Human Rabies during the COVID-19 Pandemic: Insights into Rabies Worldwide and Brazil.

Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR transmitted by dogs has decreased in Latin America, there has been a corresponding rise in transmission via wild animals. Given the lack of effective treatments and specific therapies, the management of HR relies on the availability of post-exposure prophylaxis and animal control measures. This review examines the dynamics and spread of HR during the global pandemic.

Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.

Somatic gain-of-function mutations in members of the RAS subfamily of small guanosine triphosphatases are found in > 30% of all human cancers. We recently described a syndrome of chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity associated with a mutation in NRAS affecting hematopoietic cells, and initially we classified the disease as a variant of the autoimmune lymphoproliferative syndrome. Here, we demonstrate that somatic mutations in the related KRAS gene can also be associated with a nonmalignant syndrome of autoimmunity and breakdown of leukocyte homeostasis. The activating KRAS mutation impaired cytokine withdrawal-induced T-cell apoptosis through the suppression of the proapoptotic protein BCL-2 interacting mediator of cell death and facilitated proliferation through p27(kip1) down-regulation. These defects could be corrected in vitro by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 or phosphatidyl inositol-3 kinase inhibition. We suggest the use of the term RAS-associated autoimmune leukoproliferative disease to differentiate this disorder from autoimmune lymphoproliferative syndrome.

FAS haploinsufficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome.

The autoimmune lymphoproliferative syndrome (ALPS) is characterized by early-onset lymphadenopathy, splenomegaly, immune cytopenias, and an increased risk for B cell lymphomas. Most ALPS patients harbor mutations in the FAS gene, which regulates lymphocyte apoptosis. These are commonly missense mutations affecting the intracellular region of the protein and have a dominant-negative effect on the signaling pathway. However, analysis of a large cohort of ALPS patients revealed that ∼30% have mutations affecting the extracellular region of FAS, and among these, 70% are nonsense, splice site, or insertions/deletions with frameshift for which no dominant-negative effect would be expected. We evaluated the latter patients to understand the mechanism(s) by which these mutations disrupted the FAS pathway and resulted in clinical disease. We demonstrated that most extracellular-region FAS mutations induce low FAS expression due to nonsense-mediated RNA decay or protein instability, resulting in defective death-inducing signaling complex formation and impaired apoptosis, although to a lesser extent as compared with intracellular mutations. The apoptosis defect could be corrected by FAS overexpression in vitro. Our findings define haploinsufficiency as a common disease mechanism in ALPS patients with extracellular FAS mutations.

Human Rabies during the COVID-19 Pandemic: Insights into Rabies Worldwide and Brazil

ABSTRACT Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR transmitted by dogs has decreased in Latin America, there has been a corresponding rise in transmission via wild animals. Given the lack of effective treatments and specific therapies, the management of HR relies on the availability of post-exposure prophylaxis and animal control measures. This review examines the dynamics and spread of HR during the global pandemic.

Prevention of HIV infection among migrant population groups in Northeast Brazil.

HIV infection is spreading among the poor, women, and migrant communities in the interior of Northeast Brazil. The research focused on different configurations, beliefs, representations, and forms of social organization of behavior thought to be associated with the population's capacity to efficiently follow AIDS prevention measures. Participants located in neighborhoods known for having large migrant populations were identified by Family Health Program Workers in Fortaleza and Teresina. The study adopted a qualitative methodology. Several belief-system concepts and values, as well as the social organization of sexuality revealed in the study, represent obstacles both to AIDS prevention and condom use. Hunger, lack of prospects, and fear are associated with a social situation of poverty, exclusion, prejudice, and total absence of basic human rights. When examined together, these elements define different configurations in the migrants' increased vulnerability to HIV/AIDS. The groups' increased vulnerability relates to the socioeconomic complexity that must be considered in HIV/AIDS control and prevention programs.

Survival of adult AIDS patients in a reference hospital of a metropolitan area in Brazil.

OBJECTIVE: To evaluate the influence of sociodemographic, clinical, and epidemiological factors in AIDS patients survival in a reference hospital. METHODS: A sample of 502 adult AIDS patients out of 1,494 AIDS cases registered in a hospital in Fortaleza, Brazil, was investigated between 1986 and 1998. Sixteen cases were excluded due to death at the moment of the AIDS diagnosis and 486 were analyzed in the study. Socioeconomic and clinical epidemiological were the variables studied. Statistical analysis was conducted using the Kaplan-Meier survival analysis and the Cox proportional hazards model. RESULTS: Three hundred and sixty two out of the 486 patients studied took at least one antiretroviral drug and their survival was ten times longer than those who did not take any drug (746 and 79 days, respectively, p <0.001). Patients who took two nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitor were found to have higher survival rates (p <0.001). The risk of dying in the first year was significantly lower for patients who took NRTI and a protease inhibitor compared to those who took only NRTI. In addition, this risk was much lower from the second year on (0.10; 95%CI: 0.42-0.23). The risk of dying in the first year was significantly higher for less educated patients (15.58; 95%CI: 6.64-36.58) and those who had two or more systemic diseases (3.03; 95%CI: 1.74-5.25). After the first year post-diagnosis, there was no risk difference for these factors. CONCLUSIONS: Higher education revealed to exert a significant influence in the first-year survival. Antiretroviral drugs had a greater impact in the survival from the second year on. A more aggressive antiretroviral therapy started earlier could benefit those patients.

Survival of adult AIDS patients in a reference hospital of a metropolitan area in Brazil

Objetivo: Avaliar, em um hospital de referência, a influência de fatores sociodemográficos e clínico-epidemiológicos na sobrevivência de pacientes com Aids. Métodos: Foi estudada uma amostra de 486 adultos com Aids atendidos em hospitais de referência no Ceará, entre 1986 e 1998. Foram avaliadas as variáveis socioeconômicas e clínico-epidemiológicas. A análise foi realizada pelo método Kaplan-Meier e por regressäo de Cox. Resultados: Dos 486 pacientes estudados, 362 utilizaram pelo menos uma droga anti-retroviral e tiveram sobrevida dez vezes maior que os que näo a utilizaram (746 e 79 dias, respectivamente; p<0,001). O risco de morrer, no primeiro ano, foi significativamente menor (0,25; IC95 por cento: 0,12-0,50) para os que fizeram uso de dois inibidores de transcriptase reversa ou HAART e menor a partir do segundo ano (0,10; IC95 por cento:0,42-0,23) em relaçäo aos que näo os usaram. Indivíduos sem nível universitário (15,58; IC95 por cento:6,64-36,58) e que apresentaram duas ou mais doenças sistêmicas (3,03; IC95 por cento:1,74-5,25) tiveram risco significativamente maior de morrer no primeiro ano. Após o primeiro ano, näo se observou diferença. Conclusäo: O melhor nível socioeconômico, medido indiretamente pela escolaridade, demonstrou grande influência na sobrevivência no primeiro ano. As drogas anti-retrovirais tiveram mais impacto na sobrevivência a partir do segundo ano, assim igualaram o risco de morrer de pacientes com duas ou mais doenças sistêmicas àqueles que näo tiveram nenhuma no mesmo período. Concluiu-se que uma introduçäo mais precoce e mais agressiva dos anti-retrovirais poderia beneficiar os pacientes

Prevention of HIV infection among migrant population groups in Northeast Brazil

A infecçäo pelo HIV entre pobres, mulheres e populaçöes migrantes do interior do Nordeste Brasileiro vem crescendo. As diferentes configuraçöes, crenças e representaçöes e formas de organizaçäo do comportamento, associadas à capacidade de seguir adequadamente medidas de prevençäo, foram o foco desta investigaçäo. Os participantes foram localizados em bairros com altas taxas de migraçäo através do Programa Saúde da Família em Fortaleza e Teresina. Empregou-se a metodologia qualitativa nesta investigaçäo. Vários sistemas de crenças, valores e organizaçäo social da sexualidade desta populaçäo representam obstáculos à prevençäo da AIDS e inibem o uso do preservativo. Pobreza, falta de perspectiva e medo estäo associados à situaçäo de pobreza, exclusäo social e preconceito e à total ausência de direitos humanos. Quando examinados conjuntamente, estes fatores definem diferentes configuraçöes dos migrantes com uma elevada vulnerabilidade ao HIV/AIDS. A alta vulnerabilidade destes grupos, relacionada à complexidade sócio-econômica, deve ser considerada nos programas de prevençäo e controle da AIDS.(AU)

Prevention of HIV infection among migrant population groups in Northeast Brazil

A infecção pelo HIV entre pobres, mulheres e populações migrantes do interior do Nordeste Brasileiro vem crescendo. As diferentes configurações, crenças e representações e formas de organização do comportamento, associadas à capacidade de seguir adequadamente medidas de prevenção, foram o foco desta investigação. Os participantes foram localizados em bairros com altas taxas de migração através do Programa Saúde da Família em Fortaleza e Teresina. Empregou-se a metodologia qualitativa nesta investigação. Vários sistemas de crenças, valores e organização social da sexualidade desta população representam obstáculos à prevenção da AIDS e inibem o uso do preservativo. Pobreza, falta de perspectiva e medo estão associados à situação de pobreza, exclusão social e preconceito e à total ausência de direitos humanos. Quando examinados conjuntamente, estes fatores definem diferentes configurações dos migrantes com uma elevada vulnerabilidade ao HIV/AIDS. A alta vulnerabilidade destes grupos, relacionada à complexidade sócio-econômica, deve ser considerada nos programas de prevenção e controle da AIDS.