The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy

Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

Ocorrência e distribuição de esporos de Clostridium botulinum tipos C e D em áreas de criação de búfalos na Baixada Maranhense

Botulismo é enzoótico na criação de búfalos da Baixada Maranhense, Estado do Maranhão. No presente trabalho foram realizados estudos para verificar a ocorrência e distribuição de esporos de Clostridium botulinum tipos C e D em amostras de solo, limo e fezes de búfalos, colhidas aleatoriamente em áreas inundáveis da criação de búfalos nessa Baixada. A evidenciação de esporos foi realizada em 40 amostras de fezes, 65 de limo e 35 de solo, provenientes de quatro municípios, pelo cultivo em meio de cultura com carne cozida e posterior inoculação do sobrenadante filtrado em camundongo, na tentativa de verificação da presença de toxina botulínica. A tipificação de amostras positivas foi realizada pela microfixação de complemento. Os resultados revelaram que 104 (74,28%) das 140 amostras examinadas foram positivas para a presença de esporos de C. botulinum pelo teste indireto. Não houve diferença significativa (P>0,05) entre os valores obtidos quando das análises das amostras de solo (77,1%), limo (60,0%) e fezes (95,0%). Das 28 amostras de solo, limo e fezes positivas, que foram utilizadas para a tipificação, quatro (14,29%) foram classificadas como tipo C, 23 (82,14%) como tipo D e uma (3,5%) como pertencente ao complexo CD. Os resultados revelaram uma alta contaminação ambiental por C. botulinum em áreas de criação de búfalos da Baixada Maranhen-se. A identificação de outros tipos e de subtipos de C. botulinum não foi realizada.

The C-peptide response to a standard mixed meal in a group of Brazilian type 1 diabetic patients

In order to analyze the different parameters used in the interpretation of C-peptide response in a functional test, we compared a group of 26 type 1 diabetics aged 21.1 ± 8.2 years, with a diabetes duration of 7.9 ± 6.7 months, with a group of 24 non-diabetic subjects aged 25.0 ± 4.4 years. A standard mixed meal of 317 kcal was used as a stimulus. Blood sampling for C-peptide determinations was performed at regular intervals. Although all the studied C-peptide variables were significantly lower in the diabetic group (P<0.0001), some overlapping of parameters was observed between the two groups. The highest degree of overlapping was found for basal value (BV) (30.8%) and percent increase (42.31%), and the lowest for incremental area, absolute increase, peak value (PV) (3.8%), and total area (7.7%) (CE="Symbol">c2 = 31.6, P<0.0001). We did not observe a definite pattern in the time of maximum response among the 21 diabetics who showed an increase in C-peptide levels after the stimulus. In this group, however, there was a highly significant number of late responses (120 min) (CE="Symbol">c2 = 5.7, P<0.002). Although BV showed a significant correlation with PV (rS = 0.95, P<0.0001), the basal levels of C-peptide did not differentiate the groups with and without response to the stimulus. We conclude that the diabetic group studied showed delayed and reduced C-peptide responses, and that the functional test can be an important tool for the evaluation of residual ß cell function.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia

The C/T-13910 mutation is the major factor responsible for the persistence of the lactase-phlorizin hydrolase (LCT) gene expression. Mutation G/A-22018 appears to be only in co-segregation with C/T-13910. The objective of the present study was to assess the presence of these two mutations in Brazilian individuals with and without lactose malabsorption diagnosed by the hydrogen breath test (HBT). Ten milk-tolerant and 10 milk-intolerant individuals underwent the HBT after oral ingestion of 50 g lactose (equivalent to 1 L of milk). Analyses for C/T-13910 and G/A-22018 mutations were performed using a PCR-based method. Primers were designed for this study based on the GenBank sequence. The CT/GA, CT/AA, and TT/AA genotypes (lactase persistence) were found in 10 individuals with negative HBT. The CC/GG genotype (lactase non-persistence) was found in 10 individuals, 9 of them with positive HBT results. There was a significant agreement between the presence of mutations in the LCT gene promoter and HBT results (kappa = -0.9, P < 0.001). The CT/AA genotype has not been described previously and seems to be related to lactase persistence. The present study showed a significant agreement between the occurrence of mutations G/A-22018 and C/T-13910 and lactose absorption in Brazilian subjects, suggesting that the molecular test used here could be proposed for the laboratory diagnosis of adult-type primary hypolactasia.

Distribution of human immunodeficiency virus type 1 subtypes in the state of Amazonas, Brazil, and subtype C identification

Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF_BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible "homogenous" subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country.

Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection

The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9%) outpatients and in 34 of 186 (18.7%) dialysis patients. Among HCV+ patients, 32 were men (43.8%). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 µKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 µKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 µKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 µM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7%; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.

Avaliação da toxigênese de c. botulinum em mortadela e presunto

Na presente pesquisa foi realizada uma avaliação do risco de transmissão de botulismo por consumo de mortadela e presunto. Numa primeira fase, 25 amostras de mortadela e presunto cozido, coletadas ao acaso no varejo do município de Campinas - SP, foram analisadas quanto ao pH, atividade de água (Aa), concentração de cloreto de sódio e de nitrito de sódio e umidade. Nesta fase, ainda foram determinados o tempo e a temperatura de estocagem na revenda. Considerando-se isoladamente os fatores que controlam o desenvolvimento do C. botulinum, apenas quatro (16%) amostras de mortadela coletadas no varejo apresentaram valores de atividade de água capazes de irnpedir a oxigênese, ou seja, inferiores a 0,94. Na segunda fase, mortadela e presunto foram preparados em usina experimental e artificialmente contaminados com 10(4) esporos de C botulinum tipos A e B por amostra. A seguir, foram submetidos à estocagem inadequada, à temperatura de 30°C. A formação de toxina botulínica foi observada nas amostras de presunto artificialmente contaminadas, após 12 dias de estocagem à temperatura de 30°C. Nas amostras de mortadela não foi detectada toxina ao fim de 28 dias de estocagem, à mesma temperatura.

Incidence rate and spatio-temporal clustering of type 1 diabetes in Santiago, Chile, from 1997 to 1998

OBJECTIVE: To estimate the incidence rate of type 1 diabetes in the urban area of Santiago, Chile, from March 21, 1997 to March 20, 1998, and to assess the spatio-temporal clustering of cases during that period. METHODS: All sixty-one incident cases were located temporally (day of diagnosis) and spatially (place of residence) in the area of study. Knox's method was used to assess spatio-temporal clustering of incident cases. RESULTS: The overall incidence rate of type 1 diabetes was 4.11 cases per 100,000 children aged less than 15 years per year (95% confidence interval: 3.06--5.14). The incidence rate seems to have increased since the last estimate of the incidence calculated for the years 1986--1992 in the metropolitan region of Santiago. Different combinations of space-time intervals have been evaluated to assess spatio-temporal clustering. The smallest p-value was found for the combination of critical distances of 750 meters and 60 days (uncorrected p-value = 0.048). CONCLUSIONS: Although these are preliminary results regarding space-time clustering in Santiago, exploratory analysis of the data method would suggest a possible aggregation of incident cases in space-time coordinates.

Serologic studies on the behaviour of influenza virus type A in persons of greater São Paulo during 1976, 1978 and 1979

Sera of persons of different age groups collected in 1976, 1978 and 1979 were tested for the presence of HI antibodies against various strains of the H3N2 and H1N1 subtypes of influenza virus. The occurrence of infection by H3N2 subtype was recorded during the 1976-1978 period but in 1979, circulation of this subtype of virus was limited. The prevalence of antibody against A/São Paulo/1/78 (H1N1) was significantly higher than that of antibody to A/USSB/90/77 (HIND in 1978. However in 1979 the predominant strain was A/USSR/90/77 (HIND. Persons under 20 years of age were the most affected by H1N1 subtype. Antibodies to H1N1 subtype were detected in sera of individuals older than 20 years in 1976, before the re-emergence of this strain. Serological results indicate that infections by H3N2 subtype in 1978 occurred in 65.4% of young children (0-4 year group). About 47.0% of children from the 0-4 year group had antibodies to H1N1 subtype in 1979. Antibodies to swine influenza virus were detected in 60% of 60+ year old people.

Dengue type 2 outbreak in the south of the State of Bahia, Brazil: laboratorial and epidemiological studies

During March 1994 cases of a exanthematic acute disease were reported in the municipalities of Itagemirim, Eunápolis and Belmonte, state of Bahia. Dengue fever was confirmed by serology (MAC-ELISA) and by dengue virus type 2 isolation, genotype Jamaica. Signs and symptoms of classic dengue fever were observed with a high percentual of rash (73.8%) and pruritus (50.5%). Major haemorrhagic manifestations were unfrequent and only bleeding gum was reported. Dengue virus activity spreaded rapidly to important tourism counties like Porto Seguro, Ilhéus, Santa Cruz de Cabrália, Prado, Alcobaça and others, representing a risk for the spreading of dengue virus into the country and abroad.

Histopathology and immunocytochemical study of type 3 and type 4 complement receptors in the liver and spleen of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

The objective of this study was to compare the histopathological changes and expression of CR3 and CR4 in the liver and spleen of dogs naturally and experimentally infected with L. chagasi. The basic histopathological lesions observed mainly in naturally infected dogs were: epithelioid hepatic granulomas, hyperplasia and hypertrophy of Kupffer cells, Malpigui follicles and mononucleated cells of the red pulp of the spleen. Sections from the liver and spleen by immunocytochemistry technique showed the presence of CD11b,c\CD 18 antigens in the control and infected animals and no qualitative or quantitative differences in the liver. Nevertheless, CD18 was always increased in the spleen of naturally and experimentally infected dogs. These results indicate that there is a difference in the activaton of CD 18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.

Progression of Salmonella Enteritidis phage type 4 strains in São Paulo State, Brazil

A total of 574 S. Enteritidis strains (383 from human sources and 191 from non-human sources) isolated between 1975-95, in São Paulo State, Brazil, were phagetyped. Among the strains isolated during the period of 1975-92, 80.9% of them belonged to phage type 8 (PT-8), but in 1993 strains of PT-4 accounted for 65.2% of all the S. Enteritidis isolates. In the following years, PT-4 strains accounted for 99.7% and 98.4% of phagetyped S. Enteritidis strains. The results obtained suggested that the current epidemic of S. Enteritidis in São Paulo State is clearly associated with the progression of PT-4 strains.

Chronic hepatitis C virus infections in Brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy

The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-interferon-alpha (r-IFN-CE="Symbol">a) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-CE="Symbol">a, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0.005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of cirrhosis was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of cirrhosis were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-CE="Symbol">a therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide.

Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.

Serotype, mating type and ploidy of Cryptococcus neoformans strains isolated from patients in Brazil

Serotype, mating type and ploidy of 84 strains of Cryptococcus neoformans isolated from 61 AIDS and 23 non-AIDS patients admitted in a tertiary teaching hospital in São Paulo, Brazil were examined. Among 61 strains isolated from AIDS patients, 60 strains were var. grubii (serotype A). Only one strain was var. gattii (serotype B). No var. neoformans (serotype D) was found. Among 23 strains isolated from non-AIDS patients, 15 were var. grubii (serotype A) and the remaining 8 were var. gattii, all of which were serotype B. Seventy-three of the 75 serotype A strains were the heterothallic alpha type (MATalpha) and the remaining 2 were untypable (asexual). Most of the MATalpha strains (69/73) were haploid and the remaining 4 strains were diploid. Similarly, both of the 2 asexual strains among the 75 serotype A strains were haploid. There were no alpha-mating type (MATalpha) strains among the 84 isolates. All of the 8 var. gattii strains were serotype B and haploid. Among a total of 84 strains tested, neither serotype AD nor serotype D were found. Neither triploid nor tetraploid were found. These results suggest that the serological, sexual and ploidy characteristics in C. neoformans strains isolated from AIDS patients in São Paulo were rather simple, whereas strains isolated from non-AIDS patients presented serotype A and B with predominance of serotype A.