Seroprevalence of the Hepatitis E Virus in Indigenous and Non-Indigenous Communities from the Brazilian Amazon Basin.

Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis in tropical regions. In Brazil, HEV G3 is the only genotype detected to date. Reports on HEV prevalence are heterogeneous. We aimed to compare the prevalence of anti-HEV among three populations living in the Brazilian Amazon basin. Two cross-sectional studies were conducted in urban, rural, and Yanomami indigenous areas. Plasma samples from 428 indigenous and 383 non-indigenous subjects were tested for anti-HEV IgG using enzyme-linked immunosorbent assays. The overall prevalence of anti-HEV was 6.8% (95%CI: 5.25-8.72), with 2.8% (12/428) found in the Yanomami areas, 3% (3/101) in an urban area, and 14.2% (40/282) in a rural area. Multivariate logistic analysis indicated that patients aged 31-45 years or ≥46 years are more likely to present anti-HEV positivity, with a respective aOR of 2.76 (95%CI: 1.09-7.5) and 4.27 (95%CI: 1.58-12.35). Furthermore, residence in a rural area (aOR: 7.67; 95%CI: 2.50-33.67) represents a relevant risk factor for HEV infection. Additional studies detecting HEV RNA in fecal samples from both humans and potential animal reservoirs are necessary to comprehensively identify risk factors associated with HEV exposure.

Seroprevalence of hepatitis B, C, and D and associated factors in the semi-isolated Yanomami Amazonian indigenous community.

BACKGROUND: Viral hepatitis is a significant health concern among indigenous population in the Americas. In Brazil, reports find high endemicity of HBV and HDV infections has been reported in several indigenous groups. However, few studies have documented the prevalence of HBV, HCV and HDV in the Yanomami. In this study, the prevalence of hepatitis B, C, and D serological markers and potential risk factors were investigated to provide guidance for the development of strategies aimed at reducing viral transmission in the Yanomami indigenous villages. METHODS: This cross-sectional study was carried out in March 2015 and included 430 individuals from four Yanomami villages: Alapusi (n = 78), Castanha/Ahima (n = 126), Gasolina (n = 105), and Taibrapa (n = 121). A rapid test was used for detection of HBsAg and anti-HCV and chemiluminescent immunoassay for anti-HBs, anti-HBc, and anti-HDV antibodies. RESULTS: HBsAg, anti-HBc, and anti-HBs were detected in 8.8, 45.5, and 49.4% of the participants, respectively. The estimated HBV status: current infection 9.6% (38/395); resolved infection 43.3% (171/395); vaccine immunity 20.5% (81/395), and susceptible to HBV 26.6% (105/395). Gasolina presented the lowest prevalence of HBV infection (6.5%) and the highest prevalence of vaccine immunity (26.9%). Children < 15 years old were highly susceptible to infection, as 53.1% did not have antibodies to HBV, while more than 80% of individuals over 45 years of age had been exposed to HBV. The markers for HDV were founded among 12.5% (4/32) of the HBsAg carriers. Anti-HCV was identified in all villages, with the highest prevalence in Alapusi (5.1%). Possible risk factors such as the use of piercings, tattoos, and contact with prospectors showed no statistical difference between the groups. CONCLUSIONS: Viral hepatitis B and serological markers for HCV and HDV were found to be widely distributed among the Yanomami indigenous community, while the prevalence of vaccine immunity to HBV was low. This finding reinforces the importance of promoting systematized diagnostic and vaccination strategies in indigenous communities. Our data confirm that isolated and difficult-to-reach indigenous communities lack appropriate access to diagnosis, treatment, and vaccination.

Malarial and intestinal parasitic co-infections in indigenous populations of the Brazilian Amazon rainforest.

The Brazilian Amazon rainforest region has a significant prevalence of malarial and intestinal parasitic infections in indigenous populations, accounting for a disproportionate burden. Thus, a cross-sectional study was conducted to assess the prevalence and association between malarial and intestinal protozoan and helminth infections in four remote indigenous villages in the Brazilian Amazon Forest. A total of 430 individuals participated in the study, and Plasmodium infections were diagnosed by examination of thick blood smears and PCR. Stool samples 295 individuals (69%) were examined by direct smear and the Kato-Katz technique. The overall prevalence of malaria, intestinal protozoan infection, and intestinal helminth infection was 14.2%, 100%, and 39.3%, respectively. Polyparasitism was predominant (83.7%), and most infected individuals had at least two or more different species of intestinal protozoan and/or helminth parasites. The prevalence of co-infection was 49.5%, and in individuals with intestinal protozoa and helminth infections (34%), Entamoeba. coli, Entamoeba histolytica, and Ascaris lumbricoides were the most common parasites. In individuals with malaria and protozoa infections (10.2%), P. vivax, E. coli, and E. histolytica predominated, and in individuals with malaria, protozoa, and helminth infections (5.4%). P. vivax, E. coli, E. histolytica, and A. lumbricoides predominated. Intestinal polyparasitism was common in the study population, and the presence of helminths was associated with an increased number of intestinal parasitic species. However, Plasmodium infections were neither a risk nor a protective factor for helminth infections; the same was true for helminth infections in relation to Plasmodium. The high prevalence of intestinal polyparasitism with Plasmodium co-infections highlights the need for combining strategies that may help control both malaria and intestinal parasite and generate a health approach aligned with indigenous perspectives.

Genomic Variability of Hepatitis B Virus Circulating in Brazilian Western Amazon.

The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host's immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease.

Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon.

BACKGROUND: Brazil has seen a great decline in malaria and the country is moving towards elimination. However, for eventual elimination, the control program needs efficient tools in order to monitor malaria exposure and transmission. In this study, we aimed to evaluate whether seroprevalence to the circumsporozoite protein (CSP) is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon. METHODS: Cross-sectional surveys were conducted in a rural area of Porto Velho, Rondônia state. Parasite infection was detected by microscopy and polymerase chain reaction. Antibodies to the sporozoite CSP repeats of Plasmodium vivax, P. falciparum, and P. malariae (PvCS, PfCS, and PmCS) were detected using the enzyme-linked immunosorbent assay technique. Human leukocyte antigen (HLA)-DRB1 and DQB1 genes were typed using Luminex® xMAP® technology. RESULTS: The prevalence of immunoglobulin G against P. vivax CSP peptide (62%) was higher than P. falciparum (49%) and P. malariae (46%) CSP peptide. Most of the studied individuals had antibodies to at least one of the three peptides (72%), 34% had antibodies to all three peptides and 28% were non-responders. Although the majority of the population was not infected at the time of the survey, 74.3% of parasite-negative individuals had antibodies to at least one of the CSPs. Importantly, among individuals carrying the haplotypes DRB1*04~DQB1*03, there was a significantly higher frequency of PfCS responders, and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders. In contrast, HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P. vivax and P. falciparum CSP repeats, and the haplotype DRB1*01~DQB1*05 was also associated with non-responders, including non-responders to P. malariae. CONCLUSIONS: Our results show that in low transmission settings, naturally acquired antibody responses against the CSP repeats of P. vivax, P. falciparum, and P. malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure, especially in an area with a high prevalence of P. vivax. Furthermore, HLA class II molecules play an important role in antibody response and require further study with a larger sample size. It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.

Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon

BACKGROUND: Brazil has seen a great decline in malaria and the country is moving towards elimination. However, for eventual elimination, the control program needs efficient tools in order to monitor malaria exposure and transmission. In this study, we aimed to evaluate whether seroprevalence to the circumsporozoite protein (CSP) is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon. METHODS: Cross-sectional surveys were conducted in a rural area of Porto Velho, Rondônia state. Parasite infection was detected by microscopy and polymerase chain reaction. Antibodies to the sporozoite CSP repeats of Plasmodium vivax, P. falciparum, and P. malariae (PvCS, PfCS, and PmCS) were detected using the enzyme-linked immunosorbent assay technique. Human leukocyte antigen (HLA)-DRB1 and DQB1 genes were typed using Luminex® xMAP® technology. RESULTS: The prevalence of immunoglobulin G against P. vivax CSP peptide (62%) was higher than P. falciparum (49%) and P. malariae (46%) CSP peptide. Most of the studied individuals had antibodies to at least one of the three peptides (72%), 34% had antibodies to all three peptides and 28% were non-responders. Although the majority of the population was not infected at the time of the survey, 74.3% of parasite-negative individuals had antibodies to at least one of the CSPs. Importantly, among individuals carrying the haplotypes DRB1*04~DQB1*03, there was a significantly higher frequency of PfCS responders, and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders. In contrast, HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P. vivax and P. falciparum CSP repeats, and the haplotype DRB1*01~DQB1*05 was also associated with non-responders, including non-responders to P. malariae. CONCLUSIONS: Our results show that in low transmission settings, naturally acquired antibody responses against the CSP repeats of P. vivax, P. falciparum, and P. malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure, especially in an area with a high prevalence of P. vivax. Furthermore, HLA class II molecules play an important role in antibody response and require further study with a larger sample size. It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations

Hepatitis delta: virological and clinical aspects.

There are an estimated 400 million chronic carriers of HBV worldwide; between 15 and 20 million have serological evidence of exposure to HDV. Traditionally, regions with high rates of endemicity are central and northern Africa, the Amazon Basin, eastern Europe and the Mediterranean, the Middle East and parts of Asia. There are two types of HDV/HBV infection which are differentiated by the previous status infection by HBV for the individual. Individuals with acute HBV infection contaminated by HDV is an HDV/HBV co-infection, while individuals with chronic HBV infection contaminated by HDV represent an HDV/HBV super-infection. The appropriate treatment for chronic hepatitis delta is still widely discussed since it does not have an effective drug. Alpha interferon is currently the only licensed therapy for the treatment of chronic hepatitis D. The most widely used drug is pegylated interferon but only approximately 25% of patients maintain a sustained viral response after 1 year of treatment. The best marker of therapeutic success would be the clearance of HBsAg, but this data is rare in clinical practice. Therefore, the best way to predict a sustained virologic response is the maintenance of undetectable HDV RNA levels.

The influence of intestinal parasites on Plasmodium vivax-specific antibody responses to MSP-119 and AMA-1 in rural populations of the Brazilian Amazon.

BACKGROUND: Polyparasitism is a common condition in humans but its impact on the host immune system and clinical diseases is still poorly understood. There are few studies of the prevalence and the effect of malaria-intestinal parasite co-infections in the immune response to malaria vaccine candidates. The present study determines whether the presence of malaria and intestinal parasites co-infection is associated with impaired IgG responses to Plasmodium vivax AMA-1 and MSP-119 in a rural population of the Brazilian Amazon. METHODS: A cross-sectional survey was performed in a rural area of Rondonia State and 279 individuals were included in the present study. At recruitment, whole blood was collected and Plasmodium and intestinal parasites were detected by microscopy and molecular tests. Blood cell count and haemoglobin were also tested and antibody response specific to P. vivax AMA-1 and MSP-119 was measured in plasma by ELISA. The participants were grouped according to their infection status: singly infected with Plasmodium (M); co-infected with Plasmodium and intestinal parasites (CI); singly infected with intestinal parasites (IP) and negative (N) for both malaria and intestinal parasites. RESULTS: The prevalence of intestinal parasites was significantly higher in individuals with malaria and protozoan infections were more prevalent. IgG antibodies to PvAMA-1 and/or PvMSP-119 were detected in 74 % of the population. The prevalence of specific IgG was similar for both proteins in all four groups and among the groups the lowest prevalence was in IP group. The cytophilic sub-classes IgG1 and IgG3 were predominant in all groups for PvAMA-1 and IgG1, IgG3 and IgG4 for PvMSP-119. In the case of non-cytophilic antibodies to PvAMA-1, IgG2 was significantly higher in IP and N group when compared to M and CI while IgG4 was higher in IP group. CONCLUSIONS: The presence of intestinal parasites, mainly protozoans, in malaria co-infected individuals does not seem to alter the antibody immune responses to P. vivax AMA-1 and MSP-119. However, IgG response to both AMA1 and MSP1 were lower in individuals with intestinal parasites.

Intestinal parasites coinfection does not alter plasma cytokines profile elicited in acute malaria in subjects from endemic area of Brazil.

In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO) concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan) does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.