Vaccine In South Africa Research Articles

Risk factors associated with hospitalisation for influenza-associated severe acute respiratory illness in South Africa: A case-population study

BackgroundInfluenza is a common cause of severe respiratory illness, but risk factors for hospitalisation in low income settings with a high HIV prevalence are not well described. We aimed to assess risk factors associated with influenza-associated severe acute respiratory illness (SARI) hospitalisation in South Africa. MethodsWe conducted a case-population study using data on risk conditions in patients hospitalised with SARI and the national prevalence of these conditions. Data on hospitalised cases were from the national SARI surveillance program while data on the referent population were from the latest national census or health and demographic surveillance surveys. FindingsFrom 2009 to 2012, we identified 3646 (7.9%) of 46,031 enrolled cases of SARI that were associated with influenza infection. Risk factors associated with hospitalisation included previous history of smoking [case-population ratio (CPR) 3.82, 95% confidence interval (CI) 3.5–4.16], HIV infection (CPR 3.61, 95% CI 3.5–3.71), asthma (CPR 2.45, 95% CI 2.19–2.73), previous history of hospital admission in the past 12months (CPR 2.07, 95% CI 1.92–2.23), and tuberculosis (CPR 1.85, 95% CI 1.68–2.02). When stratified by age, there is increased risk of hospitalisation in those ⩽5yearsof age (CPR 3.07, 95% CI 2.93–3.21) and among those 35yearsof age and above (CPR 1.23, 95% CI 1.28–1.18). Male sex (CPR 0.85, 95% CI 0.82–0.88) and completion of pneumococcal conjugate vaccination schedule in children <5yearsof age (CPR 0.74, 95% CI 0.71–0.77) were associated with decreased risk of hospitalisation. ConclusionThese results identify groups at high-risk for severe influenza who should be considered potential targets for influenza vaccination in South Africa and similar settings.

Trivalent and quadrivalent influenza vaccination effectiveness in Australia and South Africa: results from a modelling study.

BackgroundA modelling study was conducted to determine the effectiveness of trivalent (TIV) and quadrivalent (QIV) vaccination in South Africa and Australia.ObjectivesThis study aimed to determine the potential benefits of alternative vaccination strategies which may depend on community‐specific demographic and health characteristics.MethodsTwo influenza A and two influenza B strains were simulated using individual‐based simulation models representing specific communities in South Africa and Australia over 11 years. Scenarios using TIV or QIV, with alternative prioritisation strategies and vaccine coverage levels, were evaluated using a country‐specific health outcomes process.ResultsIn South Africa, approximately 18% fewer deaths and hospitalisations would be expected to result from the use of QIV compared to TIV over the 11 modelled years (P = 0·031). In Australia, only 2% (P = 0·30) fewer deaths and hospitalisations would result. Vaccinating 2%, 5%, 15% or 20% of the population with TIV using a strategy of prioritising vulnerable age groups, including HIV‐positive individuals, resulted in reductions in hospitalisations and mortality of at least 7%, 18%, 57% and 66%, respectively, in both communities.ConclusionsThe degree to which QIV can reduce health burden compared to TIV is strongly dependent on the number of years in which the influenza B lineage in the TIV matches the circulating B lineages. Assuming a moderate level of B cross‐strain protection, TIV may be as effective as QIV. The choice of vaccination prioritisation has a greater impact than the QIV/TIV choice, with strategies targeting those most responsible for transmission being most effective.

The Case for Adolescent HIV Vaccination in South Africa: A Cost-Effectiveness Analysis.

Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness.The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective.The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values.School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective.

Evidence for shifting hepatitis B virus population epidemiology after nearly two decades of universal hepatitis B vaccination in South Africa

Background: The heptitis B vaccine has been part of the South African Expanded Programme on Immunization since April 1995 but its long-term impact remains unknown. Methods & Materials: This study tested 1206 sera collected frompatients aged1 to25years fromvarioushealth facilities across the country for HBV serologicalmakers andHBVDNA. Based on the year thevaccinewas introduced, sampleswere stratifiedbyage into preand post-vaccine introduction populations, which were then compared for evidence of immunity and chronic carriage using the chi-square test.WhereHIV statuswas known, subset analyseswere performed. Results: Immunity to HBV infection increased from 13.0% in the preto 57.0% in the post-vaccine introduction population (p<0.001). This decreased with increasing age within the postvaccine introduction population (76.1% for 1-5 year olds, 50.0% for 6-10 year olds and 46.3% for 11-16 year olds). In addition HBV chronic carriage was significantly (p=0.003) reduced in the post(1.4%) compared to the pre-vaccine introduction population (4.2%) but increased with increasing age (0.5% in 1-5 year olds, 1.3% in 6-10 year olds and 2.2% in 11-16 year olds). The difference in prevalence of activeHBV infection in the serologically exposed preversus post-vaccine introduction populations was not statistically significant. Subset analyses showed that evidence of immunitywas significantly (p<0.001) higher in the HIV negative compared to the HIV positive subset in both populations. Conclusion: Universal hepatitis B vaccination has been a remarkable success, with a significant increase in immunity to HBV infection. The observation that HBV chronic carriage increases as immunitywanes over time calls into questionwhether the timehas come to consider a pre-adolescence vaccine booster dose policy.

Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa

The hepatitis B vaccine has been part of the South African Expanded Program on Immunization since April 1995 but its long-term impact remains unknown. This study tested 1,206 sera collected from patients aged 1-25 years from various health facilities across the country for HBV serological markers and HBV DNA. Based on the year the vaccine was introduced, samples were stratified by age into pre- and post-vaccine introduction populations, which were then compared for evidence of immunity and chronic carriage using the Chi-square test. Where HIV status was known, subset analyses were performed. Immunity to HBV infection increased from 13.0% in the pre- to 57.0% in the post-vaccine introduction population (P < 0.001). This decreased with increasing age within the post-vaccine introduction population (76.1% for 1-5 years, 50.0% for 6-10 years, and 46.3% for 11-16 years). In addition, HBV chronic carriage was significantly (P = 0.003) reduced in the post- (1.4%) compared to the pre-vaccine introduction population (4.2%). The difference in prevalence of active HBV infection in the serologically exposed pre- and post-vaccine introduction populations was not statistically significant. Subset analyses showed that evidence of immunity was significantly (P < 0.001) higher in the HIV negative compared to the HIV positive subset in both populations. Universal hepatitis B vaccination has been a remarkable success, with a significant increase in immunity to HBV infection. The observation that HBV chronic carriage increases as immunity wanes over time calls into question whether the time has come to consider a pre-adolescence vaccine booster dose policy.

Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study

The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18-35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13-2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2-9·5] for vaccine recipients vs 8·8% [7·1-10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council.

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa

BackgroundIn low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide–protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa. Methods and findingsWe developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30–54% of infant GBS cases compared to doing nothing. For vaccine prices between $10 and $30, and mid-range efficacy, its cost ranges from $676 to $2390 per disability-adjusted life-year (DALY) averted ($US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of $240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of $664–2128/DALY. ConclusionsVaccination would substantially reduce the burden of infant GBS disease in South Africa and would be very cost-effective by WHO guidelines. RFB-IAP is also very cost-effective, but prevents only 10% of cases. Vaccination plus RFB-IAP is more effective and more costly than vaccination alone, and consistently very cost-effective.

Global Evidence Reaffirms the Case for Routine HPV and Potential HIV Adolescent Vaccination in South Africa

ABSTRACT: The availability of two prophylactic HPV vaccines, coupled with a potential prophylactic HIV vaccine delivered to adolescents through a school-based sexual and reproductive health platform represents a potentially significant, potent long-term primary prevention strategy against two sexually transmitted infections: HPV and HIV infection within a highly susceptible group. South Africa has earmarked the re-engineering of school health services. This initiative ensures a ‘health presence in every school’ focused on developing a social, sexual and reproductive health platform within secondary schools addressing HIV/AIDS prevention, teenage pregnancies and social concerns such as drug abuse. Despite this opportunistic platform for HIV and HPV vaccines introduction among adolescents, much work remains to overcome existing ethical and financial and programmatic barriers.

Potential Cost-Effectiveness of a New Infant Tuberculosis Vaccine in South Africa - Implications for Clinical Trials: A Decision Analysis

Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical development. This study seeks to estimate the potential cost-effectiveness of a BCG booster vaccine, while accounting for costs of large-scale clinical trials, using the MVA85A vaccine as a case study for estimating potential costs. We conducted a decision analysis from the societal perspective, using a 10-year time frame and a 3% discount rate. We predicted active tuberculosis cases and tuberculosis-related costs for a hypothetical cohort of 960,763 South African newborns (total born in 2009). We compared neonatal vaccination with bacille Calmette-Guérin alone to vaccination with bacille Calmette-Guérin plus a booster vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to 70%, relative to bacille Calmette-Guérin alone. We accounted for the costs of Phase III clinical trials. The booster vaccine was assumed to prevent progression to active tuberculosis after childhood infection, with protection decreasing linearly over 10 years. Trial costs were prorated to South Africa's global share of bacille Calmette-Guérin vaccination. Vaccination with bacille Calmette-Guérin alone resulted in estimated tuberculosis-related costs of $89.91 million 2012 USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years. Addition of the booster resulted in estimated cost savings of $7.69–$16.68 million USD, and 2,800–4,160 cases averted, for assumed efficacy values ranging from 40%–70%. A booster tuberculosis vaccine in infancy may result in net societal cost savings as well as fewer active tuberculosis cases, even if efficacy is relatively modest and large scale Phase III studies are required.

Distinct T-Cell Responses When BCG Vaccination Is Delayed From Birth to 6 Weeks of Age in Ugandan Infants

In Uganda, the tuberculosis vaccine BCG is administered on the first day of life. Infants delivered at home receive BCG vaccine at their first healthcare facility visit at 6 weeks of age. Our aim was to determine the effect of this delay in BCG vaccination on the induced immune response. We assessed CD4(+) and CD8(+) T-cell responses with a 12-hour whole-blood intracellular cytokine/cytotoxic marker assay, and with a 6-day proliferation assay. We enrolled 92 infants: 50 had received BCG vaccine at birth and 42 at 6 weeks of age. Birth vaccination was associated with (1) greater induction of CD4(+) and CD8(+) T cells expressing either interferon γ (IFN-γ) alone or IFN-γ together with perforin and (2) induction of proliferating cells that had greater capacity to produce IFN-γ, tumor necrosis factor α (TNF-α), and interleukin 2 together, compared with delayed vaccination. Distinct patterns of T-cell induction occurred when BCG vaccine was given at birth and at 6 weeks of age. We propose that this diversity might impact protection against tuberculosis. Our results differ from those of studies of delayed BCG vaccination in South Africa and the Gambia, suggesting that geographical and population heterogeneity may affect the BCG vaccine-induced T-cell response.

Does participation in an HIV vaccine efficacy trial affect risk behaviour in South Africa?

BackgroundIncreased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. Methods801 participants were enrolled. Risk behaviours were assessed with an interviewer-administered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. ResultsA decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p<0.0001 for each). Men (22%) were more likely than women (14%) to report behaviour change after unblinding (p=0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p<0.0001), and attributed this to receiving the vaccine. ConclusionWe did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.

Knowledge and awareness of human papillomavirus and intention with regard to human papillomavirus vaccine uptake by female tertiary students in the Eastern Cape province

In 2008, two human papillomavirus (HPV) vaccines, Cervarix ® and Gardasil ® , were licensed for use in South Africa. Initial models showed that vaccination could lead to an approximate 70% decline in cervical cancer cases. This paper describes the knowledge, awareness and health beliefs about HPV and the HPV vaccine, and the intentions of female tertiary students with respect of being vaccinated with the latter. An observational, descriptive and analytical cross-sectional survey was conducted among 150 female tertiary students at a university in the Eastern Cape province in this regard. Knowledge and awareness of HPV and the HPV vaccine were poor. Only 22.7% of the students were aware of HPV and that an HPV vaccine was available in South Africa. However, most respondents (80%) reported a willingness to be vaccinated. Being aware of the existence of a Papanicolaou smear, higher knowledge of HPV, higher perceived vaccine effectiveness and higher perceived severity of HPV infection were significantly associated with increased willingness to be vaccinated. There is a need for education on HPV and its vaccination in South Africa. An effective vaccine marketing strategy should emphasise the effectiveness of the vaccine, the susceptibility of women to contracting HPV and the severity of being infected with the human immunodeficiency virus.

Sequence-based in silico analysis of well studied Hepatitis C Virus epitopes and their variants in other genotypes (particularly genotype 5a) against South African human leukocyte antigen backgrounds

BackgroundHost genetics influence the outcome of HCV disease. HCV is also highly mutable and escapes host immunity. HCV genotypes are geographically distributed and HCV subtypes have been shown to have distinct repertoires of HLA-restricted viral epitopes which explains the lack of cross protection across genotypes observed in some studies. Despite this, immune databases and putative epitope vaccines concentrate almost exclusively on HCV genotype 1 class I-epitopes restricted by the HLA-A*02 allele. While both genotype and allele predominate in developed countries, we hypothesise that HCV variation and population genetics will affect the efficacy of proposed epitope vaccines in South Africa. This in silico study investigates HCV viral variability within well-studied epitopes identified in genotype 1 and uses algorithms to predict the immunogenicity of their variants from other less studied genotypes and thus rate the most promising vaccine candidates for the South African population. Six class I- and seven class II- restricted epitope sequences within the core, NS3, NS4B and NS5B regions were compared across the six HCV genotypes using local genotype 5a sequence data together with global data. Common HLA alleles in the South African population are A30:01, A02:01, B58:02, B07:02; DRB1*13:01 and DRB1*03:01. Epitope binding to 13 class I- and 8 class –II alleles were described using web-based prediction servers, Immune Epitope Database, (IEDB) and Propred. Online population coverage tools were used to assess vaccine efficacy.ResultsDespite the homogeneity of genotype 1 and genotype 5 over the epitopes, there was limited promiscuity to local HLA-alleles.Host differences will make a putative vaccine less effective in South Africa. Of the 6 well-characterized class I- epitopes, only 2 class I- epitopes were promiscuous and 3 of the 7 class-II epitopes were better conserved and promiscuous. By fine tuning the putative vaccine using an optimal cocktail of genotype 1 and 5a epitopes and local HLA data, the coverage was raised from 65.85% to 91.87% in South African Blacks.ConclusionWhile in vivo and in vitro studies are needed to confirm immunogenic epitopes, in silico HCV epitope vaccine design which takes into account HCV variation and host allele frequency will maximize population coverage in different ethnic groups.

Key issues in the clinical development and implementation of TB vaccines in South Africa

Significant progress has been made in advancing the development pipeline for a new and more effective TB vaccine with some candidate vaccines now in late stage clinical evaluation. However, progress has been hampered by an incomplete understanding of the components of a protective immune response and limited animal models, rendering the field unable to reliably predict vaccine efficacy earlier in preclinical development, including by evaluation in animal models, and limiting the predictive utility of comparing immunogenic effects across vaccine candidates in phase I/II studies. Consequently, new candidate vaccines have to be evaluated for efficacy in large-scale phase II/III trials using clinical endpoints. Apart from the technical challenges of characterising TB incidence in target populations at high risk of acquiring TB disease and standardising case definitions in order to improve both the sensitivity and more importantly the specificity of trial endpoints, there is an urgency in expanding and supporting the considerable trial infrastructure that will be required to evaluate and ultimately license a new TB vaccine. In the longer term, implementation strategies are dependent on what policy makers most value. Economic analyses will be essential to guide policy and implementation. This paper outlines the gaps and challenges and identifies solutions for effectively developing and efficiently introducing a new TB vaccine.

Serotype and antimicrobial profile distribution of invasive pneumococcal isolates in the pre-vaccine introduction era in Pretoria, South Africa, 2005 through 2009

A description of invasive Streptococcus pneumoniae isolates over a 5-year period from blood culture and cerebrospinal fluid culture follows, in Pretoria South Africa January 2005 through December 2009. Isolates were identified using standard microbiological techniques, serotyped, and a MIC determined for penicillin and cefotaxime. A total of 177 isolates were included in the analysis. Eighty percent of patients in the 18- to 45-year age group tested positive for HIV. In children <5 years of age, 66% (n = 49) of serotypes were those present in the heptavalent pneumococcal conjugate vaccine (PCV-7). Fifty-nine percent (n = 29) were from PCV-7 serotypes in the <1-year-old age group. An additional peak of invasive disease was also seen in the 18- to 45-year age group. Only 1 of 177 isolates had resistance to penicillin (MIC ≥2 μg/mL); none was resistant to cefotaxime. The introduction of the PCV-7 vaccine in South Africa will decrease invasive pneumococcal disease caused by vaccine serotypes.

A Relative Standard for Minimal Risk is Unnecessary and Potentially Harmful to Children: Lessons from the Phambili Trial

This commentary discusses the Phambili trial and whether or not it is ethical to enroll 16- and 17-year old adolescents into the ongoing study of an HIV vaccine in South Africa. It provides a background and an ethical analysis on the vaccine trial. It recommends that adolescent subjects should not be included in the Phambili (HVTN 503) study until after the interim efficacy analysis and a decision to permit adolescent enrollment would require a trend in favor of the experimental HIV vaccine at the interim efficacy analysis.

Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study

The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C. We did a phase 2b double-blind, randomised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa. Randomisation was by a computer-generated random number sequence. The vaccine and placebo were given by intramuscular injection on a 0, 1, 6 month schedule. Our coprimary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint. These endpoints were assessed independently in the modified intention-to-treat (MITT) cohort with two-tailed significance tests stratified by sex. We assessed immunogenicity by interferon-γ ELISPOT in peripheral-blood mononuclear cells. After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study, enrolment and vaccination in our study was halted, treatment allocations were unmasked, and follow-up continued. This study is registered with the South Africa National Health Research Database, number DOH-27-0207-1539, and ClinicalTrials.gov, number NCT00413725. 801 of a scheduled 3000 participants, of whom 360 (45%) were women, were randomly assigned to receive either vaccine or placebo. 445 participants (56%) had adenovirus serotype 5 (Ad5) titres greater than 200, and 129 men (29%) were circumcised. 34 MITT participants in the vaccine group were diagnosed with HIV-1 (incidence rate 4·54 per 100 person-years) and 28 in the placebo group (3·70 per 100 person-years). There was no evidence of vaccine efficacy; the hazard ratio adjusted for sex was 1·25 (95% CI 0·76-2·05). Vaccine efficacy did not differ by Ad5 titre, sex, age, herpes simplex virus type 2 status, or circumcision. The geometric mean viral-load setpoint was 20,483 copies per mL (n=33) in the vaccine group and 34,032 copies per mL (n=28) in the placebo group (p=0·39). The vaccine elicited interferon-γ-secreting T cells that recognised both clade B (89%) and C (77%) antigens. The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine. The US National Institute of Allergy and Infectious Disease and Merck and Co Inc.

Accounting for the full benefits of childhood vaccination in South Africa.

While remarkable gains in health have been achieved since the mid-20th century, they have been unequally distributed, and mortality and morbidity burdens in some regions remain enormous. Of the almost 10 million children under 5 years of age who died in 2006, only 100 000 died in industrialised countries, while 4.8 million died in sub-Saharan Africa. In deciding whether to finance an intervention to improve population health, policy makers commonly weigh the expected population health gains against the costs of the intervention. Most vaccinations included in national immunisation schedules, such as measles vaccination, are both effective in preventing ill health and relatively inexpensive. Newer vaccinations, such as those with pneumococcal conjugate vaccine (PCV) or rotavirus vaccine, can effectively prevent child mortality and morbidity but are expensive relative to the vaccinations currently included in national immunisation schedules. Policy makers may therefore decide that - at current prices - the comparison of health gains with costs does not justify the free public provision of these vaccinations. We argue that in addition to the health benefits of vaccinations, their effects on education and income and their benefits for unvaccinated community members can be considerable and should therefore be included in calculations to establish the value of vaccinations.

Preparing for HPV vaccination in South Africa: Key challenges and opinions

This article reports on qualitative research investigating key challenges and barriers towards human papillomavirus (HPV) vaccine introduction in the Western Cape Province, South Africa. A total of 50 in-depth interviews and 6 focus groups were conducted at policy, health service and community levels of enquiry. Respondents expressed overall support for the HPV vaccine, underscored by difficulties associated with the current cervical screening programmes and the burgeoning HIV/AIDS epidemic in South Africa. Overall poor community knowledge of cervical cancer and the causal relationship between HPV and cervical cancer suggests the need for continued education around the importance of regular cervical screening. The optimal target populations for HPV vaccination was influenced by the perceived median age of sexual activity in South African girls (9–15 years), with an underlying concern that high levels of sexual abuse had significantly decreased the age of sexual exposure suggesting vaccination should commence as early as 9 years. Vaccination through schools with the involvement of other stakeholders such as sexual and reproductive health and the advanced programme on immunization (EPI) were suggested. Opposition to the HPV vaccine was not anticipated if the vaccine was marketed as preventing cervical cancer rather than a sexually transmitted infection. The findings assist in identifying potential barriers and facilitating factors towards HPV vaccines and will inform the development of policy and programs to support HPV vaccination introduction in South Africa and other African countries.

The potential effect of an HIV/AIDS vaccine in South Africa

This paper presents a model for assessing the potential effect of an HIV/AIDS vaccine in South Africa, and for calculating the amount of vaccine that would be required. A number of different hypothetical vaccine profiles and vaccine distribution strategies are considered. Results suggest that a sterilising vaccine could reduce the HIV incidence between 2015 and 2025 by up to 50%, while a disease-modifying vaccine would be unlikely to reduce HIV incidence by more than a third. The effect on AIDS mortality over the same period would be substantially smaller, and it is unlikely that any preventive vaccine would reduce AIDS mortality by more than 10% between 2015 and 2025. Keywords: HIV/AIDS; vaccine; model; South Africa South African Acturial Journal Vol. 7 2007: pp. 49-72