Roberta Maia de Castro Romanelli

Congenital Toxoplasmosis in Southeastern Brazil: Results of Early Ophthalmologic Examination of a Large Cohort of Neonates

OBJECTIVE To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening. DESIGN Cross-sectional analysis of a cohort. PARTICIPANTS A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil. METHODS From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed. MAIN OUTCOME MEASURES Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded. RESULTS Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%). CONCLUSIONS A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement ( approximately 80%) and many active lesions (in approximately 50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.

Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy.

OBJECTIVE To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTION The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborns serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. COMMENTS It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

Perfil das gestantes infectadas pelo HIV atendidas em pré-natal de alto risco de referência de Belo Horizonte

OBJECTIVES: identify HIV infected pregnant women in a referral center and investigate characteristics related to infection and parity. METHODS: a cross-sectional study comprising all HIV infected women treated at the High Risk Prenatal Care in the Hospital das Clinicas da Universidade Federal de Minas Gerais, in 2004. Demographic data, HIV epidemiology infection and obstetrical history were collected. For statistical analysis SPSS 12.0 was used. RESULTS: eighty five women median aged 29.1 and 90 pregnancies were followed-up. In 55 pregnancies (61.1%) women had prior information of the infection. Sixty four (71.1%) informed they lived together. Probably they all acquired HIV in heterosexual relations. Fifty four (60%) were diagnosed during one of the pregnancies. The global pregnancies median was 3.5, and 1.71 following diagnosis. Patients with prior diagnosis had a higher pregnancy median as compared to those who were diagnosed during their pregnancies (p = 0.002). Eighty six pregnant women made use of anti-retroviral medication, 56.7% through therapeutic indication. No vertical transmission cases were determined. CONCLUSIONS: new pregnancies in HIV infected women are not rare notwithstanding contraceptive resources offered. Therefore, further investigations are necessary to identify what difficulties not previously approached they have during routine medical assistance.

Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV-infected children

OBJECTIVE The use of antiretroviral therapy in HIV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children. METHODS The study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis. RESULTS A total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001). CONCLUSION Triple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HIV-infected children. Therefore, triple therapy should be the treatment of choice.

Prognostic markers of symptomatic congenital cytomegalovirus infection

The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV) infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP) from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR). Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS--15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters). When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02). Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

Adverse socioeconomic conditions and oocyst-related factors are associated with congenital toxoplasmosis in a population-based study in Minas Gerais, Brazil.

Objective Congenital toxoplasmosis is a public health problem in Brazil. This study aimed to determine risk factors associated with congenital toxoplasmosis in Minas Gerais which is the second largest Brazilian State based on number of inhabitants, and its territorial extension is larger than that of France. Methods: Population-based case-control study to assess the association between congenital toxoplasmosis and maternal exposure to infection risk factors. The study included mothers/children participating in the Minas Gerais Newborn Screening Program. The cases consisted of 175 mothers of infected children, and the controls consisted of 278 mothers of children without suspected infection. The associations were assessed through binomial logistic regression with p≤0.05. Results The variables associated with lower probability of toxoplasmosis were: older mother age (OR = 0.89; CI95% = 0.85–0.93), higher level of education (OR = 0.85; CI95% = 0.78–0.92), access to potable water (OR = 0.21; CI95% = 0.08–0.51), and home with flush toilet (OR = 0.18; CI95% = 0.04–078). The variables associated with higher probability of infection were: cats in the neighborhood (OR = 2.27; CI95% = 1.27–4.06), owning or visiting homes with domestic cats (OR = 1.90; CI95% = 1.09–3.31), handling the soil (OR = 2.29; CI95% = 1.32–3.96), and eating fresh meat not previously frozen (OR = 3.97; CI95% = 2.17–7.25). After stratification according region of residence (rural or urban/peri-urban), home with flush toilet and consumption of treated water were protective against the disease only in the rural stratum. Conclusions In Minas Gerais, congenital toxoplasmosis has been associated with poor socioeconomic conditions. Considering maternal exposure to sources of Toxoplasma gondii, the predominating risk factors were those related to the ingestion of oocysts. It is expected that these results will contribute to development of a program for prevention of congenital toxoplasmosis adapted to the reality of the population of Minas Gerais. The differences between populations living in rural and urban areas regarding the main risk factors for toxoplasmosis point to the need of considering regional specificities in planning strategies to control congenital toxoplasmosis.

Diagnosis of meningitis with reagent strips

OBJETIVO: determinar a utilidade de fitas reagentes para a avaliacao liquorica de pleocitose, glicorraquia e proteinorraquia no diagnostico precoce e rapido de meningites em criancas. METODOS: Foram incluidas no estudo amostras de liquor provenientes de 164 criancas admitidas no ambulatorio de doencas infecto-contagiosas do Centro Geral de Pediatria (CGP-FHEMIG), com suspeita clinica de meningite, no periodo diurno de Maio/97 a Maio/99. A faixa etaria dos pacientes variou de um mes a 12 anos (mediana de 12 meses), sendo obtidos resultados da citobioquimica liquorica (celularidade, glicorraquia e proteinorraquia) de 154 desses pacientes. Esses achados foram comparados com reacoes do liquor em fitas reagentes. RESULTADOS: Atraves da citobioquimica liquorica foram identificados 43 casos de provavel meningite bacteriana, 19 provavelmente viroticas e 83 amostras sem alteracoes. Pelas fitas reagentes, detectaram-se 41 casos de provavel meningite bacteriana, dois casos de infeccao meningea provavelmente virotica, e em 71 exames nao se verificaram alteracoes. Comparando os resultados obtidos por meio das fitas reagentes com a citobioquimica convencional, observou-se sensibilidade, especificidade, valores preditivos positivo e negativo e acuracia (90,7; 98,1; 95,1; 96,4; 96,1%, respectivamente). Ademais, a analise estatistica pelo teste de Mc Nemar nao evidenciou discordância significativa no diagnostico de meningite bacteriana obtido atraves de ambos os metodos (p=0,68) e, pela estatistica Kappa, verificou-se elevado grau de concordância entre os testes (p<0,0001). CONCLUSOES: Os resultados sugerem que o emprego de fitas reagentes pode se tornar recurso auxiliar util para o diagnostico de meningites bacterianas, principalmente em casos de dificuldades para a obtencao de volume suficiente do liquor e/ou para direcionar a terapeutica inicial.

Risk factors and lethality of laboratory-confirmed bloodstream infection caused by non-skin contaminant pathogens in neonates

OBJECTIVE To evaluate risk factors and lethality of late onset laboratory-confirmed bloodstream infection (LCBI) in a Brazilian neonatal unit for progressive care (NUPC). METHODS This was a case-control study, performed from 2008 to 2012. Cases were defined as all newborns with late onset LCBI, excluding patients with isolated common skin contaminants. Controls were newborns who showed no evidence of late onset LCBI, matched by weight and time of permanence in the NUPC. Variables were obtained in the Hospital Infection Control Committee (HICC) database. Analysis was performed using the Statistical Package for the Social Sciences (SPSS). The chi-squared test was used, and statistical significance was defined as p < 0.05, followed by multivariate analysis. RESULTS 50 patients with late onset LCBI were matched with 100 patients without late onset LCBI. In the group of patients with late onset LCBI, a significant higher proportion of patients who underwent surgical procedures (p = 0.001) and who used central venous catheter (CVC) (p = 0.012) and mechanical ventilation (p = 0.001) was identified. In multivariate analysis, previous surgery and the use of CVC remained significantly associated with infection (p = 0.006 and p = 0.047; OR: 4.47 and 8.99, respectively). Enterobacteriacea was identified in 14 cases, with three (21.4%) deaths, and Staphylococcus aureus was identified in 20 cases, with three (15%) deaths. CONCLUSIONS Surgical procedures and CVC usage were significant risk factors for LCBI. Therefore, prevention practices for safe surgery and CVC insertion and manipulation are essential to reduce these infections, in addition to training and continuing education to surgical and assistance teams.

Visceral leishmaniasis in liver transplant recipients from an endemic area.

Visceral leishmaniasis (VL) is a parasitic infection generally caused by the Leishmania donovani complex, and in Brazil by Leishmania chagasi. Every year, half a million new cases are diagnosed worldwide, and five countries— Nepal, Bangladesh, Brazil, India, and Sudan—account for up to 90% of cases (1, 2). Although considered a rare disease among transplant recipients, the number of reported cases has increased over the last two decades (3). VL diagnosis should also be considered in transplant recipients from nonendemic areas, in view of increasing migration and the globalized world. We report three cases of VL in liver transplantation (LT) recipients in a single center from Brazil. Hospital records of 595 patients who underwent LT from September 1994 to December 2009 at the Federal University Hospital of Minas Gerais, Brazil, were reviewed. Three of the 595 liver transplanted patients were diagnosed with VL. Their detailed clinical characteristics are shown in Table 1. A case is defined as the presence of Leishmania amastigotes in bone marrow aspirate or specimens of other reticuloendothelial system organs in patients with symptoms consistent with VL. The typical clinical picture is characterized by fever, splenomegaly, weight loss, blood cytopenia, and hypergammaglobulinemia (2, 4). All patients presented with fatigue, pancytopenia, and hypergammaglobulinemia, and two patients had fever and splenomegaly. Diagnosis was established by the presence of Leishmania amastigotes in bone marrow aspirate (Fig. 1) in all cases. Initial therapy was amphotericin B deoxycholate, which caused nephrotoxicity in all three patients and was replaced by liposomal amphotericin B. Immunosuppression was reduced once the VL diagnosis was established, and maintained at the lowest possible level for a few months. Two patients are alive and free of disease. The other patient is alive but experienced a VL relapse; he was retreated with liposomal amphotericin B and has continued on monthly secondary prophylaxis (3 mg/kg/monthly). VL infection in transplant recipients may occur in four ways: (1) the recipient may be infected by the graft; (2) by transfusion; (3) a previously infected recipient may reactivate a latent infection; and (4) immunosuppressed patients may develop de novo infections (3, 5). Because specific antibody responses are not protective (6), suppression of the T-cell host response after organ transplantation may reactivate a latent VL infection. In the present series, it was not possible to identify the way of transmission. The rising number of transplants, including in VL-endemic regions, justifies the increasing interest in such a neglected disease. Timely diagnosis followed by prompt treatment can have an impact on the high lethality rates (3). Until now, only 10 cases of VL in LT recipients have been described, one of them by our group (7–14). Cases are probably underestimated by misdiagnosis. Given that the liver is a reticuloendothelial organ preferentially affected by the protozoan, the risk of transmission through the graft may be greater than in other transplants. Transplanted patients should benefit from lipid formulations as of the beginning of treatment, because immunosuppressive drugs are also nephrotoxic and renal dysfunction is frequent. Cure is generally defined by clinical and hematological criteria (resolution of fever, hepatosplenomegaly, and pancitopenia). Follow-up is recommended for 6 months after treatment (15, 16). Although some authors also consider negative bone marrow biopsies or aspirate cultures after treatment (17), these are invasive procedures and absence of parasites does not define resolution or exclude relapse (18). VL cure rates after amphotericin treatment in transplanted patients are approximately 80%. However, relapse may occur in up to 35% of the cases, associated to poor prognosis (13). One described patient, despite adequate treatment, presented a relapse 5 months after amphotericin discontinuation. He was then retreated and remains on secondary prophylaxis with monthly liposomal amphotericin. Some studies have shown that secondary prophylaxis may prevent a VL relapse, but they were carried out in HIV patients (18, 19). The evidence of this recommendation in transplanted patients is not yet established, but it should be considered in those who relapse. Asymptomatic infection (from donors or recipients) in the pretransplant phase could facilitate the suspicion of VL after LT in the presence of certain symptoms (19). We do not perform VL serology routinely for screening liver donors and recipients before transplant, but this is the matter of an ongoing research project. At present, if recipients or donors have a positive result, we perform a stricter follow-up with a lower threshold of suspicion for VL. In conclusion, VL is a potential infectious complication in liver transplanted patients, mainly in endemic areas, and probably remains underestimated and underdiagnosed in these patients. Prompt diagnosis and treatment are essential to reduce lethality.

Risk factors and preventive measures for catheter-related bloodstream infections

OBJECTIVE To review the risk factors of central venous catheter-related bloodstream infection and the recommendations for its prevention. SOURCES PubMed, Cochrane Collaboration and Bireme were reviewed using the following inclusion criteria: studies published between 2000 and 2010, study design, hospitalized pediatric population with central venous catheters and studies about central venous catheter-related bloodstream infection. In addition, reference documents were retrieved from the Centers for Disease Control and Prevention and the Brazilian Health Surveillance Agency. SUMMARY OF THE FINDINGS Associated risk factors were: duration of central venous catheter use; length of hospitalization time; long-term indwelling central venous catheter; insertion of central venous catheter in intensive care unit; nonoperative cardiovascular disease; parenteral nutrition; and administration of blood products. The preventive measures recommended by studies in the literature are: development of records and multidisciplinary guidelines of care for central venous catheter insertion and maintenance; correct use of central venous catheter insertion technique; use of chlorhexidine-impregnated dressings; early catheter removal; and adoption of continued education programs for the healthcare team. CONCLUSION The control of risk factors may lead to a reduction of 40% or greater in the incidence of catheter-related bloodstream infection. Insertion surveillance and special attention to central venous catheter in pediatric populations should guide the standardization of healthcare routines to achieve standards for comparisons within and between institutions.