Factors Associated with Schistosoma mansoni Infestation in Northeast Brazil: A Need to Revisit Individual and Community Risk Factors.

In Brazil, schistosomiasis continues to be an important health issue. The aim of this study was to identify factors associated with Schistosoma mansoni infestation. A cross-sectional study was performed to assess factors associated with S. mansoni endemicity in a municipality in Northeast Brazil with a history of reporting schistosomiasis. Participants were divided into four groups: 1) new S. mansoni cases (n = 44), 2) past history of S. mansoni treatment (n = 78), 3) immediate neighbors (n = 158), and 4) nearby controls (n = 35). Multiple comparisons analysis was performed. Subjects had a mean of 6.6 ± 3.9 years of education, and no difference was observed regarding family income (one-way analysis of variance, P = 0.215). A total of 95.9% of the individuals had rudimentary cesspit as sanitary wastewater. The mean body mass index was 28.3 ± 5.1, with 41.0% and 24.1% overweight and obesity, respectively. Of note, 28.9% of adults had hypertension. Hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin were higher in the recent S. mansoni treated group (Wilks' lambda, P < 0.001). Male gender was more prevalent in new S. mansoni cases (likelihood ratio, P < 0.001), close proximity to water collections was a risk for S. mansoni infestation (likelihood ratio, P < 0.001), and a better hematological status was observed in individuals recently treated with praziquantel. This study indicates the need to maintain surveillance for S. mansoni in low-transmission areas and the need to establish community-based interventions to control transmission.

Bayesian compartmental model for an infectious disease with dynamic states of infection.

Population-level proportions of individuals that fall at different points in the spectrum [of disease severity], from asymptomatic infection to severe disease, are often difficult to observe, but estimating these quantities can provide information about the nature and severity of the disease in a particular population. Logistic and multinomial regression techniques are often applied to infectious disease modeling of large populations and are suited to identifying variables associated with a particular disease or disease state. However, they are less appropriate for estimating infection state prevalence over time because they do not naturally accommodate known disease dynamics like duration of time an individual is infectious, heterogeneity in the risk of acquiring infection, and patterns of seasonality. We propose a Bayesian compartmental model to estimate latent infection state prevalence over time that easily incorporates known disease dynamics. We demonstrate how and why a stochastic compartmental model is a better approach for determining infection state proportions than multinomial regression is by using a novel method for estimating Bayes factors for models with high-dimensional parameter spaces. We provide an example using visceral leishmaniasis in Brazil and present an empirically-adjusted reproductive number for the infection.

Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum.

BACKGROUND: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.

Egos has a reduced capacity to predicts GBS prognosis in Northeast Brazil.

OBJECTIVE: The Erasmus Guillain Barre Outcome Score (EGOS) is a prognostic model that predicts the chance of being able to walk independently at 6 months after Guillain Barré syndrome (GBS). This study was conducted aiming to determine the validity of EGOS in a Brazilian population. MATERIAL AND METHODS: Data collected from GBS patients in Rio Grande do Norte, Brazil, were used to determine the validity of EGOS. GBS disability score was assessed in the second week of disease and at 6 months. RESULTS: A total of 206 subjects were studied. The Brazilian patients were younger, with a more severe clinical presentation, with higher percentage of cranial nerve involvement and upper respiratory infection. There was no difference relative to sex or presence of anti-gangliosides antibodies. The demyelinating variant was more common (73.9%). However, only 24% of the Brazilians with EGOS 5.5-7 were not able to walk after 6 months, compared to 52% to European Group. Nine patients (3.8%) presented nodopathies, of these four had an EGOS >5, but only one of the latter group was unable to walk after 6 months of GBS. CONCLUSIONS: Erasmus Guillain Barre Outcome Score was not a good predictor for the ability to walk after 6 months of GBS in Rio Grande do Norte, Brazil. Differences could be that the Brazilian GBS were younger, or alternatively, it could be due to a different infection profile or in the incidence of nodopathies.

Changing epidemiology of visceral leishmaniasis in northeastern Brazil: a 25-year follow-up of an urban outbreak.

Background: Visceral leishmaniasis (VL) continues to be a deadly parasitic disease in Brazil but the epidemiology has changed. The objective of this study was to assess the evolution of urban VL in the city of Natal, Brazil, over the past 25 y. Methods: A retrospective study of human VL was performed, considering reported cases over the past 25 y in Natal. Analyses considered the spatial distribution of VL cases, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) co-infection, Leishmania infantum infection in dogs, density of the insect vector (Lutzomyia longipalpis) and socio-economic factors. Results: Paralleling migration of the population, VL cases changed from mostly rural to predominantly urban regions. The incidence of human VL was highest during the initial years (1990-1994) of our study. Human VL was positively associated with a high density of L. longipalpis, a high prevalence of canine L. infantum infection and HIV/AIDS co-infection. The average age at diagnosis increased over prior years and males were more frequently affected. The overall fatality rate was 6%. Socio-economic variables indicative of poverty were associated with a greater incidence of VL and clusters of VL. Conclusion: VL has become endemic in Natal. The disease is associated with poverty and male gender. Surprisingly, there has been an increase in the age at diagnosis.

Feeding preferences of Lutzomyia longipalpis (Diptera: Psychodidae), the sand fly vector, for Leishmania infantum (Kinetoplastida: Trypanosomatidae).

Leishmania infantum, the causative agent of visceral leishmaniasis (VL) in Brazil, is spread mostly by the bite of the sand fly Lutzomyia longipalpis (Lutz & Neiva). We trapped sand flies in endemic neighborhoods near Natal, Brazil, where cases of human and dog VL were documented. Amplification of species-specific cytochrome b (Cyt b) genes by polymerase chain reaction revealed that sand flies from rural and periurban areas harbored blood from different sources. The most common source ofbloodmeal was human, but blood from dog, chicken, and armadillo was also present. We tested the preference for a source of bloodmeal experimentally by feeding L. longipalpis F1 with blood from different animals. There were significant differences between the proportion of flies engorged and number of eggs laid among flies fed on different sources, varying from 8.4 to 19 (P < 0.0001). Blood from guinea pig or horse was best to support sand fly oviposition, but human blood also supported sand fly oviposition well. No sand flies fed on cats, and sand flies feeding on the opossum Monodelphis domestica Wagner produced no eggs. These data support the hypothesis that L. longipalpis is an eclectic feeder, and humans are an important source of blood for this sand fly species in periurban areas of Brazil.

Active surveillance of Hansen's Disease (leprosy): importance for case finding among extra-domiciliary contacts.

Hansen's disease (leprosy) remains an important health problem in Brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world's new cases detected in that year. The purpose of this study was to use home visits as a tool for surveillance of Hansen's disease in a hyperendemic area in Brazil. A total of 258 residences were visited with 719 individuals examined. Of these, 82 individuals had had a previous history of Hansen's disease, 209 were their household contacts and 428 lived in neighboring residences. Fifteen new Hansen's disease cases were confirmed, yielding a detection rate of 2.0% of people examined. There was no difference in the detection rate between household and neighbor contacts (p = 0.615). The two groups had the same background in relation to education (p = 0.510), household income (p = 0.582), and the number of people living in the residence (p = 0.188). Spatial analysis showed clustering of newly diagnosed cases and association with residential coordinates of previously diagnosed multibacillary cases. Active case finding is an important tool for Hansen's disease control in hyperendemic areas, enabling earlier diagnosis, treatment, decrease in disability from Hansen's disease and potentially less spread of Mycobacterium leprae.

Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter.

Visceral leishmaniasis (VL) is endemic in large cities in Brazil, including Natal. We determined the prevalence of asymptomatic human infection with Leishmania infantum chagasi and associated environmental risks around Natal. Infection was detected by Leishmania skin test (LST) and anti-leishmanial antibodies in humans and anti-leishmanial antibodies in dogs. Amongst 345 humans, 24.6% were seropositive, and 38.6% were LST-positive. Prevalence of positive serology was similar in both sexes and across all ages. However, positive LST responses increased with age, suggesting that LST is long-lasting and cumulative. Multinomial logistic analysis showed that LST response varied with location (P = 0.007) and that males were more frequently LST-positive (P = 0.027). Indicators of lower socioeconomic status associated significantly with human infection. Furthermore, there was geographic coincidence of seropositive humans and dogs (r = 0.7926, P = 0.011). These data suggest that dog and human L. i. chagasi infection are intimately interrelated in environmental conditions associated with low income.

Family history of hypertension as an important risk factor for the development of severe preeclampsia.

OBJECTIVE: To determine the risk of preeclampsia in a population with respect to maternal and sister histories of chronic hypertension, preeclampsia and eclampsia. DESIGN: A case-control study of severe preeclampsia. SETTING: Maternity hospital in Natal, Brazil. PARTICIPANTS: A total of 412 subjects were enrolled, 148 cases and 264 controls. MAIN OUTCOME MEASURES: Personal and familial histories of hypertensive disorders. Odds ratio estimates of preeclampsia with respect to family history of hypertensive diseases. RESULTS: Women with a history of hypertensive disorders were more frequent in the case group (p = 0.001). Women whose mothers had a history of hypertension (p = 0.003), preeclampsia (p = 0.007) or eclampsia (p = 0.038) were at increased risk of severe preeclampsia. The risk of preeclampsia was greater when the woman had a sister with a history of hypertension (OR 2.60, 95% CI 1.60-4.21, p < 0.001), preeclampsia (OR 2.33, 95% CI 1.58-3.45, p < 0.001), or eclampsia (OR 2.57, 95% CI 1.28-5.16, p = 0.008). The risk of preeclampsia was also higher for women who had both a mother and sister with a history of hypertension (OR 3.65, 95% CI 1.65-8.09, p = 0.001). CONCLUSIONS: A family history of hypertensive disorders increased the risk of eclampsia and hemolysis elevated liver enzymes and low platelet (HELLP) syndrome in a Brazilian population.

Improved sanitation and income are associated with decreased rates of hospitalization for diarrhoea in Brazilian infants.

Diarrhoeal diseases remain a major cause of morbidity and mortality in Brazilian children. However, from 1992 to 2001 there was a significant decline in hospitalizations for acute diarrhoea in children below 1 year of age in Brazil. A significant improvement in child health was also observed in the state of Rio Grande do Norte (RN), with a decrease in child mortality from 70 to 40 deaths per 1000. Using distributed lag analysis we analysed a number of factors possibly connected with decreased hospitalization in RN and found that hospitalization was correlated up to lag 3 with poverty (P<0.001) and inflation (P<0.001). Improvements in public health infrastructure such as better waste collection, presence of city water supply and increased sanitation, socio-economic variables such as education and literacy, and increased investment in health services were all important in reducing severe early childhood diarrhoeas and thus directly associated with the decrease in hospitalization. We also observed a positive seasonal correlation between rainfall and hospitalizations with an increased in rainfall impacting positively on hospitalization in all lags. The data suggests that increased buying power and reductions in poverty played a crucial role in reducing hospitalizations for acute diarrhoea in infants in RN.

Canine visceral leishmaniasis in urban and rural areas of Northeast Brazil.

The purpose of this study was to determine the clinical and laboratory profiles of canine leishmaniasis in two distinct areas. Dogs from urban and rural areas were examined. The population studied in the metropolitan area included 54 dogs. Of these, 20 (37%) animals did not present with any signs suggestive of visceral leishmaniasis (VL). Among these, only eight were confirmed negative by ELISA (rK39 and CE) and 12 dogs, clinically negative for leishmaniasis, were seropositive by ELISA (rK39 and CE). Thinness, conjunctivitis and onychogryphosis were the most frequent clinical signs in the urban areas, followed by crusty lesions, alopecia, ulcerated lesions, hyperkeratosis and exfoliation. In the metropolitan area human VL cases occurred mainly in 1991, 1992, 1999 and 2000. In the rural areas the ELISA rK39 test detected a seroprevalence of 11.3% and ELISA CE (Leishmania crude extract) of 20.6%. Thirty-nine dogs were examined 6 months after the first visit. Serological exams using rK39 antigen showed seroconversion of only one dog, whereas Leishmania CE showed seroconversion of 13 (33.4%) dogs. In this rural environment 83.3% of the positive dogs were asymptomatic. Lutzomyia intermedia and Lu. longipalpis were the most predominant sandfly vector species. Amastigotes were identified in spleen and liver fragments of symptomatic necropsied animals. PCR amplification of DNA isolated from promastigote culture indicated that the species was Leishmania chagasi. This finding suggests that delayed diagnosis and euthanasia of potentially infectious animals may occur with an increased transmission risk to sandflies and subsequently to humans.

Association of nutritional status with the response to infection with Leishmania chagasi.

Outcomes of infection with Leishmania chagasi range from self-resolving infection to visceral leishmaniasis (VL). Risk factors determining development of disease are not totally understood, but probably include environmental influences and host genetics. We assessed whether nutrition influenced the outcome of Leishmania infection by comparing relatives of children with VL with either self-resolving Leishmania spp. infection or apparently uninfected households. We observed a decrease in body mass index (P < 0.0005) and mid-upper arm circumference for age (P = 0.022) z-scores for children with VL. Levels of vitamin A were lower in active children with VL as measured by serum retinol (P = 0.035) and the modified-relative-dose-response test (P = 0.009). Higher birth weight (P = 0.047) and albumin concentrations (P = 0.040) protected against disease. Increased breastfeeding time (P = 0.036) was associated with asymptomatic infection. The results indicate that modifiable nutritional aspects are associated with the outcome of Leishmania spp. infection in humans.

Leptospirosis in a subsistence farming community in Brazil.

Leptospirosis has been reported in rural areas of Brazil. However, there is limited information about the exposure risk or the risk of Leptospira infection for rural-based populations. A cross-sectional study was carried out in order to determine the prevalence and risk factors for prior Leptospira infection in a rural subsistence farming region of the state of Rio Grande do Norte, an area in which outbreaks of leptospirosis have occurred. Among 290 individuals enrolled, 44 (15.2%) had anti-Leptospira IgM antibodies as determined by IgM ELISA. Infection tended to occur with activities related to the rice fields (P=0.08). Our findings indicate that Leptospira infection occurs even in years of low rainfall, and may have an important impact among poor rural-based subsistence farmers in Brazil. Additional studies are needed to characterize the mode of transmission in this region.

Genetic polymorphism in the sulfotransferase SULT1A1 gene in cancer.

Cytosolic sulfotransferases are enzymes that catalyze the conjugation of sulfate groups to a variety of xenobiotic and endogenous substrates. A mutation in the SULT1A1 gene has been associated with decreased sulfotransferase activity. We studied 125 cancer patients and 100 healthy controls from Brazil matched by age and gender. The objective of this study was to assess the impact of the SULT1A1 polymorphism on sulfotransferase activity in a population of cancer patients. Both heterozygous and homozygous individuals for the mutant allele had significantly decreased sulfotransferase enzymatic activity. This decrease was more significant in cancer patients. The frequency of the SULT1A1( *)2 allele was increased in the myeloma group (odds ratio=0.53). These data suggest a functional role for the SULT1A1 gene polymorphism in cancer.

Changing epidemiology of American cutaneous leishmaniasis (ACL) in Brazil: a disease of the urban-rural interface.

American cutaneous leishmaniasis (ACL) was first reported from the south-western region of the state of Rio Grande do Norte in 1987. São Miguel municipality and adjacent areas have accounted for 90% of the American cutaneous leishmaniasis cases in the region since then. A population survey conducted in São Miguel and adjacent areas was undertaken to identify individuals with a history of ACL. The incidence of ACL, distribution by age and gender, clinical characteristics, family clustering, relationship to animals, association with skin test responses, and development of mucosal lesions were determined. Males and females were equally likely to be infected by Leishmania. Thirty-eight percent of the individuals tested were found to be Montenegro skin test positive. No difference in the Montenegro skin test was observed with gender, but the response increased with age. Among the 140 ACL cases treated in a 4-year period in São Miguel, five (3.6%) developed mucosal involvement. Sandflies capable of transmitting Leishmania were captured inside households and in the areas surrounding them. The high density of sandfly species potentially able to transmit Leishmania species and the age distribution of cases of cutaneous leishmaniasis suggest that transmission of the parasite occurred inside or in close proximity to houses.