RESUMO
OBJECTIVES: We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil. METHODS: This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR). RESULTS: A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes. CONCLUSIONS: Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection.
Assuntos
Doenças Fetais/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adulto , Brasil , Feminino , Humanos , Recém-Nascido , Filogenia , Gravidez , Adulto Jovem , Zika virus/classificação , Zika virus/genéticaRESUMO
Infectious diseases frequently have multiple potential routes of intraspecific transmission of pathogens within wildlife and other populations. For pathogens causing zoonotic diseases, knowing whether these transmission routes occur in the wild and their relative importance, is critical for understanding maintenance, improving control measures and ultimately preventing human disease. The Norway rat (Rattus norvegicus) is the primary reservoir of leptospirosis in the urban slums of Salvador, Brazil. There is biological evidence for potentially three different transmission routes of leptospire infection occurring in the rodent population. Using newly obtained prevalence data from rodents trapped at an urban slum field site, we present changes in cumulative risk of infection in relation to age-dependent transmission routes to infer which intra-specific transmission routes occur in the wild. We found that a significant proportion of animals leave the nest with infection and that the risk of infection increases throughout the lifetime of Norway rats. We did not observe a significant effect of sexual maturity on the risk of infection. In conclusion, our results suggest that vertical and environmental transmission of leptospirosis both occur in wild populations of Norway rats.
Assuntos
Leptospira , Leptospirose , Doenças dos Roedores , Envelhecimento , Animais , Peso Corporal , Brasil/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/transmissão , Portador Sadio/veterinária , Feminino , Transmissão Vertical de Doenças Infecciosas , Leptospirose/epidemiologia , Leptospirose/transmissão , Leptospirose/veterinária , Masculino , Prevalência , Ratos , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/transmissão , Análise de SobrevidaRESUMO
Urban slum environments in the tropics are conducive to the proliferation and the spread of rodent-borne zoonotic pathogens to humans. Calodium hepaticum (Brancroft, 1893) is a zoonotic nematode known to infect a variety of mammalian hosts, including humans. Norway rats (Rattus norvegicus) are considered the most important mammalian host of C. hepaticum and are therefore a potentially useful species to inform estimates of the risk to humans living in urban slum environments. There is a lack of studies systematically evaluating the role of demographic and environmental factors that influence both carriage and intensity of infection of C. hepaticum in rodents from urban slum areas within tropical regions. Carriage and the intensity of infection of C. hepaticum were studied in 402 Norway rats over a 2-year period in an urban slum in Salvador, Brazil. Overall, prevalence in Norway rats was 83% (337/402). Independent risk factors for C. hepaticum carriage in R. norvegicus were age and valley of capture. Of those infected the proportion with gross liver involvement (i.e. >75% of the liver affected, a proxy for a high level intensity of infection), was low (8%, 26/337). Sixty soil samples were collected from ten locations to estimate levels of environmental contamination and provide information on the potential risk to humans of contracting C. hepaticum from the environment. Sixty percent (6/10) of the sites were contaminated with C. hepaticum. High carriage levels of C. hepaticum within Norway rats and sub-standard living conditions within slum areas may increase the risk to humans of exposure to the infective eggs of C. hepaticum. This study supports the need for further studies to assess whether humans are becoming infected within this community and whether C. hepaticum is posing a significant risk to human health.
Assuntos
Capillaria/isolamento & purificação , Portador Sadio/veterinária , Infecções por Enoplida/veterinária , Carga Parasitária , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/parasitologia , Animais , Brasil/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/parasitologia , Infecções por Enoplida/epidemiologia , Infecções por Enoplida/parasitologia , Infecções por Enoplida/patologia , Áreas de Pobreza , Prevalência , Ratos , Fatores de Risco , Doenças dos Roedores/patologiaRESUMO
Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. The disease is globally distributed and a major public health concern. The Norway rat (Rattus norvegicus) is the main reservoir of the pathogen in urban slums of developing and developed countries. The potential routes of intra-specific leptospire transmission in rats are largely unknown. Herein, we identified pathogenic Leptospira spp. in breast tissue and milk of naturally infected rats. We examined kidney, breast tissue and milk from 24 lactating rats for the presence of leptospires using immunofluorescence, immunohistochemistry, polymerase chain reaction (PCR) and scanning electronic microscopy. All 24 rats had evidence for Leptospira in the kidneys, indicating chronic carriage. The majority of kidney-positive rats had detectable leptospires in milk (18, 75%) and breast tissue (16, 67%), as evidenced by immunofluorescence assay and immunohistochemistry. Four (17%) milk samples and two (8%) breast tissue samples were positive by quantitative real-time PCR. Scanning electron microscopy confirmed the presence of leptospires in breast tissue. No major pathological changes in breast tissue were found. This study, for the first time, identified leptospires in the milk and breast tissue of wild Norway rats, suggesting the possibility of milk-borne transmission of leptospirosis to neonates.
Assuntos
Transmissão Vertical de Doenças Infecciosas/veterinária , Leptospira/isolamento & purificação , Leptospirose/veterinária , Glândulas Mamárias Animais/microbiologia , Leite/microbiologia , Doenças dos Roedores/epidemiologia , Animais , Brasil/epidemiologia , Feminino , Imunofluorescência/veterinária , Imuno-Histoquímica/veterinária , Leptospira/classificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , Microscopia Eletrônica de Varredura/veterinária , Ratos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Doenças dos Roedores/microbiologiaRESUMO
There is scarce data on the burden of leptospirosis and its epidemiological characteristics in Argentina. This study aimed to evaluate distribution of leptospirosis cases and identify risk factors for the disease during national laboratory-based surveillance. From January 1999 to December 2005, 812 suspected cases were referred to the national reference laboratory, of which 182 and 463 had respectively, laboratory confirmed and unconfirmed diagnosis of leptospirosis. The diagnosis of leptospirosis was discarded in 167 cases. The most prevalent presumptive infecting serogroup was Icterohaemorrhagie followed by Pomona, Ballum and Canicola. The majority of cases occurred during the worm and rainy months. Confirmed cases were predominantly adults and males, who presented with fever, headache and myalgias. Severe clinical manifestations included jaundice and acute renal insufficiency. Conjunctival suffusion, a hallmark clinical sign of leptospirosis, was found in 55% of confirmed cases, and 43% of the cases with discarded diagnosis (p=0.036). After multivariate analyses, age >30 years (OR=2.16; 1.05-4.41), occupation in a rural setting (OR=3.41; 1.45-8.06), contact with contaminated surface water (OR=2.17; 1.01-4.68), and contact with floods (OR=4.49; 1.17-17.25) were significantly associated with leptospirosis. In conclusion, although activities associated with rural occupations remain important risk factors in Argentina, exposures occurring during flooding events have emerged to be the major risk factor for leptospirosis.
Assuntos
Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/fisiopatologia , Adulto , Fatores Etários , Argentina/epidemiologia , Feminino , Humanos , Incidência , Leptospira/classificação , Leptospirose/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estações do Ano , Fatores SexuaisRESUMO
LipL32 is the major lipoprotein in the membrane of pathogenic leptospira. In this work, we report on the production of monoclonal antibodies (MAbs) against recombinant LipL32 (rLipL32) and on the evaluation of their potential for use as reagents in diagnostic tests for leptospirosis. The MAbs were all of the IgG(2b) isotype and reacted specifically with native LipL32 in pathogenic serovars only. MAbs reacted in the same region of the rLipL32 molecule and their affinity constant was between 5x10(7) M(-1) and 6x10(6) M(-1). These results suggest that although the MAbs cannot be used together, they are well suited for diagnostic tests of leptospirosis based on LipL32 detection.
Assuntos
Anticorpos Monoclonais/química , Proteínas da Membrana Bacteriana Externa/imunologia , Leptospirose/diagnóstico , Lipoproteínas/imunologia , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/isolamento & purificação , Especificidade de Anticorpos/imunologia , Proteínas da Membrana Bacteriana Externa/análise , Testes Diagnósticos de Rotina , Humanos , Isotipos de Imunoglobulinas/análise , Testes Imunológicos , Leptospirose/imunologia , Lipoproteínas/análiseRESUMO
Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.
Assuntos
Genoma Bacteriano , Genômica , Leptospira interrogans/fisiologia , Leptospira interrogans/patogenicidade , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Cricetinae , Humanos , Leptospira interrogans/classificação , Leptospira interrogans/genética , Leptospirose/microbiologia , Camundongos , Dados de Sequência Molecular , Análise de Sequência de DNA , Sorotipagem , Virulência/genéticaRESUMO
Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging to the genus Leptospira. An understanding of leptospiral protein expression regulation is needed to develop new immunoprotective and serodiagnostic strategies. We used the humoral immune response during human leptospirosis as a reporter of protein antigens expressed during infection. Qualitative and quantitative immunoblot analysis was performed using sera from 105 patients from Brazil and Barbados. Sera from patients with other diseases and healthy individuals were evaluated as controls. Seven proteins, p76, p62, p48, p45, p41, p37, and p32, were identified as targets of the humoral response during natural infection. In both acute and convalescent phases of illness, antibodies to lipopolysaccharide were predominantly immunoglobulin M (IgM) while antibodies to proteins were exclusively IgG. Anti-p32 reactivity had the greatest sensitivity and specificity: positive reactions were observed in 37 and 84% of acute- and convalescent-phase sera, respectively, while only 5% of community control individuals demonstrated positive reactions. Six immunodominant antigens were expressed by all pathogenic leptospiral strains tested; only p37 was inconsistently expressed. Two-dimensional immunoblots identified four of the seven infection-associated antigens as being previously characterized proteins: LipL32 (the major outer membrane lipoprotein), LipL41 (a surface-exposed outer membrane lipoprotein), and heat shock proteins GroEL and DnaK. Fractionation studies demonstrated LipL32 and LipL41 reactivity in the outer membrane fraction and GroEL and DnaK in the cytoplasmic fraction, while p37 appeared to be a soluble periplasmic protein. Most of the other immunodominant proteins, including p48 and p45, were localized to the inner membrane. These findings indicate that leptospiral proteins recognized during natural infection are potentially useful for serodiagnosis and may serve as targets for vaccine design.
Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Leptospirose/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias , Fracionamento Celular , Eletroforese em Gel Bidimensional/métodos , Humanos , Leptospira/imunologia , Leptospirose/sangue , CoelhosRESUMO
Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis. Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin. Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000). Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates. Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns. Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns. These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.
Assuntos
Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Resistência às Penicilinas , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Antibacterianos/farmacologia , Brasil/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos , Vigilância da População , Fatores de Risco , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
The response to recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis was evaluated. Twenty patients with cutaneous leishmaniasis who had lesions for 60 days were enrolled in a double-blind placebo trial of GM-CSF with standard parenteral sodium stibogluconate (20 mg/kg-1/day-1) for 20 days. Ten patients were randomized to receive intralesionally injected GM-CSF (200 microgram) at enrollment and 1 week after, and 10 patients received saline as placebo. GM-CSF- and antimony-treated patients healed faster than patients who received antimony alone (49+/-32.8 vs. 110+/-61.6 days, P<.05). Seven of 10 patients were healed of their lesions before 40 days after therapy in the GM-CSF group, compared with only 1 of 10 patients in the placebo group (relative risk, 7; 95% confidence interval, 1.04-47.00). Thus, GM-CSF plus antimony significantly increased the chance of lesion healing in 40 days.
Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Adolescente , Adulto , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Leptospirosis has, traditionally, been considered a sporadic rural disease. We describe a large urban outbreak of leptospirosis. METHODS: Active surveillance for leptospirosis was established in an infectious-disease referral hospital in Salvador, Brazil, between March 10 and Nov 2, 1996. Patients meeting case criteria for severe manifestations of leptospirosis were recruited into the study. The diagnosis was confirmed in the laboratory with the microagglutination test and identification of leptospires in blood or urine. Risk factors for death were examined by multivariate analyses. FINDINGS: Surveillance identified 326 cases of which 193 (59%) were laboratory-confirmed (133) or probable (60) cases. Leptospira interrogans serovar copenhageni was isolated from 87% of the cases with positive blood cultures. Most of the cases were adult (mean age 35.9 years [SD 15.9]), and 80% were male. Complications included jaundice (91%), oliguria (35%), and severe anaemia (26%). 50 cases died (case-fatality rate 15%) despite aggressive supportive care including dialysis (in 23%). Altered mental status was the strongest independent predictor of death (odds ratio 9.12 [95% CI 4.28-20.3]), age over 37 years, renal insufficiency, and respiratory insufficiency were also significant predictors of death. Before admission to hospital, 42% were misdiagnosed as having dengue fever in the outpatient clinic; an outbreak of dengue fever was taking place concurrently. INTERPRETATION: An epidemic of leptospirosis has become a major urban health problem, associated with high mortality. Diagnostic confusion with dengue fever, another emerging infectious disease with a similar geographic distribution, prevents timely intervention that could minimise mortality.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Saúde da População Urbana/estatística & dados numéricos , Doença de Weil/epidemiologia , Adulto , Brasil/epidemiologia , Dengue/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Leptospira interrogans/isolamento & purificação , Masculino , Vigilância da População , Doença de Weil/diagnósticoRESUMO
We have produced a number of monoclonal antibodies, protective and non-protective, which recognize a complex of schistosomula antigens, including the 38 kDa antigen. Eight different protective and non-protective monoclonal antibodies, varying in isotypes, were used in the binding assays. Lectin inhibition studies suggested that the monoclonal antibodies probably recognized carbohydrate epitopes on the antigen(s). Immunoprecipitation studies showed that at least two of the monoclonal antibodies recognized different epitopes on the same molecule. Additionally, we tested for monoclonal antibody binding after the antigens were treated with; 1) proteases, 2) periodate, 3) various exo- and endoglycosidases, 4) mild acid hydrolysis. We also tested for binding of the antibodies to keyhole limpet hemocyanin (KLH). Using the 8 monoclonal antibodies as probes, we were able to define at least 4 different carbohydrate epitopes related to the protective monoclonal antibodies, and at least one epitope which is seen by the non-protective antibodies. The epitope seen by the non-protective antibodies was shown to be cross-reactive with epitopes on KLH. These results demonstrate the importance of epitope mapping studies for any defined vaccine.