The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

Public health opportunities resulting from sufficient HPV vaccine supply and a single-dose vaccination schedule.

Many countries with the highest burdens of cervical cancer have not yet offered human papillomavirus (HPV) vaccines to most of their age-eligible girls, who as adults also have limited or no access to effective cervical cancer screening or treatment. There are now 2 complementary developments that could make HPV vaccines more accessible and affordable: 1) the current and projected increases in HPV vaccine supply; and 2) the permissive recommendation for single-dose HPV vaccination schedules. This change in policy paired with the healthier HPV vaccine supply is an incredible opportunity to facilitate rapid access and expansion of HPV vaccination. Female adolescent vaccination including multiage cohorts must be prioritized. In the coming decades, this is the most cost-effective approach to avert millions of projected cervical cancer cases, which account for most HPV-related cancers globally.

The quest for more effective vaccine markets - Opportunities, challenges, and what has changed with the SARS-CoV-2 pandemic.

The past two decades have seen important progress in access to timely, reliable, affordable, and quality-assured supplies of vaccines of global public health importance. The new vaccines developed are powerful tools to fight killers such as pneumonia, diarrhea, and cervical cancer. Global and regional financing and pooled procurement haveshortened the lag between access in high- andlower-income countries. The COVID-19 pandemic has shown that by addressing shortcomings and seizing opportunities, we can do even more. In response to COVID-19, vaccine development and access shifted from a sequential, risk-averse paradigm to a rapid approach with maximum compression of time to market while ensuring quality. Vast public investments and innovative technologies were key facilitators. The pandemic has shown that governments play a crucial role in investing in new vaccines and manufacturing capacity and sharing risks with industry. Despite impressive progress, equity in access remains elusive with important moral, economic, and health-related consequences. Global leaders are working on a new International Treaty for Pandemic Prevention, Preparedness, and Response. To apply the lessons of COVID-19, that treaty should include a new paradigm for access to vaccines in which governments agree to:This would ensure that COVID-19 catalyzes a shift toward greater access for all under Immunization Agenda 2030.

Identifying people with deteriorating mental health using a mental state assessment.

Research indicates that approximately one in six people will experience a common mental health condition such as depression or anxiety, while people with severe mental illness commonly experience significant health inequalities. Nurses will come into frequent contact with people experiencing mental health issues in hospitals and in the community. Mental state assessment is a tool that enables nurses to develop an understanding of an individual's mental health that will be universally recognised across healthcare services. This article provides an outline of the various elements involved in a mental state assessment, so that clinicians such as non-mental health nurses can identify people experiencing deteriorating mental health.

HIV immunoprophylaxis: preparing the pathway from proof of concept to policy decision and use.

Various long-awaited efficacy studies of vaccines and broadly neutralising antibodies for prevention of HIV are now well underway in highly endemic settings. One broadly neutralising monoclonal antibody is being assessed for proof of concept, and combinations are in the pipeline. Two multicomponent prime-and-boost vaccine regimens are being evaluated, one of which is designed for global coverage. These multicomponent vaccines present a new level of complexity that will challenge health delivery systems. We recommend that while awaiting the results, which will appear in 2020-22, the target product profiles and full public value proposition for both categories of products should be defined, and the regulatory, policy, and implementation pathways should be prepared. Economic and health benefits, cost of goods, administrative complexity, and user perspectives will be key considerations for the roll-out of effective products. Investments in manufacturing capacity and public-sector delivery systems will be needed to prepare for product introduction and scale-up. We propose a prioritisation of activities on the basis of a broad stakeholder consultation organised by WHO and UNAIDS.

The impact of decentralising colposcopy services from tertiary-level to primary-level care in inner-city Johannesburg, South Africa: a before and after study.

OBJECTIVE: To assess whether decentralising colposcopy services to a primary care facility in inner-city Johannesburg, South Africa raises access to colposcopy. DESIGN: Before-after study comparing 2 years before and 2 years after decentralisation, using clinical records and laboratory data on cervical cytology and histology. PRIMARY OUTCOME: The proportion of all women attending Hillbrow Community Health Centre (HCHC) with an abnormal Papanikolaou (Pap) smear who had a colposcopy post-decentralisation. SETTING: Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) has provided colposcopy services for several decades. HCHC, located about 3 km away, began colposcopy services in 2014. PARTICIPANTS: Women, aged above 18 years, who had a colposcopy for diagnosis and treatment of precancerous cervical lesions following a Pap smear, from 2012 to 2016 at CMJAH or HCHC. RESULTS: Pre-decentralisation at CMJAH, 910 women had colposcopy (2012-2014). Post-decentralisation (2014-2016), 721 had colposcopy at CMJAH and 399 at HCHC, the decentralised facility. The number who had a Pap smear at HCHC and then a colposcopy rose threefold post-decentralisation (114 vs 350). Post-decentralisation, 43 women at HCHC were referred to CMJAH for colposcopy, compared with 114 pre-decentralisation. Post-decentralisation, 47.3% of women at CMJAH waited >6 months for colposcopy, while 35.5% did at HCHC (p<0.001). Across all three groups, 26.9%-30.3% of women had cervical intraepithelial neoplasia III lesions or carcinoma on colposcopy. The proportion of invalid specimens was similar at CMJAH and HCHC (1.8%-2.8%). Of 401 women who had an abnormal Pap smear at HCHC post-decentralisation, 267 had colposcopy (66.6%). CONCLUSION: Decentralisation can decrease the time to colposcopy and reduce the workload of tertiary hospitals. Overall, more women accessed services. Colposcopy coverage at HCHC is higher than other sites, but could be further improved. Decentralisation did not appear to undermine the quality of services and this model could be extended to similar settings in South Africa and elsewhere.

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.

BACKGROUND: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. METHODS: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. RESULTS: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). CONCLUSIONS: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Expanding global access to essential medicines: investment priorities for sustainably strengthening medical product regulatory systems.

Access to quality-assured medical products improves health and save lives. However, one third of the world's population lacks timely access to quality-assured medicines while estimates indicate that at least 10% of medicine in low- and middle-income countries (LMICs) are substandard or falsified (SF), costing approximately US$ 31 billion annually. National regulatory authorities are the key government institutions that promote access to quality-assured medicines and combat SF medical products but despite progress, regulatory capacity in LMICs is still insufficient. Continued and increased investment in regulatory system strengthening (RSS) is needed. We have therefore reviewed existing global normative documents and resources and engaged with our networks of global partners and stakeholders to identify three critical challenges being faced by NRAs in LMICs that are limiting access to medical products and impeding detection of and response to SF medicines. The challenges are; implementing value-added regulatory practices that best utilize available resources, a lack of timely access to new, quality medical products, and limited evidence-based data to support post-marketing regulatory actions. To address these challenges, we have identified seven focused strategies; advancing and leveraging convergence and reliance initiatives, institutionalizing sustainability, utilizing risk-based approaches for resource allocation, strengthening registration efficiency and timeliness, strengthening inspection capacity and effectiveness, developing and implementing risk-based post-marketing quality surveillance systems, and strengthening regulatory management of manufacturing variations. These proposed solutions are underpinned by 13 focused recommendations, which we believe, if financed, technically supported and implemented, will lead to stronger health system and as a consequence, positive health outcomes.

Estimating the Population Size of Female Sex Workers in Three South African Cities: Results and Recommendations From the 2013-2014 South Africa Health Monitoring Survey and Stakeholder Consensus.

BACKGROUND: Robust population size estimates of female sex workers and other key populations in South Africa face multiple methodological limitations, including inconsistencies in surveillance and programmatic indicators. This has, consequently, challenged the appropriate allocation of resources and benchmark-setting necessary to an effective HIV response. A 2013-2014 integrated biological and behavioral surveillance (IBBS) survey from South Africa showed alarmingly high HIV prevalence among female sex workers in South Africa's three largest cities of Johannesburg (71.8%), Cape Town (39.7%), and eThekwini (53.5%). The survey also included several multiplier-based population size estimation methods. OBJECTIVE: The objective of our study was to present the selected population size estimation methods used in an IBBS survey and the subsequent participatory process used to estimate the number of female sex workers in three South African cities. METHODS: In 2013-2014, we used respondent-driven sampling to recruit independent samples of female sex workers for IBBS surveys in Johannesburg, Cape Town, and eThekwini. We embedded multiple multiplier-based population size estimation methods into the survey, from which investigators calculated weighted estimates and ranges of population size estimates for each city's female sex worker population. Following data analysis, investigators consulted civil society stakeholders to present survey results and size estimates and facilitated stakeholder vetting of individual estimates to arrive at consensus point estimates with upper and lower plausibility bounds. RESULTS: In total, 764, 650, and 766 female sex workers participated in the survey in Johannesburg, Cape Town, and eThekwini, respectively. For size estimation, investigators calculated preliminary point estimates as the median of the multiple estimation methods embedded in the IBBS survey and presented these to a civil society-convened stakeholder group. Stakeholders vetted all estimates in light of other data points, including programmatic experience, ensuring inclusion only of plausible point estimates in median calculation. After vetting, stakeholders adopted three consensus point estimates with plausible ranges: Johannesburg 7697 (5000-10,895); Cape Town 6500 (4579-9000); eThekwini 9323 (4000-10,000). CONCLUSIONS: Using several population size estimates methods embedded in an IBBS survey and a participatory stakeholder consensus process, the South Africa Health Monitoring Survey produced female sex worker size estimates representing approximately 0.48%, 0.49%, and 0.77% of the adult female population in Johannesburg, Cape Town, and eThekwini, respectively. In data-sparse environments, stakeholder engagement and consensus is critical to vetting of multiple empirically based size estimates procedures to ensure adoption and utilization of data-informed size estimates for coordinated national and subnational benchmarking. It also has the potential to increase coherence in national and key population-specific HIV responses and to decrease the likelihood of duplicative and wasteful resource allocation. We recommend building cooperative and productive academic-civil society partnerships around estimates and other strategic information dissemination and sharing to facilitate the incorporation of additional data as it becomes available, as these additional data points may minimize the impact of the known and unknown biases inherent in any single, investigator-calculated method.

Model-estimated effectiveness of single dose 9-valent HPV vaccination for HIV-positive and HIV-negative females in South Africa.

BACKGROUND: Women in sub-Saharan Africa have high dual burden of HPV and HIV infections, which can interact to increase cervical cancer (CC) risk. The 9-valent HPV (9vHPV) vaccine has high demonstrated effectiveness against HPV types causing 90% of CC. Additionally, one dose of the 9vHPV vaccine has the potential to achieve greater coverage at lower costs than a two-dose schedule. However, the potential impact of single-dose 9vHPV vaccine accounting for HPV-HIV interactions has not been estimated. METHODS: We adapted a dynamic HIV transmission model to include HPV acquisition and CC pathogenesis and projected the impact of a single dose 9vHPV preadolescent vaccination in KwaZulu-Natal, South Africa. We report health impacts of HPV vaccination separately for HIV-positive women stratified by HIV treatment and CD4 count and HIV-negative women. RESULTS: At 90% coverage of females age 9 years with 80% lifelong vaccine efficacy, single dose HPV vaccination was projected to reduce CC incidence by 74% and mortality by 71% in the general female population at 70 years after the start of the vaccination program. Age-standardized CC incidence and mortality reductions were comparable among HIV-negative women, HIV-positive women, and HIV-positive women on ART. Health benefits were reduced when assuming waning protection at 10, 15 and 20 years after vaccination. DISCUSSION: Single dose 9vHPV vaccination is projected to avert substantial CC burden in South Africa and similar high HIV prevalence settings. Health benefits were comparable across all female subpopulations stratified by HIV status, CD4 count, and ART status.

Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?

Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. The WHO and UNAIDS have made PrEP implementation a priority for populations at highest risk, and several countries have developed guidelines and national plans accordingly, largely based on evidence generated by demonstration projects. PrEP presents the opportunity to change the face of HIV prevention by offering a new option for protection against HIV and disrupting current HIV prevention systems. Nevertheless, as with all new technologies, both practical and social requirements for implementation must be taken into account if there is to be sustained and widespread adoption, which will also apply to forthcoming prevention technologies. Defining and building success for PrEP within the scope of scale-up requires careful consideration. This review summarises where the PrEP field is today, lessons learned from the past, the philosophy and practicalities of how successful programming may be defined, and provides perspectives of costs and affordability. We argue that a successful PrEP programme is about effective intervention integration and ultimately keeping people HIV negative.

Advancing STI priorities in the SDG era: priorities for action.

The Sustainable Development Goals present an opportunity to reimagine and then reconfigure the approach to controlling sexually transmitted infections (STIs). The predilection of STIs for women and for vulnerable populations means that services that ameliorate STIs, by their nature, enhance equity, a key focus of the goals. Given the considerable breadth and depth of the goals, it is important to locate points of convergence between the SDGs and STIs, further craft synergies with HIV and select a few population groups and settings to prioritise. There are many opportunities for STI aficionados in this era to advance the field and global control of these infections.

HIV pre-exposure prophylaxis and early antiretroviral treatment among female sex workers in South Africa: Results from a prospective observational demonstration project.

BACKGROUND: Operational research is required to design delivery of pre-exposure prophylaxis (PrEP) and early antiretroviral treatment (ART). This paper presents the primary analysis of programmatic data, as well as demographic, behavioural, and clinical data, from the TAPS Demonstration Project, which offered both interventions to female sex workers (FSWs) at 2 urban clinic sites in South Africa. METHODS AND FINDINGS: The TAPS study was conducted between 30 March 2015 and 30 June 2017, with the enrolment period ending on 31 July 2016. TAPS was a prospective observational cohort study with 2 groups receiving interventions delivered in existing service settings: (1) PrEP as part of combination prevention for HIV-negative FSWs and (2) early ART for HIV-positive FSWs. The main outcome was programme retention at 12 months of follow-up. Of the 947 FSWs initially seen in clinic, 692 were HIV tested. HIV prevalence was 49%. Among those returning to clinic after HIV testing and clinical screening, 93% of the women who were HIV-negative were confirmed as clinically eligible for PrEP (n = 224/241), and 41% (n = 110/270) of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment. Of the remaining women who were HIV-positive, 93% were eligible for early ART (n = 148/160). From those eligible, 98% (n = 219/224) and 94% (n = 139/148) took up PrEP and early ART, respectively. At baseline, a substantial fraction of women had a steady partner, worked in brothels, and were born in Zimbabwe. Of those enrolled, 22% on PrEP (n = 49/219) and 60% on early ART (n = 83/139) were seen at 12 months; we observed high rates of loss to follow-up: 71% (n = 156/219) and 30% (n = 42/139) in the PrEP and early ART groups, respectively. Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days, with high levels of consistent condom use with clients and low use with steady partners in both study groups. There were no seroconversions on PrEP and 7 virological failures on early ART among women remaining in the study. Reported adherence to PrEP varied over time between 70% and 85%, whereas over 90% of participants reported taking pills daily while on early ART. Data on provider-side costs were also collected and analysed. The total cost of service delivery was approximately US$126 for PrEP and US$406 for early ART per person-year. The main limitations of this study include the lack of a control group, which was not included due to ethical considerations; clinical study requirements imposed when PrEP was not approved through the regulatory system, which could have affected uptake; and the timing of the implementation of a national sex worker HIV programme, which could have also affected uptake and retention. CONCLUSIONS: PrEP and early ART services can be implemented within FSW routine services in high prevalence, urban settings. We observed good uptake for both PrEP and early ART; however, retention rates for PrEP were low. Retention rates for early ART were similar to retention rates for the current standard of care. While the cost of the interventions was higher than previously published, there is potential for cost reduction at scale. The TAPS Demonstration Project results provided the basis for the first government PrEP and early ART guidelines and the rollout of the national sex worker HIV programme in South Africa.

Reducing health inequalities for people with serious mental illness.

People with serious mental illness (SMI) are at risk of dying many years earlier than the general population. Providing an effective, cost-efficient healthcare service requires a holistic approach, and improving the physical health of people with SMI should be integral to all healthcare roles. It is important for nurses to identify and understand the barriers that people with SMI may experience when accessing physical healthcare. A range of factors contribute to reduced life expectancy, including lifestyle factors, symptoms of mental illness and the side effects of medications. This article discusses four areas of health that commonly affect people with SMI: metabolic syndrome, smoking, oral health and sexual health. Metabolic syndrome is a cluster of risk factors that increase an individual's risk of cardiovascular disease, stroke and type 2 diabetes mellitus. Smoking is increasingly prevalent in people with SMI, with rates remaining steady despite a decline in smoking rates nationally. Oral health and sexual health can negatively affect the physical health and well-being of people with SMI; however, these aspects of health are often neglected. This article identifies ways that nurses in all practice settings can use health promotion, assessment and treatment to improve the physical health of people with SMI in relation to these four areas.

Pre-exposure rabies prophylaxis: a systematic review.

OBJECTIVE: To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings. METHODS: We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. FINDINGS: Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. CONCLUSION: Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

Growing inequities in maternal health in South Africa: a comparison of serial national household surveys.

BACKGROUND: Rates of maternal mortality and morbidity vary markedly, both between and within countries. Documenting these variations, in a very unequal society like South Africa, provides useful information to direct initiatives to improve services. The study describes inequalities over time in access to maternal health services in South Africa, and identifies differences in maternal health outcomes between population groups and across geographical areas. METHODS: Data were analysed from serial population-level household surveys that applied multistage-stratified sampling. Access to maternal health services and health outcomes in 2008 (n = 1121) were compared with those in 2012 (n = 1648). Differences between socio-economic quartiles were quantified using the relative (RII) and slope (SII) index of inequality, based on survey weights. RESULTS: High levels of inequalities were noted in most measures of service access in both 2008 and 2012. Inequalities between socio-economic quartiles worsened over time in antenatal clinic attendance, with overall coverage falling from 97.0 to 90.2 %. Nationally, skilled birth attendance remained about 95 %, with persistent high inequalities (SII = 0.11, RII = 1.12 in 2012). In 2012, having a doctor present at childbirth was higher than in 2008 (34.4 % versus 27.8 %), but inequalities worsened. Countrywide, levels of planned pregnancy declined from 44.6 % in 2008 to 34.7 % in 2012. The RII and SII rose over this period and in 2012, only 22.4 % of the poorest quartile had a planned pregnancy. HIV testing increased substantially by 2012, though remains low in groups with a high HIV prevalence, such as women in rural formal areas, and from Gauteng and Mpumalanga provinces. Marked deficiencies in service access were noted in the Eastern Cape ad North West provinces. CONCLUSIONS: Though some population-level improvements occurred in access to services, inequalities generally worsened. Low levels of planned pregnancy, antenatal clinic access and having a doctor present at childbirth among poor women are of most concern. Policy makers should carefully balance efforts to increase service access nationally, against the need for programs targeting underserved populations.