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.

Towards an inclusive digital literacy: An experimental intervention study in a rural area of Brazil.

About half of the world's population remains without access to internet in an era of digital transformation. In this study, we aimed to investigate the impact of implementing the use of logic and mathematics through digital literacy on a population of elementary school students in a town in Northeast Brazil. In a non-randomized experimental longitudinal intervention study, 5th-grade students were followed during one semester. They underwent observational testing during class with the use of scales to evaluate their activities in a digital environment, and they were evaluated with respect to their ability to use digital devices. A logic/math assessment was applied prior to and at the end of the course for intervention group and compared to a control group. Questionnaires were used to assess the educators', legal guardians' and students' perceptions on digital habits and their respective sociodemographic features. The intervention consisted of a 16-h long course developed consisting of 8 2-h long classes which focused on digital technology, digital culture, and computational thinking. The students had a strong interest in the classes. Although some students did not have prior contact with computers, their development was outstanding. Digital literacy competencies and technology-use behavior increased throughout the semester independent of family income and use of digital devices at home. Students progressively improved their interaction with the computer (e.g. touchpad and typing skills) and their confidence in the digital environment. Students' scores on the logic/math assessment showed significant improvement. This was not observed in the control group, demonstrating the importance of this type of intervention even with one provided by a 16-h course. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10639-021-10711-z.

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.

Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis.

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

Preeclampsia is associated with increased maternal body weight in a northeastern Brazilian population.

BACKGROUND: Preeclampsia is a disease with great variability in incidence across the world. The mortality is higher in lower income countries, where it is the leading cause of maternal mortality. This study aimed to determine the frequency of and risk factors for preeclampsia in a low income population from an urban area of Brazil. METHODS: A prospective case control study of 242 women of which 30 developed preeclampsia, 4 had gestational hypertension, 2 had superimposed hypertension, 11 had spontaneous abortion, 13 were lost to follow up and 192 had normal pregnancy. This latter group was considered the normotensive controls. The rate of preeclampsia and the risk of cardiovascular disease, after onset of preeclampsia, were determined. RESULTS: Of the 218 women who completed the study, the frequency of hypertensive disorder of pregnancy was 16.5% (36 of 218) and of preeclampsia was 13.8% (30 of 218). Women with preeclampsia had a higher body mass index (BMI), mean of 25.3 ± 4.8 compared to 23.5 ± 3.7 for the normotensive controls, p = 0.02. The risk of preeclampsia increased with BMI [Odds ratio (OR) 1.12, 95% Confidence Interval (CI = 1.02;1.24, p-value = 0.023)]. Women with preeclampsia developed chronic hypertension more often than normotensive controls (p = 0.043) and their systolic and ambulatory blood pressure monitoring was elevated (p = 0.034). Women with preeclampsia had higher BMI even 5 years post-pregnancy (p = 0.008). CONCLUSIONS: Women who are overweight or older have an increased risk of preeclampsia. Previous history of preeclampsia increases the risk of early onset of chronic hypertension. Therefore, effective preventive measures are needed, particularly women at lower social economic stratum who have less access to proper medical care and adequate nutrition.

Geographic information systems and applied spatial statistics are efficient tools to study Hansen's disease (leprosy) and to determine areas of greater risk of disease.

Applied Spatial Statistics used in conjunction with geographic information systems (GIS) provide an efficient tool for the surveillance of diseases. Here, using these tools we analyzed the spatial distribution of Hansen's disease in an endemic area in Brazil. A sample of 808 selected from a universe of 1,293 cases was geocoded in Mossoró, Rio Grande do Norte, Brazil. Hansen's disease cases were not distributed randomly within the neighborhoods, with higher detection rates found in more populated districts. Cluster analysis identified two areas of high risk, one with a relative risk of 5.9 (P = 0.001) and the other 6.5 (P = 0.001). A significant relationship between the geographic distribution of disease and the social economic variables indicative of poverty was observed. Our study shows that the combination of GIS and spatial analysis can identify clustering of transmissible disease, such as Hansen's disease, pointing to areas where intervention efforts can be targeted to control disease.

Effect of abiotic factors on seasonal population dynamics of Lutzomyia longipalpis (Diptera: Psychodidae) in northeastern Brazil.

The resurgence of visceral leishmaniasis in Brazil increases the need for studies to elucidate the spatial and temporal dynamics of Lutzomyia longipalpis (Lutz and Neiva) (Diptera: Psychodidae), the vector of Leishmania infantum, the causative agent of visceral leishmaniasis in Brazil. Sand flies were captured in peridomestic habitats biweekly for 3 yr. Cross-correlation tests and spectral analysis were used to analyze the simultaneous and lag-time correlations between Lu. longipalpis population densities and abiotic factors of temperature, relative humidity, wind velocity, and rainfall. Distinct seasonal patterns were observed for males and females, with intervals of 6 mo between population peaks for males and 12 mo for females. Peak female population densities lagged 3 mo behind the maximum annual temperature. Female population density was negatively correlated with relative humidity. An increase in average wind velocity was followed by a decrease in the number of females for 2 wk. Understanding the relationship between the seasonal population dynamics of Lu. longipalpis and abiotic factors will contribute to the design of better control measures to decrease transmission of L. infantum and consequently the incidence of leishmaniasis.

Estudo de parâmetros salivares em crianças asmáticas usuárias de antiinflamatórios / Study of salivary parameters in asthmatic children using anti-inflammatory agents

Este estudo longitudinal compreendeu um período de 210 dias, durante os quais os parâmetros salivares pH, capacidade tampäo (CTS), velocidade do fluxo salivar (VFS) e o percentual do cálcio foram analisados mensalmente, em 14 crianças asmáticas, entre 7-13 anos de idade, usuárias de aerossol de dipropionato de beclometasona (DPB) e de cromoglicato de sódio (CGD) por igual período de 90 dias, e um grupo-controle de 35 crianças clinicamente saudáveis, näo-usuárias de medicaçäo, com a mesma faixa etária. No tratamento estatístico, utilizou-se o teste T para amostras independentes, a fim de verificar se o uso das medicaçöes por 30 dias afetaria alguns fatores de proteçäo salivar do grupo experimental em relaçäo ao grupo-controle e comparar longitudinalmente os efeitos das medicaçöes na saliva das crianças asmáticas. Concluiu-se que as alteraçöes desses fatores observadas durante o uso do DPB e CGD reforçam a necessidade de lavagem da cavidade oral após o uso dessas medicaçöes e a preconizaçäo de medidas odontológicas preventivas durante o tratamento da asma brônquica com aerossol por tempo prolongado.

Mastócitos no granuloma periapicodental / Mast cells in periapical granuloma

This paper describes a study that was carried out about the relationship between the age of the patient and the quantity of mastocites in the periapicodental granuloma. The analyses of quantitative variation concerning the entities studied did not show interference of this factor in the minor or higher ocurrence of the cells population on the studie material