Are pvcrt-o and pvmdr1 Gene Mutations Associated with Plasmodium vivax Chloroquine-Resistant Parasites?

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum, there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1, T958M and F1076L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976F was not detected. (4) Conclusions: Since K10-pvcrt-o and F1076L/T958M-pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.

Adolescent pregnancy in Cruzeiro do Sul, Acre, Brazil: socioeconomic characteristics, prenatal and obstetric care. / Parturientes adolescentes em Cruzeiro do Sul, Acre, Brasil: características socioeconômicas e obstétricas.

The present study aimed to investigate the socioeconomic and obstetric characteristics of adolescent mothers and the complications they cause to maternal and neonatal health. This baseline data analysis of the MINA-Brazil birth cohort was conducted in the municipality of Cruzeiro do Sul, state of Acre, Brazil. The chi-square test was used to compare characteristics of adolescent and adult postpartum women, and multiple Poisson regression models with robust variance were used to assess associated factors. Among the postpartum women, 26.2% (95%CI: 24.0-28.4) were adolescents. Factors associated with childbirth in adolescence included: nine years or less of schooling (adjPR:1.36; 95%CI: 1.14-1.61), belongs to the lowest quartiles of the wealth index (1st quartile: adjPR:1.40; 95%CI: 1.08-1.80) (2nd quartile: adjPR:1.37; 95%CI: 1.08-1.74), primigravidae (adjPR:3.69; 95%CI: 2.98-4.57), low pre-pregnancy BMI (adjPR:1.28; CI95%: 1.04-1.57), urinary tract infection during pregnancy (adjPR:1.25; CI95%: 1.07-1.46) and less than six prenatal consultations (adjPR:1.42; 95%CI: 1.21-1.66). Poverty, little schooling, primigravidae, low pre-pregnancy BMI, urinary tract infection during pregnancy and few prenatal consultations were associated with childbirth during adolescence in a municipality in the Northern region of Brazil.

O objetivo do estudo foi investigar as características socioeconômicas e obstétricas de parturientes adolescentes e suas complicações sobre a saúde materna e neonatal. Trata-se de uma análise de dados da linha de base da coorte de nascimentos MINA-Brasil conduzida no município de Cruzeiro do Sul, estado do Acre. Utilizou-se teste qui-quadrado para comparar características das puérperas adolescentes com as adultas e modelos múltiplos de regressão de Poisson com variância robusta para avaliar fatores associados. Entre as puérperas estudadas, 26,2% (IC95%: 24,0-28,4) eram adolescentes. Os fatores associados ao parto na adolescência foram ter nove anos ou menos de estudo (RPaj:1,36; IC95%: 1,14-1,61), pertencer aos menores quartis do índice de riqueza (1° quartil: RPaj:1,40; IC95%: 1,08-1,80) (2° quartil: RPaj:1,37; IC95%: 1,08-1,74), ser primigesta (RPaj:3,69; IC95%: 2,98-4,57), baixo IMC pré-gestacional (RPaj:1,28; IC95%: 1,04-1,57), infecção urinária na gravidez (RPaj:1,25; IC95%: 1,07-1,46) e menos de seis consultas de pré-natal (RPaj:1,42; IC95%: 1,21-1,66). Pobreza, baixa escolaridade, primigestação, baixo IMC pré-gestacional, infecção urinária na gestação e menor número de consultas de pré-natal foram associados ao parto na adolescência em município da região Norte do Brasil.

Parturientes adolescentes em Cruzeiro do Sul, Acre, Brasil: características socioeconômicas e obstétricas / Adolescent pregnancy in Cruzeiro do Sul, Acre, Brazil: socioeconomic characteristics, prenatal and obstetric care

Resumo O objetivo do estudo foi investigar as características socioeconômicas e obstétricas de parturientes adolescentes e suas complicações sobre a saúde materna e neonatal. Trata-se de uma análise de dados da linha de base da coorte de nascimentos MINA-Brasil conduzida no município de Cruzeiro do Sul, estado do Acre. Utilizou-se teste qui-quadrado para comparar características das puérperas adolescentes com as adultas e modelos múltiplos de regressão de Poisson com variância robusta para avaliar fatores associados. Entre as puérperas estudadas, 26,2% (IC95%: 24,0-28,4) eram adolescentes. Os fatores associados ao parto na adolescência foram ter nove anos ou menos de estudo (RPaj:1,36; IC95%: 1,14-1,61), pertencer aos menores quartis do índice de riqueza (1° quartil: RPaj:1,40; IC95%: 1,08-1,80) (2° quartil: RPaj:1,37; IC95%: 1,08-1,74), ser primigesta (RPaj:3,69; IC95%: 2,98-4,57), baixo IMC pré-gestacional (RPaj:1,28; IC95%: 1,04-1,57), infecção urinária na gravidez (RPaj:1,25; IC95%: 1,07-1,46) e menos de seis consultas de pré-natal (RPaj:1,42; IC95%: 1,21-1,66). Pobreza, baixa escolaridade, primigestação, baixo IMC pré-gestacional, infecção urinária na gestação e menor número de consultas de pré-natal foram associados ao parto na adolescência em município da região Norte do Brasil.

Abstract The present study aimed to investigate the socioeconomic and obstetric characteristics of adolescent mothers and the complications they cause to maternal and neonatal health. This baseline data analysis of the MINA-Brazil birth cohort was conducted in the municipality of Cruzeiro do Sul, state of Acre, Brazil. The chi-square test was used to compare characteristics of adolescent and adult postpartum women, and multiple Poisson regression models with robust variance were used to assess associated factors. Among the postpartum women, 26.2% (95%CI: 24.0-28.4) were adolescents. Factors associated with childbirth in adolescence included: nine years or less of schooling (adjPR:1.36; 95%CI: 1.14-1.61), belongs to the lowest quartiles of the wealth index (1st quartile: adjPR:1.40; 95%CI: 1.08-1.80) (2nd quartile: adjPR:1.37; 95%CI: 1.08-1.74), primigravidae (adjPR:3.69; 95%CI: 2.98-4.57), low pre-pregnancy BMI (adjPR:1.28; CI95%: 1.04-1.57), urinary tract infection during pregnancy (adjPR:1.25; CI95%: 1.07-1.46) and less than six prenatal consultations (adjPR:1.42; 95%CI: 1.21-1.66). Poverty, little schooling, primigravidae, low pre-pregnancy BMI, urinary tract infection during pregnancy and few prenatal consultations were associated with childbirth during adolescence in a municipality in the Northern region of Brazil.

B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon.

The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from Brazilian exposed individuals and that its components are immunogenic in natural infection by P. falciparum. In addition, anti-GMZ2.6c antibodies increase with exposure to infection and may contribute to parasite immunity. Therefore, identifying epitopes of proteins recognized by antibodies may be an important tool for understanding protective immunity. Herein, we identify and validate the B-cell epitopes of GMZ2.6c as immunogenic and immunodominant in individuals exposed to malaria living in endemic areas of the Brazilian Amazon. Specific IgG antibodies and subclasses against MSP-3, GLURP, and Pfs48/45 epitopes were detected by ELISA using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3 and GLURP or identified by BepiPred for Pfs48/45. The results showed that the immunodominant epitopes were P11 from GLURP and MSP-3c and DG210 from MSP-3. The IgG1 and IgG3 subclasses were preferentially induced against these epitopes, supporting previous studies that these proteins are targets for cytophilic antibodies, important for the acquisition of protective immunity. Most individuals presented detectable IgG antibodies against Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and Pfs48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.

Silent circulation of Chikungunya virus among pregnant women and newborns in the Western Brazilian Amazon before the first outbreak of chikungunya fever.

The prevalence of immunity to Chikungunya virus (CHIKV) in pregnant women and newborns in the Western Brazilian Amazon was assessed at a time when previous studies did not report chikungunya fever in the area. In 435 asymptomatic pregnant women and 642 healthy unrelated newborns, the presence of IgM and IgG antibodies to CHIKV were determined by a commercial ELISA. All participants were negative to IgM anti-CHIKV. Anti-CHIKV IgG was identified in 41 (9.4%) pregnant women and 66 (10.3%) newborns. The presence of anti-CHIKV IgG was positively associated with the lowest socioeconomic status in pregnant women (OR 2.54, 95% CI 1.15-5.62, p=0.021) and in the newborns' mothers (OR 5.10, 95% CI 2.15-12.09, p< 0.001). Anti-CHIKV IgG was also associated with maternal age in both, the pregnant women (OR 1.06, 95% CI 1.00-1.11, p=0.037) and the newborns'mothers (OR 1.08, 95% CI 1.03-1.12, p=0.001). Pregnancy outcomes in which the mother or the newborn was anti-CHIKV IgG positive proceeded normally. Negative CHIKV serology was associated with being positive for DENV antibodies and having had malaria during pregnancy. These findings showed that there was already a silent circulation of CHIKV in this Amazon region before the first outbreak of chikungunya fever. Furthermore, seropositivity for CHIKV was surprisingly frequent (10%) in both, pregnant women and newborns, affecting mainly low-income women.

Efficacy of the 20-minute whole blood clotting test (WBCT20) in the diagnosis of coagulation alteration related to snakebites in a Western Brazilian Amazon hospital.

INTRODUCTION: The efficacy of 20-minute whole blood clotting (WBCT20) and the Lee-White clotting time (LWCT) tests in diagnosing coagulation alterations from snakebites were compared. Methods: We evaluated 89 snakebite cases treated at the Hospital Regional do Juruá em Cruzeiro do Sul, Acre, Brazil. Results: WBCT20 results were normal in 33.7% and unclottable in 66.3% of cases, while LWCT results were normal in 23.6% and altered (prolonged or unclottable) in 76.4% of cases, with no significant differences. Conclusions: The WBCT20 is important for rapidly diagnosing coagulation alterations from snakebites. Furthermore, it is efficient, inexpensive, and can be deployed in isolated hospitals.

Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon.

BACKGROUND: Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon. METHODS AND FINDINGS: We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn's anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69-24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29-9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes. CONCLUSIONS: This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections.

Efficacy of the 20-minute whole blood clotting test (WBCT20) in the diagnosis of coagulation alteration related to snakebites in a Western Brazilian Amazon hospital

Abstract Introduction: The efficacy of 20-minute whole blood clotting (WBCT20) and the Lee-White clotting time (LWCT) tests in diagnosing coagulation alterations from snakebites were compared. Methods: We evaluated 89 snakebite cases treated at the Hospital Regional do Juruá em Cruzeiro do Sul, Acre, Brazil. Results: WBCT20 results were normal in 33.7% and unclottable in 66.3% of cases, while LWCT results were normal in 23.6% and altered (prolonged or unclottable) in 76.4% of cases, with no significant differences. Conclusions: The WBCT20 is important for rapidly diagnosing coagulation alterations from snakebites. Furthermore, it is efficient, inexpensive, and can be deployed in isolated hospitals.

Association between NDO-LID and PGL-1 for leprosy and class I and II human leukocyte antigen alleles in an indigenous community in Southwest Amazon

The frequencies of the Human leukocyte antigen (HLA) alleles in the Puyanawa indigenous reserve population and their association with the NDO-LID and ELISA PGL-1 rapid serological test was assessed. This was a cross-sectional study with an epidemiological clinical design conducted in two indigenous communities in the state of Acre, Brazil. Blood was collected in a tube with EDTA to identify HLA alleles and perform serological tests. DNA was obtained using the salting out procedure. The LabType™ technique (One-Lambda-USA) was used for HLA class I (loci A*, B* and C*) and II (loci DRB1*, DQA1* and DQB1*) typing. Allele frequency was obtained by direct count, and the chi-square test was used to assess the association with the NDO-LID and PGL-1 tests. The most frequent alleles in the two communities were: HLA-A*02:01, HLA-B*40:02, HLA-DRB1*16:02, HLA-DQA1*05:05 and HLA-DQB1*03:01. The allele HLA-C*04:01 was the most common in the Barão community, and the allele HLA-C*07:01 in Ipiranga. Among individuals who presented seropositivity to the NDO-LID test, the association with alleles HLA-A*02 (43.18% vs 24.8%, p = 0.03, OR = 2.35) and HLA-B*53 (6.83% vs 0.0%, p = 0.03, OR = 8.95) was observed in the Barão community. HLA-B*15 was associated with non-seroconversion to the NDO-LID test in Ipiranga. In both communities, HLA-B*40 and HLA-C*03 were associated with positive serological response to ELISA PGL-1. The HLA class I and II alleles most frequently found in this study have already been described among Terena indigenous groups, and HLA class I contributes to seroconversion to NDO-LID and PGL-1 tests in inhabitants of the Barão and Ipiranga communities(AU).

Association between NDO-LID and PGL-1 for leprosy and class I and II human leukocyte antigen alleles in an indigenous community in Southwest Amazon.

The frequencies of the Human leukocyte antigen (HLA) alleles in the Puyanawa indigenous reserve population and their association with the NDO-LID and ELISA PGL-1 rapid serological test was assessed. This was a cross-sectional study with an epidemiological clinical design conducted in two indigenous communities in the state of Acre, Brazil. Blood was collected in a tube with EDTA to identify HLA alleles and perform serological tests. DNA was obtained using the salting out procedure. The LabType™ technique (One-Lambda-USA) was used for HLA class I (loci A*, B* and C*) and II (loci DRB1*, DQA1* and DQB1*) typing. Allele frequency was obtained by direct count, and the chi-square test was used to assess the association with the NDO-LID and PGL-1 tests. The most frequent alleles in the two communities were: HLA-A*02:01, HLA-B*40:02, HLA-DRB1*16:02, HLA-DQA1*05:05 and HLA-DQB1*03:01. The allele HLA-C*04:01 was the most common in the Barão community, and the allele HLA-C*07:01 in Ipiranga. Among individuals who presented seropositivity to the NDO-LID test, the association with alleles HLA-A*02 (43.18% vs 24.8%, p=0.03, OR=2.35) and HLA-B*53 (6.83% vs 0.0%, p=0.03, OR=8.95) was observed in the Barão community. HLA-B*15 was associated with non-seroconversion to the NDO-LID test in Ipiranga. In both communities, HLA-B*40 and HLA-C*03 were associated with positive serological response to ELISA PGL-1. The HLA class I and II alleles most frequently found in this study have already been described among Terena indigenous groups, and HLA class I contributes to seroconversion to NDO-LID and PGL-1 tests in inhabitants of the Barão and Ipiranga communities.

Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity. (AU)

Relationship between snake size and clinical, epidemiological and laboratory aspects of Bothrops atrox snakebites in the Western Brazilian Amazon

In the Brazilian Amazon, snakebites are a significant problem, especially for populations in rural areas, particularly in forests, where victims are a considerable distance from hospital care. Several factors are associated with the severity of the accident, such as the size and age of the snake. This study aims to compare the clinical, epidemiological and laboratory aspects of envenomation to the size of Bothrops atrox snakes. Clinical, epidemiological and laboratory variables were collected from patients bitten by B. atrox and who were admitted to a hospital in the city of Cruzeiro do Sul (western Brazilian Amazon). When the two punctures of the teeth were present in the bite sign, the distance between these was measured. When taken to the hospital, the snake was measured; otherwise, its size was estimated via interviews with patients. In 92 cases, the size of the snake was estimated, and most of these were caused by small snakes. Bites of small snakes occur mainly on the feet, while larger specimens reach the legs or higher regions. Small snakes were associated primarily with mild and moderate snakebites, with more presence of hemorrhagic manifestations, while larger snakes were responsible for severe cases and characterized by local effects (necrosis, edema, flictena, compartment syndrome, and infection) and patients were treated with a higher amount of antivenom and for a longer period of hospitalization. The distance of the punctures was related to the size of the snake and the severity of the local envenomation. The observation of the distance between puncture marks when present, which is correlated with the length of the specimen, as well as the estimation of the snake size by the patient, may provide more support for the health professional on the prognosis of envenomation. The use of boots in activities in rural areas and forests could contribute to a lower rate of cases of snakebites, and health education on preventive measures and first aid for populations is fundamental.

Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia / Aspectos clínicos e epidemiológicos de acidentes ofídicos na região do Alto Juruá, oeste da Amazônia brasileira

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity

Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia / Aspectos clínicos e epidemiológicos de acidentes ofídicos na região do Alto Juruá, oeste da Amazônia brasileira

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia / Hepatitis B y Delta: aspectos clínicos de pacientes en el Amazonas brasileño Occidental / Hepatite B e Delta: aspectos clínicos de pacientes na Amazônia Ocidental brasileira

ABSTRACT Objective: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. Method: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. Results: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). Conclusion: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

RESUMEN Objetivo: Analizar los aspectos clínicos, serológicos, bioquímicos y hematológicos de pacientes infectados por el virus de las hepatitis B (VHB) y Delta (VHD). Método: Se trata de un estudio transversal, descriptivo, retrospectivo, realizado entre pacientes crónicos infectados de VHB y sobre infectados de VHD. Resultados: Entre los 112 pacientes seleccionados, el 74% estaba mono infectado por VHB (Grupo VHB) y el 26%, sobre infectado por VHD (Grupo VHB+VHD). No se encontró diferencia en la distribución por género. La edad promedio era 36 años, con desviación típica de ±12 años. Los síntomas y signos sobresalían en mayor proporción en el grupo VHB+VHD (p=0,001). Para ambos grupos, la mayoría de los pacientes estaba con AgHBe no reactivo. El registro de alteraciones bioquímicas y hematológicas atribuyó proporción más grande al grupo VHB+VHD (p<0,05). Conclusión: El estudio demostró que los pacientes, en la consulta inicial para el seguimiento de la condición crónica, estaban en diferentes estadios clínicos de la enfermedad. El perfil clínico sugiere que la gravedad de la enfermedad hepática es mayor entre pacientes sobre infectados de VHD.

RESUMO Objetivo: Analisar aspectos clínicos, sorológicos, bioquímicos e hematológicos entre pacientes infectados por vírus das hepatites B (VHB) e Delta (VHD). Método: Estudo transversal, descritivo, retrospectivo, realizado com pacientes cronicamente infectados por VHB e superinfectados por VHD. Resultados: Entre os 112 pacientes selecionados, 74% estavam monoinfectados por VHB (Grupo VHB) e 26% superinfectados por VHD (Grupo VHB+VHD). Não houve diferença na distribuição por gênero. A idade média foi de 36 anos, com desvio padrão de ±12 anos. Os sintomas e sinais apresentaram maior proporção no grupo VHB+VHD (p=0,001). Para ambos os grupos, a maioria dos pacientes estava com AgHBe não reagente. O registro de alterações bioquímicas e hematológicas apresentou maior proporção no grupo VHB+VHD (p<0,05). Conclusão: O estudo revelou que os pacientes estavam em diferentes estágios clínicos da doença na consulta inicial para acompanhamento de condição crônica. O perfil clínico sugere maior gravidade da doença hepática entre os pacientes superinfectados por VHD.

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia.

OBJECTIVE: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. METHOD: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. RESULTS: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). CONCLUSION: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon.

Importance: Malaria during pregnancy is associated with adverse events for the fetus and newborn, but the association of malaria during pregnancy with the head circumference of the newborn is unclear. Objective: To investigate the association of malaria during pregnancy with fetal head growth. Design, Setting, and Participants: Two cohort studies were conducted at the general maternity hospital of Cruzeiro do Sul (Acre, Brazil) in the Amazonian region. One cohort study prospectively enrolled noninfected and malaria-infected pregnant women who were followed up until delivery, between January 2013 and April 2015. The other cohort study was assembled retrospectively using clinical and malaria data from all deliveries that occurred between January 2012 and December 2013. Data analyses were conducted from January to August 2017 and revised in November 2018. Clinical data from pregnant women and anthropometric measures of their newborns were evaluated. A total of 600 pregnant women were enrolled through volunteer sampling (prospective cohort study), and 4697 pregnant women were selected by population-based sampling (retrospective cohort study). After application of exclusion criteria, data from 251 (prospective cohort study) and 232 (retrospective cohort study) malaria-infected and 158 (prospective cohort study) and 3650 (retrospective cohort study) noninfected women were evaluated. Exposure: Malaria during pregnancy. Main Outcomes and Measures: The primary end point was the incidence of altered head circumference in newborns delivered from malaria-infected mothers compared with that from noninfected mothers. Secondary end points included measures of placental pathology relative to newborn head circumference. Results: In total, 4291 maternal-child pairs were analyzed. Among 409 newborns in the prospective cohort study, the mothers of 251 newborns had malaria during pregnancy, infected with Plasmodium vivax, Plasmodium falciparum, or both. Among 3882 newborns in the retrospective cohort study, 232 were born from mothers that had malaria during pregnancy. The prevalence of newborns with a small head (19 [30.7%] in the prospective cohort study and 30 [36.6%] in the retrospective cohort study) and the prevalence of microcephaly among newborns (5 [8.1%] in the prospective cohort study and 6 [7.3%] in the retrospective cohort study) were higher among newborns from women infected with P falciparum during pregnancy. Multivariate logistic regression analyses revealed that P falciparum infection during pregnancy represented a significant risk factor for the occurrence of small head circumference in newborns (prospective cohort study: odds ratio, 3.15; 95% CI, 1.52-6.53; P = .002; retrospective cohort study: odds ratio, 1.91; 95% CI, 1.21-3.04; P = .006). Placental pathologic findings corroborated this association, with more syncytial nuclear aggregates and inflammatory infiltrates occurring in placentas of newborns born with decreased head circumference. Conclusions and Relevance: This study indicates that falciparum malaria during pregnancy is associated with decreased head circumference in newborns, which is in turn associated with evidence of placental malaria.

Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia

Background The Alto Juruá region, located in the extreme western part of the Brazilian Amazonia, possesses an indigenous and riverine population which is involved in agricultural and forest extraction activities, and is a region that stands out for its high incidence of snakebites. Objectives To assess the attitudes of the victims, the characteristics of the snakes and the circumstances of the snakebites which occurred in a region where human populations are highly exposed to snakes. Methods The study was conducted at the Regional Hospital of Juruá in the Municipality of Cruzeiro do Sul (Acre), which regularly attends victims of snakebites in the Alto Juruá region. The snakes that caused the envenomations were identified from clinical and epidemiological diagnosis of the symptoms and signs that patients presented during hospital, and by enzyme immunoassay for venom detection using serum samples of the patients, or by identification of the snake responsible for the envenomation when it was taken to the hospital or photographed. People who suffered or witnessed the snakebite were interviewed to assess the circumstances of the bite, the attitude adopted after the accident and whether they recognized the species of snake that caused the envenomation. Results There were 133 cases of snakebite (76.24/100.000 inhabitants), mainly involving male individuals living in the rural area and who had a low level of education. The most affected groups were farmers (48%) and children and teenagers (39%). It was observed that 8.3% of them presented a history of recurrence for bites. The lower limbs were the most affected anatomical region (84%). The Bothrops atrox snake, mainly small specimens (mostly juveniles), was the main species involved in the envenomations (83.4%). Snakebites occurred mainly in forest areas, backyards of houses in rural areas and near to aquatic environments, during activities (walking, farming, extractivism, hunting). Most of the time, the snake was on the ground and the bite occurred because of the approximation of the individual, either by trampling or by approximation of a hand. Half of the victims performed some kind of inadequate first aid (not drinking water, use of tourniquet, incision at the site of the bite, use of black stone, drinking a compound "Específico Pessoa"). Conclusions Snakebite is an important cause of morbidity in the Alto Juruá region. Bothrops bites are mostly caused by small-sized specimens, probably due to the greater abundance of B. atrox juveniles, and also because small snakes are more difficult for people to see. People are more often bitten on the lower limbs probably due to the size of B. atrox (small and medium) and because the snakes are usually on the ground in most situations. Many victims resort to ineffective actions that can cause complications and also delay serotherapy. A low level of education is a factor that may contribute to worse outcomes in snakebites since it is associated with a lack of knowledge of preventive and first aid measures.

Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia

Background The Alto Juruá region, located in the extreme western part of the Brazilian Amazonia, possesses an indigenous and riverine population which is involved in agricultural and forest extraction activities, and is a region that stands out for its high incidence of snakebites. Objectives To assess the attitudes of the victims, the characteristics of the snakes and the circumstances of the snakebites which occurred in a region where human populations are highly exposed to snakes. Methods The study was conducted at the Regional Hospital of Juruá in the Municipality of Cruzeiro do Sul (Acre), which regularly attends victims of snakebites in the Alto Juruá region. The snakes that caused the envenomations were identified from clinical and epidemiological diagnosis of the symptoms and signs that patients presented during hospital, and by enzyme immunoassay for venom detection using serum samples of the patients, or by identification of the snake responsible for the envenomation when it was taken to the hospital or photographed. People who suffered or witnessed the snakebite were interviewed to assess the circumstances of the bite, the attitude adopted after the accident and whether they recognized the species of snake that caused the envenomation. Results There were 133 cases of snakebite (76.24/100.000 inhabitants), mainly involving male individuals living in the rural area and who had a low level of education. The most affected groups were farmers (48%) and children and teenagers (39%). It was observed that 8.3% of them presented a history of recurrence for bites. The lower limbs were the most affected anatomical region (84%). The Bothrops atrox snake, mainly small specimens (mostly juveniles), was the main species involved in the envenomations (83.4%). Snakebites occurred mainly in forest areas, backyards of houses in rural areas and near to aquatic environments, during activities (walking, farming, extractivism, hunting). Most of the time, the snake was on the ground and the bite occurred because of the approximation of the individual, either by trampling or by approximation of a hand. Half of the victims performed some kind of inadequate first aid (not drinking water, use of tourniquet, incision at the site of the bite, use of black stone, drinking a compound "Específico Pessoa"). Conclusions Snakebite is an important cause of morbidity in the Alto Juruá region. Bothrops bites are mostly caused by small-sized specimens, probably due to the greater abundance of B. atrox juveniles, and also because small snakes are more difficult for people to see. People are more often bitten on the lower limbs probably due to the size of B. atrox (small and medium) and because the snakes are usually on the ground in most situations. Many victims resort to ineffective actions that can cause complications and also delay serotherapy. A low level of education is a factor that may contribute to worse outcomes in snakebites since it is associated with a lack of knowledge of preventive and first aid measures.

Evidências científicas sobre a hepatite Delta no Brasil: revisão integrativa da literatura / Scientific evidence on hepatitis Delta in Brazil: integrative literature review

Resumo Objetivo: Descrever o nível de evidência científica sobre a infecção por vírus da hepatite Delta (VHD) no Brasil. Métodos: Revisão integrativa da literatura, com buscas realizadas nas bases de dados do Medical Literature Analysis and Retrieval System Online, Literatura Latino-americana e do Caribe em Ciências da Saúde, Scientific Eletronic Library Online e Scopus, com análise centrada no nivelamento do rigor metodológico de acordo com o modelo de Melnyk e Fineout-Overholt. Resultados: A busca revelou uma média de duas publicações por ano no intervalo entre 1987 e 2017. Foram selecionados 33 artigos, tendo a maioria (91%) apresentado nível de evidência VI. As publicações ficaram concentradas em periódicos da área de medicina tropical (46%) e virologia (15%). Dos trabalhos, 85% tinha profissional médico com autor e o delineamento mais encontrado foi o descritivo/transversal (69,6%). Conclusão: A produção científica sobre a infecção por VHD no Brasil está centrada em estudos de prevalência, mostrando-se incipiente quanto à produção de estudos com delineamentos mais rígidos como ensaios clínicos.

Abstract Objective: Describe the level of scientific evidence on infections by the hepatitis Delta virus (HDV) in Brazil. Methods: Integrative literature review, with research in the databases of the Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Center on Health Sciences Information, Scientific Eletronic Library Online and Scopus, with analysis focusing on the leveling of the methodological rigor according to the model of Melnyk and Fineout-Overholt. Results: The search revealed an average of two publications a year between 1987 and 2017. We selected 33 articles, the majority (91%) presented level of evidence VI. The publications were concentrated in the area of tropical medicine (46%) and virology (15%). The authors of 85% of the studies were medical professionals and the most common design was the descriptive/cross-sectional (69.6%). Conclusion: Scientific literature on HDV infections in Brazil is focused on prevalence studies, showing incipiency regarding the production of studies with stricter guidelines, such as clinical trials.