Disease burden of congenital Zika virus syndrome in Brazil and its association with socioeconomic data.

Zika virus (ZIKV) infection became a global public health concern, causing an epidemic in Latin America from 2015 to 2016, when a sudden increase in cases of microcephaly and other congenital anomalies was observed. In 2016, the Centers for Disease Control and Prevention and the World Health Organization defined congenital Zika-associated syndrome (CZS) as a set of congenital anomalies seen in children born to mothers with a history of gestational Zika fever, who have microcephaly as the most prevalent clinical sign. In order to describe the magnitude of CZS in Brazil, this study estimated the burden of disease due to CZS in Brazil using the disability-adjusted life years (DALY) indicator and other frequency measures, such as incidence and mortality rate, during the years 2015-2020. The association of these indicators with socioeconomic variables was also evaluated using Spearman's correlation coefficient. Choropleth maps were used to evaluate the spatial distribution of the indicators evaluated and the spatial autocorrelation was verified by the Bivariate Moran Local Index. From 2015 to 2020, 3,591 cases of CZS were confirmed in Brazil, with an incidence of 44.03 cases per 1000 live births, and a specific mortality of 12.35 deaths per 1000 live births. A global loss of 30,027.44 DALYs was estimated from 2015 to 2020. The Northeast region had the highest values for all health indicators assessed. Spatial correlation and autocorrelation analyses showed significant associations between health and socioeconomic indicators, such as per capita income, Gini index, illiteracy rate and basic sanitation. The study allowed us to have access to all reported cases of CZS, showing us the possible situation of the disease in Brazil; therefore, we believe that our results can help in the understanding of future studies.

Adherence to antiretroviral therapy in people living with HIV with moderate or severe mental disorder.

Human immunodeficiency virus (HIV) infection remains a serious public health concern, with an estimated 38 million people living with HIV (PLHIV). PLHIV are often affected by mental disorders at higher rate than the general population. One challenge in the control and prevention of new HIV infections is adherence to antiretroviral therapy (ART), with PLHIV with mental disorders having seemingly lower adherence than PLHIV without mental disorders. This cross-sectional study assessed adherence to ART in PLHIV with mental disorders who attended the Psychosocial Care Network health facilities in Campo Grande, Mato Grosso do Sul, Brazil, from January 2014 to December 2018. Data from health and medical databases were used to describe clinical-epidemiological profiles and adherence to ART. To assess the associated factors (potential risk or predisposing factors) with ART adherence, we used logistic regression model. Adherence was extremely low (16.4%). Factors associated with poor adherence were lack of clinical follow-up, particularly in middle-aged PLHIV. Other apparently associated factors were living on the streets and having suicidal ideation. Our findings reinforce the need for improvements in the care for PLHIV with mental disorders, especially in the integration between specialized mental health and infectious disease health facilities.

Congenital anomalies during the 2015-2018 Zika virus epidemic: a population-based cross-sectional study.

BACKGROUND: Congenital anomalies are associated with several clinical and epidemiological complications. Following the Zika epidemic onset in Latin America, the incidence of congenital anomalies increased in Brazil. This study aimed to determine the frequency of congenital anomalies in one Brazilian state and assess potential factors associated with them. METHODS: This cross-sectional descriptive study was based on data concerning congenital anomalies recorded in the Brazilian Live-Born Information System during the Zika epidemic in Mato Grosso do Sul state from 2015 to 2018. Congenital anomalies were stratified according to year of birth and classified using ICD-10 categories. RESULTS: In total, 1,473 (0.85%) anomalies were registered. Within the number of cases recorded, microcephaly showed the greatest frequency and variations, with a 420% increase observed in the number of cases from 2015 to 2016. We identified an increase in the incidence of central nervous system anomalies, with the highest peak observed in 2016 followed by a subsequent decrease. Musculoskeletal, nervous, and cardiovascular system anomalies, and eye, ear, face, and neck anomalies represented 73.9% of all recorded anomalies. There was an increased chance of congenital anomalies in uneducated (odds ratio [OR] 5.56, 95% confidence interval [CI] 2.61-11.84) and Indigenous (OR 1.32, 95% CI 1.03-1.69) women, as well as among premature births (OR 2.74, 95% CI 2.39-3.13). CONCLUSIONS: We estimated the incidence of congenital anomalies during the Zika epidemic. Our findings could help to support future research and intervention strategies in health facilities to better identify and assist children born with congenital anomalies.

Canine Visceral Leishmaniasis in an Area of Sporadic Transmission in Brazil.

Canine visceral leishmaniasis is a zoonotic disease caused by the protozoan Leishmania infantum in Latin America. Visceral leishmaniasis (VL) diagnosis in Brazil includes two serological tests according to the Ministry of Health (MH) protocol. Sensitivity and specificity of diagnostic tests, as well as clinical signs of VL, are usually reported in disease-endemic areas; however, it is known that local epidemiological factors can influence these results. This study aimed to evaluate the clinical features, sensitivity, and specificity of TR-DPP® and EIE-LVC in naturally infected dogs in a region of sporadic VL transmission to humans in Brazil. A total of 288 dogs were clinically evaluated and serological and parasitological (lymph node aspirates) samples were collected for VL diagnosis. TR-DPP and EIE-LVC showed poor sensitivity (0.62 and 0.44, respectively) to detect infected animals, compared with the direct parasitological examination, which is considered a gold standard method. Thus, the protocol of MH presented low sensitivity (0.42) to estimate prevalence and control measures in this region. TR-DPP presented a high negative predictive value (0.89), resulting in its indication as a confirmatory test in sporadic transmission areas. Classical clinical signs of VL were not frequently observed; therefore, clinical scoring systems might not be useful in this region. Veterinarians of nonendemic areas should be alert for asymptomatic dogs, especially those presenting lymph adenomegaly.

Neurological Development, Epilepsy, and the Pharmacotherapy Approach in Children with Congenital Zika Syndrome: Results from a Two-Year Follow-up Study.

Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant drugs, which in the long term are related to impairments in the child's neuropsychomotor development. Here, we describe the results from a two-year follow-up of a cohort of children diagnosed with CZS related to the growth of the head circumference and some neurological and motor outcomes, including the pharmacological approach, and its results in the treatment of epileptic seizures. This paper is part of a prospective cohort study carried out in the state of Mato Grosso Sul, Brazil, based on a Zika virus (ZIKV)-exposed child population. Our data were focused on the assessment of head circumference growth and some neurological and motor findings, including the description of seizure conditions and pharmacological management in two periods. Among the 11 children evaluated, 8 had severe microcephaly associated with motor impairment and/or epilepsy. Seven children were diagnosed with epilepsy. Of these, 3 had West syndrome. In four children with other forms of epilepsy, there was no pharmacological control.

Health demands and care of children with congenital Zika syndrome and their mothers in a Brazilian state.

BACKGROUND: A Zika virus (ZIKV) infection outbreak occurred in Brazil in 2015, accompanied by a marked increase in the number of newborns presenting with microcephaly and other neurological disorders. This characteristic set of birth defects was later termed congenital Zika syndrome (CZS). The therapeutic itinerary of mothers and children infected by ZIKV can be determined by several factors, including the relationship established with existing healthcare services. Here, we aimed to describe and analyze the extent to which children with CZS, born from 2015 to 2018 in the state of Mato Grosso do Sul, Brazil, and their mothers were treated according to the guidelines established by the Brazilian Ministry of Health. METHODS: This was a descriptive cross-sectional study that considered all children (and respective mothers) with confirmed or suspected CZS born in Mato Grosso do Sul. Children and their mothers were identified based on all suspected or confirmed cases of congenital anomalies in Mato Grosso do Sul that were reported to the Registry of Public Health Events. We analyzed data on the epidemiological profile of mother-child pairs and the care received by them. Data were summarized using statistical descriptive analysis. RESULTS: We showed that most mothers were white women (57%) with low income. Among pregnant women, 73% had a diagnosis of fever caused by ZIKV infection at a primary health care institution (PHCI), but only 36% received the necessary information regarding the risk of CZS. Over a third (36%) of the mothers did not receive guidance about childcare follow-up and 73% did not receive guidance regarding the availability of social support after childbirth. Gaps in medical care were observed mainly in pregnant women treated at a PHCI. Specialized assistance for children was adequate in most cases. Psychosocial support was not made available to women throughout their therapeutic itineraries. CONCLUSIONS: Here, we identified gaps in the care of families and children with disabilities, which can have an important impact on their quality of life. Beyond protocols, practical interventions must cover all the needs that arise throughout the therapeutic itineraries not only of children but also of pregnant women and mothers.

Synanthropy and diversity of Phlebotominae in an area of intense transmission of visceral leishmaniasis in the South Pantanal floodplain, Midwest Brazil.

Phlebotomines have been recorded from a wide variety of habitats, and some of these vector species have shown preference for human environments, with high levels of adaptation. This study evaluated the degree of preference of these vectors for urban, rural, and forested environments (synanthropic behavior), as well as the diversity of these species, in three areas (forested, rural, and urban, exhibiting different degrees of anthropogenic changes) in a region of intense transmission of visceral leishmaniasis in Corumbá county, Mato Grosso do Sul, Brazil. Using light traps, sand fly specimens were collected from the three environments simultaneously, from May 2015 to April 2017, totaling 7 213 sand flies of 14 species in eight genera. Nuorteva's synanthropy index was determined for the species Lutzomyia cruzi, Brumptomyia brumpti, Micropygomyia peresi, Lu. forattinii, Martinsmyia oliveirai and Evandromyia corumbaensis. Lutzomyia cruzi, the vector of Leishmania infantum in Corumbá, was the most abundant vector species, recorded from all three areas and sampling plots, on all 24 months investigated. This species exhibited the highest synanthropic index (+75.09), indicating a strong preference for urban environments. Brumptomyia brumpti, Micropygomyia peresi, Lu. forattinii, and Martinsmyia oliveirai showed preference, albeit not strong, for urban environments. Overall, males were more abundant than females (W = 490; p < 0.0001). High density, high synanthropic index, and sustained indoor presence were found for Mi. peresi in the rural area. Monitoring changes in the ecological behavior of sand flies is of vital importance, as these changes may indicate an increased likelihood of leishmaniasis emergence or reemergence.

Standardization of DNA extraction from sand flies: Application to genotyping by next generation sequencing.

Standardization of the methods for extraction of DNA from sand flies is essential for obtaining high efficiency during subsequent molecular analyses, such as the new sequencing methods. Information obtained using these methods may contribute substantially to taxonomic, evolutionary, and eco-epidemiological studies. The aim of the present study was to standardize and compare two methods for the extraction of genomic DNA from sand flies for obtaining DNA in sufficient quantities for next-generation sequencing. Sand flies were collected from the municipalities of Campo Grande, Camapuã, Corumbá and Miranda, state of Mato Grosso do Sul, Brazil. Three protocols using a silica column-based commercial kit (ReliaPrep™ Blood gDNA Miniprep System kit, Promega®), and three protocols based on the classical phenol-chloroform extraction method (Uliana et al., 1991), were compared with respect to the yield and quality of the extracted DNA. DNA was quantified using a Qubit 2.0 fluorometer. The presence of sand fly DNA was confirmed by PCR amplification of the IVS6 region (constitutive gene), followed by electrophoresis on a 1.5% agarose gel. A total of 144 male specimens were analyzed, 72 per method. Significant differences were observed between the two methods tested. Protocols 2 and 3 of phenol-chloroform extraction presented significantly better performance than all commercial kit extraction protocols tested. For phenol-chloroform extraction, protocol 3 presented significantly better performance than protocols 1 and 2. The IVS6 region was detected in 70 of 72 (97.22%) samples extracted with phenol, including all samples for protocols 2 and 3. This is the first study on the standardization of methods for the extraction of DNA from sand flies for application to next-generation sequencing, which is a promising tool for entomological and molecular studies of sand flies.

Vector Competence of Lutzomyia cruzi Naturally Demonstrated for Leishmania infantum and Suspected for Leishmania amazonensis.

Corumbá city is one of the oldest visceral leishmaniasis-endemic foci in the state of Mato Grosso do Sul, Brazil, where the transmission of Leishmania infantum has been attributed to Lutzomyia cruzi Aiming at investigating the parameters of the vectorial capacity of Lu. cruzi for L. infantum, a project was undertaken in this city. Among these parameters, vector competence was investigated and the results obtained are reported herein. Of the 12 hamsters exposed to feed wild-caught female sandflies, two developed infection with L. infantum and surprisingly, one with Leishmania amazonensis In addition, hamsters with L. infantum infection were bitten only by females of Lu. cruzi, whereas the hamster infected with L. amazonensis was bitten by 124 Lu. cruzi females and one of Evandromyia corumbaensis Although there is a strong suspicion regarding the competence of Lu. cruzi in transmitting L. amazonensis naturally, it was not demonstrated.

Spatiotemporal analysis of sandfly fauna (Diptera: Psychodidae) in an endemic area of visceral leishmaniasis at Pantanal, central South America.

BACKGROUND: Environmental changes caused by urbanization can cause alterations in the ecology and behavior of sandflies and in the epidemiology of leishmaniasis. Geotechnological tools allow the analysis and recognition of spatiotemporal patterns by monitoring and mapping risk areas of this vector-borne disease. This study aims to describe the sandfly fauna in the municipality of Corumbá and to compare it with the data described in a three-year period from 1984 to 1986 by Galati. A further aim was to analyze the influence of environmental changes on the composition of the fauna. METHODS: Captures were conducted weekly from April 2012 to March 2013, in intra and peridomicile areas with automatic light traps, from 6:00 pm to 6:00 am. The following indices were calculated for both periods analyzed: Standardized Index of Species Abundance (SISA), Shannon's diversity index (H) and Pielou's index (J). The Normalized Difference Vegetation Index (NDVI) was extracted from a remote sensing LANDSAT-5 image. RESULTS: In total, 7,370 specimens (6,169 males and 1,201 females) were collected, distributed among 12 species. Lutzomyia cruzi was the most frequent species (93,79%) and the first in the ranking of standardized species abundance index in both studies. The dominance of the species Lu. cruzi in the neighborhoods of Maria Leite and Centro was demonstrated by the low equitability index. The neighborhood of Cristo Redentor had the greatest diversity of sandflies in the present study and the second greatest in the study performed by Galati et al. (Rev Saúde Pública 31:378-390, 1997). Analyzing the satellite images and the NDVI from 1984 and 2010, the largest amount of dense vegetation was found in the neighborhood of Cristo Redentor. CONCLUSIONS: It was, therefore, possible to show how changes caused due to urbanization have affected the density and distribution of Lu. cruzi and other species over time. Moreover, the data suggest that different populations of sandflies adapt in different ways according to environmental conditions and the adaptation does not necessarily depends on the presence of high vegetation cover.

Climatic factors and population density of Lutzomyia longipalpis (Lutz & Neiva, 1912) in an urban endemic area of visceral leishmaniasis in midwest Brazil.

The life cycle of vectors and the reservoirs that participate in the chain of infectious diseases have a strong relationship with the environmental dynamics of the ecosystems in which they live. Oscillations in population abundance and seasonality of insects can be explained by factors inherent in each region and time period. Therefore, knowledge of the relationship and influence of environmental factors on the population of Lutzomyia longipalpis is necessary because of the high incidence of visceral leishmaniasis (VL) in Brazil. This study evaluates the influence of abiotic variables on the population density and seasonal behavior of L. longipalpis in an urban endemic area of VL in Brazil. The sand fly captures were performed every two months between November, 2009 and November, 2010 in the peridomicile of 13 randomly selected residences. We captured 1,367 specimens of L. longipalpis, and the ratio of male/female flies was 2.86:1. The comparison of the total male specimens in the two seasons showed a statistical difference in the wet season, but there was no significant difference when considering the total females. With respect to climatic variables, a significant negative association was observed only with wind speed. During periods of high wind speeds, the population density of this vector decreased. The presence of L. longipalpis was found in all months of the study with bimodal behavior and population peaks during the wet season.