T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leishmania infantum co-infection.

Background: Leishmania infantum is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a ~5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL. Methods: A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in HIV positive subjects residing in the state of Rio Grande do Norte, Brazil (n=1,372) and of these a subgroup of subjects were followed longitudinally. Subsequent incident cases of VL were ascertained from a public health database through 2018. A subgroup (n=69) of the cross-sectional study subjects was chosen to assess immune status (T cell activation, senescence, exhaustion) and outcome. The data were compared between asymptomatic HIV+/L. infantum+ (HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response - Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/Non L. infantum infection (control subjects). Results: The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG Leishmania antibodies. After 3 years, 2.4% (8 of 333) of these HIV/Leish coinfected subjects developed AIDS/VL, whereas 1.05% (11 of 1,039) of HIV subjects with negative leishmania serology developed AIDS/VL. Poor adherence to antiretroviral therapy (p=0.0008) or prior opportunistic infections (p=0.0007) was associated with development of AIDS/VL. CD4+ (p=0.29) and CD8+ (p=0.38) T cells counts or viral load (p=0.34) were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV group. Likewise, senescent (CD57+) or exhausted (PD1+) CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. Conclusion: Although asymptomatic HIV/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8+T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL.

Changing demographics of visceral leishmaniasis in northeast Brazil: Lessons for the future.

BACKGROUND: Visceral leishmaniasis (VL) caused by Leishmania infantum became a disease of urban areas in Brazil in the last 30 years and there has been an increase in asymptomatic L. infantum infection with these areas. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of human VL was performed in the state of Rio Grande do Norte, Brazil, for the period of 1990-2014. The data were divided into five-time periods. For all VL cases, data on sex, age, nutritional status and childhood vaccination were collected. Geographic information system tools and statistical models were used to analyze the dispersion of human VL. The mean annual incidence of VL was 4.6 cases/100,000 inhabitants, with total 3,252 cases reported. The lethality rate was 6.4%. Over time the annual incidence of VL decreased in the 0-4 years (p<0.0001) and 5-9 (p <0.0001) age groups, but increased in ages 20-39 (p<0.001) and >40 years (p<0.0001). VL occurred more often in males (ß2 = 2.5; p<0.0001). The decreased incidence of VL in children was associated with improved nutritional status and childhood immunizations including measles, poliomyelitis, BCG, and hepatitis B. Human VL correlated temporally and geographically with canine L. infantum infection (p = 0.002, R2 = 0.438), with rainfall and with Lutzomyia longipalpis density (r = 0.762). Overall, the incidence of VL decreased, while VL-AIDS increased, especially between 2010-2014. VL was more frequently found in areas that lacked urban infrastructure, detected by lack of garbage collection and sewers, whereas HIV infection was associated with higher levels of schooling and evidence of higher socioeconomic status. CONCLUSION/SIGNIFICANCE: The demographics of VL in northeastern Brazil have changed. Disease incidence has decreased in children and increased in adults. They were associated with improvements in nutrition, socioeconomic status and immunization rates. Concurrent VL-AIDS poses a serious challenge for the future.

Fatores sociodemográficos associados com a mortalidade de mulheres em idade fértil no Rio Grande do Norte / Factores sociodemográficos asociados con la mortalidad de mujeres en edad fértil en Río Grande do Norte / Sociodemographic factors associated with mortality of women in fertile age in Rio Grande do Norte

Objective: Identifying sociodemographic factors associated with mortality of women in fertile age in Rio Grande do Norte in the period from 2006 to 2010. Method: a descriptive, quantitative study with collected data through the Mortality Information System and processed by the test of association chi-square. Results: 59.1% of the deaths occurred from preventable causes and the main underlying causes: cancer, heart disease and circulatory system and external causes. Deaths grow proportionally with age and wereassociated with: educational attainment, occupation and origin of the institution of occurrence. Conclusion: the results indicate weaknesses in the quality of care and point to the need of investing inactions that reduce inequality in access to primary care services that ensure quality and resolution at all levels of health care.

Objetivo: Identificar os fatores sociodemográficos associados com a mortalidade de mulheres em idade fértil do Rio Grande do Norte no período de 2006 a 2010. Método: Estudo descritivo, quantitativo com dados coletados através do Sistema de Informação de Mortalidade e processados pelo teste de associaçãoqui-quadrado. Resultados: 59,1% dos óbitos ocorreram por causas evitáveis sendo as principais causasbásicas: neoplasias, doenças cardíacas e do aparelho circulatório e causas externas. Os óbitos crescem proporcionalmente com a faixa etária e foram associados com anos de estudo, ocupação e origem da instituição de ocorrência. Conclusão: os resultados indicam fragilidades na qualidade da assistência oferecida e apontam para a necessidade de investimentos em ações que reduzam a desigualdade no acesso aos serviços de atendimento básico garantindo qualidade e resolutividade em todos os níveis de atenção asaúde.

Objetivo: Identificar los factores sociodemográficos asociados con la mortalidad de mujeres de edad fértilde Río Grande do Norte en el periodo 2006 hasta 2010. Método: estudio descriptivo, cuantitativo con datos colectados por el Sistema de Información de mortalidad y procesados de pruebas de asociación por qui-cuadrado. Resultados: 59,1% de las muertes ocurrieron en situaciones evitables y las principales causas básicas eran neoplasias, enfermedades cardiacas y de aparejo circulatorio y causas externas. Las muertesaumentaron proporcionalmente con el grupo de edad y fueron asociadas con: años de estudio, ocupación y origen de la institución de ocurrencia.Conclusión: los resultados indican debilidad en la cualidad de la asistencia ofrecida a la populación estudiada e indican la necesidad de investimentos en acciones que reduzcan la desigualdad en el acceso a los servicios de atendimiento básico que aseguren la cualidad y los resultados en todos los niveles de atención a la salud.