Brazil has experienced an increase in dengue disease severity in the past 5 years.
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.
Background Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. Methods We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. Findings Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34–60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20–30] vs 17 days [10–20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). Interpretation There is a wide and overlapping spectrum of neurologica...
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.
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.
A population-based survey to provide information on the prevalence of hepatitis viral infection
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-␥) 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-␥, 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-␥) 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.Leprosy is a chronic disease with a wide range of clinical outcomes. Leprosy patients are predominantly diagnosed by the appearance of disease signs, but they can also be characterized by the physical and histological attributes of skin or nerve lesions or by their immune response to crude Mycobacterium leprae antigens (25). Individuals infected with M. leprae exhibit wide-ranging immunity. One end of this immunologic spectrum comprises paucibacillary (PB) leprosy patients, who have strong cellular immunity in the form of a Th1-type response characterized by antigen-specific gamma interferon (IFN-␥) secretion. This response controls bacterial growth and limits dissemination, typically resulting in a few small and localized lesions. At the other end of the spectrum, multibacillary (MB) patients have poor cellular immunity but potent humoral immunity. Responses of MB patients do not control bacterial growth, and infection becomes systemic, typically resulting in disseminated lesions and significant nerve function impairment. Identifying antigens that are the target of the cellular immune response could direct the development of a defined leprosy vaccine.Despite vigorous efforts, conditions that permit the in vitro culture of M. leprae bacilli have not yet been identified. This has impaired the ability to produce antigens for research purposes, and until recently, studies of antigen-specific immune responses during the course of the disease hav...
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.
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