Quantifying the interconnectedness between poverty, health access, and rabies mortality.

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.

A shorter post-exposure prophylaxis regimen for rabies, Pakistan.

OBJECTIVE: To assess the cost and effectiveness of the two-site, 1-week, intradermal rabies post-exposure prophylaxis regimen recommended by the World Health Organization (WHO) in 2018. METHODS: We compared the number of rabies vaccine and rabies immunoglobulin ampoules consumed at The Indus Hospital in Karachi, Pakistan and their cost before and after implementing WHO's 2018 recommendations. In 2017, patients with suspected rabies-infected bites were treated using the two-site, 4-week, Thai Red Cross regimen, which involved administering four rabies vaccine doses intradermally over 4 weeks and infiltrating immunoglobulin into serious wounds, with the remainder injected into a distant muscle. In 2018, patients received three vaccine doses intradermally over 1 week, with a calculated amount of immunoglobulin infiltrated into wounds only. Remaining immunoglobulin was saved for other patients. The survival of patients bitten by apparently rabid dogs was used as a surrogate for effectiveness. FINDINGS: Despite treating 8.5% more patients in 2018 (5370 patients) than 2017 (4948 patients), 140 fewer ampoules of rabies vaccine and 436 fewer ampoules of rabies immunoglobulin were used, at a cost saving of 4202 United States dollars. Of 56 patients bitten by apparently rabid dogs, 50 were alive at 6-month follow-up. The remaining six patients could not be contacted but did not present to any hospital with rabies. CONCLUSION: The new regimen was more economical than the two-site, 4-week regimen and was equally effective. This regimen is recommended for preventing rabies in countries where the disease is endemic and rabies vaccine and immunoglobulin are in short supply.

The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis.

Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti's capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.

Rabies vaccination strategies in the Netherlands in 2018: a cost evaluation.

BackgroundThe risk of contracting rabies is low for travellers. However, the number of Dutch travellers potentially exposed abroad following an animal-associated injury and needing post-exposure prophylaxis (PEP) has increased, resulting in increased costs.AimHere, we evaluated the costs and the cost-effectiveness of different pre- and post-exposure interventions in the Netherlands, taking into account the 2018 World Health Organization (WHO) recommendations for the prevention of rabies.MethodsA decision tree-based economic model was constructed. We calculated and compared the cost of different WHO pre-exposure prophylaxis (PrEP) recommendations, intramuscular vs intradermal vaccination and PEP subsequent to increased vaccination coverage in risk groups. We estimated cost-effectiveness, expressed as incremental costs per rabies immunoglobulin (RIG) administration averted, using a societal perspective. Statistical uncertainty regarding number of travellers and vaccination coverage was assessed.ResultsTotal costs at the national level were highest using previous WHO recommendations from 2012, estimated at EUR 15.4 million annually. Intradermal vaccinations in combination with the current recommendations led to the lowest costs, estimated at EUR 10.3 million. Higher vaccination uptake resulted in higher overall costs. The incremental costs per RIG administration averted varied from EUR 21,300-46,800.ConclusionsThe change in rabies PrEP and PEP recommendations in 2018 reduced total costs. Strategies with increased pre-travel vaccination uptake led to fewer RIG administrations and fewer vaccinations after exposure but also to higher total costs. Although larger scale intradermal administration of rabies vaccine can reduce total costs of PrEP and can positively influence vaccination uptake, it remains a costly intervention.

Leprosy post-exposure prophylaxis in the Indian health system: A cost-effectiveness analysis.

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

Burden of rabies in Mali.

Rabies is the most dreaded neglected zoonosis worldwide. It affects mostly developing countries with limited access to post-exposure prophylaxis and a low coverage of dog vaccination. OBJECTIVE: This study estimates the burden of human rabies in Mali from the extrapolation of animal bite surveillance, mostly dogs, in the region of Sikasso and the District of Bamako in 2016 and 2017. MATERIAL AND METHODS: Monte Carlo simulations of a series of interconnected probabilities were used to estimate the burden of rabies. The data was collected from cross-sectional surveys of 8775 households of which 4172 were in the District of Bamako and 4603 in the region of Sikasso. Further data was collected in health centres and from the respective veterinary services. RESULTS: We estimate that in the year 2016 133 [95% Confidence Interval (95%CI) 87-186] people died and that 5'366 [95%CI 3'510-7'504] years of life (YLL) were lost and in 2017 et 136 [95%CI 96-181] people died and that 5530 [IC 95% 3'913-7'377] YLLs were lost. The loss of income was estimated at 3.2 million USD [95%CI 2,1-4,5] en 2016, and 3,3 million USD [95%CI 2,3-4,4] in 2017. This represents the highest financial loss from rabies, followed by the cost of postexposure prophylaxis (PEP) of 86'848 $USD and 89'371 $ USD respectively. From the whole cost of rabies in Mali, 92% of the cost in 2016 and 94% of those in 2017 were attributable to premature mortality and the cost of help seeking. The proportion of cost of PEP was 3% in 2016 and 2017 of the total cost of disease. The cost related to dog vaccination changed from 3% to 1% in the same time period. CONCLUSION: This study shows that despite the possibility of preventing human rabies by PEP, its burden remains important in Malian communities. Rabies control by mass vaccination of dogs is hardly done and access to PEP is difficult. However, Rabies elimination by mass vaccination of dogs has been demonstrated to be feasible. Hence a coordinated regional effort between countries by funding dog mass vaccination and full access to PEP can eliminate rabies in West Africa.

Health economic assessment of a rabies pre-exposure prophylaxis program compared with post-exposure prophylaxis alone in high-risk age groups in the Philippines.

OBJECTIVES: Once symptoms appear, rabies is almost always fatal and accounts for 200-300 deaths annually in the Philippines. Available rabies vaccines can be administered either in pre- exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP). After exposure, PrEP-immunized individuals require fewer doses of PEP and no rabies immunoglobulin. METHODS: A static decision-tree model was developed to assess cost-effectiveness of a PrEP+PEP program vs PEP alone. Philippines-specific data for people seeking medical advice at the Research Institute for Tropical Medicine between July 2015 and June 2016 were used in the model, together with data from published literature. RESULTS: Over a 20-year period, in a cohort of 1 million 5-year-old children in the Philippines, PrEP+PEP was expected to prevent 297 deaths compared with PEP alone. From both payer and societal perspectives, the resulting incremental cost-effectiveness ratios were 36 035 (US$759; 2016 US$ conversion) and 18 663 (US$393) Philippine Pesos (PHP) - quality-adjusted life-years gained - respectively, which are both below the willingness-to-pay threshold of PHP140 255 (US$2 953). CONCLUSION: These data suggest that a universal PrEP program targeting 5-year-olds would be cost-effective in the Philippines.

The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa.

INTRODUCTION: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3 . We investigated the cost-effectiveness of this enhanced-prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. METHODS: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standard-prophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. RESULTS: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced-prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced-prophylaxis components. Enhanced-prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced-prophylaxis still conveyed health gains in CrAg-negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost-effective unless the price of CrAg testing fell below US$2.30. CONCLUSIONS: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices.

Cost of rabies post exposure prophylaxis in different healthcare settings in six states of India.

The expenditure for rabies postexposure prophylaxis (PEP) is substantial, especially for the poor who are affected the most. The present study was conducted to determine the cost incurred to a patient and the healthcare facility for providing PEP in different healthcare settings. A multicentric, health facility-based study was conducted from May 2017 to January 2018 in the six states involving 18 healthcare facilities. The study included 529 animal bite cases; most of them belonged to either category III (54.4%) or category II (43.1%) exposures and all of them received complete PEP. The total median cost incurred to the patients for complete PEP in the government health facility was INR 1400 (USD 22) and in private hospitals was INR 3685 (USD 58). The cost of PEP for the bite victims is considerable; therefore, it has to be provided free of charge at all healthcare facilities.

Overview of rabies post-exposure prophylaxis access, procurement and distribution in selected countries in Asia and Africa, 2017-2018.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Wound-only injection of rabies immunoglobulin (RIG) saves lives and costs less than a dollar per patient by "pooling strategy".

Since 2008, we in Himachal Pradesh have used a "pooling strategy" to help patients save money by pooling vials of antirabies vaccine at a centralized hospital and sharing them using the intradermal technique. In 2014, there was an acute shortage of rabies immunoglobulins (RIG) and two patients died after four injections of rabies vaccine were administered without RIG, which was not commercially available. After an extensive literature review and technical and ethical committee clearances, in June 2014 we started to infiltrate equine RIG (eRIG) into wound/s only without the recommended systemic intramuscular (IM) injection. WHO recommended this technique in 2018. During the four-year period June 2014 to June 2018, 7506 of 10,830 patients exposed to suspected rabid animals were injected with eRIG in and around the wounds in a single clinic at DDU Hospital Shimla without any adverse outcomes. The average volume of eRIG used per patient was 0.75 mL and cost US$ 0.75. Of the 80% of patients who were followed up, all were healthy at the end of a year, including 26 patients bitten by laboratory-confirmed rabid dogs. The reaction rate after PEP administration also declined significantly. Since February 2018, Himachal has started following the new WHO recommendations on PEP regimens of three intradermal antirabies vaccines instead of four, thereby saving hundreds of vaccine vials that became useful during shortages of rabies vaccine in India. To date, more than 700 vaccine vials have been saved in a single clinic at DDU hospital during the past 6 months alone. Not giving PEP to patients who have consumed raw milk from a suspected rabid cow has also saved 62 vials. Currently, 90 "pooling centers" have been established for sharing of vaccine and eRIG vials in Himachal State, generating huge savings that have enabled the government to provide PEP free of charge to all. The new WHO guidelines are a positive step towards a rabies-free world by 2030.

Evaluation of Vietnam's post-exposure prophylaxis delivery system, 2017.

BACKGROUND: Canine-mediated human rabies deaths typically occur in poor and rural populations with limited access to rabies biologics: vaccine and immunoglobulin. A critical aspect of reducing rabies deaths is understanding how these countries procure, deliver, and forecast rabies biologics. Vietnam is one of the few endemic countries where biologics is widely available. However, a formal evaluation of its current rabies biologics distribution system has not been conducted. METHODS: In 2017, we conducted a formal evaluation of Vietnam's rabies biologics distribution system. Our goals were (1) to identify centers providing rabies biologics (2) identify costs to the patient and centers and (3) assess the rabies biologic procurement and delivery system at eligible district and provincial centers (provides and orders biologics for itself and other centers directly from the manufacture). To conduct the formal evaluation, we developed a standardized survey that was distributed to centers. RESULTS: Of the 780 designated rabies biologics centers in Vietnam, 659 (84%) of them provide rabies immunoglobulin (eRIG), vaccine, or both. Of the 177 eligible centers, 90% (160) responded to the survey. The average costs to patients were $8.45 (range: 5.43-12.77) for one dose of IM injection, $13.90 (range: 11.86-16.71) for domestic eRIG, and $23 (21.11-27.11) for imported eRIG. Respondents reported experiencing delays in receiving vaccine in 50 centers and eRIG in 14 centers within the past year. Respondents stated their top three challenges in providing biologics were: delays or shortages from manufactures, lack of funds to pay for biologics, and the high cost of biologics. CONCLUSIONS AND RELEVANCE: Despite the wide availability of biologics in Vietnam, more work is needed to provide affordable and reliable supply of biologics to patients. This includes the expansion of ID injection use throughout the country to lower vaccine demand, and decrease the costs to centers and patients. Furthermore, a more coordinated effort to share biologics among centers, possibly through a more centralized system at the provincial level may alleviate delays and shortages.

Developing and evaluating an intervention to improve care and reduce costs of rabies postexposure therapy: an observational quality improvement initiative in selected vaccination units in Sri Lanka.

BACKGROUND: Exposure to the rabies virus is fatal unless a patient is treated with a timely, accurate and complete administration of postexposure prophylaxis (PEP). The level of adherence to PEP guidelines by health service providers is therefore critical in providing high-quality care as well as preventing unnecessary costs. METHODS: We developed a simple user-friendly decision aid based on Sri Lankan national guidelines for the administration of PEP and trialed it over a 5-month period in three study settings. Pre and post levels of adherence to the national guidelines by service providers was measured in each setting. Changes to per patient cost for rabies medications and hospital admissions were also collected. RESULTS: A significant improvement in adherence to the guidelines was observed in two settings with a nonsignificant improvement observed in the third setting. We estimated a total cost saving of LKR 158 476 across the three sites, comprising LKR 14 418 in admissions cost savings and LKR 144 058 in medication savings. CONCLUSION: We conclude that the development of a decision aid for the administration of PEP is likely to be an effective and cost-saving intervention in the Sri Lankan setting. Further research is required to inform the generalizability of our findings.

Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.

Descriptive assessment of rabies post-exposure prophylaxis procurement, distribution, monitoring, and reporting in four Asian countries: Bangladesh, Bhutan, Cambodia, and Sri Lanka, 2017-2018.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The potential effect of improved provision of rabies post-exposure prophylaxis in Gavi-eligible countries: a modelling study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: World Health Organization.

Cost-effectiveness modelling studies of all preventive measures against rabies: A systematic review.

Rabies is one of the most feared infectious diseases worldwide, predominantly occurring in Asia and Africa where rabies is endemic in domestic dog populations. Whereas previous studies have demonstrated mass dog vaccination and post-exposure prophylaxis (PEP) as the most effective control strategies, successful rabies elimination has yet to be realized as these recognized effective interventions continue to face challenges of limited accessibility. In the light of new evidence towards improving programmatic feasibility and clinical practice in rabies control especially among endemic countries, a systematic review was undertaken to identify cost-effectiveness modelling studies of rabies preventive measures and to provide a critical review of published evidence through comparative evaluation and model quality assessment, and a synthesis of key findings based thereon. Our search through MEDLINE and SCOPUS identified a total of 17 studies which mostly focused on estimating the impact of increasing PEP and pre-exposure prophylaxis (PrEP) access, human rabies elimination scenarios using mass dog vaccinations only or complemented with PEP strategy. While no significant methodological inconsistency across studies was identified and the extent of reporting is generally high, we note several points for quality and internal validity improvement. Assessment of modelling approach showed that decision tree models had similar pathways. The results of the studies suggest that interventions would be cost-effective at the cost-effectiveness threshold of 1 to 3 times per capita Gross Domestic Product (GDP) as recommended by the Commission on Macroeconomics and Health's GDP based thresholds, compared with no intervention in rabies endemic countries. When compared across studies which reported incremental cost-effectiveness ratio (ICER) as cost per QALY gained or DALY averted in international dollars adjusted by purchasing power parity conversion rate, PEP vaccination yields less cost per DALY averted or QALY gained due to one year-horizon assessment compared to canine vaccination at 4- or 10-year-time horizon.

On the path to rabies elimination: The need for risk assessments to improve administration of post-exposure prophylaxis.

BACKGROUND: Costs of rabies post-exposure prophylaxis (PEP) often remain high in regions where rabies has been controlled in dogs, presenting a challenge for sustaining rabies elimination programmes. We investigated the potential for bite patient risk assessments to improve PEP provision and surveillance in settings approaching elimination of dog-mediated rabies. METHODS: We conducted a longitudinal study of patients presenting to animal bite treatment centres (ABTCs) on the island province of Bohol in the Philippines to investigate the health status of biting dogs and to quantify current expenditure on PEP. RESULTS: Incidence of bite patients presenting to ABTCs was high (>300/100,000 persons/year) and increasing, resulting in substantial health provider costs. Over $142,000 was spent on PEP in 2013 for a population of 1.3 million. From follow up of 3820 bite patients we found that  >92% were bitten by healthy dogs (alive 14 days after the bite) and just 1.4% were bitten by probable or confirmed rabid dogs. The status of dogs that bit 6% of patients could not be determined. During the course of investigations of bites by suspect dogs, we were able to obtain samples for case confirmation, identify exposed persons who had not sought PEP as well as in-contact dogs at risk of developing rabies. We calculate that expenditure on PEP could at least be halved through more judicious approaches to provision of PEP, based on the histories of biting animals determined through risk assessments with bite patients. CONCLUSIONS: We conclude that a One Health approach to surveillance based on Integrated Bite Case Management could improve the sustainability and effectiveness of rabies elimination programmes while also improving patient care by identifying those genuinely in need of lifesaving PEP.

The evaluation of operating Animal Bite Treatment Centers in the Philippines from a health provider perspective.

BACKGROUND: The Philippine government has an extensive network of 513 Animal Bite Treatment Centers (ABTCs) to supply rabies post exposure prophylaxis (PEP), reaching over 1 million bite victims in 2016. The network was evaluated using a review of existing national and provincial data, key informant interviews and surveys in sample ABTCs to determine the cost-effectiveness of this network in preventing human rabies deaths. METHODOLOGY AND PRINCIPAL FINDINGS: One urban and one rural ABTC in each of three selected provinces were studied in more detail. PEP delivery generally followed national guidance based on best practices, but there was evidence of operational challenges in supplying all ABTCs with adequate biologics and recently trained staff. Funding was contributed by different levels of government and in some clinics, patients paid for a significant fraction of the total cost. From a health provider perspective including both fixed and variable costs, the average PEP course delivered cost USD 32.91 /patient across urban ABTCs (with higher patient throughput) and USD 57.21 /patient across rural ABTCs. These costs suggests that PEP provision in the Philippines cost USD 37.6 million in 2016, with a cost per life saved of USD 8,290. An analysis of the 2,239 suspected rabies deaths from 2008 to 2016 showed no significant decline, and from 2014-16 an average of 8,534 years of life were lost annually. The incidence of rabies deaths from 2014-16 was not clearly related to the provision of ABTCs (per 100,000 population) or human population density, but deaths were more common in higher income provinces. CONCLUSIONS/SIGNIFICANCE: In the context of comprehensive rabies control (including dog vaccination and public awareness) ways to reduce this high expenditure on PEP should be explored, to most cost-effectively reach the elimination of human rabies deaths. This paper is accompanied by another containing data on the operation of ABTCs network from a patient perspective.