Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.

BACKGROUND: Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron's emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. METHODS AND FINDINGS: Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose. CONCLUSIONS: We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.

Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.

BACKGROUND: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). METHODS: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. FINDINGS: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks. INTERPRETATION: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

CoronaVac vaccine is effective in preventing symptomatic and severe COVID-19 in pregnant women in Brazil: a test-negative case-control study.

BACKGROUND: More doses of CoronaVac have been administered worldwide than any other COVID-19 vaccine. However, the effectiveness of COVID-19 inactivated vaccines in pregnant women is still unknown. We estimated the vaccine effectiveness (VE) of CoronaVac against symptomatic and severe COVID-19 in pregnant women in Brazil. METHODS: We conducted a test-negative design study in all pregnant women aged 18-49 years with COVID-19-related symptoms in Brazil from March 15, 2021, to October 03, 2021, linking records of negative and positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test-positive cases with notifications of severe, hospitalised or fatal COVID-19. Using logistic regression, we estimated the adjusted odds ratio and VE against symptomatic COVID-19 and against severe COVID-19 by comparing vaccine status in test-negative subjects to test-positive symptomatic cases and severe cases. RESULTS: Of the 19,838 tested pregnant women, 7424 (37.4%) tested positive for COVID-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received the first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic COVID-19. The effectiveness of two doses of CoronaVac was 41% (95% CI 27.1-52.2) against symptomatic COVID-19 and 85% (95% CI 59.5-94.8) against severe COVID-19. CONCLUSIONS: A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic COVID-19 and highly effective against severe illness in a setting that combined high disease burden and marked COVID-19-related maternal deaths.

Congenital Zika syndrome and living conditions in the largest city of northeastern Brazil.

BACKGROUND: The Zika virus (ZIKV) epidemic hit Brazil in 2015 and resulted in a generation of children at risk of congenital Zika syndrome (CZS). The social vulnerability of certain segments of the population contributed to the disproportional occurrence of CZS in the Brazilian Northeast, the poorest region in the country. Living conditions are essential factors in understanding the social determination of CZS, which is embedded in a complex interaction between biological, environmental, and social factors. Salvador, the biggest city in the region, played a central role in the context of the epidemic and was a pioneer in reporting the ZIKV infection and registering a high number of cases of CZS. The aim of the study was identifying the incidence and spatial distribution pattern of children with CZS in the municipality of Salvador, according to living conditions. METHODS: This is an ecological study that uses the reported cases of ZIKV and CZS registered in the epidemiological surveillance database of the Municipal Secretariat of Health of the city of Salvador between August of 2015 and July of 2016. The neighborhoods formed the analysis units and the thematic maps were built based on the reported cases. Associations between CZS and living conditions were assessed using the Kernel ratio and a spatial autoregressive linear regression model. RESULTS: Seven hundred twenty-six live births were reported, of which 236 (32.5%) were confirmed for CZS. Despite the reports of ZIKV infection being widely distributed, the cases of CZS were concentrated in poor areas of the city. A positive spatial association was observed between living in places with poorer living conditions and births of children with CZS. CONCLUSIONS: This study shows the role of living conditions in the occurrence of births of children with CZS and indicates the need for approaches that recognize the part played by social inequalities in determining CZS and in caring for the children affected.

Does deforestation drive visceral leishmaniasis transmission? A causal analysis.

Vector-borne diseases (VBDs) are important contributors to the global disease burden and are a key factor in perpetuating economic inequality. Although environmental changes are often cited as drivers of VBDs, the link between deforestation and VBD occurrence remains unclear. Here, we examined this relationship in detail using the spread of visceral leishmaniasis (VL) in São Paulo state (Brazil) as the case study. We used a two-step approach to estimate the causal effects (overall, direct, and indirect) of deforestation on the occurrence of the VL vector, canine visceral leishmaniasis (CVL), and human visceral leishmaniasis (HVL). We first estimated the parameters via a double Metropolis-Hastings algorithm and then estimated the causal effects through a Gibbs sampler. We observed that the odds of vector, CVL, and HVL occurrence were 2.63-, 2.07-, and 3.18-fold higher, respectively, in deforested compared with forested municipalities. We also identified a significant influence of the presence of vector, CVL, and HVL in one municipality on disease occurrence in previously naive neighbouring municipalities. Lastly, we found that a hypothetical reduction in deforestation prevalence from 50 to 0% across the state would reduce vector, CVL, and HVL occurrence by 11%, 6.67%, and 29.87%, respectively. Our results suggest that implementing an eco-friendly development strategy that considers trade-offs between agriculture, urbanization, and conservation could be an effective mechanism of controlling VL.

Changes in malaria patterns in Brazil over 28 years (1990-2017): results from the Global Burden of Disease Study 2017.

BACKGROUND: This study presents the malaria burden in Brazil from 1990 to 2017 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), by analyzing disease burden indicators in federated units of the Legal Amazon and Extra-Amazon regions, as well as describing malaria cases according to Plasmodium species occurring in the country. METHODS: We used estimates from the GBD 2017 to report years of life lost due to premature death (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) for malaria in Brazil, grouped by gender, age group, and Brazilian federated unit, from 1990 to 2017. Results are presented as absolute numbers and age-standardized rates (per 100,000 inhabitants) with 95% uncertainty intervals (UI). RESULTS: At the national level, the age-standardized DALYs rate due to malaria decreased by 92.0%, from 42.5 DALYs per 100,000 inhabitants (95% UI 16.6-56.9) in 1990 to 3.4 DALYs per 100,000 inhabitants (95% UI 2.7-4.7) in 2017. The YLLs were the main component of the total DALYs rate for malaria in 1990 (67.3%), and the YLDs were the main component of the metric in 2017 (61.8%). In 2017, the highest sex-age DALYs rate was found among females in the "< 1-year-old" age group, with a 6.4 DALYs per 100,000 inhabitants (95% UI 1.8-14.7) and among males in the age group of "20 to 24 years old", with a 4.7 DALYs per 100,000 inhabitants (95% UI 3.3-9.9). Within the Brazilian Amazon region, the three federated units with the highest age-standardized DALYs rates in 2017 were Acre [28.4 (95% UI 14.2-39.1)], Roraima [28.3 (95% UI 13.5-40.2)], and Rondônia [24.7 (95% UI 11.4-34.8)]. Concerning the parasite species that caused malaria, 73.5% of the total of cases registered in the period had Plasmodium vivax as the etiological agent. CONCLUSIONS: The results of the GBD 2017 show that despite the considerable reduction in the DALYs rates between 1990 and 2017, malaria remains a relevant and preventable disease, which in recent years has generated more years of life lost due to disability than deaths. The states endemic for malaria in the Amazon region require constant evaluation of preventive and control measures. The present study will contribute to the direction of current health policies aimed at reducing the burden of malaria in Brazil, as knowing the geographical and temporal distribution of the risk of death and disability of this disease can facilitate the planning, implementation, and improvement of control strategies aimed at eliminating the disease.

The burden of tuberculosis and attributable risk factors in Brazil, 1990-2017: results from the Global Burden of Disease Study 2017.

BACKGROUND: Tuberculosis (TB) continues to be an important cause of fatal and non-fatal burden in Brazil. In this study, we present estimates for TB burden in Brazil from 1990 to 2017 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017). METHODS: This descriptive study used GBD 2017 findings to report years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of TB in Brazil by sex, age group, HIV status, and Brazilian states, from 1990 to 2017. We also present the TB burden attributable to independent risk factors such as smoking, alcohol use, and diabetes. Results are reported in absolute number and age-standardized rates (per 100,000 inhabitants) with 95% uncertainty intervals (UIs). RESULTS: In 2017, the number of DALYs due to TB (HIV-negative and HIV-positive combined) in Brazil was 284,323 (95% UI: 240,269-349,265). Among HIV-negative individuals, the number of DALYs was 196,366 (95% UI: 189,645-202,394), while 87,957 DALYs (95% UI: 50,624-146,870) were estimated among HIV-positive individuals. Between 1990 and 2017, the absolute number and age-standardized rates of DALYs due to TB at the national level decreased by 47.0% and 68.5%, respectively. In 2017, the sex-age-specific TB burden was highest among males and in children under-1 year and the age groups 45-59 years. The Brazilian states with the highest age-standardized DALY rates in 2017 were Rio de Janeiro, Pernambuco, and Amazonas. Age-standardized DALY rates decreased for all 27 Brazilian states between 1990 and 2017. Alcohol use accounted for 47.5% of national DALYs due to TB among HIV-negative individuals in 2017, smoking for 17.9%, and diabetes for 7.7%. CONCLUSIONS: GBD 2017 results show that, despite the remarkable progress in reducing the DALY rates during the period, TB remains as an important and preventable cause of health lost to due premature death and disability in Brazil. The findings reinforce the importance of strengthening TB control strategies in Brazil through integrated and multisectoral actions that enable the access to prevention, early diagnosis, and timely treatment, with emphasis on high-risk groups and populations most vulnerable to the disease in the country.

Utilisation of dental services by Brazilian adults in rural and urban areas: a multi-group structural equation analysis using the Andersen behavioural model.

BACKGROUND: The utilisation of health services is determined by complex interactions. In this context, rural populations face greater barriers in accessing dental services than do urban populations, and they generally have poorer oral health status. The evaluation of the determinants of health services utilisation is important to support planning and management of dental services. The aim of this study was to evaluate the predictors of dental services utilisation of Brazilian adults living in rural and urban areas. METHODS: Data from 60,202 adults aged 18 years or older who took part in the Brazilian National Health Survey carried out in 2013 were analysed. Predisposing (age, sex, education, social networks), enabling financing (income, durable goods and household's crowding), enabling organisation (health insurance, registration in primary health care [PHC]) and need variables (eating difficulties, self-perceived tooth loss and self-perceived oral health) were selected based upon the Andersen behavioural model. Multi-group structural equation modeling assessed the direct and indirect associations of independent variables with non-utilisation of dental services and the interval since the last dental visit for individuals living in rural and urban areas. RESULTS: Adults living in urban areas were more likely to use dental services than those living in rural areas. Lower enabling financing, lower perceived dental needs and lack of PHC registration were directly associated with lower utilisation of dental services (non-utilisation, ß = - 0.36, ß = - 0.16, ß = - 0.03, respectively; and interval since last dental visit, ß = 1.25, ß = 0.82, ß = - 0.12, respectively). The enabling financing (non-utilisation, ßrural = - 0.02 [95%CI: - 0.03 to - 0.02], ßurban = 0.00 [95%CI: - 0.01 to 0.00]) and PHC registration (non-utilisation, ßrural = - 0.03 [95%CI: - 0.04 to - 0.02], ßurban = - 0.01 [95%CI, - 0.01 to - 0.01]) non-standardised total effects were stronger in rural areas. Enabling organisation (ß = 0.16) and social network (ß = - 2.59) latent variables showed a direct effect on the interval since last dental visit in urban areas. Education and social networks influenced utilisation of dental services through different pathways. Males showed less use of dental services in both urban and rural areas (non-utilisation, ßrural = - 0.07, ßurban = - 0.04; interval since last dental visit, ßrural = - 0.07, ßurban = - 0.07) and older adults have used dental services longer than younger ones, mainly in rural areas (ßrural = 0.26, ßurban = 0.17). CONCLUSION: Dental services utilisation was lower in rural areas in Brazil. The theoretical model was supported by empirical data and showed different relationships between the predictors in the two geographical contexts. In rural areas, financial aspects, education, primary care availability, sex and age were relevant factors for the utilisation of services.

Social determinants of pulmonary tuberculosis in Brazil: an ecological study.

BACKGROUND: Social determinants may influence the incidence and control of tuberculosis (TB). The aim of this study was to evaluate the correlation between social determinants and pulmonary TB (PTB) incidence and treatment outcomes in different regions in Brazil. METHODS: In this ecological study, PTB incidence and treatment outcome rates as well as HIV incidence for all 5560 Brazilian cities as reported to the Brazilian Tuberculosis Program in 2010 were correlated with two social indicators, the Human Development Index (HDI) and Gini Index (GI). Cities were stratified into six groups based on location (metropolitan region or not) and size (small, medium, and large cities), and according to the regions of the country to which they belong. The Spearman correlation coefficient was used to assess the association between variables. RESULTS: In 2010, 68,729 new PTB cases were reported in Brazil, with an incidence rate of 36 cases per 100,000 inhabitants. Incidence rates and PTB mortality demonstrated a weak negative correlation with HDI and a positive correlation with GI. The correlation between HDI and GI with cure, relapse, and lost to follow-up of treatment greatly varied in the different groups of cities and regions of the country evaluated. CONCLUSIONS: There is a weak correlation between HDI and GI and PTB incidence and mortality rate. However, there is great variation between the HDI and GI and cure, relapse, and lost to follow-up in the different groups of cities and regions of the country. This suggests that for TB determination, these outcome variables might be more related to the quality of healthcare provided by services than to social determinants in the general population.

Analytical validation of real-time quantitative PCR assays for optimum diagnosis of vivax malaria.

BACKGROUND: The prompt diagnosis of plasmodial species for effective treatment prevents worsening of individual health and avoids transmission maintenance or even malaria reintroduction in areas where Plasmodium does not exist. Polymerase chain reaction (PCR) allows for the detection of parasites below the threshold of microscopic examination. OBJECTIVE: Our aim was to develop a real-time PCR test to reduce diagnostic errors and increase efficacy. METHODS: The lower limit of quantification and the linearity/analytical sensitivity to measure sensitivity or limit of detection (LoD) were determined. Intra-assay variations (repeatability) and alterations between assays, operators, and instruments (reproducibility) were also assessed to set precision. FINDINGS: The linearity in SYBR™ Green and TaqMan™ systems was 106 and 102 copies and analytical sensitivity 1.13 and 1.17 copies/µL, respectively. Real-time PCR was more sensitive than conventional PCR, showing a LoD of 0.01 parasite (p)/µL. Reproducibility and repeatability (precision) were 100% for up to 0.1 p/µL in SYBR™ Green and 1 p/µL in TaqMan™ and conventional PCR. CONCLUSION: Real-time PCR may replace conventional PCR in reference laboratories for P. vivax detection due to its rapidity. The TaqMan™ system is the most indicated when quantification assays are required. Performing tests in triplicate when diagnosing Plasmodium-infected-asymptomatic individuals is recommended to minimise diagnostic errors.

Effectiveness of dog collars impregnated with 4% deltamethrin in controlling visceral leishmaniasis in Lutzomyia longipalpis (Diptera: Psychodidade: Phlebotominae) populations.

BACKGROUND: There is little information on the effect of using deltamethrin-impregnated dog collars for the control of canine visceral leishmaniasis. OBJECTIVES: The objective of this study was to evaluate the effectiveness of the use of 4% deltamethrin-impregnated collars (Scalibor®) in controlling visceral leishmaniasis in Lutzomyia longipalpis by comparing populations in intervention and non-intervention areas. METHODS: Phlebotomine flies were captured over 30 months in four neighbourhoods with intense visceral leishmaniasis transmission in Fortaleza and Montes Claros. We calculated the rates of domicile infestation, relative abundance of Lu. longipalpis, and Lu. longipalpis distribution in each site, capture location (intra- and peridomestic locations) and area (intervention and non-intervention areas). FINDINGS: In the control area in Fortaleza, the relative abundance of Lu. longipalpis was 415 specimens at each capture site, whereas in the intervention area it was 159.25; in Montes Claros, the relative abundance was 5,660 specimens per capture site in the control area, whereas in the intervention area it was 2,499.4. The use of dog collars was associated with a reduction in captured insects of 15% (p = 0.004) and 60% (p < 0.001) in Montes Claros and Fortaleza, respectively. MAIN CONCLUSIONS: We observed a lower vector abundance in the intervention areas, suggesting an effect of the insecticide-impregnated collars.

Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection.

In Brazil, human and canine visceral leishmaniasis (CVL) caused by Leishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescence assays (IFA) as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA), decreased sensitivity (83.3%) and increased specificity (92.5%) were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL.

Lipoprotein lipase and PPAR alpha gene polymorphisms, increased very-low-density lipoprotein levels, and decreased high-density lipoprotein levels as risk markers for the development of visceral leishmaniasis by Leishmania infantum.

In visceral leishmaniasis (VL) endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C), elevated triacylglycerol (TAG), and elevated very-low-density lipoprotein cholesterol (VLDL-C) levels. A polymorphism analysis of the lipoprotein lipase (LPL) gene using HindIII restriction digestion (N = 156 samples) (H+ = the presence and H- = the absence of mutation) revealed an increased adjusted odds ratio (OR) of VL versus noninfected individuals when the H+/H+ was compared with the H-/H- genotype (OR = 21.3; 95% CI = 2.32-3335.3; P = 0.003). The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05) and reduced HDL-C levels (P < 0.05). An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα) gene (n = 248) revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41-78.70; P = 0.014). High TAG (P = 0.021) and VLDL-C (P = 0.023) levels were associated with susceptibility to VL, whereas low HDL (P = 0.006) levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

Partial recovery of tuberculosis preventive treatment in Brazil after pandemic drawback.

Brazil was heavily affected by COVID-19 both with death toll and economically, with absence of a centralized Federal Government response. Tuberculosis (TB) notifications decreased in 2020 but partial recovery was observed in 2021. We have previously shown a sharp (93%) reduction in TB preventive treatment notifications among five Brazilian cities with more than 1,000 notifications in 2021. We hypothesized TB preventive treatment would also recover. We updated the previous analysis by adding other cities that hold more than a 1,000 notifications until 2022. Data aggregated by 2-week periods were extracted from the Information System for Notifying People Undergoing Treatment for LTBI (IL-TB). Biweekly percentage change (BPC) of notifications until October 2022 and outcomes until July 2022 (in the two weeks of TB preventive treatment initiation) were analyzed using Joinpoint software. A total of 39,701 notifications in 11 cities were included, 66% from São Paulo and Rio de Janeiro, Brazil. We found a significant increase of TB preventive treatment notifications in the beginning of 2021 (BPC range 1.4-49.6), with sustained progression in seven out of the 11 cities. Overall, median completion rates were 65%. In most cities, a gradual and steady decrease of treatment completion rates was found, except for Rio de Janeiro and Manaus (Amazonas State, Brazil), where a BPC of 1.5 and 1.2, respectively, was followed by a sustained increase. Notifications and completion proportions of TB preventive treatment were heterogeneous, which partly reflects the heterogeneity in local response to the pandemic. We found that notifications were recovered, and that the sharp 2021 decrease was no longer observed, which suggests delays in notification. In conclusion, the sharp reductions in TB preventive treatment completion rates in most cities might have been caused by delays in reporting; however, the sustained and progressive decrease are a concern.

Impact of 4% Deltamethrin-Impregnated Dog Collars on the Incidence of Human Visceral Leishmaniasis: A Community Intervention Trial in Brazil.

BACKGROUND: In Brazil, human visceral leishmaniasis (HVL) is caused by the protozoan parasite Leishmania infantum, primarily transmitted by the sand fly Lutzomyia longipalpis, with dogs acting as the main urban reservoir. This study aims to evaluate the effectiveness of 4% deltamethrin-impregnated dog collars (DMC) on HVL incidence. METHODS: This is a community intervention study carried out from 2012 to 2015 in the municipalities of Araguaína, State of Tocantins, and Montes Claros, State of Minas Gerais, Brazil. Two areas in each were randomly allocated to either (1) culling seropositive dogs + residual insecticide spraying (control area-CA) or (2) culling seropositive dogs + residual insecticide spraying + DMC fitted to dogs every six months for two years (intervention area-IA). Cases of HVL (n = 1202) occurring from 2008 to 2020 were identified from the Brazilian Reportable Diseases Information System and georeferenced to the control and intervention areas. The HVL cases from 2008 to 2012 were considered as occurring in the "pre-intervention" period. Those cases from 2013 to 2016 and from 2017 to 2020 were regarded as occurring in the "intervention" and "post-intervention" periods, respectively. We used a mixed-effects Poisson regression model to estimate the effectiveness of the intervention, comparing the changes from the pre-intervention period to the intervention and post-intervention periods in the control and intervention areas. RESULTS: In Araguaína, there was a statistically significant reduction in the incidence of HVL in both the control and intervention areas, comparing both the intervention and post-intervention periods with the pre-intervention period. The intervention with DMC was significantly associated with a reduction in HVL when comparing the intervention and pre-intervention periods, yielding an effectiveness estimate of the DMC of 27% (IC95% 1-46%, p = 0.045). No differences were observed when comparing the pre- and post-intervention periods (p = 0.827). In Montes Claros, cases reduced in both the control and intervention areas from the pre-intervention period to the intervention period (p = 0.913). In the post-intervention period, the incidence increased in the control area, while cases continued to decrease in the DMC area (p = 0.188). CONCLUSIONS: The use of DMC was associated with a reduction of 27% in the incidence of HVL during the period of DMC delivery, indicating that DMC is effective as an additional strategy for controlling visceral leishmaniasis in Brazil. However, no significant reduction associated with DMC was detected after the intervention period, suggesting that a control program based on the large-scale deployment of DMC might have to be maintained for more extended periods without interruption.

Spatio-temporal dynamics of visceral leishmaniasis in Brazil: A nonlinear regression analysis.

AIMS: This study describes the spatio-temporal dynamics of new visceral leishmaniasis (VL) cases notified in Brazil between 2001 and 2020. METHODS AND RESULTS: Data on the occurrence of the disease were obtained by means of the Notifiable Diseases Information System of the Brazilian Ministry of Health. Joinpoint, temporal generalized additive models and conditional autoregressive (CAR) models were used to analyse the temporal evolution of the rates in Brazil, states and regions. Spatio-temporal generalized additive and CAR models were used to identify the distribution of annual risks of VL occurrence in the Brazilian territory in relation to variation in the spatial average. There were 63,966 VL cases in the target period (3.198 cases/year), corresponding to a mean incidence rate of 1.68 cases/100,000 inhabitants. Of these, 4451 resulted in deaths, which gives a mean mortality rate of 0.12 deaths/100,000 inhabitants and a case fatality of 6.96%. The highest incidence rate was found in the North region, followed closely by the Northeast region, which presented the second and first highest mortality rates, respectively. For all of Brazil, and in the Northeast region, there were stability in the incidence rates, while the other regions showed an increasing trend in different time segments in the period: Central-West up to 2011, North up to 2008, Southeast up to 2004, and South up to 2010. On the other hand, all regions experienced a reduction in incidence rate during the last years of the series. The Northeast region had the highest number of municipalities with statistically significant elevated relative risks. The spatio-temporal analysis showed the highest risk area predominantly in the Northeast region in the beginning of the time series. From 2002 to 2018, this area expanded to the interior of the country. CONCLUSIONS: The present study has shown that VL has expanded in Brazil. However, the North and Northeast regions continue to have the highest incidence, and the risk of infection has decreased in recent years.

Tegumentary leishmaniasis in Brazil: priority municipalities and spatiotemporal relative risks from 2001 to 2020.

Understanding the distribution of tegumentary leishmaniasis (TL) in different periods enables the adequate conduction of actions at the public health level. The present study analyzes the spatiotemporal evolution of TL incidence rates in the municipalities of Brazil and identifies priority areas from 2001 to 2020. Notifications of new cases were analyzed employing space-time scan statistics and Local Indicators of Spatial Association. As TL incidence rates presented a downward trend in most Brazilian municipalities, spatiotemporal clusters of high relative risks (RR) were more frequent in the first decade of the series. There was a concentration of those clusters in the North and Northeast regions, mainly in the Legal Amazon area. More recent high-RR areas were identified in municipalities of different regions. The number of priority municipalities showed a stable trend in Brazil. There was a great concentration of such municipalities in the states of Acre, Mato Grosso, Rondônia, Pará, and Amapá, as well as large areas in Roraima, Amazonas, Maranhão, and Tocantins, and smaller areas in the states of Goiás, Ceará, Bahia, Minas Gerais, São Paulo, and Paraná. The present study contributes to the understanding of the historical evolution of TL in Brazil and subsidizes actions to combat the disease.