Post-exposure Prophylaxis Regimens Research Articles

Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV.

Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours. A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P>95% being clinically relevant). Overall, 29060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n=14304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR>1; P>98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR<1; P>99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR>1, P>99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status. We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays.Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity.Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14).Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34–65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (−17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity.Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

Pattern of Animal Bites and Delays in Initiating Rabies Postexposure Prophylaxis among Clients Receiving Care in Korle-Bu Teaching Hospital.

Introduction Each year, an estimated 25000 rabies death occurs in Africa. Post-exposure prophylaxis (PEP) remains the only proven approach in preventing rabies deaths. Most of rabies deaths occur among those who delayed, did not receive, or complete rabies PEP. The aim of this study was to determine the pattern of animal bite, factors associated with delays in initiating, and nonadherence to rabies PEP regimen. Method Data on clients reporting for rabies PEP in a tertiary hospital setting in Ghana were collected from 2013 to 2016. Demographics, place, and source of exposure were collected. Other information obtained included adherence to the PEP protocol and GPS coordinates of the town of animal bites. The shortest distance between the GPS coordinates of town of animal bite and the site of administration of the rabies PEP was calculated. A total of 1030 individuals received rabies PEP over the period. Results Overall, 52.9% (545) were males while 47.1% (485) were females. Majority of the cases were between the age group 1–10 years accounting for 29.2%. Dog bites accounted for 96.5% (n = 994). Cats, nonhuman primates, human bites, respectively, accounted for 1.8% (n = 18), 1.2% (n = 12), and 0.6% (n = 6) of all bites. Majority of bites occurred at home (66.2% (n = 646)). Also, 31.6% (n = 308) and 2.3% (n = 22) of bites occurred on the streets and neighbors/friends' homes, respectively. Only, 18.7% initiated PEP within 24 hours of bite. Rabies PEP regimen completion rate was 95.2% (n = 976). The median distance travelled to access rabies PEP was 7.87 km (IQR, 3.58–16.27) km. Overall, 34.7% (n = 344) had the animal bite within 4.99 km radius of the treatment room of KBTH. Clients who delayed in initiating rabies PEP were 2.6 (95% CI, 1.3–5.1) times more likely to be males and 2.0 (1.1–3.9) times more likely to receive bites in a location more than 5 km radius from the KBTH treatment room. Gender, age, and distance of bite from the treatment room were not associated with the likelihood of not completing rabies PEP schedule. Discussion. Bites from suspected rabies infected animals remain a problem in southern Ghana. There are significant delays in initiating PEP for rabies prevention. Most animal bite victims are children ten years and below. Male gender and bites more than 5 km radius from the site of rabies PEP administration were most significant factors associated with delays in initiating rabies PEP. There is the need for adopting strategies to encourage prompt initiation and adherence to PEP.

Purified Vero Cell Rabies Vaccine (PVRV, Verorab®): A Systematic Review of Intradermal Use Between 1985 and 2019.

The purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID PVRV regimen assessments. Thus, a consolidated review comparing immunogenicity of PVRV ID regimens during pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is timely and beneficial in identifying gaps in current research. A search of seven databases for studies published from 1985 to November 2019 identified 35 studies. PrEP was assessed in 10 studies (n = 926) with 1–3-site, 1–3-visit regimens of up to 3-months duration. Seroconversion (rabies virus neutralizing antibodies [RVNA] ≥ 0.5 IU/mL) rates of 90–100% were reported within weeks, irrespective of regimen, with robust booster responses at 1 year (100% seroconversion rates by day 14 post-booster). However, data are lacking for the current WHO-recommended, 2-site, 1-week ID PrEP regimen. PEP was assessed in 25 studies (n = 2136) across regimens of 1-week to 90-day duration. All ID PEP regimens assessed induced ≥ 99% seroconversion rates (except in HIV participants) by day 14–28. This review confirms ID PVRV suitability for rabies prophylaxis and highlights the heterogeneity of use in the field.

An epidemiological study of suspected rabies exposures and adherence to rabies post-exposure prophylaxis in Eastern Thailand, 2015.

BackgroundHuman rabies is a notifiable condition in Thailand, and 46 confirmed and probable cases were reported from 2010–2015; eleven were reported from Eastern Thailand. Although rabies is vaccine preventable, more than 90% of persons who died of rabies in Thailand either did not receive or inappropriately discontinued post-exposure prophylaxis (PEP). In 2012 Thailand launched a national animal rabies elimination program with the goal of elimination by 2020. One of the policies of this national program is to improve detection of animal rabies exposures, access to PEP, and adherence to vaccine schedules. To achieve this goal, several hospital-based electronic PEP surveillance systems have been instituted throughout Thailand.MethodData from a voluntary, electronic hospital-based, rabies exposure and PEP surveillance system was analyzed from eight provinces in Eastern Thailand for the time period January 1 –December 31, 2015. The surveillance system collects data from all persons who present to an R36-integrated healthcare facility with a suspected rabies exposure, including characteristics of the biting animals, categorization of the rabies exposure, and adherence to PEP recommendations. The crude rate of healthcare seeking for a suspected rabies exposure was assessed by province, and a multivariable linear regression model was developed to determine the potential extent of undetected rabies exposures due to bite treatment at healthcare facilities that do not utilize the R36 system. Suspected rabies exposures were described by patient demographics, location of wound, and disposition of the offending animal. A comparison of adherence to intramuscular and intradermal vaccination regimens was performed and odds ratios were calculated for factors related to unadvised PEP discontinuation.Result6,204 suspected rabies exposures were reported from eight Eastern Thailand provinces, yielding a crude exposure rate of 106 reported rabies exposures per 100,000 population. When adjusted for under-detection due to non-participating hospitals and province-level demographic differences, the estimated suspected rabies exposure rate was 204/100,000. Dogs were the main source of exposure (77.8%) and children age <15 years and elderly age >60 years had the highest overall reported exposure rate (189.7 and 189.2/100,000). Adherence to either the intramuscular 5-dose or the intradermal 4-dose PEP regimen was low (15.8% and 46.5%, respectively); rabies immunoglobulin was received by only 15% of persons for whom it was indicated. Persons with rabies exposures were more likely to discontinue the vaccination series against medical advice if they were male, aged 16–45, if they received immunoglobulin, or if received the intramuscular regimen.ConclusionWhen adjusting for number of reporting hospitals, province population density, number of hospitals per population and average family income, the expected report rate increased 1.9-fold, indicating that there is likely a high level of under-detection of persons seeking medical care for suspected rabies exposures. Expanded implementation of electronic surveillance systems will likely improve reporting and the epidemiologic knowledge of rabies exposures. Analysis of data collected from this system revealed very low rates of adherence to rabies vaccination recommendations. PEP adherence was better by the intradermal route, which provides more support for its use in situations where it is economically feasible.

Modeling HIV Pre-Exposure Prophylaxis.

Pre-exposure prophylaxis (PrEP) has emerged as a promising strategy for preventing the transmission of HIV. Although only one formulation is currently approved for PrEP, research into both new compounds and new delivery systems for PrEP regimens offer intriguing challenges from the perspective of pharmacokinetic and pharmacodynamic modeling. This review aims to provide an overview the current modeling landscape for HIV PrEP, focused on PK/PD and QSP models relating to antiretroviral agents. Both current PrEP treatments and new compounds that show promise as PrEP agents are highlighted, as well as models of uncommon administration routes, predictions based on models of mechanism of action and viral dynamics, and issues related to adherence to therapy. The spread of human immunodeficiency virus (HIV) remains one of the foremost global health concerns. In the absence of a vaccine, other prophylactic strategies have been developed to prevent HIV transmission. One approach, known as pre-exposure prophylaxis (PrEP), allows HIV-negative individuals who are at high risk of exposure to the virus, be it through an HIV-positive sexual partner or through the shared use of drug injection equipment, to substantially reduce the risk of developing an HIV infection. PrEP is a relatively recent approach to combating the HIV epidemic, with the only currently approved treatment being Truvada, a daily oral antiretroviral (ARV) therapy initially indicated in the treatment of active HIV-1 infections, but approved for HIV PrEP in 2012. Although PrEP therapy has consistently demonstrated high efficacy in preventing HIV infection, this efficacy is dependent on patient adherence to the prescribed treatment regimen. This can present a significant problem in low- and middle-income countries, which may lack the infrastructure to provide sufficient access to PrEP medication to maintain daily dosing regimens. Furthermore, while the conventional approach has generally been to advocate for continuous administration akin to regimens used for viral suppression in infected patients, there has been some discussion of whether a better treatment paradigm might be to push for PrEP therapy primarily during those known periods of heightened exposure risk, while relying on post-exposure prophylaxis regimens to prevent infection after unanticipated exposures during low-risk periods. These considerations have led to a push for the development of long-duration and on-demand PrEP formulations, including subdermal and subcutaneous implants, slow-release intramuscular depot injections, vaginal and rectal antimicrobial gels, and intravaginal rings and dissolving films. PrEP therapy is a quickly evolving field, with a variety of antiretroviral compounds and formulations under investigation. This review aims to report on notable drugs and formulations from a pharmacokinetic/pharmacodynamic (PK/PD) modeling perspective. Given the nature of PrEP as a preventive therapy designed for long-term use, clinical trials for PrEP therapies can last for months or even years, particularly in the case of long-duration formulations. Furthermore, in contrast to antiretroviral trials in infected patients, pharmacodynamic endpoints in PrEP therapies are difficult to quantify, as the primary endpoint for efficacy is generally the rate of seroconversion. Computational modeling approaches offer flexible and powerful tools to provide insight into drug behavior in clinical settings, and can ultimately reduce the time, expense, and patient burden incurred in the development of PrEP therapies.

Single Dose of Doxycycline for the Prevention of Tick-borne Relapsing Fever

The current postexposure prophylaxis regimen for tick-borne relapsing fever (TBRF) consists of 5 days' doxycycline. In this observational study of 77 spelunkers at high risk for TBRF, a single dose of 100 mg doxycycline taken up to 72 hours after exposure to ticks was 100% effective in preventing the disease.

Post-exposure prophylaxis following consented sexual exposure: impact of national recommendations on user profile, drug regimens and estimates of averted HIV infections.

The aim of the study was to describe the characteristics, impact and outreach of post-exposure prophylaxis (PEP) for sexual exposure in Brazil. We used secondary data from the Brazilian Ministry of Health to describe the impact of national guidelines on the frequency of prescription, user profile and antiretroviral regimens. We also estimated the number of potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. A total of 260457 PEP regimens were prescribed to individuals≥14years old; 104613 (40.2%) were prescribed for consented sexual exposure, with an increasing frequency since 2011. Drugs used in PEP regimens underwent significant modifications during the period, reflecting national recommendations. We estimated that there were up to 3138 potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. In the context of a combined HIV prevention strategy, PEP is still an essential tool for individuals for whom other methods are contraindicated or fail to be applied.

WHO's new rabies recommendations: implications for high incidence countries.

Rabies is virtually always fatal; however, it is nearly 100% preventable with timely and appropriate prophylactic immunization. This review summarizes the recently revised WHO guidelines for rabies prophylaxis published in 2018, following a scientific review by a strategic advisory group of experts on immunization. The scientific basis for the major changes and its implications for countries with high disease burden are also discussed. The key changes in the updated WHO 2018 guidelines for rabies prophylaxis include abbreviated vaccination regimens for pre and postexposure prophylaxis. These cost and dose-sparing regimens allow equitable sharing of vaccines, necessitate fewer clinic visits and thus can enhance patient compliance. The recommendations on rabies immunoglobulin administration permit prioritization and optimal use of this life-saving biologic, especially in areas with scarcity. However, there is a need for additional evidence to support the abridgment of some regimens and need for data on the safety and immunogenicity of these regimens in special groups such as infants and the immunocompromised. National health authorities in high incidence countries need to develop consensus for effective implementation of simplified, cost-effective, and logistically feasible regimens for rabies prophylaxis, on the basis of the revised WHO guidelines.

Improving human rabies post-exposure prophylaxis

In The Lancet Infectious Diseases, Tineke Cantaert and colleagues 1 Cantaert T Borand L Kergoat L et al. A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study. Lancet Infect Dis. 2019; (published online Sept 27)https://doi.org/10.1016/S1473-3099(19)30311-1 PubMed Scopus (12) Google Scholar illustrate a strong commitment in Cambodia to preventing human rabies by rapid intradermal delivery of post-exposure prophylaxis. The investigators included 116 people bitten by rabies virus-positive dogs and 20 people bitten by rabies virus-negative dogs who attended Institut Pasteur du Cambodge, Phnom Penh, Cambodia, between April 20, 2016, and Feb 9, 2018. Patients received intradermal vaccination on days 0, 3, 7, and 28, and serum samples were obtained for detection of rabies virus neutralising antibodies on days 0, 7, 28, and 42. This well designed cohort study showed that exposed people had rabies virus neutralising antibody titres after three rabies vaccine sessions (of two intradermal doses each) that were similar to titres observed immediately before a fourth vaccine session on day 28. The authors concluded that rabies post-exposure prophylaxis could be abridged to a 1-week (three sessions of two doses on days 0, 3, and 7) intradermal regimen. Recognising the possibility of long incubation periods, the investigators contacted all patients after 1 year and found that all were still alive. These compelling data help identify the best use of human rabies post-exposure prophylaxis in developing countries, which should be used in combination with mass vaccination of dogs. A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort studyThe fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients. Full-Text PDF

A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study

The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030. This effort will require improving access to adequate and timely rabies post-exposure prophylaxis as compliance is low with WHO-recommended regimens (given in four to five visits over 1 month). Access could be substantially improved by an abridged regimen to reduce doses, direct and indirect costs, and improve vaccine equity by better sharing of available vaccine. We aimed to compare rabies virus neutralising antibody titres before and after the fourth visit to determine whether that session was needed or the current regimen could be abridged. In this observational cohort study, we measured rabies virus neutralising antibody titres using rapid fluorescent focus inhibition tests in 116 people bitten by dogs with laboratory-confirmed rabies and 20 control individuals. Percentages of circulating plasmablasts were determined by flow cytometry. All individuals had been referred to the rabies prevention clinic at Institut Pasteur in Cambodia and received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28 (Thai Red Cross regimen) with or without equine rabies immunoglobulin, as per 2010 WHO recommendations. All individuals had rabies virus neutralising antibody titres considered protective (≥0·5 IU/mL) and plasmablast activation on day 28 before the last injection. The median rabies virus neutralising antibody concentration in the group of individuals bitten by rabies virus-positive dogs was 1·08 IU/mL (IQR 0·37-3·09) on day 7, 26·86 (22·68-49·50) on day 28, and 26·74 (11·78-49·06) on day 42. No significant differences were observed in titres between days 28 and 42, after titres reached a plateau. These titres were reached notwithstanding equine rabies immunoglobulin use, age, sex, nutrition status as indicated by upper-arm circumference in children or BMI in adults, or dog infection status. Titres or plasmablast percentages did not increase between the day of the last injection and 2 weeks later. All patients were alive 1 year after post-exposure prophylaxis. The fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients. Institut Pasteur.

Simplification of Rabies Postexposure Prophylaxis: A New 2-Visit Intradermal Vaccine Regimen.

.A 2-visit multiple-site intradermal (ID) vaccine protocol would be the most economical, immunogenic, and practicable regimen for postexposure rabies prophylaxis (PEP) in clinics seeing few patients a month. This regimen with an additional day 28 dose is now recommended by the WHO. The difficulties surrounding ID rabies vaccination have hindered progress in provision of prophylaxis, especially in rural Asia and Africa. Although the latest WHO recommendations include 1-week ID postexposure vaccine regimens, these are unlikely to prove economical where rabies vaccination is presently unavailable. The new protocol uses a whole vial of vaccine divided between 4-sites ID on the first day and half a vial at 2-sites ID on day 7. Gavi has recently approved support for rabies PEP. This 2-visit 4-site ID regimen, with or without a day 28 dose, should be considered for implementation in this remarkable new initiative.

Occupational blood and body fluid exposures and human immunodeficiency virus post-exposure prophylaxis amongst intern doctors

Background: Healthcare workers (HCWs) are constantly vulnerable to occupational blood and body fluid exposures (OBBFEs). Exposed HCWs experience emotional, physical and psychological trauma. Less experienced HCWs, such as intern doctors, are more prone to OBBFEs. Objectives: The aim of this study was to investigate the prevalence and practices pertaining to OBBFEs amongst a select group of intern doctors in the Gauteng province of South Africa. Methods: A quantitative cross-sectional descriptive study using a questionnaire based on a practical model was used. Intern doctors were recruited from four major hospitals in Gauteng. Results: A total of 175 intern doctors participated in the study. There was a total of 182 (mean = 1.04, standard deviation [s.d] 0.88) reported OBBFEs amongst 136 (77.7%) subjects. The exposures occurred predominantly whilst subjects were working in surgery ( n = 50, 27.5%), obstetrics and gynaecology ( n = 49, 26.9%) and internal medicine ( n = 48, 26.4%) departments; were superficial wounds ( n = 69, 37.9%); were acquired during vascular puncture or intravenous line insertion ( n = 69, 37.9%); and occurred when subjects were working &gt;12 h shifts ( n = 101, 55.5%). Human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP) was initiated in 141 (77.5%) out of the 182 exposures. Only 90 (63.8%) subjects completed the recommended 28-day course of PEP. Two (1.1%) subjects reported that they had acquired HIV infection as a consequence of the OBBFE. Conclusion: Occupational blood and body fluid exposures are common amongst intern doctors. It is recommended that regular training, health education and monitoring compliance should be incorporated during the induction of medical intern doctors in hospitals. The availability of PEP regimens with better tolerability will encourage compliance.

Occupational blood and body fluid exposures and human immunodeficiency virus post-exposure prophylaxis amongst intern doctors.

BackgroundHealthcare workers (HCWs) are constantly vulnerable to occupational blood and body fluid exposures (OBBFEs). Exposed HCWs experience emotional, physical and psychological trauma. Less experienced HCWs, such as intern doctors, are more prone to OBBFEs.ObjectivesThe aim of this study was to investigate the prevalence and practices pertaining to OBBFEs amongst a select group of intern doctors in the Gauteng province of South Africa.MethodsA quantitative cross-sectional descriptive study using a questionnaire based on a practical model was used. Intern doctors were recruited from four major hospitals in Gauteng.ResultsA total of 175 intern doctors participated in the study. There was a total of 182 (mean = 1.04, standard deviation [s.d] 0.88) reported OBBFEs amongst 136 (77.7%) subjects. The exposures occurred predominantly whilst subjects were working in surgery (n = 50, 27.5%), obstetrics and gynaecology (n = 49, 26.9%) and internal medicine (n = 48, 26.4%) departments; were superficial wounds (n = 69, 37.9%); were acquired during vascular puncture or intravenous line insertion (n = 69, 37.9%); and occurred when subjects were working >12 h shifts (n = 101, 55.5%). Human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP) was initiated in 141 (77.5%) out of the 182 exposures. Only 90 (63.8%) subjects completed the recommended 28-day course of PEP. Two (1.1%) subjects reported that they had acquired HIV infection as a consequence of the OBBFE.ConclusionOccupational blood and body fluid exposures are common amongst intern doctors. It is recommended that regular training, health education and monitoring compliance should be incorporated during the induction of medical intern doctors in hospitals. The availability of PEP regimens with better tolerability will encourage compliance.

Post exposure compliance of rabies vaccination among cases attending anti-rabies clinic at tertiary care centre, Rajasthan

Background: Rabies is one of the deadliest diseases of mankind, and has terrified since antiquity. It is 100 per cent fatal, however, 100% preventable. In India, rabies causes an estimated 20,565 deaths with 17.4 million exposures to animal bites, mainly dog bites, occurring every year. In India a person is bitten by an animal in every 2 seconds and someone dies from rabies every 30 second. Complete post-exposure prophylaxis is necessary among the animal bite cases for complete protection. Hence this study aims to determine the patient’s compliance for intradermal anti-rabies vaccination and also to determine the constraints for compliance.Methods: A retrospective record based study was conducted in the ARC of S.M.S.M.C, Jaipur where patients were provided intradermal rabies vaccination (updated Thai Red Cross regimen) for post-exposure prophylaxis. The records maintained at ARC-SMSMC under department of community medicine from March 2016- February 2017 were analysed. The total number of patients was 8873 from which 8590 subjects were recruited for the study after excluding category I cases, pre-exposure cases rat bite, human bite, re-exposure and pre-exposure cases. The major constraints were found out by interviewing the patient/guardian through the telephone.Results: The compliance rate for intradermal rabies vaccination (IDRV) is 81.87%. The major constraints were timings not convenient, personal or social workload, long distance from the hospital, forgotten the dates.Conclusions: The compliance rate for rabies vaccination is considerably low for this highly fatal disease. Considering these major constraint factors, the animal bite victims should be motivated effectively through health education at the time of initiation of vaccination course to attain the goal of rabies free India.

Cost Savings of Using Updated Thai Red Cross Intradermal Regimen in a High-Throughput Anti-Rabies Clinic in New Delhi, India

Replacement of the Essen intramuscular (EIM) by the updated Thai Red Cross intradermal (UTRCID) regimen for rabies post-exposure prophylaxis (PEP), in high-throughput hospitals of India, has been advocated since 2006 thanks to its cost-effectiveness. However, several anti-rabies clinics in India and other parts of the world have not initiated this switchover of regimens because of the paucity of financial literature, generated in realistic settings, regarding the same. We calculated the procurement costs of various items required for providing rabies vaccinations via the EIM regimen and UTRCID regimen, on an annual basis, a year before and after the switchover. From a healthcare provider’s perspective, the cost of vaccination per patient was calculated to be 5.60 USD for the EIM regimen and 2.40 USD for the UTRCID regimen. The switchover to the UTRCID regimen from the EIM regimen reduced the financial burden of the rabies vaccination by almost 60%. Procurement of vaccine vials contributed to the majority of the cost (>94%) in both of the regimens. Procurement of syringes with fixed needles contributed negligibly (<6%) to the financial burden in both the regimens. A policy to progressively switch over to the UTRCID regimen from the EIM in all high-throughput anti-rabies centers of India would dramatically reduce the economic burden of running a successful anti-rabies program.

Influence des connaissances des patients consultant au centre antirabique de Treichville, Côte d’Ivoire, sur l’observance de la prophylaxie post-exposition

Human rabies is a major public health problem in many African countries, including Ivory Coast. The objective of this study was to evaluate the influence of human rabies knowledge on compliance with post-exposure prophylaxis. We conducted a descriptive and analytical cross-sectional study from September 2014 to May 2015 at the Abidjan Rabid Center, Treichville. After having given their consent, were interviewed, patients who came for a first consultation and who gave a mobile phone number available for the appointment reminder after abandoning or not starting the post-exposure prophylaxis. Data were processed with Epi Info version 3.5.3. Pearson's chi-square test and Fisher's exact test were used for statistical analysis with a significance level of 5%. A total of 744 patients were interviewed. Men accounted for the majority (58.2%) of those surveyed, with a sex ratio (M/F) of 1.7. The average age of patients was 24.55 (±17.3) years. The analysis showed that 42.6% (317/744) of the interviewees had heard of human rabies. However, having heard of human rabies did not influence adherence to post-exposure prophylaxis (P>0.05). Nevertheless, the post-exposure prophylaxis regimen was completed more often by subjects who knew that agitation is a sign of rabies than those who did not (ORa=0.4343, 95%CI=[0.204-0.925]). Subjects knowledgeable about disease transmission (animal bites) were less likely to continue their post-exposure prophylaxis than those unaware of this relationship (ORa=8.544, 95%CI=[1.002-72.869]). The main factors identified in this study that influenced the observance of post-exposure prophylaxis were knowledge of the manifestation of human rabies (signs of agitation) and of the mode of transmission of this disease (animal bites). With a view for better prevention against human rabies, rural and urban populations should be informed, educated and sensitized about this 100% life-threatening but vaccination-preventable disease.

Modelling to inform prophylaxis regimens to prevent human rabies

BackgroundThe Strategic Advisory Group of Experts (SAGE) Working Group on rabies vaccines and immunoglobulins was established in 2016 to develop practical and feasible recommendations for prevention of human rabies. To support the SAGE agenda we developed models to compare the relative costs and potential benefits of rabies prevention strategies. MethodsWe examined Post-Exposure Prophylaxis (PEP) regimens, protocols for administration of Rabies Immunoglobulin (RIG) and inclusion of rabies Pre-Exposure Prophylaxis (PrEP) within the Expanded Programme on Immunization (EPI). For different PEP regimens, clinic throughputs and consumables for vaccine administration, we evaluated the cost per patient treated, costs to patients and potential to treat more patients given limited vaccine availability. ResultsWe found that intradermal (ID) vaccination reduces the volume of vaccine used in all settings, is less costly and has potential to mitigate vaccine shortages. Specifically, the abridged 1-week 2-site ID regimen was the most cost-effective PEP regimen, even in settings with low numbers of bite patients presenting to clinics. We found advantages of administering RIG to the wound(s) only, using considerably less product than when the remaining dose is injected intramuscularly distant to the wound(s). We found that PrEP as part of the EPI programme would be substantially more expensive than use of PEP and dog vaccination in prevention of human rabies. ConclusionsThese modeling insights inform WHO recommendations for use of human rabies vaccines and biologicals. Specifically, the 1-week 2-site ID regimen is recommended as it is less costly and treats many more patients when vaccine is in short supply. If available, RIG should be administered at the wound only. PrEP is highly unlikely to be an efficient use of resources and should therefore only be considered in extreme circumstances, where the incidence of rabies exposures is extremely high.

2491. Post-Exposure Prophylaxis With Ribavirin Plus Lopinavir/Ritonavir for Middle East Respiratory Syndrome in Healthcare Workers

BackgroundIn 2015, an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection occurred in South Korea involving 186 patients, 39 of whom were healthcare workers (HCWs) exposed to the infection. An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection; however, there is no consensus regarding PEP for MERS-CoV infection. In this study, we assessed (1) the efficacy of oral ribavirin and lopinavir/ritonavir as PEP for HCWs exposed to patients with severe MERS-CoV pre-isolation pneumonia, and (2) safety of the PEP regimen.MethodsWe retrospectively enrolled 43 HCWs with high-risk exposure to MERS-CoV from 5 hospitals affected during this outbreak in South Korea. The rate of MERS-CoV infection was compared between 22 workers at 1 hospital who received PEP consisting of oral ribavirin and lopinavir/ritonavir after exposure to patients with severe MERS-CoV pre-isolation pneumonia and 21 workers at other hospitals who did not receive PEP.ResultsSix workers (14%) developed MERS-CoV infection; all of these subjects belonged to the non-PEP group. The attack rate was lower in the PEP group compared with the non-PEP group (0% vs. 28.6%; Odds ratio = 0.405, 95% confidence interval = 0.274–0.599; P = 0.009). The most commonly reported side effects of PEP therapy were nausea and diarrhea, but there were no severe adverse effects associated with PEP therapy.ConclusionPEP with a combination of oral ribavirin and lopinavir/ritonavir appears to be effective and generally safe for preventing MERS-CoV infection after high-risk exposure in healthcare workers.Disclosures All authors: No reported disclosures.

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

SummaryBackgroundTens 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.MethodsWe 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.FindingsWe 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.InterpretationInvesting 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.FundingWorld Health Organization.