HTLV in South America: Origins of a silent ancient human infection.

The description of the first human retrovirus, human T-lymphotropic virus 1 (HTLV-1), was soon associated with an aggressive lymphoma and a chronic inflammatory neurodegenerative disease. Later, other associated clinical manifestations were described, affecting diverse target organs in the human body and showing the enormous burden carried by the virus and the associated diseases. The epidemiology of HTLV-1 and HTLV-2 showed that they were largely distributed around the world, although it is possible to locate geographical areas with pockets of low and very high prevalence and incidence. Aboriginal Australians and indigenous peoples of Brazil are examples of the large spread of HTLV-1 and HTLV-2, respectively. The epidemiological link of both situations is their occurrence among isolated, epidemiologically closed or semi-closed communities. The origin of the viruses in South America shows two different branches with distinct timing of entry. HTLV-1 made its probable entrance in a more recent route through the east coast of Brazil at the beginning of the slave trade from the African continent, starting in the 16th century and lasting for more than 350 years. HTLV-2 followed the ancient route of human migration from the Asian continent, crossing the Behring Strait and then splitting in South America as the population became separated by the Andes Mountains. By that time, HTLV-2c probably arose and became isolated among the indigenous populations in the Brazilian Amazon. The study of epidemiologically closed communities of indigenous populations in Brazil allowed tracing the most likely route of entry, the generation of a new molecular subtype (HTLV-2c), the elucidation of the vertical transmission of HTLV-2, the intrafamilial aggregation of cases and the escape and spread of the virus to other areas in Brazil and abroad. Despite the burden and impact of both viruses, they are maintained as silent infections among human populations because 1, health authorities in most South American countries in which national surveillance is poor have little interest in the disease, 2, the information is commonly lost as indigenous groups do not have specific policies for HTLV and other sexually transmitted infections, and 3, health access is not feasible or properly delivered.

Prevalence and Molecular Epidemiology of Human T-Lymphotropic Virus (HTLV) Infection in People Living With HIV/AIDS in the Pará State, Amazon Region of Brazil.

The human T-lymphotropic virus (HTLV) is part of the group of retroviruses that share similar routes of transmission to the human immunodeficiency virus (HIV). Coinfection of these viruses can affect the clinical course of both infections, and reports have shown a quicker progression to AIDS and the development of HIV-related opportunistic infections. The current study investigated the demographic characteristics, prevalence, and the subtypes of HTLV among people living with HIV/AIDS (PLWHA) in the State of Pará, Northern Brazil. Blood samples were obtained from patients who were attending a reference unit that provides medical assistance to HIV-infected individuals in the State of Pará, Brazil, during the period of May 2016 to June 2017. Plasma samples were screened by ELISA tests to detect antibodies anti-HTLV-1/2. DNA and viral types were identified by real-time polymerase chain reaction (qPCR). All samples with viral DNA were submitted to nested PCR and nucleotide sequencing. The overall coinfection rate was 1.4% (5/368), and all samples were from subtype HTLV-1a. No cases of HTLV-2 infection were detected. The prevalence of HTLV-1 was higher in females (80%), individuals between 31 and 50 years of age, heterosexual, unmarried, with low monthly income, with secondary educational level or higher, sporadic condom usage, limited number of sexual partners, and no history of sexually transmitted infections. All samples from HTLV-1-infected patients were identified as strains belonging to the subtype 1a (Cosmopolitan), subgroup A (Transcontinental). This study identified that the prevalence of HIV/HTLV coinfection has dropped from 8 to 1.3% in the current investigation. There was a shift of HTLV subtype from a predominance of HTLV-2 infection in the past to an actual exclusively HTLV-1a. There was no significant association between economic, sociodemographic, and behavioral characteristics in HIV/HTLV coinfection.

Low prevalence of human pegivirus 1 (HPgV-1) in HTLV-1 carriers from Belém, Pará, North Region of Brazil.

INTRODUCTION: Human pegivirus 1 (HPgV-1) is a single-stranded, positive-sense RNA virus belonging to the Flaviviridae family with limited cause-effect evidence of the causation of human diseases. However, studies have shown a potential beneficial impact of HPgV-1 coinfection in HIV disease progression. Human T lymphotropic virus-1 (HTLV-1) is a retrovirus known for causing diseases, especially in muscle and white blood cells, in approximately 5% of patients. Thus, this study aimed to investigate the potential effects of an HPgV-1 infection in patients carrying HTLV-1 in the state of Pará in the North Region of Brazil. METHODS: A group of HTLV-1 carriers was compared to healthy controls. Blood samples were collected, data from medical regards were collected, and a questionnaire was administered. HPgV-1 and HTLV-1 positivity was determined by quantitative polymerase chain reaction (qRT-PCR). The data were analyzed to correlate the effects of HPgV-1 coinfection in HTLV-1 carriers. RESULTS: A total of 158 samples were included in the study: 74 HTLV-1-positive patients (46,8%) and 84 healthy controls (53,2%). The overall HPgV-1 positivity rate was 7.6% (12/158), resulting in a prevalence of 5.4% (4/74) and 9.5% (8/84) in HTLV-1 carriers and healthy controls, respectively. No significant differences were found when comparing any clinical or demographic data between groups. CONCLUSION: This study indicated that the prevalence of HPgV-1 infection is low in HTLV-1 carriers in Belém, Pará, and probably does not alter the clinical course of HTLV-1 infection, however, further studies are still needed.

Prevalence of syphilis in female sex workers in three countryside cities of the state of Pará, Brazilian Amazon.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) transmitted from person to person mainly by sexual intercourse or through vertical transmission during pregnancy. Female sex workers (FSWs) are exposed especially to syphilis infection, and besides all the efforts to control the spread of STIs, syphilis prevalence is still rising, mainly occurring in low-income countries. This study aimed to investigate the syphilis prevalence, demographic characteristics and sexual habits among FSWs in the Amazon region of Brazil. METHODS: A cross-sectional study was carried out including 184 FSWs from 3 countryside cities of the state of Pará, Amazon region of Brazil. A venereal disease research laboratory test and an indirect immunoenzyme assay to test antibodies against Treponema pallidum were used for screening syphilis infection, while sexual habits and demographic data information were collected through a semi-structured questionnaire. Data was analyzed comparing groups with/without syphilis. Poisson regression models were used to estimate the reasons of prevalence (RP). RESULTS: The overall prevalence of syphilis was 14.1% (95% CI = 9.8-17.8). FSWs had between 15 and 56 years of age, most were unmarried (65.7%), had attended less than 8 years of formal education (64.1%), had between 10 and 20 partners per week (64.1%), and reported no previous history of STIs (76.1%) and regular use of condom (52.7%). Low level of education attending up to the primary school (RP adjusted = 3.8; 95% CI = 1.4-9.2) and high frequency of anal sex during the past year (RP adjusted = 9.3; 95% CI = 3.5-28.7) were associated with a higher prevalence of syphilis. CONCLUSIONS: A high prevalence of syphilis among FSWs in the Brazilian Amazon region was identified, showing that syphilis is more likely to be transmitted in FSW working in low-income areas, which is attributed to the low level of education. Anal intercourse was found as a risk factor associated with syphilis. Health programs focused on risk populations appear as a rational way to control syphilis spread, which is a rising problem in Brazil and in other several countries.

Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Belém, Pará, Northern Brazil.

BACKGROUND: Prenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil. METHODS: A cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010. After the interview and blood collection, the patients were screened for antibodies and/or antigens against HIV-1/2, HTLV-1/2, CMV, rubella virus and HBV. The epidemiological variables were demonstrated using descriptive statistics with the G, χ2 and Fisher exact tests. RESULTS: The mean age of the participants was 15.8 years, and the majority (65.4%) had less than 6 years of education. The mean age at first intercourse was 14.4 years, and 60.8% reported having a partner aged between 12 and 14 years. The prevalence of HIV infection was 0.3%, and of HTLV infection was 0.6%. Regarding HBV, 0.6% of the participants had acute infection, 9.9% had a previous infection, 16.7% had vaccine immunity and 72.8% were susceptible to infection. The presence of anti-HBs was greater in adolescent between 12 and 14 years old (28.8%) while the anti-HBc was greater in adolescent between 15 and 18 years old (10.3%). Most of the adolescents presented the IgG antibody to CMV (96.3%) and rubella (92.3%). None of the participants had acute rubella infection, and 2.2% had anti-CMV IgM. CONCLUSIONS: This study is the first report of the seroepidemiology of infectious agents in a population of pregnant adolescents in the Northern region of Brazil. Most of the adolescents had low levels of education, were susceptible to HBV infection and had IgG antibodies to CMV and rubella virus. The prevalence of HBV, HIV and HTLV was similar to that reported in other regions of Brazil. However, the presence of these agents in this younger population reinforces the need for good prenatal follow-up and more comprehensive vaccination campaigns against HBV due to the large number of women susceptible to the virus.

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region

Abstract JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215 bp) and IG (610 bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4+/TCD8+ lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region.

JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.

Gene Polymorphisms and Serum Levels of Pro- and Anti-Inflammatory Markers in Dengue Viral Infections.

Pro- and anti-inflammatory markers (tumor necrosis factor [TNF]-α, TNF-ß, interferon [IFN]-γ, interleukin [IL]-6, IL-8, IL-10, and C-reactive protein [CRP]) were investigated in 80 patients infected with dengue viruses, 100 patients presenting with febrile illness but negative for dengue, and 99 healthy subjects. Immunoenzyme methods were used for quantitative assays in the plasma. Polymorphisms of TNF-α, TNF-ß, IL-6, IL-8, and IL-10 genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific oligonucleotide (ASO)-PCR for the IFN-γ. The highest mean serum levels of TNF-α, IFN-γ, IL-8, and CRP were observed in dengue-positive individuals. TNF-ß, IL-6, and IL-10 levels were significantly higher in the dengue-negative individuals. No cytokine expression pattern was evidenced according to virus serotype. Genotypic frequency distributions were statistically significant for the polymorphisms of TNF-α and IFN-γ among positive, negative, and control dengue groups and IFN-γ among groups DENV-1, DENV-2, DENV-3, and controls. Modulation of cytokine expression and polymorphisms is a complex matter and needs further explanation considering the ethnic origins of the Brazilian population.

IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy.

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-ß (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-ß and IFN-γ levels.

Lack of Association between Polymorphisms of the TLR4 Gene and Infection with the Hepatitis B and C Viruses.

Toll-like receptor 4 (TLR4) plays a crucial role in the early recognition of pathogenic microorganisms and provides an ideal model to investigate the consequences of genetic variation and susceptibility to diseases. The present study investigated the occurrence of the single nucleotide polymorphisms (SNPs) rs4986790 (A>G) and rs4986791 (C>T) in the TLR4 gene in chronic carriers of the hepatitis B (HBV) and C (HCV) viruses. A total of 420 blood samples were collected (HBV, 49; HCV, 72; and controls, 299) at the liver disease outpatient clinic of Hospital da Fundação Santa Casa de Misericórdia do Pará (FSCMPA). Genomic DNA extracted from leukocytes was subjected to real-time polymerase chain reaction (qPCR) analysis to identify the genetic profile of the participants. No significant differences were found in the allele and genotype frequencies between the infected participants and controls. No significant associations were found between the investigated polymorphisms and inflammatory activity, fibrosis, and the presence of cirrhosis; the same results were obtained in the haplotype analysis. The results showed a lack of association between the rs4986790 and rs4986791 SNPs and susceptibility to infection with HBV and HCV, as well as clinical and laboratory information of the patients.

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection.

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection.

Chlamydia trachomatis serotype A infections in the Amazon region of Brazil: prevalence, entry and dissemination.

INTRODUCTION: Chlamydia infection is associated with debilitating human diseases including trachoma, pneumonia, coronary heart disease and urogenital diseases. Serotypes of C. trachomatis show a fair correlation with the group of diseases they cause, and their distribution follows a well-described geographic pattern. Serotype A, a trachoma-associated strain, is known for its limited dissemination in the Middle East and Northern Africa. However, knowledge on the spread of bacteria from the genus Chlamydia as well as the distribution of serotypes in Brazil is quite limited. METHODS: Blood samples of 1,710 individuals from ten human population groups in the Amazon region of Brazil were examined for antibodies to Chlamydia using indirect immunofluorescence and microimmunofluorescence assays. RESULTS: The prevalence of antibodies to Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all serotypes of C. trachomatis tested; furthermore, we report clear evidence of the as-yet-undescribed occurrence of serotype A of C. trachomatis. CONCLUSIONS: Specific seroreactivity not only accounts for the large extent of dissemination of C. trachomatis in the Amazon region of Brazil but also shows an expanded area of occurrence of serotype A outside the epidemiological settings previously described. Furthermore, these data suggest possible routes of Chlamydia introduction into the Amazon region from the massive human migration that occurred during the 1,700s.

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection. .

Chlamydia trachomatis serotype A infections in the Amazon region of Brazil: prevalence, entry and dissemination

INTRODUCTION: Chlamydia infection is associated with debilitating human diseases including trachoma, pneumonia, coronary heart disease and urogenital diseases. Serotypes of C. trachomatis show a fair correlation with the group of diseases they cause, and their distribution follows a well-described geographic pattern. Serotype A, a trachoma-associated strain, is known for its limited dissemination in the Middle East and Northern Africa. However, knowledge on the spread of bacteria from the genus Chlamydia as well as the distribution of serotypes in Brazil is quite limited. METHODS: Blood samples of 1,710 individuals from ten human population groups in the Amazon region of Brazil were examined for antibodies to Chlamydia using indirect immunofluorescence and microimmunofluorescence assays. RESULTS: The prevalence of antibodies to Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all serotypes of C. trachomatis tested; furthermore, we report clear evidence of the as-yet-undescribed occurrence of serotype A of C. trachomatis. CONCLUSIONS: Specific seroreactivity not only accounts for the large extent of dissemination of C. trachomatis in the Amazon region of Brazil but also shows an expanded area of occurrence of serotype A outside the epidemiological settings previously described. Furthermore, these data suggest possible routes of Chlamydia introduction into the Amazon region from the massive human migration that occurred during the 1,700s. .

Polymorphisms in the IFNγ, IL-10, and TGFß genes may be associated with HIV-1 infection.

OBJECTIVE: This study investigated possible associations between the TNFα-308G/A, IFN+874A/T, IL-6-174C/G, IL-10-1082A/G, and TGFß-509C/T polymorphisms with HIV-1 infection, in addition to correlation of the polymorphisms with clinical markers of AIDS progression, such as levels of CD4+/CD8+ T lymphocytes and plasma viral load. METHODS: A total of 216 individuals who were infected with HIV-1 and on antiretroviral therapy (ART) and 294 individuals from the uninfected control group were analyzed. RESULTS: All individuals evaluated were negative for total anti-HBc, anti-HCV, anti-T. pallidum, and anti-HTLV-1/2. The polymorphisms were identified by PCR-RFLP. Individuals presenting the IFN+874A allele as well as the AA genotype were more frequent in the HIV-1 infected group compared to the control group (P < 0.05), in addition to having lower levels of CD4+ T lymphocytes. The CD8+ T lymphocytes count was significantly lower in individuals with the IL-10-1082 GG genotype. The TGFß-509TT genotype was associated with higher plasma viral load. CONCLUSIONS: The results suggest that the presence of the IFN+874A allele confers susceptibility to HIV-1 infection and a decrease in the number of CD4+ T lymphocytes. In addition, the genotype associated with high serum levels of TGFß may be associated with an increase in plasma viral load.

Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals.

INTRODUCTION: The present study investigated the association between mannose-binding lectin (MBL) gene polymorphism and serum levels with infection by HIV-1. METHODS: Blood samples (5 mL) were collected from 97 HIV-1-infected individuals resident in Belém, State of Pará, Brazil, who attended the Special Outpatient Unit for Infections and Parasitic Diseases (URE-DIPE). CD4+ T-lymphocyte count and plasma viral load were quantified. A 349bp fragment of exon 1 of the MBL was amplified via PCR, using genomic DNA extracted from controls and HIV-1-infected individuals, following established protocols. MBL plasma levels of the patients were quantified using an enzyme immunoassay kit. RESULTS: Two alleles were observed: MBL*O, with a frequency of 26.3% in HIV-1-infected individuals; and the wild allele MBL*A (73.7%). Similar frequencies were observed in the control group (p > 0.05). Genotype frequencies were distributed according to the Hardy-Weinberg equilibrium in both groups. Mean MBL plasma levels varied by genotype, with statistically significant differences between the AA and AO (p < 0.0001), and AA and OO (p < 0.001) genotypes, but not AO and OO (p = 0.17). Additionally, CD4+ T-lymphocytes and plasma viral load levels did not differ significantly by genotype (p > 0.05). CONCLUSIONS: The results of this study do not support the hypothesis that MBL gene polymorphism or low plasma MBL concentrations might have a direct influence on HIV-1 infection, although a broader study involving a large number of patients is needed.

Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals / Caracterização dos polimorfismos genéticos e dos níveis plasmáticos da lectina ligante de manose em indivíduos infectados pelo HIV-1

INTRODUCTION: The present study investigated the association between mannose-binding lectin (MBL) gene polymorphism and serum levels with infection by HIV-1. METHODS: Blood samples (5mL) were collected from 97 HIV-1-infected individuals resident in Belém, State of Pará, Brazil, who attended the Special Outpatient Unit for Infections and Parasitic Diseases (URE-DIPE). CD4+ T-lymphocyte count and plasma viral load were quantified. A 349bp fragment of exon 1 of the MBL was amplified via PCR, using genomic DNA extracted from controls and HIV-1-infected individuals, following established protocols. MBL plasma levels of the patients were quantified using an enzyme immunoassay kit. RESULTS: Two alleles were observed: MBL*O, with a frequency of 26.3 percent in HIV-1-infected individuals; and the wild allele MBL*A (73.7 percent). Similar frequencies were observed in the control group (p > 0.05). Genotype frequencies were distributed according to the Hardy-Weinberg equilibrium in both groups. Mean MBL plasma levels varied by genotype, with statistically significant differences between the AA and AO (p < 0.0001), and AA and OO (p < 0.001) genotypes, but not AO and OO (p = 0.17). Additionally, CD4+ T-lymphocytes and plasma viral load levels did not differ significantly by genotype (p > 0.05). CONCLUSIONS: The results of this study do not support the hypothesis that MBL gene polymorphism or low plasma MBL concentrations might have a direct influence on HIV-1 infection, although a broader study involving a large number of patients is needed.

INTRODUÇÃO: O presente estudo investigou a associação entre o polimorfismo no gene da lectina ligante de manose (MBL) e os níveis séricos da proteína com a infecção pelo HIV-1. MÉTODOS: As amostras de sangue (5mL) foram coletadas de 97 indivíduos infectados pelo HIV-1 residentes em Belém, Estado do Pará, Brasil, que frequentavam a Unidade de Referência Especial para Doenças Infecciosas e Parasitárias Especiais (URE-DIPE). Os níveis de linfócitos T CD4+ e da carga viral plasmática foram quantificados. Um fragmento de 349pb do exon 1 da MBL foi amplificado via PCR, utilizando DNA genômico extraído das amostras controles e dos indivíduos portadores do HIV-1, seguindo protocolos previamente estabelecidos. O nível plasmático de MBL nos pacientes foi quantificado usando kit de ensaio imunoenzimático. RESULTADOS: Dois alelos foram observados - MBL*O, com uma frequência de 26,3 por cento em indivíduos infectados e o alelo selvagem MBL*A (73,7 por cento). Frequências similares foram observadas no grupo controle (p > 0,05). As frequências genotípicas estavam em equilíbrio de Hardy-Weinberg em ambos os grupos. A média dos níveis plasmáticos MBL variou por genótipo, com diferenças significativas entre os genótipos AA e AO (p < 0,0001), e AA e OO (p < 0,001), mas não entre AO e OO (p=0,17). Além disso, os linfócitos T CD4+ e os níveis plasmáticos de carga viral não diferiram significativamente de acordo com o genótipo (p>0,05). CONCLUSÕES: Os resultados deste estudo não apoiam a hipótese de que o polimorfismo no gene MBL ou baixa concentração plasmática de MBL poderia ter uma influência direta sobre a infecção pelo HIV-1, embora um estudo com número maior de pacientes seja necessário.

High diversity of HHV-8 molecular subtypes in the Amazon region of Brazil: evidence of an ancient human infection.

The present study describes the molecular epidemiology of Human herpesvirus 8 (HHV-8) among four Indian tribes (Kararao, Arara Laranjal, Tiriyo, and Zo'e) of the Amazon region of Brazil and a group of HIV-1-infected subjects from the urban population of Belem, Para. Infection was characterized by the presence of antibodies using ELISA (measuring antibodies to ORF59, ORF65, K8.1A, K8.1B, and ORF73), and molecular assays (gene amplification of the regions ORF26 and the variable region VR1). Antibodies to HHV-8 were detected in 66 samples of the 221 Brazilian Amerindians, namely, 6 (25%) in the Kararao, 18 (19.6%) in the Arara Laranjal, 24 (42.9%) in the Tiriyo, and 18 (36.7%) in the Zo'e. Among the 477 HIV-1-infected subjects, antibodies to HHV-8 were present in 74 (15.5%) persons. The ORF26 region was amplified in seven samples, one of the Arara Laranjal, one of the Tiriyo, two of the Zo'e, and three of the HIV-1-infected group. Subtyping of HHV-8 described a high multiplicity of molecular subtypes, including C (Zo'e), E (Tiriyo), and B (HIV-1 infected). Serological results confirm the high prevalence of HHV-8 among Amerindians and the presence of three subtypes in the Amazon region of Brazil, including a unique subtype, which favors the idea of HHV-8 as an ancient human infection within this particular geographical region.

Mannose-binding lectin gene polymorphism and its impact on human immunodeficiency virus 1 infection.

Mannose-binding lectin (MBL) is a serum protein whose low concentration is associated with the occurrence of allele variants named MBL*B, MBL*C and MBL*D. The present study investigated the association between MBL gene polymorphism and the susceptibility to HIV-1 infection. The study of 145 HIV-1-infected subjects and 99 healthy controls showed the presence of alleles MBL*A, MBL*B and MBL*D, whose frequencies were 69%, 22% and 09% among patients and 71%, 13% and 16% among healthy controls, respectively. The presence of the variant MBL*B was associated with higher plasma viral load levels, suggesting the importance of the MBL gene polymorphism in the clinical evolution of HIV-1-infected patients.

Epidemiological aspects of retrovirus (HTLV) infection among Indian populations in the Amazon Region of Brazil.

HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.