Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.

Retrospective analysis of post-exposure to human anti-rabies treatment in Botucatu, São Paulo State, Brazil

This analysis aimed to identify characteristics of accidents that would, probably, provoke rabies infection. A total of 14,409 survey questionnaires for surveillance of human rabies from the Brazilian Information System for Disease Notification (SINAN), from 2000 to 2005, were analyzed. Regarding demographics, it was observed that 7,377 (51.5%) of the victims were white, 4,458 (30.93%) were children and 8,008 (55.58%) were males. Urban cases were prevalent (88.10%) while dogs were the animals most frequently involved in accidents, in 11,700 cases (81.19%). Bites (84.35%) and scratches (19.15%) were the most prevalent exposure types, and occurred predominantly on victims' extremities (38.79%). The prophylactic measure taken in 6,179 cases comprised anti-rabies vaccine; of these victims, 421 (2.92%) showed systemic reactions while 693 (4.80%) reported no response. The importance of developing awareness in professionals that should correctly report post-exposure immunoprophylaxis cases is emphasized given the high number of individuals who receive this type of treatment annually.

MORTALITY OF ANTICARSIA GEMMATALIS (LEPIDOPTERA: NOCTUIDAE) CATERPILLARS POST EXPOSURE TO A COMMERCIAL NEEM (AZADIRACHTA INDICA, MELIACEAE) OIL FORMULATION

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Pro-phylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.

Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention: prospective studies in HIV-uninfected men and women

Thesis (Ph.D.)--University of Washington, 2016-06

Pre-exposure prophylaxis for the prevention of HIV infection: a new prevention paradigm?

Pre-exposure prophylaxis" (PrEP) has been recently developed as a prevention strategy which involves the administration of drugs to non-infected individuals who present high exposure or susceptibility to HIV. Although this use is not approved in our country, several guidelines recommend PrEP as a prevention option in adult MSM, heterosexual men and women, and users of parenteral drugs at risk of acquiring the infection. This article presents the characteristics that an ideal agent to be used as PrEP should meet, recent efficacy published data and barriers for the implementation of this new strategy. On the other hand, the role of hospital pharmacists will be discussed.

Immunovirological Correlates in Human Rabies Treated With Therapeutic Coma

A 37-year-old woman was admitted to hospital and over the next 5 days developed a progressive encephalitis. Nuchal skin biopsy, analyzed using a Rabies TaqMan(C) PCR, demonstrated rabies virus RNA. She had a history in keeping with exposure to rabies whilst in South Africa, but had not received pre- or post-exposure prophylaxis. She was treated with a therapeutic coma according to the

Case report:Evidence of rise in rabies cases in southern Malawi--better preventative measures are urgently required

We describe five children who died of clinical rabies in a three month period (September to November 2011) in the Queen Elizabeth Central Hospital. From previous experience and hospital records, this number of cases is higher than expected. We are concerned that difficulty in accessing post-exposure prophylaxis (PEP) rabies vaccine may be partly responsible for this rise. We advocate: (a) prompt course of active immunisation for all patients with significant exposure to proven or suspected rabid animals. (b) the use of an intradermal immunisation regime that requires a smaller quantity of the vaccine than the intramuscular regime and gives a better antibody response. (c) improved dog rabies control measures.

Riesgo de accidentes biológicos en estudiantes de la salud: revisión de la literatura en los últimos 14 años.

Introducción: Todos los trabajadores del área de la salud están en riesgo de padecer un accidente biológico. No obstante los estudiantes de estas aéreas, pueden presentar más riesgo porque apenas están en formación y no tienen la práctica o experiencia suficiente. Existen varios artículos que han estudiado la incidencia y prevalencia de accidentes biológicos en los trabajadores del área de la salud, Sin embargo, sobre esta problemática de la población estudiantil del área de la salud, se encuentra menos literatura. Por lo tanto con esta revisión sistemática se busca analizar y actualizar este tema. Métodos: Se realizó una revisión de la literatura científica de artículos publicados en los últimos 14 años, en relación con la prevalencia de accidentes biológicos en estudiantes de medicina, odontología, enfermería y residentes del área de la salud a nivel mundial. Se llevó a cabo la búsqueda en la base de datos de Pubmed, encontrando un total de 100 artículos, escritos en inglés, francés, español o portugués. Resultados: Las prevalencias encontradas sobre accidentes biológicos en estudiantes fueron las siguientes: en países europeos a nivel de enfermería los valores oscilan entre 10.2 % a 32%, en medicina fueron del 16%-58.8%, y en odontología del 21 %. En países asiáticos, se encontró que en enfermería el porcentaje varía de 49%-96 %, en medicina van del 35% -68%, y en odontología varia de 68.a 75.4%. En Norte América, en medicina las cifras fluctúan alrededor del 11-72.7 % y en odontología giran alrededor del 19.1%. Finalmente respecto a Suramérica la prevalencia fue de 31.2 a 46.7% en medicina, y del 40% en enfermería. Conclusiones: Por lo anterior se pudo concluir que, la prevalencia de accidentes biológicos en los estudiantes del área de la salud es elevada y varía según el continente en el que se encuentren.

Avaliação da conduta de profilaxia antirrábica indicada para pessoas envolvidas em agravos com cães e gatos no município de Jaboticabal, SP, no período de 2000 a 2006

Objetivando analisar as indicações de profilaxia antirrábica humana no Município de Jaboticabal-SP, foi realizado um estudo retrospectivo descritivo no período de 2000 a 2006, com levantamento de dados registrados nas fichas de investigação de atendimento e cálculo do custo com as vacinas destinadas à profilaxia pós-exposição. Constatou-se que 2.493 pessoas agredidas por animais foram submetidas à profilaxia com uso de vacina, num total de 7.108 doses e um custo de R$ 179.105,14. da totalidade de casos notificados, 2.184 (71,5 %) foram causados por cães e gatos clinicamente sadios no momento da agressão e que assim se mantiveram durante o período de observação, a qual foi feita pela própria vítima ou pelo dono do animal. Considerando este fato e também a situação epidemiológica da raiva no Município, pode-se inferir que essas vítimas poderiam ter sido dispensadas da profilaxia; entretanto, apenas 464 o foram, ou seja, 1.720 pessoas podem ter recebido vacina sem necessidade, ou seja 4.590 doses a um custo de R$ 114.420,81. em comparação com os números de outros municípios do Estado de São Paulo e com a média nacional, constata-se que o número de profilaxias pós-exposição contra raiva é muito alto em Jaboticabal, evidenciando que na conduta não se considerou o estado do agressor e a condição do Município de área controlada para raiva. Recomenda-se conscientização e capacitação permanentes das equipes de saúde pública quanto à epidemiologia da doença e à necessidade de observação adequada do animal agressor. É essencial a integração dos serviços médicos e veterinários no atendimento às vitimas, visando uma melhor avaliação do caso para que a decisão de se instituir ou não a profilaxia pós-exposição seja feita com critério e segurança.

Caracterização de agravos causados por cães e gatos a seres humanos no município de jaboticabal, são paulo, durante o período de 2000 A 2009

The lack of proper control of dogs and cats population and irresponsible pet ownership are factors that favor animal attack and pose serious public health concern. The aim of the present study was to characterize the injuries caused by dogs and cats to humans in the municipality of Jaboticabal, between the years 2000 and 2009, with a view to demonstrate the importance of aggression control in reducing both the risk for rabies transmission and the number of post exposure prophylaxis administration. A retrospective and descriptive study was conducted. 3,972 out of 4,149 records of patients who sought the public health service after being attacked by an animal were analyzed. Dogs were the species that most caused injuries. In the moment of the attack, the doǵs clinical status was declared as healthy in 81.8% of records; and in 81.1% of cases this status were maintained throughout the entire observation period of the aggressor. Most of injuries were characterized by bites in hands or feet, with multiple and superficial wounds. The number of injuries was high, therefore it is crucial to implement strategies to reduce injuries caused by animal attack through health promotion, educational activities and strengthening of integration of public health and veterinary services so that the decision to institute post-exposure prophylaxis is taken with criteria and safety.

Avaliação dos registros de profilaxia anti-rábica humana pós-exposição no Município de Jaboticabal, são Paulo, no período de 2000 a 2006

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Profilaxia antirrábica humana: proposta de uma nova metodologia de ação

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Eficácia terapêutica de RNAs de interferência (siRNAS) e avaliação da resposta imune em camundongos infectados com vírus da raiva de origem de cão e de morcego

Pós-graduação em Cirurgia Veterinária - FCAV