Rabies Elimination in Rural Kenya: Need for Improved Availability of Human Vaccines, Awareness and Knowledge on Rabies and Its Management Among Healthcare Workers.

Background: In Africa, rabies causes an estimated 24,000 human deaths annually. Mass dog vaccinations coupled with timely post-exposure prophylaxis (PEP) for dog-bite patients are the main interventions to eliminate human rabies deaths. A well-informed healthcare workforce and the availability and accessibility of rabies biologicals at health facilities are critical in reducing rabies deaths. We assessed awareness and knowledge regarding rabies and the management of rabies among healthcare workers, and PEP availability in rural eastern Kenya. Methodology: We interviewed 73 healthcare workers from 42 healthcare units in 13 wards in Makueni and Kibwezi West sub-counties, Makueni County, Kenya in November 2018. Data on demographics, years of work experience, knowledge of rabies, management of bite and rabies patients, and availability of rabies biologicals were collected and analyzed. Results: Rabies PEP vaccines were available in only 5 (12%) of 42 health facilities. None of the health facilities had rabies immunoglobulins in stock at the time of the study. PEP was primarily administered intramuscularly, with only 11% (n = 8) of the healthcare workers and 17% (7/42) healthcare facilities aware of the dose-sparing intradermal route. Less than a quarter of the healthcare workers were aware of the World Health Organization categorization of bite wounds that guides the use of PEP. Eighteen percent (n = 13) of healthcare workers reported they would administer PEP for category I exposures even though PEP is not recommended for this category of exposure. Only one of six respondents with acute encephalitis consultation considered rabies as a differential diagnosis highlighting the low index of suspicion for rabies. Conclusion: The availability and use of PEP for rabies was sub-optimal. We identified two urgent needs to support rabies elimination programmes: improving availability and access to PEP; and targeted training of the healthcare workers to improve awareness on bite wound management, judicious use of PEP including appropriate risk assessment following bites and the use of the dose-sparing intradermal route in facilities seeing multiple bite patients. Global and domestic funding plan that address these gaps in the human health sector is needed for efficient rabies elimination in Africa.

Background paper for developing a policy for the use of rabies biologicals and vaccination of humans in India.

National Rabies Control Programme, India, is in operation since 2012-2013 without much impact due to poor funding and no set policy for the rabies prevention and control. An effort was made to develop a draft policy paper which can help the Government of India to develop a national rabies vaccination policy for humans and for achieving the goal of zero dog-mediated human rabies deaths by the year 2030. A technical stakeholders meeting was held under the chairmanship of the Drug Controller General of India at New Delhi in December 2017 to discuss the problems and solutions for providing essential rabies postexposure prophylaxis (PEP). The following problems and dilemmas were identified: frequent shortages of life-saving rabies vaccines and rabies immunoglobulin for PEP; as rabies vaccines are mostly procured by the state governments that often face resource crunch and hurdles in logistics within the states; production levels of rabies biologicals in the public sector are low; and the export of rabies biologicals from the private sector needs to be critically evaluated in the context of frequent stock-outs in the domestic market and also the national vaccine security.

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.

Using a modified rabies immunoglobulin protocol in a crisis of unavailability: Ethical and practical challenges.

Rabies is a dreaded disease of zoonotic origin, responsible for an estimated 55,000 deaths annually, of which 20,000 deaths are in India. Some animal bite patients need rabies immunoglobulin (RIG) for post exposure prophylaxis, in addition to the vaccine against rabies. The major reason for the high death rate in India is the high cost of RIG. Until 2017, the WHO-recommended protocol required a large amount of RIG. I describe how a cost-saving protocol for RIG was implemented in Himachal Pradesh. The published results contributed to the modification of the WHO's global recommendations on RIG use.

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.

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.

Nonoccupational post-exposure prophylaxis source tracing: is it really feasible in Australia?

OBJECTIVE: A Swiss nonoccupational post-exposure prophylaxis (NPEP) source-tracing study successfully reduced unnecessary NPEP prescriptions by recruiting and testing source partners of unknown HIV serostatus. The Victorian NPEP Service in Australia attempted to replicate this study with the addition of HIV rapid testing and a mobile service. METHODS: Patients presenting to two busy NPEP sites who reported a source partner of unknown HIV status were routinely asked if their source could be traced. If the exposed person indicated that their source partner was traceable they were asked to contact them and discuss the possibility of having an HIV test. RESULTS: No sources were enrolled and the study was terminated. CONCLUSION: We hypothesize that there are a number of differences between Australia and Switzerland that make source tracing unfeasible in Australia.

Cost-effectiveness of HIV nonoccupational post-exposure prophylaxis in Australia.

OBJECTIVE: The aim of the study was to determine the cost-effectiveness of HIV nonoccupational post-exposure prophylaxis (NPEP) in Australia. METHODS: A retrospective cost analysis of a population-based observational cohort of 1601 participants eligible for NPEP in Australia between 1998 and 2004 was carried out. We modelled NPEP treatment costs and combined them with effectiveness outcomes to calculate the cost per seroconversion avoided. We estimated the cost-utility of the programme, and sensitivity and threshold analysis was performed on key variables. RESULTS: The average NPEP cost per patient was A$1616, of which A$848 (52%) was for drugs, A$331 (21%) for consultations, A$225 (14%) for pathology and A$212 (13%) for other costs. The cost per seroconversion avoided in the cohort was A$1 647,476 in our base case analysis, and A$512,410 when transmission rates were set at their maximal values. The cost per quality-adjusted life-year (QALY) was between A$40,673 and A$176,772, depending on the risks of HIV transmission assumed. CONCLUSIONS: In our base case, NPEP was not a cost-effective intervention compared with the widely accepted Australian threshold of A$50,000 per QALY. It was only cost-effective after receptive unprotected anal intercourse exposure to an HIV-positive source. Although NPEP was a relatively well-targeted intervention in Australia, its cost-effectiveness could be improved by further targeting high-risk exposures.