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Tens of thousands of people die from dog-mediated rabies annually. Deaths can be prevented through post-exposure prophylaxis for people who have been bitten, and the disease eliminated through dog vaccination. Current post-exposure prophylaxis use saves many lives, but availability remains poor in many rabies-endemic countries due to high costs, poor access, and supply. We developed epidemiological and economic models to investigate the effect of an investment in post-exposure prophylaxis by Gavi, the Vaccine Alliance. We modelled post-exposure prophylaxis use according to the status quo, with improved access using WHO-recommended intradermal vaccination, with and without rabies immunoglobulin, and with and without dog vaccination. We took the health provider perspective, including only direct costs. We predict more than 1 million deaths will occur in the 67 rabies-endemic countries considered from 2020 to 2035, under the status quo. Current post-exposure prophylaxis use prevents approximately 56 000 deaths annually. Expanded access to, and free provision of, post-exposure prophylaxis would prevent an additional 489 000 deaths between 2020 and 2035. Under this switch to efficient intradermal post-exposure prophylaxis regimens, total projected vaccine needs remain similar (about 73 million vials) yet 17·4 million more people are vaccinated, making this an extremely cost-effective method, with costs of US$635 per death averted and $33 per disability-adjusted life-years averted. Scaling up dog vaccination programmes could eliminate dog-mediated rabies over this time period; improved post-exposure prophylaxis access remains cost-effective under this scenario, especially in combination with patient risk assessments to reduce unnecessary post-exposure prophylaxis use. Investing in post-exposure vaccines would be an extremely cost-effective intervention that could substantially reduce disease burden and catalyse dog vaccination efforts to eliminate dog-mediated rabies. World Health Organization.

IntroductionDoxycycline postexposure prophylaxis (doxy-PEP) can prevent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW). STI rates are high among MSM and TGW in China, and implementation strategies are needed to optimise doxy-PEP services. Pay-it-forward and social network distribution approaches may increase uptake of STI services and could increase the uptake of doxy-PEP. We present the protocol for a randomised controlled trial evaluating the effectiveness of pay-it-forward strategies with and without adjunctive social network distribution among MSM and TGW in China.Methods and analysisA total of 399 MSM and TGW will be recruited at seven sites in China and randomly allocated in a 1:1:1 ratio to (1) self-pay, (2) pay-it-forward alone or (3) pay-it-forward with adjunctive social network distribution of doxy-PEP. Participants assigned to the self-pay arm can purchase a doxy-PEP packet out-of-pocket. Participants in the pay-it-forward arm will be offered a free doxy-PEP packet and the opportunity to donate to support doxy-PEP for future participants. Participants in the pay-it-forward arm with social network distribution will receive the pay-it-forward intervention as well as additional free doxy-PEP packets to distribute to peers. Those randomised to the self-pay and the pay-it-forward with social network distribution arms (ie, index participants) will receive and distribute referral cards to recruit additional peers (ie, alter participants). Alter participants recruited through the control arm will be referred to the clinic to purchase doxy-PEP. Alter participants recruited through the pay-it-forward with adjunctive social network distribution arm will receive doxy-PEP directly from referring index participants. Both index and alter participants in each arm will be asked to complete a follow-up survey 3 and 6 months after enrolment. The primary outcome will be the proportion of participants who report using doxy-PEP within 72-hours of condomless anal or oral sex on one or more occasions during follow-up.Ethics and disseminationEthical approval was obtained from the ethics review committee of the Dermatology Hospital of Southern Medical University (Approval number: 2023109). The findings will be disseminated in peer-reviewed publications.Trial registration numberThe study has been registered with the Chinese Clinical Trial Registry (trial ID ChiCTR2300074903). Date of registration: 18 August 2023.

Rabies is a neglected zoonotic disease with a global burden of approximately 59,000 human deaths a year. Once clinical symptoms appear, rabies is almost invariably fatal; however, with timely and appropriate post-exposure prophylaxis (PEP) consisting of wound washing, vaccine, and in some cases rabies immunoglobulin (RIG), the disease is almost entirely preventable. Access to PEP is limited in many countries, and when available, is often very expensive. We distributed a standardized assessment tool electronically to a convenience sample of 25 low- and middle-income countries in Asia and Africa to collect information on rabies PEP procurement, forecasting, distribution, monitoring and reporting. Information was collected from national rabies focal points, focal points at the World Health Organization (WHO) country offices, and others involved in procurement, logistics and distribution of PEP. Because RIG was limited in availability or unavailable in many countries, the assessment focused on vaccine. Data were collected between January 2017 and May 2018. We received responses from key informants in 23 countries: 11 countries in Asia and 12 countries in Africa. In 9 of 23 (39%) countries, rabies vaccine was provided for free in the public sector and was consistently available. In 10 (43%) countries, all or some patients were required to pay for the vaccine in the public sector, with the cost of a single dose ranging from US$ 6.60 to US$ 20/dose. The primary reason for the high cost of the vaccine for patients was a lack of funding at the central level to subsidize vaccine costs. In the remaining 4 (17%) countries, vaccine was provided for free but was often unavailable so patients were required to purchase it instead. The majority of countries used the intramuscular route for vaccine administration and only 5 countries exclusively used the dose-sparing intradermal (ID) route. Half (11/22; 50%) of all countries assessed had a standardized distribution system for PEP, separate from the systems used for routine childhood vaccines, and almost half used separate storage facilities at both central and health facility levels. Approximately half (9/22; 41%) of all countries assessed reported having regular weekly, monthly or quarterly reporting on rabies vaccination. While all countries in our assessment had rabies vaccines available in the public sector to some extent, barriers to access include the high cost of the vaccine to the government as well as to patients. Countries should be encouraged to use ID administration as this would provide access to rabies vaccine for many more people with the same number of vaccine vials. In addition, standardized monitoring and reporting of vaccine utilization should be encouraged, in order to improve data on PEP needs.

Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.

Background Post-exposure prophylaxis (PEP) following sexual exposure to HIV has been recommended as a method of preventing HIV infection in the UK. Men who have sex with men (MSM) are the group most affected by HIV in the UK and their sexual risk taking behaviour is reported to be increasing. One-to-one behavioural interventions, such as motivational interviewing (MI) have been recommended to reduce HIV in high risk groups. The Information, Motivation and Behavioral skills (IMB) model has been shown to provide a good basis for understanding and predicting HIV-relevant health behaviour and health behaviour change, however the IMB has yet to be applied to PEP after risky sexual exposure. The primary aim of this trial is to examine the impact of MI augmented with information provision and behavioural skills building (informed by the IMB Model), over and above usual care, on risky sexual behaviour in MSM prescribed PEP after potential sexual exposure. A secondary aim of this research is to examine the impact of the intervention on adherence to PEP. This study will also provide estimates of the cost-effectiveness of the intervention. Methods A manualised parallel group randomised controlled trial with economic evaluation will be conducted. The primary outcome is the proportion of risky sexual practices. Secondary outcomes include: i) Levels of adherence to PEP treatment; ii) Number of subsequent courses of PEP; iii) Levels of motivation to avoid risky sexual behaviours; iv) Levels of HIV risk-reduction information/knowledge; v) Levels of risk reduction behavioural skills; vi) Diagnosis of anal gonorrhoea, Chlamydia and/or HIV. 250 participants will be asked to self-complete a questionnaire at four time points during the study (at 0,3,6,12 months). The intervention will consist of a two-session, fixed duration, telephone administered augmented MI intervention based on the IMB model. A newly developed treatment manual will guide the selection of persuasive communication strategies as appropriate for each participant and will be based on underlying change mechanisms specified by the IMB theoretical framework. Information provision and skills building will also be included in the intervention package through the use of information leaflets and tailored action plans. Fidelity of intervention delivery will be assessed. Discussion The results from this NIHR funded study will identify whether it is appropriate and cost-effective to intervene using one-to-one telephone calls with MSM seeking PEP. If the intervention is effective, further work will be needed on training staff to deliver the intervention competently. Trial registration numbers UKCRN ID:11436; ISRCTN00746242 .

There are approximately 35,000 human deaths from rabies in Asia annually. Rabies can be prevented through timely post-exposure prophylaxis (PEP) consisting of wound washing, rabies vaccine, and in some cases, rabies immunoglobulin (RIG). However, access to rabies PEP often remains limited to urban areas and is cost-prohibitive. There is little information on procurement, distribution, monitoring, and reporting of rabies PEP. We interviewed key informants in the public sector from various levels in Bangladesh, Bhutan, Cambodia, and Sri Lanka between March 2017 and May 2018 using a descriptive assessment tool to obtain information on procurement, distribution, monitoring, and reporting of rabies PEP. These four countries in Asia were chosen to showcase a range of rabies PEP systems. National rabies focal points were interviewed in each country and focal points helped identify additional key informants at lower levels. A total of 22 key informants were interviewed at various levels (central level to health facility level) including national rabies focal points in each country. Each country has a unique system for managing rabies PEP procurement, distribution, monitoring, and reporting. There are varying levels of PEP access for those with potential rabies exposures. Rabies PEP is available in select health facilities throughout the country in Bangladesh, Bhutan, and Sri Lanka. In Cambodia, rabies PEP is limited to two urban centers. The availability of RIG in all four countries is limited. In these four countries, most aspects of the rabies PEP distribution system operate independently of systems for other vaccines. However, in Bhutan, rabies PEP and Expanded Programme on Immunization (EPI) vaccines share cold chain space in some locations at the lowest level. All countries have a monitoring system in place, but there is limited reporting of data, particularly to the central level. Systems to procure, deliver, monitor, and report on rabies PEP are variable across countries. Sharing information on practices more widely among countries can help programs to increase access to this life-saving treatment.

Pre-exposure prophylactic rabies vaccination (PrEP) is advised for travellers to countries with high rabies incidence, but rarely available for local residents. Some studies suggest poor cost-effectiveness of PrEP in such settings, but have generally focused upon post-exposure prophylaxis (PEP) cost savings as the main benefit of PrEP, without considering lives saved by PrEP efficacy. We compared incremental cost-effectiveness ratios (ICERs) of use of rabies PrEP, against an alternative of using only PEP, by adapting a decision-tree model previously used to inform Gavi's investment in rabies PEP. We consider scenarios including: a range of PrEP efficacies in individuals unable to access PEP; PrEP costs significantly below current prices (through single-dose approaches, inclusion in childhood vaccination schedules, increased manufacturing volume and/or new low-cost products); and variable rabies exposure risk and PEP access. We also present results from a simplified model, designed for ease of understanding. Modelled ICERs were <1000 USD per quality adjusted life year (QALY) across a range of plausible combinations of rabies exposure risk, PEP access, PrEP cost and PrEP efficacy. If PrEP efficacy exceeds 50 % over 15 years, we estimate ICERs <500 USD/QALY where rabies incidence ≥3 per 100,000 per year and cost of vaccination is ≤5 USD/child. Under scenarios with lower rabies incidence of around 0.3 per 100,000 per year, due either to more limited exposure or greater access to PEP, ICERs <3000 USD may still be achieved even if PrEP efficacy is as low as 30 %. Routine childhood PrEP may be cost-effective in settings with modest willingness-to-pay, and rabies exposure risks plausible across much of Africa and South Asia. Cost-effectiveness requires low-cost PrEP regimes and some efficacy of PrEP in individuals unable to access PEP. Under such conditions, PrEP may be an attractive additional tool in the fight against rabies.

Introduction Post‐exposure prophylaxis (PEP) for HIV prevention has been inadequately promoted, provided and used. Expanded access and task sharing could increase the HIV prevention impact of PEP, but scientific evidence to inform programmatic and policy decisions has not been synthesized. Methods To inform World Health Organization guidelines, we conducted a systematic review of studies examining the provision of PEP in community settings, and by trained lay health workers or through task sharing. We searched CINAHL, PsycINFO, PubMed, EMBASE and scientific conferences for studies published between January 2012 and October 2023. We screened s and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies; risk of bias was assessed using Cochrane Collaboration and Evidence Project tools, and the certainty of the evidence was assessed using GRADE. We also summarized implementation case studies, values and preferences studies, and cost and cost‐effectiveness studies. Results For provision of PEP in community settings, we identified one effectiveness study, three case studies, one values and preferences study, and one cost study. Very low certainty evidence from one study in Kenya and Uganda suggested that PEP uptake, when offered as part of a dynamic prevention package, was highest in the community setting (vs. outpatient or antenatal care settings). For provision of PEP by trained lay health workers or task sharing, we identified three effectiveness studies, two case studies, four values and preferences studies, and one cost study. Very low certainty evidence from Kenya, Uganda and the United States suggested that engagement of lay providers or pharmacists increased PEP uptake and completion and decreased HIV acquisition. Studies from six countries found most health workers supported PEP provision by non‐specialist providers. One modelling study suggested community‐based provision may be cost‐effective or cost‐saving in Africa. Discussion Evidence on expanding PEP access through community delivery or task sharing is limited but generally suggests positive outcomes, feasibility, acceptability and cost‐effectiveness of these approaches. Indirect evidence from HIV treatment and pre‐exposure prophylaxis further supports these approaches. Conclusions Programmes should be expanded to include community delivery and task sharing to dispense, distribute, provide and monitor PEP.

Introduction Post‐exposure prophylaxis (PEP) is an efficacious HIV prevention tool when used soon after a potential exposure. Understanding the drivers of cost‐effectiveness of PEP in different contexts will likely play a role in determining local policies for providing PEP. Discussion The cost‐effectiveness of PEP depends upon the likelihood of exposure to HIV, the transmission probability per sexual act and the efficacy of PEP, along with associated costs. The transmission probability per sex act will be greater in the first few acts in a partnership than on average across all acts owing to heterogeneity in the transmission probability between partnerships. In settings with high HIV prevalence and low treatment coverage, appropriately focused PEP is cost‐saving. As treatment coverage improves, PEP can remain cost‐effective with HIV prevalences above 15% with treatment coverage achieving 90:90:90 treatment targets. At 95:95:95 treatment levels, it is unlikely to be cost‐effective. PEP is only cost‐effective for the first few sex acts within a partnership. The cost‐effectiveness of PEP is sensitive to assumptions about the proportion of the population of partners with unsuppressed HIV, the pattern of mixing of those with unsuppressed virus, the transmission probability per sexual act, PEP efficacy, the costs of PEP and the value attached to preventing HIV acquisition. Where possible local parameters should be used in evaluating PEP cost‐effectiveness in our model. Conclusions We illustrate the use of simple calculations to define the cost‐effectiveness of PEP. In populations where there is a high prevalence of unsuppressed HIV, PEP is likely to be cost‐effective but only if used for one off sexual encounters and the first few sex acts within a partnership.

The global 2030 goal set by the World Organization for Animal Health (WOAH), the World Health Organization (WHO), and the Food and Agriculture Organization (FAO), to eliminate dog-mediated human rabies deaths, has undeniably been a catalyst for many countries to re-assess existing dog rabies control programmes. Additionally, the 2030 agenda for Sustainable Development includes a blueprint for global targets which will benefit both people and secure the health of the planet. Rabies is acknowledged as a disease of poverty, but the connections between economic development and rabies control and elimination are poorly quantified yet, critical evidence for planning and prioritisation. We have developed multiple generalised linear models, to model the relationship between health care access, poverty, and death rate as a result of rabies, with separate indicators that can be used at country-level; total Gross Domestic Product (GDP), and current health expenditure as a percentage of the total gross domestic product (% GDP) as an indicator of economic growth; and a metric of poverty assessing the extent and intensity of deprivation experienced at the individual level (Multidimensional Poverty Index, MPI). Notably there was no detectable relationship between GDP or current health expenditure (% GDP) and death rate from rabies. However, MPI showed statistically significant relationships with per capita rabies deaths and the probability of receiving lifesaving post exposure prophylaxis. We highlight that those most at risk of not being treated, and dying due to rabies, live in communities experiencing health care inequalities, readily measured through poverty indicators. These data demonstrate that economic growth alone, may not be enough to meet the 2030 goal. Indeed, other strategies such as targeting vulnerable populations and responsible pet ownership are also needed in addition to economic investment.