novel TB vaccines is likely to be cost-effective and affordable given the resource and budget constraints in South Africa.

Electronic consent in a COVID-19 vaccine implementation trial in South Africa: Participant perspectives

The COVID-19 pandemic has warranted modifications to clinical research implementation to ensure adherence to public health and safety measures. Often, this modification has necessitated a deviation from the traditional face-to-face approach to an electronic or hybrid consent process. We assessed the acceptability and preference for electronic consent and explored understanding of the electronic consent information – an outcome which is vital in providing reassurance that consent is provided with full appreciation of the risks and benefits of study participation. In this descriptive study, healthcare professionals (HCPs) were invited, through a database of HCP contacts, snowball sampling and advertisement, to participate in an online survey between 14 July 2021 and 17 September 2021, to explore their experiences of providing electronic consent for enrolment into the largest implementation trial of a COVID vaccine in South Africa (SISONKE Trial). Descriptive analysis was used to characterise respondents and categorical data were expressed as frequencies. The prevalence of recurring responses to open-ended questions allowed for the identification of themes. A total of 1025 HCPs completed the online survey. Access to a COVID-19 vaccine was the strongest motivating factor for enrolment (82.3%) into the SISONKE Trial. Over a third of participants (38.6%) were not able to discuss the study with research staff. While the majority of participants (85.2%) indicated that online consent was acceptable, it was recognised that acceptability was context specific. Although 64% indicated awareness that reporting both a positive COVID test and adverse events were requirements, a significant percentage (32%) did not recall that the reporting period was 2 years. The electronic consent process was easily navigated by educated HCPs with access to electronic devices and data. Vaccine access was the most important motivation for participation, thus raising questions about how voluntary the consent process was and the role of desperation in deciding to participate. Significance: Navigation of the electronic consent process for participation in a COVID-19 vaccine implementation trial is not a challenge for educated healthcare professionals with access to electronic devices and data. However, technical skills and access to technology may impact the integrity of the informed consent process for lay research participants. Motivation to join research studies for access to scarce resources impacts negatively on the authenticity of the consent processes, as participation may be informed but not truly voluntary, and is an issue that ethics committees and researchers should address.

COVID-19 vaccine hesitancy in rural South Africa: Deepening understanding to increase uptake and access.

BackgroundTo date, COVID-19 vaccine coverage in the African region falls far too short of global goals. Increasing vaccination rates requires understanding barriers to vaccination so that effective interventions that sensitively and effectively address barriers to vaccination can be implemented.MethodsTo assess COVID-19 vaccination levels and identify major barriers to vaccine uptake we conducted a population-based, cross-sectional survey among 1662 adults 18 and older from August 25 to October 29 2021 in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area, Mpumalanga, South Africa.ResultsHalf of participants reported receiving a COVID-19 vaccine (50.4%) with 41.1% being fully vaccinated and 9.3% being partially vaccinated; 49.6% were unvaccinated. More women than men were vaccinated (55.5% vs 42.8%, P < 0.001), and older age groups were more likely to be vaccinated than younger age groups (P < 0.001). Among the unvaccinated, 69.0% planned to get vaccinated as soon as possible, while 14.7% reported definitely not wanting the vaccine. Major barriers to vaccination included lacking information on eligibility (12.3%) or where to get vaccinated (13.0%), concerns about side effects (12.5%), and inconvenient hours and locations for vaccination (11.0%). Confidence in the safety and efficacy of COVID-19 vaccines was higher among those vaccinated than unvaccinated (75.3% vs 51.2%, 75.8% vs 51.0%, both P < 0.001, respectively).ConclusionsIncreasing vaccination in South Africa beyond current levels will require a concerted effort to address concerns around vaccine safety and increase confidence in vaccine efficacy. Clarifying eligibility and ensuring access to vaccines at times and places that are convenient to younger populations, men, and other vulnerable groups is necessary.

Costs of seasonal influenza vaccination in South Africa.

BackgroundInfluenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010.MethodsWe adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country‐specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key‐informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs.ResultsTotal financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively.ConclusionWe adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost‐effectiveness analyses of seasonal influenza vaccination programmes.

Development of inactivated heartwater (Ehrlichia ruminantium) vaccine in South Africa

Heartwater, Ehrlichia ruminantium infection in cattle, sheep, goats, and some wild ruminants, is an economically important disease in Africa characterized by high mortality rates in susceptible populations. In South Africa, the current commercial heartwater vaccine is an infection and treatment type of immunization using virulent live E. ruminantium organisms generated from blood of infected sheep with subsequent treatment of the animals with antibiotics at specific times during the course of infection. This vaccine has several inherent problems preventing its wide use as the vaccine must be administered intravenously and it does not protect against all the South African field isolates. A vaccine based on inactivation of Zimbabwean E. ruminantium Mbizi strain organisms produced in endothelial cell cultures can be a sustainable option because it will not require antibiotic treatment and will be safe as there is no potential for reversion to virulence. Previous data generated in laboratory trials and under natural field setting provides support for this vaccine approach.Four inactivated vaccine formulations using the E. ruminantium Mbizi strain were tested for their efficacy in Merino sheep compared to an unvaccinated control group (11 sheep per group). Two vaccines were prepared by beta-propiolactone (BPL) inactivation, and two were inactivated with binary ethylenimine (BEI) while purification was done with both percoll and polyethylene glycol (PEG). The four vaccine preparations were formulated with Montanide ISA 50V2 adjuvant and administered twice subcutaneously (2 ml per dose) at an interval of 4 weeks. All groups were challenged with a virulent homologous cell-cultured E. ruminantium inoculated via the intra-venous route on day 56. The primary variable of efficacy was measured by the percentage survival rate or mortality between the Controls and Vaccine Groups.Three vaccine formulations (BEI/Percoll (Group 3), BEI/PEG (Group 4), BPL/Percoll, (Group 1) had a significantly higher percent of animal surviving challenge compared to the unvaccinated control (p-values 0.001, 0.035, 0.030, respectively). The highest number of survivors was obtained in Group 3 BEI/Percoll; 10/11 (91%). Groups 4 (BEI/PEG) and Group 1 (BPL/Percoll) produced similar percentage of survivals of 64%. In contrast, the lowest survival rate of 50% was observed in Group 2 (BPL/PEG) which was numerically different but not significantly different from the unvaccinated control which had an 18% survival rate (2/11).The inactivated vaccine using BEI or BPL as inactivating agents blended with ISA 50 adjuvant induced protective immunity against challenge. The BEI/Percoll (Group 3) vaccination regimen was most efficacious against a lethal heartwater challenge as it significantly protected sheep against mortality which is the most important aspect of heartwater infections. Future work should be directed towards improvement of this vaccine formulation especially from the down-stream processing point of view as the percoll method is not scalable for commercialization purposes.

Cost-Effectiveness of Bivalent, Quadrivalent, and Nonavalent HPV Vaccination in South Africa.

Background and ObjectivesIn South Africa, the prevalence of human papillomavirus (HPV) and associated diseases, such as cervical cancer and genital warts, is among the highest in the world. This study evaluates the cost-effectiveness of bivalent, quadrivalent, and nonavalent HPV vaccination for 9- to 14-year-old girls from the South African healthcare system perspective.MethodsA Markov model portraying the natural HPV disease progression from high-risk infection to cervical intraepithelial neoplasia (CIN) I, CIN II/III, or cervical cancer and from low-risk infection to genital warts was built. Transition probability, utility, and efficacy data were sourced from peer-reviewed literature. Vaccination costs were calculated based on the World Health Organization (WHO) guidelines. The model was populated with a cohort of 520,000 9-year-old girls to calculate incremental cost-effectiveness ratios (ICER) in South African Rand (R) per quality-adjusted life-years (QALYs) gained for each vaccination strategy.ResultsAll HPV vaccination strategies dominate the no vaccine strategy. Compared with the bivalent vaccine, the nonavalent strategy increases QALYs by 0.14 and costs by R1793 (ICER: R13,013 per QALY) per person, while the quadrivalent vaccination provides −0.02 incremental QALYs and R1748 costs (ICER: −R116,397 per QALY). Consequently, at the South African willingness-to-pay threshold of R23,630 per QALY, nonavalent vaccination is the preferred strategy, with a probability of 90.2%. Scenario analysis demonstrated that results are influenced by vaccine coverage, efficacy, and duration of efficacy.ConclusionsThe introduction of nonavalent for bivalent HPV vaccination is a cost-effective intervention in South Africa. HPV vaccination should be part of a multifaceted public health strategy entailing screening, condoms, and education of all stakeholders to reduce the significant burden of sexual transmitted diseases in South Africa. Sex-neutral and catch-up vaccinations are subjects for further research.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-022-01138-6.

Knowledge, attitude and practice of female university students regarding human papillomavirus and self-sampling in KwaZulu-Natal, South Africa: a cross-sectional survey

BackgroundHuman papillomavirus (HPV) infection remains a major cause of cervical cancer. Screening practice in South Africa has remained persistently low, with the invasiveness of pelvic examination as a major barrier to screening. This occasions the need to assess women’s knowledge, attitude, and practice regarding HPV testing and self-sampling.MethodThis is a cross-sectional quantitative study which enrolled 386 female students between the ages of 18 and 65 years at the University of KwaZulu-Natal, South Africa. Data was collected through a self-administered structured questionnaire, from February to March 2020. Data on participants’ socio-demographic characteristics, knowledge, attitudes and practices regarding HPV, HPV testing and self-sampling were obtained.ResultsOut of the 386 respondents, 30.6% were unaware that HPV can be transmitted through unprotected sex, only 25.1% knew about the availability of HPV vaccines in South Africa, 16.1% knew that the vaccines are accessible for free, while 79.0% were oblivious to the asymptomatic nature of HPV infection. Furthermore, a vast majority (95.8%) had never heard about self-sampling while only 1.0% had undergone HPV testing prior to this study. Although 52.9% knew that HPV testing could prevent cervical cancer, it did not positively impact screening practice. However, 57.7% of participants were willing to undergo future screening if allowed to self-sample.ConclusionSelf-sampling is a more acceptable means of sample collection compared to pelvic examination. Therefore, encouraging self-sampling and providing self-sampling kits will aid increased screening participation and address certain barriers associated with HPV testing. Awareness and educational campaigns about HPV and its causative relationship with cervical cancer will occasion better attitude towards screening participation.

Cost-effectiveness of routine adolescent vaccination with an M72/AS01E-like tuberculosis vaccine in South Africa and India

The M72/AS01E tuberculosis vaccine showed 50% (95%CI: 2–74%) efficacy in a phase 2B trial in preventing active pulmonary tuberculosis disease, but potential cost-effectiveness of adolescent immunisation is unknown. We estimated the impact and cost-effectiveness of six scenarios of routine adolescent M72/AS01E-like vaccination in South Africa and India. All scenarios suggested an M72/AS01E-like vaccine would be highly (94–100%) cost-effective in South Africa compared to a cost-effectiveness threshold of $2480/disability-adjusted life-year (DALY) averted. For India, a prevention of disease vaccine, effective irrespective of recipient’s M. tuberculosis infection status at time of administration, was also highly likely (92–100%) cost-effective at a threshold of $264/DALY averted; however, a prevention of disease vaccine, effective only if the recipient was already infected, had 0–6% probability of cost-effectiveness. In both settings, vaccinating 50% of 18 year-olds was similarly cost-effective to vaccinating 80% of 15 year-olds, and more cost-effective than vaccinating 80% of 10 year-olds. Vaccine trials should include adolescents to ensure vaccines can be delivered to this efficient-to-target population.

Allergic reactions to the Ad26.COV2.S vaccine in South Africa.

The Janssen-Ad26.COV2.S vaccine is authorized for use in several countries, with more than 30 million doses administered. Mild and severe allergic adverse events following immunization (AEFI) have been reported. We sought to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. A single dose of the Ad26.COV2.S vaccine was administered to 4,77,234 South African health care workers between February 17 and May 17, 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as "allergy." Anaphylaxis adjudication was performed using the Brighton Collaboration and National Institute of Allergy and Infectious Disease case definitions. Only 251 (0.052%) patients reported any allergic-type reaction (<1 in 2000), with 4 cases of adjudicated anaphylaxis (Brighton Collaboration level 1, n= 3) (prevalence of 8.4 per million doses). All anaphylaxis cases had a previous history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest nonanaphylatic reactions and included self-limiting, transient/localized rashes requiring no health care contact (n= 92) or isolated urticaria and/or angioedema (n= 70; median onset, 48 [interquartile range, 11.5-120] hours postvaccination) that necessitated health care contact (81%), antihistamine (63%), and/or systemic/topical corticosteroid (16%). All immediate (including adjudicated anaphylaxis) and most delayed AEFI (65 of 69) cases resolved completely. Allergic AEFI are rare following a single dose of Ad26.COV, with complete resolution in all cases of anaphylaxis. Although rare, isolated, delayed-onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.

Human Papillomavirus Vaccination in South Africa: Programmatic Challenges and Opportunities for Integration With Other Adolescent Health Services?

Compared to other regions of the world, sub-Saharan Africa has made limited progress in the implementation and performance of nationwide human papillomavirus (HPV) vaccination programmes. Without urgent intervention, this will serve to undermine cervical cancer elimination efforts in this region. The primary intent of this narrative review is to highlight the programmatic successes and challenges of the school-based HPV vaccination programme in South Africa since its inception in 2014, with the aim of contributing to the evidence base needed to accelerate implementation and improve programme performance in other sub-Saharan African countries. As of 2020, the proportion of adolescent girls aged 15 years who had received at least one dose of the HPV vaccine at any time between ages 9–14 years was 75%, while 61% had completed the full recommended two-dose schedule. This gives some indication of the reach of the South African HPV vaccination programme over the past 6 years. Despite this, vaccine coverage and dose completion rates have persistently followed a downward trend, slowing progress toward attaining global elimination targets. There is evidence suggesting that declining public demand for the HPV vaccine may be a result of weakening social mobilization over time, inadequate reminder and tracking systems, and vaccine hesitancy. Another concern is the disproportionate burden of HPV and HIV co-infections among adolescent girls and young women in South Africa, which predisposes them to early development of invasive cervical cancer. Moving forward, national policy makers and implementers will have to explore reforms to current age eligibility criteria and vaccine dose schedules, as well as implement strategies to support vaccine uptake among populations like out-of-school girls, girls attending private schools, and HIV positive young women. Additional opportunities to strengthen the South African HPV vaccination programme can be achieved by scaling up the co-delivery of other adolescent health services such as comprehensive sexual and reproductive health and rights education, deworming, and health screening. This calls for reinforcing implementation of the integrated school health policy and leveraging existing adolescent health programmes and initiatives in South Africa. Ultimately, establishing tailored, adolescent-centered, integrated health programmes will require guidance from further operational research.