Herpes simplex virus type 2 infection in pregnancy: asymptomatic viral excretion at delivery and seroepidemiologic survey of two socioeconomically distinct populations in São Paulo, Brazil

The objective of the present study was to estimate the prevalence of herpes simplex virus type 2 (HSV 2) antibodies in child bearing women of 2 Brazilian populations with different socioeconomic status and to determine the risk of neonatal HSV exposure by means of maternal cultures at the onset of labor. The study was conducted at 2 hospitals: A, serving very low income patients and B, serving middle socioeconomic class. 173 participants from group A and 127 from B answered a questionnaire which showed that the patients had similar ages (27.7 and 26.8 years, respectively) but differed with regard to socioeconomic status, age at first intercourse (18.6 vs 20.6 years), number of sex partners (1.5 vs 1.2) and previous sexually transmitted diseases (15% vs. 1.5%). History of genital herpes was given by 11% of group A participants and by a similar number, 7%, of patients from group B. In addition, 200 serum samples from population A and 455 from B were tested by ELISA for and HSV antibodies and 92% and 86%, respectively, were found to be positive. Sixty seropositive samples from group A and 90 from B were further analyzed by Western blot, which showed the presence of type 2 specific antibodies in 46% and 36%, respectively, suggesting an overall HSV 2 prevalence of 42% in group A and 31% in B. Cervical specimens were obtained for culture from 299 asymptomatic patients of population A and 313 of B. HSV was isolated from one specimen in each group, indicating a 0.3% incidence of asymptomatic viral excretion in both populations. In conclusion, the prevalence of type 2 antibodies in childbearing women was very high, but it did not differ with the socioeconomic status. The risk of HSV perinatal transmission was also similar in the 2 study populations and it was comparable with the data from developed countries. Our findings do not indicate the need of special screening programs for asymptomatic HSV excretion in Brazilian pregnant women.

Schistosomiasis mansoni in an area of low transmission: II. Risk factors for infection

Risk factors for Schistosoma mansoni infection were identified using a 1:1 matched case-control design. The work was conducted in the municipality of Pedro de Toledo, São Paulo State, Brazil, an area where the snail host is Biomphalaria tenagophila. Information on water contact patterns, knowledge, attitudes and pratices (kap), socioeconomic and sanitary conditions were obtained by mean of questionnaires. The crude odds ratio estimates and the adjusted odds ratio estimates using the logistic regression model are presented. Most of the examined individuals admitted recent water contacts (90.6% of the cases). The most frequent reason for contact was swimming, playing and fishing and the preferential site of contact was the river. According to the logistic regression technique, the main risk factors for infection were: a) water contact through swimming, playing and fishing; b) fording; c) bad hygiene. We concluded that recreational activities are the main reasons for schistosomiasis transmission in Pedro de Toledo and leisure alternatives should be offered to the local population.

A multivariate analysis of the relationship between work ability and S. japonicum infection in Dongting Lake Region, in China

A cross-sectional case-control study on the association between the reduced work ability and S. japonicum infection was carried out in a moderate endemic area for schistosomiasis japonica in the southern part of Dongting lake in China. A total of 120 cases with reduced work ability and 240 controls paired to the case by age, sex, occupation and without reduced work ability, participated in the study. The mean age for individuals was 37.6 years old (21-60), the ratio of male: female was 60:40, the prevalence of S. japonicum in the individuals was 28.3%. The results obtained in this study showed that the infection of S. japonicum in case and control groups was 49.2% (59/120) and 17.9% (43/240), respectively. Odds ratio for reduced work ability among those who had schistosomiasis was 4.34 (95%), confidence interval was 2.58-7.34, and among those who had S. japonicum infection (egg per gram > 100) was up to 12.67 (95%), confidence interval was 3.64-46.39. After odds ratio was adjusted by multiple logistic regression, it was confirmed that heavier intensity of S. japonicum infection and splenomegaly due to S. japonicum infection were the main risk factors for reduced work ability in the population studied.

Nocardia infection in renal transplant recipient: diagnostic and therapeutic considerations

In the present report the authors discuss the diagnostic difficulties, therapeutic measures and the clinical course of Nocardia infection which occurred among renal transplant recipients at the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (UH-FRP), from 1968 to 1991. Among 500 individuals submitted to renal transplant, 9 patients developed Nocardiosis at varying times after transplant (two months to over two years). All the patients had pulmonary involvement and their most common symptoms were fever, cough and pleural pain. Dissemination of the process is common and three patients presented cutaneous abscesses, four CNS involvement and one had pericarditis due to Nocardia. The diagnostic is quite difficult since there is no specific clinical picture, concomitant infections are frequent and the microorganism presents slow growth in culture (ranging from four to forty days, in our experience). In this report, three cases were only diagnosed by necropsy. The treatment of choice is a combination of Sulfamethoxazole and Trimethoprim (SMX-TMP). In the present series, overall mortality was 77% (7 cases) and in five of the patients who died the diagnosis was late. All the patients who had CNS involvement died.

Laboratory acquired infection by the virus SP H 114202 (Arenavirus: Arenaviridae): clinical and laboratory findings

Here in is described the clinical and laboratorial findings of a laboratory-acquired infection caused by the virus SP H 114202 (Arenavirus, family Arenaviridae) a recently discovered agent responsible for a viral hemorrhagic fever. The patient was sick for 13 days. The disease had an abrupt onset characterized by high fever (39ºC.), headache, chills and myalgias for 8 days. In addition, on the 3rd day, the patient developed nauseas and vomiting, and in the 10th, epigastralgia, diarrheia and gengivorrhagia. Leucopenia was seen within the 1 st week of onset, with counts as low as 2,500 white cells per mm³. Counts performed after the 23th day of the onset were within normal limits. With the exception of moderate lymphocitosis, no changes were observed in differential counts. An increase in the liter of antibodies by complement fixation, neutralization and ELISA (IgM) was detected. Suckling mice and baby hamsters were inoculated intracerebrally with 0.02 ml of blood samples collected in the 2nd and 7th days of disease. Attempts to isolate the virus were also made in Vero cells. No virus was isolated. This virus was isolated before in a single occasion in São Paulo State, in 1990, from the blood of a patient with hemorrhagic fever with a fatal outcome. The manipulation of the virus under study, must be done carefully, since the transmission can occur through aerosols.

Mediterranean spotted fever and identification of new agents of rickettsioses in Portugal : epidemiological determinants, host and microbial features in portuguese patients

Resumo: a febre botonosa, também conhecida por febre escaro-nodular (FEN) é uma doença endémica nos Países da bacia do Mediterrâneo, África, Médio Oriente, Índia e Paquistão. O agente etiológico responsável por esta patologia é a bactéria Rickettsia conorii. Contudo, em alguns países, como Portugal e Itália, esta patologia é causada por duas estirpes diferentes: R conorii Malish e R conorii Israeli spotted fever strain. O principal vector e reservatório é o ixodídeo Rhipicephalus sanguineus. Mesmo com uma elevada taxa de subnotificação detectada no nosso País, a taxa incidência da FEN é de 8.4/105 habitantes (1989-2005), uma das mais altas quando comparada coom a de outros países da bacia do Mediterrâneo. De todos os distritos portugueses, Bragança e Beja são aqueles que apresentam as taxas de incidência mais elevadas, 56,8/105 habitantes e 47,4 / 105 habitantes respectivamente. Em Portugal, as alterações climáticas verificadas na última década, nomeadamente a subida das temperaturas médias anuais, parecem ter influenciado o ciclo de vida do vector e a sua dinâmica sazonal, permitindo ao R. sanguineus completar mais de um ciclo de vida por ano. Este facto, e a possibilidade deste vector se manter activo noutros meses do ano, nomeadamente nos meses de inverno, tem influenciado consequentemente o padrão de distribuição anual dos casos de FEN. A febre escaro-nodular caracteriza-se clinicamente como uma doença exantemática, com um processo de vasculite generalizado. Apesar de na generalidade ser considerada uma doença benigna (quando tratada atempadamente e com terapêutica adequada e específica)e de estarem descritos casos graves em cerca de 5-6% dos doentes, em Portugal essa percentagem aumentou e consequentemente levou a um aumento de casos fatais. Este facto tornou-se mais evidente em 1997, no Hospital Distrital de Beja e no Hospital Garcia de Orta, onde a taxa de letalidade atingiu os 32% e 18% respectivamente.Para além dos factores de co-morbilidade encontrados nos doentes mais graves, como diabetes mellitus, ou o atraso na instituição da terapêutica específica, foi colocada de que a estirpe R. conorii Israel spotted fever strain pudesse ser mais virulenta ou então estivesse associada a diferentes manifestações clínicas que dificultassem o diagnóstico clínico e a instituição atempada da terapêutica. Houve ainda a necessidade de avaliar alguns parâmetros imunológicos dos doentes e tentar identificar que factores, nomeadamente que citoquinas, poderiam estar envolvidos na resposta a uma infecção por R.conorii.Face a estas questões foi avaliada e comparada a epidemiologia, manifestações clínicas e laboratoriais de 140 doentes (71 infectados com R. conorii Malish e 69 infectados com R. conorii Israel spotted fever strain). Concluiu-se que existe uma sobreposição de manifestações clinicas entre os dois grupos de doentes, mas que a percentagem da escara de inoculação é significativamente inferior em doentes infectados com R. conorii Israel spotted fever strain. Dos resultados mais importantes encontrados neste estudo concluiu-se que a estirpe R. conorii Malish e é demonstrado, pela primeira vez, estatisticamente que o alcoolismo é um factor de risco para a morte de doentes com FEN. Associadas a factores de um mau prognósitco da doença, estão as manifestações gastrointestinais, que poderão ser ou não reflexo de alterações do sistema nervoso central, e ainda a alteração de parâmetros laboratoriais como a presença de hiperbilirubinemia e aumento dos valores da ureia.A maior parte dos estudos realizados sobre os mecanismos da resposta imunitária à infecção por R. conorii e as interacções hospedeiro - agente etiológico têm sido elucidados com base em modelos animais. Poucos estudos têm sido efectuados em doentes e nenhum estudo prévio tinha sido realizado no sentido de avaliar localmente (escara/pele) quais os mediadores ou outras moléculas envolvidas na resposta imunitária às rickettsioses. Foi avaliado o nível de expressão génica de RNA mensageiro (RNAm)de diferentes citoquinas em amostras de pele de doentes com FEN pela técnica de PCR em tempo real.Os resultados deste estudo mostraram que, quando comparado com o grupo controlo, os 23 doentes analisados apresentavam níveis estatisticamente significativos, mais elevados de expressão génica de interferão (IFN-γ, Tumor necrosis factor (TFN-α, interleucina 10 (IL-10, RANTES (regulated by activation, normal T-cell-expressed and secreted chemokine)e indolamina 2-3 desoxigenase (IDO),uma enzima envolvida no controlo e limitação do crescimento intracelular das rickettsias, através da degradação do triptofano. Seis dos 23 doentes apresentaram ainda niveis de expressão elevados de óxido nítrico indutível (iNOS)que actua como microbicida. Encontrou-se uma correlação positiva entre a expressão de RNAm de TNF-α, γ, iNOS e IDO e os casos menos graves de FEN sugerindo um tipo de resposta imunitária tipo Th1, i.e. com papel protector na resposta à infecção.Verificou-se também que os valores de expressão genética do RNAm de IL-10, estavam inversamente correlacionados com a expressão do RNAm de TNF-α e IFN-γ. Os casos menos graves de FEN parecem assim envolver um balanço entre a resposta pró-inflamatória e anti-inflamatória. Já os níveis de expressão génica do RNAm de IL-10 estavam inversamente correlacionados com a expressão RNAm de TNF-α e IFN-γ. Os casos menos graves de FEN parecem assim envolver um balanço entre uma resposta pró-inflamatória e anti-inflamatória. Já os níveis de expressão RNAm da quimoquina RANTES foram estatisticamente mais elevados em doentes graves.Nesta dissertação é ainda descrita uma nova rickettsiose presente em Portugal, causada pela bactéria R. sibirica mongolitimonae, que foi identificada laboratorialmente por isolamento do agente, e por detecção do DNA em biopsia de pele. A presença deste agente foi ainda corroborada pela detecção em paralelo do mesmo agente no ixodídeos como R. africae like e em pulgas como R. felis e R.typhi alertam para a possibilidade de existência de outras rickettsioses que possam estar diagnosticadas em Portugal. Abstract: Mediterranean spotted fever (MSF), a tick-borne disease caused by Rickettsia conorii, is widley distributed in the Old World, being endemic in the southern Europe, Africa, Middle East, India and Pakistan. In Portugal two strains cause disease: R.conorii Malish and R.conorii Israeli spotted fever.Rhipicephalus sanguineus, the brown dog tick, is considered the main vector and reservoir. MSF is characterized by seasonality, and most of cases are encountered in late spring and summer, peaking in July and August. However, CEVDI/INSA laboratory has observed that the incidence of MSF cases has changed during winter season.The increasing annual averages of air temperatures and warmer and drier winters might have influenced the dynamics of the life cycle and activity of R. sanguineus, and indirectley the number MSF cases during the so called MSF off-season.In the period of 1989-2005, the incidence rate of MSF was 8.4/105 inhabitants, one of the highest rates compared with other endemic countries. In the Portugal during the same period, the highest incidence rates were reported in the districts of Bragança, with 56.8/105 inhabitants, and Beja, with 47.4/105 inhabitants. Severe cases of MSF are reported in 6% of the patients, but it seems that this pattern of disease in Portugal has been changing.This factor became more evident in 1997, with a reported case fatality rate of 32% and 18% in patients with MSF admited at Beja and Garcia Orta Hospitals, respectively. Although it was found that diabetes mellitus and delay in therapy have been implicated as a risk factor for death, the hypothesis was considered, that the new ISF strain isolated from Portugueses patients in the same year (1997)causes different or atypical clinical conorii Malish strain. The local (skin biopsies) immune response to R. conorii infection was also evaluated.A prospective study was performed to characterized epidemiological, clinical, laboratory features and determined risk factors for a fatal outcome. One hundred forty patients (51% patients were infected with Rickettsia conorii Malish stain and 49% with Israeli spotted fever strain)with diagnosis documented with identification of the causative rickettsial strain were admitted to 13 Portugueses Hospitals during 1994-2006.Comparison of the clinical manifestations of MSF caused by Malish and ISF strains revealed tremendous overlap that would not permit clinical recognition of the strain envolved, but an eschar was observed in a significantly higher percentage of patients with Malish than ISF strain.A fatal outcome was significantly more likely for patients with ISF strain infection meaning that ISF strain was more virulent than Malish strain, and also alcoholism was a host risk factor for a fatal outcome.The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, confusion/obtundation, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated hepatic enzymes and creatine kinase. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strong associated with a fatal oucome of infections with both strains.The immune response to R. conorii infection determined with both strains. The immune response to R. conorii infection determined by the expression levels of inflammatory and immune mediators in skin biopsies collected from untreated patients with Mediterranean spotted fever reveal that intralesional expression of mRNA of TNF-α, IFN-γ, IL-10, RANTES, and indoleamine-2, 3-dioxygenase (IDO)an enzyme involved in limiting rickettsial growth by tryptophan degradation, were elevated in skin of MSF patients compared to controls. Six patients had elevated levels of inducible nitric oxide synthase (NOS2, a source microbicidal nitric oxide.Positive correlations among TNF-α, IFN-γ, NOS2,IDO and mild-to-moderate disease suggested that type 1 polarization plays a protective role. Significantly high levels of intralesional IL-10 were inversely correlated with IFN-γ and TNF-α. The chemokine RANTES was significantly higher in patients with several MSF. It seems that MSF patients with mild-to-moderate disease have a strong and balanced intralesional pro-inflammatory and anti-inflammatory response, while severe disease is associated with higher chemokine expression.Whether these findings are simply a correlate of mild and severe disease or contribute to anti-rickettsial immunity and pathogenesis remains to be determined.In this dissertation is also described a new rickettsiois present in Portugal caused by R.sibirica mongolitimonae strain, identified based on agent isolation and DNA detection by PCR technique in a skin biopsy.The presence of this agent corroborated by its detection also in Rhipicephalus pusillus tick. Also, pathogenic tick and flea-borne rickettsial agents such as R. africae strain detected in Rhipicephalus bursa tick, and R.felis and R.typhi detected in different fleas species raise the alert for the possible existence of other rickettsioses in Portugal that might be underdiagnosed.

Schistosoma mansoni: evaluation of the activity of oxamniquine on schistosomules, at 24 hours after infection

Mice transcutaneously infected with about 400 cercariae were submitted to treatment with oxamniquine (400 mg/kg), 24 hours after infection. The recovery of schistosomules, at 4, 24, 48 and 72 hours and 35 days after treatment, showed the activity of the drug on the parasites, thus practically preventing their migration from the skin to the lungs. Worm recovery performed in the lungs (96 hours after treatment) showed recovery means of 0.6 worms/mouse in the treated group and 53.8 in the control group (untreated). The perfusion of the portal system carried out at 35 days after treatment clearly showed the elimination of all the parasites in the treated group, whereas a recovery mean of 144.7 worms/mouse was detected in the control group (untreated). These findings confirm the efficacy of oxamniquine at the skin phase of infection, and also show similarity with the immunization method that uses irradiated cercariae. The practical application of these findings in the medical clinic is discussed too

Evaluation of the resistance to Schistosoma mansoni infection in Nectomys squamipes (Rodentia: Cricetidae), a natural host of infection in Brazil

The development of resistance in three stages throughout an active infection (pre-ovular, acute and initial chronic stages) was studied, comparing the total number of adult worms recovered from the reinfected group and the control groups. It was shown that Nectomys squamipes was unable to develop resistance in the tested conditions and, on the other hand, reinfection in the pre-ovular period of the parasite led the rodent to present the phenomenonacilitation, with reduction of natural resistance and an increase in the parasite load. These results suggest the existence of other forms of immunity diverse from the concomitant immunity in the host-parasite relationship, according to the employed model.

Identification of factors and groups at risk of infection with Schistosoma mansoni: a strategy for the implementation of control measures?

A fourteen year schistosomiasis control program in Peri-Peri (Capim Branco, MG) reduced prevalence from 43.5 to 4.4%; incidence from 19.0 to 2.9%, the geometric mean of the number of eggs from 281 to 87 and the level of the hepatoesplenic form cases from 5.9 to 0.0%. In 1991, three years after the interruption of the program, the prevalence had risen to 19.6%. The district consists of Barbosa (a rural area) and Peri-Peri itself (an urban area). In 1991, the prevalence in the two areas was 28.4% and 16.0% respectively. A multivariate analysis of risk factors for schistosomiasis indicated the domestic agricultural activity with population attributive risk (PAR) of 29.82%, the distance (< 10 m) from home to water source (PAR = 25.93%) and weekly fishing (PAR = 17.21%) as being responsible for infections in the rural area. The recommended control measures for this area are non-manual irrigation and removal of homes to more than ten meters from irrigation ditches. In the urban area, it was observed that swimming at weekly intervals (PAR = 20.71%), daily domestic agricultural activity (PAR = 4.07%) and the absence of drinking water in the home (PAR=4.29%) were responsible for infections. Thus, in the urban area the recommended control measures are the substitution of manual irrigation with an irrigation method that avoids contact with water, the creation of leisure options of the population and the provision of a domestic water supply. The authors call attention to the need for the efficacy of multivariate analysis of risk factors to be evaluated for schistosomiasis prior to its large scale use as a indicator of the control measures to be implemented.

"In vivo" leukocyte chemotaxis in experimental mice Schistosoma mansoni infection

The "in vivo" chemotaxis was studied in C57B1/10 mice 10, 30, 50 and 60 days after a Schistosoma mansoni infection in comparison to a control group (uninfected mice). Staphylococcal protein A was injected into a connective tissue air pouch of control and experimental mice and the leukocyte chemotaxis was counted. A decrease in polymorphonuclear (PMN) leukocyte response was found in infected mice in comparison to the control group (p<0.05). The 10 day infected mice showed a decreased PMN leukocyte response respecting the control group (p<0.05) and this finding became more evident 30 and 50 days post-infection. Although the PMN leukocyte response of 60 day infected mice increased in comparison to 50 day infected animals, it was still significantly lower the control response. The mononuclear leukocyte response was not significantly different between infected or uninfected mice.

Difficulties in diagnosing atypical primary HIV-1 infection

Several cases of primary HIV-1 infection are not identified, either because the diagnosis is not suspected or because they test negative for HIV-1 antibody. This work presents an uncommon case of primary HIV-1 infection in an young parenteral drug abuser man, who presented symptoms of acute hepatitis. During the initial acute phase the serum sample of the patient tested negative for the presence of antibodies against several viruses, including HIV-1. Nevertheless, the diagnosis of primary HIV-1 infection was suspected by using an alternative method for"in vitro" induced antibody production (IVIAP), and confirmed by p24 antigen serum positivity and seroconversion in serial plasma samples of the patient. The authors suggest the use of the IVIAP and others complementary assays to help the diagnosis of acute HIV-1 infection in persons at high risk conditions.

First case of human infection by Trichophyton vanbreuseghemii in Brazil

This paper reports the first case of human infection caused by Ttrichophyton vanbreuseghemii in Brazil.

Cutaneous Nocardia asteroides infection of nontraumatic origin

This paper reports a case of cutaneous infection of nontraumatic origin caused by Nocardia asteroides in a hospitalized patient with chronic obstructive pulmonary disease. Diagnosis was established by direct and histological examination, cultures from exudate and biopsy specimen. We discuss the classification of clinical forms of Nocardia infections affecting the skin.

Murine virus contaminant of Trypanosoma cruzi experimental infection

The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi experimental infection was investigated. Data obtained showed that CBA/J mice infected with stocks of parasite maintained in mice (Y1UEC) presented higher level of parasitemia and shorter survival times than those infected with a stock (Y1TC) which was also maintained in mice but had been previously passaged in cell culture. Mouse antibody production tests, performed with the filtered plasma of mice infected with Y1UEC, indicated the presence of mouse hepatitis virus (MHV) while no virus was detected when testing the plasma of Y1TC infected mice. Filtered plasma of Y1EUC infected mice was shown to contain a factor able to enhance the level of parasitemia and to reduce the mean survival time of mice challenged with 10(5) Y1TC. This factor, that could be serially passaged to naïve mice was shown to be a coronavirus by neutralization tests.