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1.
Am J Trop Med Hyg ; 102(5): 982-984, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32157994

RESUMEN

The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.


Asunto(s)
Criptorquidismo/virología , Microcefalia/virología , Infección por el Virus Zika/complicaciones , Brasil , Preescolar , Criptorquidismo/etiología , Humanos , Lactante , Recién Nacido , Masculino , Microcefalia/etiología , Factores de Riesgo , Infección por el Virus Zika/congénito
2.
Epilepsia ; 61(3): 509-518, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32065676

RESUMEN

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

3.
PLoS Negl Trop Dis ; 13(3): e0007246, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30856223

RESUMEN

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Dengue/diagnóstico , Microcefalia/epidemiología , Microcefalia/etiología , Complicaciones Infecciosas del Embarazo/diagnóstico , Infección por el Virus Zika/diagnóstico , Adolescente , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Dengue/epidemiología , Virus del Dengue/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto Joven , Virus Zika/inmunología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología
4.
Infect Dis Poverty ; 6(1): 116, 2017 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-28764747

RESUMEN

Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations. BACKGROUND: Currently, in Brazil, there is a co-circulation of the four dengue (DENV-1 to DENV-4) serotypes. This study aimed to assess whether different serotypes and antibody response patterns were associated with the severity of the disease during a dengue outbreak, which occurred in 2012/2013 in centre of Brazil. METHODS: We conducted a prospective study with 452 patients with laboratory confirmed dengue in central Brazil, from January 2012 to July 2013. The clinical outcome was the severity of cases: dengue, dengue with warning signs, and severe dengue. The patients were evaluated at three different moments. Blood sampling for laboratory testing and confirmatory tests for dengue infection were performed. We performed a multinomial analysis considering the three categories of the dependent variable, as outlined above. The odds ratios (ORs) were calculated. A multinomial logistic regression model was applied for variables with a P-value <0.20. Statistical analysis was performed with STATA 12.0 software. RESULTS: Four hundred fifty-two patients (452/632, 71.5%) were diagnosed with dengue. The dengue virus (DENV) serotypes were identified in 243 cases. DENV-4 was detected in 135 patients (55.6%), DENV-1 in 91 (37.4%), DENV-3 in 13 (5.3%), and DENV-2 in 4 (1.6%). Patients with the DENV-1 serotype were more prone to present with several clinical and laboratory features as compared with DENV-4 patients, including spontaneous bleeding (P = 0.03), intense abdominal pain (P = 0.004), neurological symptoms (P = 0.09), and thrombocytopenia (P = 0.01). Secondary infection was more predominant among DENV-4 cases (80.0%) compared with DENV-1 cases (62.3%) (P = 0.03). The univariate analysis showed that females (OR = 2.12; 95% CI: 1.44-3.13; P < 0.01) had a higher risk of having dengue with warning signs. The multinomial analysis showed that severe dengue cases with secondary infection had an adjusted OR of 2.80 (95% CI: 0.78-10.00; P = 0.113) as compared with dengue fever with primary infection when adjusted for age and sex. CONCLUSION: The current data show that 5.8% of patients recruited for treatment in healthcare centres and hospitals during the study period had severe dengue. DENV-4 was the predominant serotype, followed by DENV-1, in a large outbreak of dengue in central Brazil. Our findings contribute to the understanding of clinical differences and immune status related to the serotypes DENV-1 and DENV-4 in central of Brazil.


Asunto(s)
Virus del Dengue/genética , Dengue/epidemiología , Brotes de Enfermedades , Serogrupo , Adolescente , Adulto , Anciano , Brasil/epidemiología , Niño , Preescolar , Coinfección/epidemiología , Coinfección/virología , Dengue/virología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Dengue Grave/epidemiología , Dengue Grave/virología , Adulto Joven
5.
Am J Med Genet A ; 173(4): 841-857, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28328129

RESUMEN

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.


Asunto(s)
Brotes de Enfermedades , Enfermedades Fetales/epidemiología , Microcefalia/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/epidemiología , Anticuerpos Antivirales/líquido cefalorraquídeo , Encéfalo/anomalías , Encéfalo/virología , Brasil/epidemiología , Femenino , Enfermedades Fetales/diagnóstico por imagen , Enfermedades Fetales/patología , Feto , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Lactante , Microcefalia/complicaciones , Microcefalia/diagnóstico por imagen , Microcefalia/patología , Neuroimagen , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/patología , Síndrome , Virus Zika/crecimiento & desarrollo , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico por imagen , Infección por el Virus Zika/patología
6.
J Infect Dis ; 214(2): 265-72, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-27056951

RESUMEN

BACKGROUND: Maternal-fetal transferred dengue virus (DENV)-specific antibodies have been implicated in the immunopathogenesis of dengue during infancy. METHODS: A prospective birth cohort was established in a dengue-endemic area in the Northeast Region of Brazil. DENV-specific immunoglobulin G (IgG) and DENV-1-4 serotype-specific neutralizing antibody (NAb) levels were assessed in 376 paired maternal and umbilical cord blood samples. The kinetics of enhancing activity by maternally acquired DENV antibodies was determined in serum samples from children enrolled in the cohort. RESULTS: Mothers were mostly immune to DENV-3 alone (53.7%) or combined with DENV-4 (30.6%). Levels of DENV-specific IgG, DENV-3 NAbs, and DENV-4 NAbs were significantly higher in newborns than in their respective mothers. Mothers immune to a single serotype transferred greater levels of DENV-specific IgG (P = .02) and DENV-3 NAbs (P = .04) than mothers immune to multiple DENV serotypes. Maternally acquired DENV-3 NAbs disappeared in >90% of the children by the age of 4 months. The peak enhancing activity was detected by the age of 2 months (P < .0001) and rapidly declined by the age of 4 months (P = .0035). CONCLUSIONS: Unlike Asian infants, the enhancing activity of DENV infection by maternally transferred DENV antibodies occurs at earlier ages in Brazilian children. These findings might explain the low occurrence of severe dengue among infants in our setting.


Asunto(s)
Anticuerpos Bloqueadores/sangre , Anticuerpos Antivirales/sangre , Acrecentamiento Dependiente de Anticuerpo , Virus del Dengue/inmunología , Dengue/inmunología , Exposición Materna , Adolescente , Adulto , Factores de Edad , Anticuerpos Neutralizantes/sangre , Brasil , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Adulto Joven
7.
Am J Trop Med Hyg ; 92(1): 108-14, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25448239

RESUMEN

The objective of this study was to ascertain risk factors for complications (reactions or neuritis) in leprosy patients at the time of diagnosis in three leprosy-endemic countries. Newly diagnosed patients were enrolled in Brazil, the Philippines, and Nepal, and risk factors for reactions and neuritis were assessed using a case-control approach: "cases" were patients with these complications, and controls were patients without complications. Of 1,972 patients enrolled in this study, 22% had complications before treatment. Type 1 reaction was diagnosed in 13.7% of patients, neuritis alone in 6.9.%, and type 2 reaction in 1.4%. The frequency of these complications was higher in Nepal, in lepromatous patients, in males, and in adults versus children. Reactions and neuritis were seen in patients at diagnosis, before treatment was started. Reactions were seen in adults and children, even in patients with only a single lesion. Neuritis was often present without other signs of reaction. Reactions and neuritis were more likely to occur in lepromatous patients, and were more likely to be seen in adults than in children.


Asunto(s)
Enfermedades Endémicas , Lepra/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Nepal/epidemiología , Filipinas/epidemiología , Factores de Riesgo , Adulto Joven
8.
BMC Infect Dis ; 13: 254, 2013 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-23725365

RESUMEN

BACKGROUND: Maternal dengue antibodies are considered to play a significant role in dengue pathogenesis among infants. Determining the transplacental specific antibody transfer is invaluable for establishing the optimal vaccination age among infants in endemic regions. METHODS: We conducted a cross-sectional study among pairs of maternal and corresponding umbilical cord blood samples in public hospitals. The prevalence and incidence of dengue infection were determined in 505 pairs of pregnant women and neonates during a large outbreak (2009-2010) in central Brazil. The women were interviewed at late pregnancy to assess current or past symptoms of dengue. All parturients and their neonates were screened using Dengue IgG Indirect ELISA (Panbio) to assess previous dengue exposure. A semi-quantitative measurement of the IgG antibody expressed by the index ratio was calculated using optical density (OD) values according to the manufacturer's instructions. The studied population of parturients and their offspring was also screened for recent dengue infection by the Dengue IgM-capture ELISA (Panbio). Those participants with history of fever and two or more symptoms of dengue at least 10 days before the delivery were also tested for the dengue NS1 antigen using the Dengue Early ELISA (Panbio) and RT-PCR. RESULTS: The mean maternal age was 25.8 (SD = 6.4), and 83.6% of deliveries were between 37 and 41 weeks. Approximately half of the 505 women and neonates were IgG-seropositive, yielding 99.3% co-positive mother-child frequency of antibody transfer (Kappa = 0.96). The incidence of dengue infection was 2.8% (95% CI 1.4-4.4%) among the women considering 14 IgM-positive results and one DENV2 detected by RT-PCR. The dengue NS1 antigen was undetectable in the matched pairs. CONCLUSION: This study provides critical data on the prevalence of transplacental transferred maternal-infant anti-dengue antibodies and incidence of infection. The design of future vaccine trials should consider diverse regional epidemiological scenarios.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , Adulto , Brasil/epidemiología , Estudios Transversales , Dengue/inmunología , Dengue/transmisión , Femenino , Sangre Fetal/química , Sangre Fetal/virología , Humanos , Inmunoglobulina G/sangre , Incidencia , Recién Nacido , Placenta/inmunología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/inmunología , Prevalencia
9.
BMC Infect Dis ; 13: 60, 2013 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-23374914

RESUMEN

BACKGROUND: Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. METHODS: The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case-control approach. RESULTS: The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%-1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. CONCLUSIONS: The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.


Asunto(s)
Hepacivirus , Hepatitis C/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Niño , Estudios Transversales , Femenino , Genotipo , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/historia , Anticuerpos contra la Hepatitis C/sangre , Anticuerpos contra la Hepatitis C/inmunología , Historia del Siglo XXI , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Población Urbana , Adulto Joven
10.
Am J Trop Med Hyg ; 81(2): 240-7, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19635877

RESUMEN

This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast, Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall, 7,881 persons were included; < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings; healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.


Asunto(s)
Hepatitis B/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Estudios Transversales , Femenino , Anticuerpos contra la Hepatitis B/sangre , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Caracteres Sexuales , Factores Socioeconómicos , Adulto Joven
11.
BMC Public Health ; 8: 361, 2008 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-18937868

RESUMEN

BACKGROUND: Dengue virus (DENV) affects nonimunne human populations in tropical and subtropical regions. In the Americas, dengue has drastically increased in the last two decades and Brazil is considered one of the most affected countries. The high frequency of asymptomatic infection makes difficult to estimate prevalence of infection using registered cases and to locate high risk intra-urban area at population level. The goal of this spatial point analysis was to identify potential high-risk intra-urban areas of dengue, using data collected at household level from surveys. METHODS: Two household surveys took place in the city of Goiania (approximately 1.1 million population), Central Brazil in the year 2001 and 2002. First survey screened 1,586 asymptomatic individuals older than 5 years of age. Second survey 2,906 asymptomatic volunteers, same age-groups, were selected by multistage sampling (census tracts; blocks; households) using available digital maps. Sera from participants were tested by dengue virus-specific IgM/IgG by EIA. A Generalized Additive Model (GAM) was used to detect the spatial varying risk over the region. Initially without any fixed covariates, to depict the overall risk map, followed by a model including the main covariates and the year, where the resulting maps show the risk associated with living place, controlled for the individual risk factors. This method has the advantage to generate smoothed risk factors maps, adjusted by socio-demographic covariates. RESULTS: The prevalence of antibody against dengue infection was 37.3% (95%CI [35.5-39.1]) in the year 2002; 7.8% increase in one-year interval. The spatial variation in risk of dengue infection significantly changed when comparing 2001 with 2002, (ORadjusted = 1.35; p < 0.001), while controlling for potential confounders using GAM model. Also increasing age and low education levels were associated with dengue infection. CONCLUSION: This study showed spatial heterogeneity in the risk areas of dengue when using a spatial multivariate approach in a short time interval. Data from household surveys pointed out that low prevalence areas in 2001 surveys shifted to high-risk area in consecutive year. This mapping of dengue risks should give insights for control interventions in urban areas.


Asunto(s)
Dengue/epidemiología , Composición Familiar , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Recolección de Datos , Dengue/sangre , Dengue/diagnóstico , Dengue/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población/métodos , Estudios Seroepidemiológicos , Adulto Joven
12.
Clin Vaccine Immunol ; 15(11): 1659-65, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18784342

RESUMEN

The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-gamma) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-gamma, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-gamma) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.


Asunto(s)
Antígenos Bacterianos/inmunología , Lepra/inmunología , Mycobacterium leprae/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Proteínas Bacterianas/inmunología , Brasil , Células Cultivadas , Femenino , Humanos , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/inmunología
13.
Cad. saúde colet., (Rio J.) ; 16(2): 363-376, abr.-jun. 2008. tab, graf
Artículo en Inglés | LILACS | ID: lil-529797

RESUMEN

Single skin lesion, paucibacillary (SSL PB) leprosy is considered an early disease manifestation. This study evaluated the clinical outcome of a cohort of 259 newly diagnosed SSL PB treated with one dose of rifampicin, ofloxacin, minocycline (ROM) and followed up three years. Patients were recruited from the North, Central West and Southeast regions in Brazil (1997-2001). The result expected with ROM therapy was disappearance or the reduction of lesion size. Manifestations that required additional intervention were considered as poor clinical outcome: type 1 reaction (T1R) with or without neuritis, neuritis alone, increase in lesion size and shift from paucibacillary to multibacillary. The incidence of poor clinical outcome was calculated by person month and with the Kaplan Meier methods. 61,8 percent of the participants were females, mean age 32.2 and 67,2 percent had borderline tuberculoid (BT) or tuberculoid forms. TIR was the predominant event; shift from paucibacillary to multibacillary was rare. 92 percent of the volunteers shown no events during the first year, the same occurring to 80,6 percent of them after 3 years of clinical monitoring. The probability of remaining event free was highest among those 40 years old or younger. Poor outcome predominated among BT patients. Extended monitoring of SSL PB leprosy cases under minimal therapy provided valuable case management information for reference centers.


Asunto(s)
Lepra/terapia , Brasil , Estudios de Cohortes
14.
J Infect Dis ; 197(6): 817-24, 2008 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-18269315

RESUMEN

BACKGROUND: Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. METHODS: A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. RESULTS: Of the 185 symptomatic patients >14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/or thrombocytopenia [platelet count, < or =50,000 platelets/mm3]) and DHF, respectively. The onset of intermediate DF/DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a >3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/DHF. CONCLUSIONS: Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.


Asunto(s)
Anticuerpos Antivirales/biosíntesis , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Dengue Grave/diagnóstico , Viremia/diagnóstico , Adulto , Formación de Anticuerpos , Estudios de Cohortes , Dengue/sangre , Dengue/inmunología , Dengue/virología , Femenino , Humanos , Masculino , Serotipificación , Dengue Grave/sangre , Dengue Grave/inmunología , Dengue Grave/virología , Índice de Severidad de la Enfermedad , Viremia/inmunología , Viremia/virología
15.
Am J Trop Med Hyg ; 77(5): 829-33, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17984336

RESUMEN

Leprosy affects skin and peripheral nerves, and acute inflammatory type 1 reactions (reversal reaction) can cause neurologic impairment and disabilities. Single skin lesion paucibacillary leprosy volunteers (N = 135) recruited in three Brazilian endemic regions, treated with single-dose rifampin, ofloxacin, and minocycline (ROM), were monitored for 3 years. Poor outcome was defined as type 1 reactions with or without neuritis. IgM anti-phenolic glycolipid I, histopathology, Mitsuda test, and Mycobacterium leprae DNA polymerase chain reaction (ML-PCR) were performed at baseline. chi(2) test, Kaplan-Meir curves, and Cox proportional hazards were applied. The majority of volunteers were adults with a mean age of 30.5 +/- 15.4 years; 44.4% were ML-PCR positive. During follow-up, 14.8% of the patients had a poor clinical outcome, classified as a type 1 reaction. Older age (> or = 40 years), ML-PCR positivity, and lesion size > 5 cm were associated with increased risk. In multivariate analysis, age (> or = 40 years) and ML-PCR positivity remained baseline predictors of type 1 reaction among monolesion leprosy patients.


Asunto(s)
ADN Bacteriano/aislamiento & purificación , Eritema Nudoso/epidemiología , Lepra/tratamiento farmacológico , Lepra/microbiología , Minociclina/uso terapéutico , Mycobacterium leprae/aislamiento & purificación , Ofloxacino/uso terapéutico , Rifampin/uso terapéutico , Adolescente , Adulto , Envejecimiento , Estudios de Cohortes , Eritema Nudoso/sangre , Eritema Nudoso/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Factores de Tiempo
16.
Clin Vaccine Immunol ; 14(11): 1400-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17898185

RESUMEN

Leprosy is a chronic and debilitating human disease caused by infection with the Mycobacterium leprae bacillus. Despite the marked reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. This indicates that M. leprae is still being transmitted and that, without earlier diagnosis, M. leprae infection will continue to pose a health problem. Current diagnostic techniques, based on the appearance of clinical symptoms or of immunoglobulin M (IgM) antibodies that recognize the bacterial phenolic glycolipid I, are unable to reliably identify early-stage leprosy. In this study we examine the ability of IgG within leprosy patient sera to bind several M. leprae protein antigens. As expected, multibacillary leprosy patients provided stronger responses than paucibacillary leprosy patients. We demonstrate that the geographic locations of the patients can influence the antigens they recognize but that ML0405 and ML2331 are recognized by sera from diverse regions (the Philippines, coastal and central Brazil, and Japan). A fusion construct of these two proteins (designated leprosy IDRI diagnostic 1 [LID-1]) retained the diagnostic activity of the component antigens. Upon testing against a panel of prospective sera from individuals who developed leprosy, we determined that LID-1 was capable of diagnosing leprosy 6 to 8 months before the onset of clinical symptoms. A serological diagnostic test capable of identifying and allowing treatment of early-stage leprosy could reduce transmission, prevent functional disabilities and stigmatizing deformities, and facilitate leprosy eradication.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos , Lepra/diagnóstico , Lepra/inmunología , Mycobacterium leprae/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Niño , Diagnóstico Precoz , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Lepra/microbiología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/inmunología
17.
An. bras. dermatol ; 80(5): 511-522, set.-out. 2005. ilus, tab
Artículo en Portugués | LILACS | ID: lil-418794

RESUMEN

FUNDAMENTOS: A hanseníase persiste como problema de saúde pública, e episódios de ENH são eventos agudos que ocorrem antes, durante e após PQT. Na última década, o uso da talidomida como agente imunomodulador foi expandido a outras doenças. OBJETIVOS: realizar revisão sistemática dos ensaios clínicos publicados sobre a eficácia e efeitos colaterais da talidomida no ENH. Descrever metodologia e resultados da triagem para recrutamento de ensaio clínico visando avaliar dose-resposta da talidomida seguida de desmame no ENH moderado e grave, realizado no Brasil. MÉTODOS: Analisaram-se ensaios publicados sobre talidomida no ENH. Foi delineado um ensaio clínico duplo-cego randomizado para avaliar dose de 100 thalid 300mg/dia de talidomida durante fase aguda de ENH, seguida de desmame da talidomida, thalid placebo. Para este ensaio clínico descreve-se metodologia e dados de recrutamento de pacientes, com ênfase na gravidade dos episódios de ENH. RESULTADOS: Os seis ensaios clínicos publicados nas décadas de 1960 e 1970 apontam para o benefício da talidomida no ENH, embora diferenças metodológicas dificultem a comparação. Na fase de recrutamento do ensaio brasileiro, dos 143 pacientes de ENH triados, 65 por cento eram potencialmente elegíveis. A associação com neurite em 56,4 por cento dos ENH moderados e graves exigiu co-intervenção com corticosteróide. CONCLUSÃO: O padrão de recrutamento dos pacientes evidenciou alta freqüência de neurite nos episódios de ENH. O esquema de talidomida isolada no ENH foi avaliado como infreqüente na prática clínica brasileira. O desafio atual é acumular evidências sobre a eficácia e efeitos colaterais da talidomida em associação com corticosteróides.


Asunto(s)
Eritema Nudoso , Neuritis , Talidomida
18.
Am J Trop Med Hyg ; 71(5): 594-7, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15569790

RESUMEN

Data from a six-year follow-up of Trypanosoma cruzi-infected adolescents enrolled in a randomized, double-blind, clinical trial of benznidazole showed successful chemotherapy in 64.7% (95% confidence interval [CI] = 50.2-78.7) and 84.7% (95% CI = 66.8-92.9), respectively, by intention-to treat and by per protocol analysis measured by seronegativity in a chemiluminescent enzyme-linked immunosorbent assay with a purified trypomastigote mucin antigen. No incident case of cardiomyopathy was detected by electrocardiogram assessment in this cohort of adolescents who had been infected in childhood. The persistent and consistently long-term negative serologic reactions suggest the absence of the parasite in the treated patients and reinforces the recommendation of early benznidazole chemotherapy for T. cruzi-infected infants as a public health policy in endemic areas.


Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/inmunología , Nitroimidazoles/administración & dosificación , Tripanocidas/administración & dosificación , Trypanosoma cruzi/inmunología , Adolescente , Servicios de Salud del Adolescente , Adulto , Animales , Antígenos de Protozoos/análisis , Enfermedad de Chagas/sangre , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
Am J Trop Med Hyg ; 71(5): 646-51, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15569799

RESUMEN

Urban dengue fever is now considered a major public health threat in most American countries. A household survey was conducted in the city of Goiania in central Brazil in 2001 to assess prevalence of dengue infection and individual and area-based risk factors. Spatial point pattern analysis was performed using the dual Kernel method. A total of 1,610 households were surveyed; 1,585 individuals more than five years old had blood and data collected. Sera were tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based indicators derived from census data were linked to geocoded residential address. The seroprevalence of dengue was 29.5% and the estimate prevalence surface reached 50% in the outskirts areas. The risk of infection was significantly associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.82-6.55), and low income (OR = 1.32, 95% CI = 1.02-1.71) in multivariate analysis. This study highlighted the heterogeneity of dengue transmission within the city and can assist in spatial targeting control interventions.


Asunto(s)
Dengue/epidemiología , Adolescente , Adulto , Animales , Anticuerpos Antivirales/análisis , Brasil/epidemiología , Niño , Preescolar , Culicidae , Demografía , Dengue/sangre , Dengue/etiología , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Insectos Vectores , Masculino , Persona de Mediana Edad , Características de la Residencia , Factores de Riesgo , Estudios Seroepidemiológicos
20.
Am J Trop Med Hyg ; 71(5): 679-84, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15569804

RESUMEN

Co-infections with human immunodeficiency virus (HIV) and Mycobacterium leprae represent unique opportunities to investigate the interaction of both pathogens. We determined the immunologic, virologic, and histopathologic characteristics of 22 co-infected Brazilian patients (median age = 38 years, 81.8% males, 72.2% with paucibacillary leprosy, and 95.4% with acquired immunodeficiency syndrome). The HIV-1 subtypes B and BF predominated in envelope and gag heteroduplex mobility analysis. Borderline tuberculoid (BT), tuberculoid, lepromatous, and indeterminate morphology with CD3+, CD8+, and CD68+ cell distributions compatible with leprosy patients not infected with HIV were observed. Histologic evidence of nerve damage was observed in BT lesions. IgM antibody to M. leprae-specific phenolic glycolipid I was not detected. Two of six co-infected patients monitored during highly active antiretroviral therapy (HAART) developed a leprosy type 1 reaction after an increase in CD4+ cells, suggesting an immune restoration phenomenon. Clinical, immunologic, histopathologic, and virologic features among these HIV-leprosy co-infected patients indicate that each disease progressed as in single infection. However, HAART immune reconstitution may trigger potential adverse effects, such as leprosy acute inflammatory episodes.


Asunto(s)
Infecciones por VIH/epidemiología , Lepra/epidemiología , Adulto , Anticuerpos Antibacterianos/análisis , Brasil/epidemiología , Recuento de Linfocito CD4 , Estudios de Cohortes , Comorbilidad , ADN Viral/análisis , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Lepra/sangre , Lepra/complicaciones , Masculino , Mycobacterium leprae/inmunología , Mycobacterium leprae/aislamiento & purificación
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