Jailson B. Correia

Effectiveness of monovalent rotavirus vaccine (rotarix) against severe diarrhea caused by serotypically unrelated G2P[4] strains in Brazil.

BACKGROUND. In a Latin American trial, a monovalent G1P[8] rotavirus vaccine showed high efficacy against severe rotavirus diarrhea. Protection was lower against serotypically unrelated G2P[4] strains, which circulated infrequently. This case-control study was undertaken to assess the effectiveness of this monovalent G1P[8] rotavirus vaccine against G2P[4] strains in Brazil. METHODS. Case patients were children with severe G2P[4] rotavirus diarrhea who presented at a hospital in Recife, Brazil, from March 2006 through September 2008. Vaccination rates among case patients were compared with rates among 2 groups of control participants-children with rotavirus-negative diarrhea and children admitted for acute respiratory tract infection (ARI)-to calculate vaccine effectiveness, after controlling for the birth month and year. RESULTS. We enrolled 70 G2P[4] rotavirus-positive case patients with severe diarrhea, 484 rotavirus-negative control participants with diarrhea, and 416 control participants with ARI, aged 6 months. Among children aged 6-11 months, the effectiveness of the vaccine against G2P[4] diarrhea was 77% (95% confidence interval [CI], 42%-91%) and 77% (95% CI, 43%-90%) among the rotavirus-negative control participants with diarrhea and control participants with ARI, respectively. Vaccine effectiveness in children aged 12 months decreased to -24% (95% CI, -190% to 47%) and 15% (95% CI, -101 to 64) among the rotavirus-negative control groups with diarrhea and ARI, respectively. CONCLUSIONS. This monovalent G1P[8] rotavirus vaccine was effective against severe G2P[4] rotavirus diarrhea among children aged 6-11 months. Effectiveness declined among children aged 12 months, which suggests waning immunity.

Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years

Background Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil. Methods Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA. Findings 407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia. Interpretation This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.

Apparent extinction of non-G2 rotavirus strains from circulation in Recife, Brazil, after the introduction of rotavirus vaccine.

The introduction of a G1P[8] rotavirus vaccine in Recife, Brazil, caused a decrease in rotavirus detection from 27% (March–May, 2006) to 5.0% (March–May, 2007), with all strains becoming G2, against which less protection had been predicted.

Incidence of Rotavirus and All-Cause Diarrhea in Northeast Brazil Following the Introduction of a National Vaccination Program

BACKGROUND & AIMS Rotavirus vaccines were introduced in Brazil in 2006; we evaluated their effects in the state of Sergipe, Brazil. METHODS We performed a cross-sectional survey of children with diarrhea attending emergency services in Aracaju, Brazil, between October 2006 and April 2008 and a cluster sampling survey to assess vaccination coverage. Vaccine efficacy was assessed using the screening method. Diarrhea consultation and hospitalization data (2003-2007) were obtained from state and national surveillance systems. RESULTS Rotavirus was detected in 59 of 534 stool samples (11%) from children attending emergency services. The number of rotavirus-positive samples decreased from 18 of 74 (24%) in 2006 to 31 of 321 (9.5%) in 2007 and 10 of 136 (7.4%) in 2008 (P < .01). Diarrhea severity was greater in children with rotavirus (P < .01) but decreased over time (P < .001). Of the rotaviruses detected, 56 of 59 (95%) were P[4]G2 genotype, 1 was P[4]G-non-typeable (NT), 1 was P[NT]G2, and 1 was P[NT]GNT. Diarrhea consultations decreased from 3020 in 2004 to 604 in 2007; reductions were greatest among children under 5 years old. Diarrhea hospitalizations decreased from 2121 in 2003 to 1176 in 2007. Vaccine coverage was 90.3%. Vaccines were highly effective against the strain P[8]G1; efficacy against P[4]G2 genotype was 89% (95% confidence interval: 0.87-0.92) in Aracaju and 95% in Sergipe. CONCLUSIONS Since vaccines were introduced in 2006, there has been an overall reduction in diarrhea consultations and hospitalizations in northeast Brazil, with the greatest reductions in young children. This might have resulted from vaccination and improved sanitation. Although a single rotavirus genotype (P[4]G2) was recovered, vaccine efficacy was high against this genotype.

Visceral leishmaniasis: clinical and epidemiological features of children in an endemic area

OBJECTIVE To describe the clinical and epidemiological features of children with visceral leishmaniasis admitted to a pediatric referral hospital, and to describe treatment measures and the case fatality rate. METHODS Retrospective analysis of biological, demographic, clinical and laboratory data from children with visceral leishmaniasis admitted to Instituto Materno Infantil de Pernambuco (Recife, state of Pernambuco, northeastern Brazil) between 1996 and 2001. RESULTS 431 children were included in the study. Age ranged from 4 months to 13.7 years. 50.3% were female and 82.5% came from the interior of the state of Pernambuco. 70% of the patients lived in brick homes, and 70% were not served with piped water and sewage services. Average maternal schooling was 3 years. Clinical presentation included splenomegaly (97%), fever (95.6%) and malnourishment (44.5%). Associated infections were diagnosed in 10.9% of cases. The mean values for laboratory variables were: hemoglobin 6 g/dl, leukocyte count 3,516/mm(3), and platelet count 118,641/mm(3). The first line treatment used in 98% of the cases was glucantime. Amphotericin B was used in seven cases. The case fatality rate was 10.2%. The main immediate causes of death were associated infections, bleeding and liver failure. CONCLUSIONS Health care workers should be trained for the early recognition and appropriate management of visceral leishmaniasis and its complications.

Risk factors for death in children with visceral leishmaniasis.

Background Despite the major public health importance of visceral leishmaniasis (VL) in Latin America, well-designed studies to inform diagnosis, treatment and control interventions are scarce. Few observational studies address prognostic assessment in patients with VL. This study aimed to identify risk factors for death in children aged less than 15 years admitted for VL treatment in a referral center in northeast Brazil. Methodology/Principal Findings In a retrospective cohort, we reviewed 546 records of patients younger than 15 years admitted with the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years, and 275 (50%) were male. There were 57 deaths, with a case-fatality rate of 10%. In multivariate logistic regression, the independent predictors of risk of dying from VL were (adjusted OR, 95% CI): mucosal bleeding (4.1, 1.3–13.4), jaundice (4.4, 1.7–11.2), dyspnea (2.8, 1.2–6.1), suspected or confirmed bacterial infections (2.7, 1.2–6.1), neutrophil count <500/mm3 (3.1, 1.4–6.9) and platelet count <50,000/mm3 (11.7, 5.4–25.1). A prognostic score was proposed and had satisfactory sensitivity (88.7%) and specificity (78.5%). Conclusions/Significance Prognostic and severity markers can be useful to inform clinical decisions such as whether a child with VL can be safely treated in the local healthcare facility or would potentially benefit from transfer to referral centers where advanced life support facilities are available. High risk patients may benefit from interventions such as early use of extended-spectrum antibiotics or transfusion of blood products. These baseline risk-based supportive interventions should be assessed in clinical trials.

Impact of rotavirus vaccination on diarrhoea mortality and hospital admissions in Brazil

Objective  To analyse the data reported by the national surveillance system of Brazil, including data on diarrhoea mortality and hospital admissions before and after rotavirus vaccine introduction, and evaluate the impact of its widespread use under operational conditions.

Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expression of the B cell differentiation factor BAFF.

Background The mechanisms regulating antibody expression within the human lung during airway infection are largely unknown. In this study, our objectives were to determine if infection with respiratory syncytial virus (RSV) upregulates expression of the B cell differentiation factors A proliferation inducing ligand (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a common feature of viral airway infection, and how this is regulated in human airway epithelial cells. Methods We measured BAFF and APRIL protein expression in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and healthy control children, and in nasopharyngeal aspirates from preschool children with other single respiratory viral infections. We also measured mRNA expression in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric primary airway epithelial cell cultures (pAEC). Beas-2B cell cultures were used to examine mechanisms regulating BAFF expression. Results BAFF protein and mRNA were elevated (in marked contrast with APRIL) in BAL and bronchial brushings, respectively, from RSV-infected infants. BAFF protein was also found in upper airway secretions from children with human metapneumovirus, H1N1, bocavirus, rhinovirus, RSV and Mycoplasma pneumoniae infection. BAFF mRNA and protein were expressed following in vitro RSV infection of both pAEC and Beas-2B cultures, with mRNA expression peaking 12-h postinfection. BAFF induction was blocked by addition of a neutralising anti-interferon-β antibody or palivizumab. Conclusions BAFF, produced through an interferon-β-dependant process, is a consistent feature of airway infection, and suggests a role for the airway epithelia in supporting protective antibody and B cell responses in the lung.

Incidence and risk factors for health care-associated pneumonia in a pediatric intensive care unit.

Objectives:To determine the incidence and risk factors for health care-associated pneumonia in a pediatric intensive care unit. Design:Prospective cohort study. Setting:Pediatric intensive care unit with 16 medical and surgical beds in a tertiary teaching hospital in Recife, northeast Brazil. Patients:Patients aged <18 yrs were consecutively enrolled between January 2005 and June 2006 into a cohort set to investigate health care-associated infections. Newborns and patients admitted for surveillance and those staying for <24 hrs were excluded. Patients were followed up daily throughout the stay and until 48 hrs after discharge from the unit. Interventions:None. Measurements and Main Results:This report focuses on health care-associated pneumonia, defined as pneumonia that occurs >48 hrs after admission but that was not incubating at the time of admission, as the primary outcome. Intrinsic and extrinsic variables were prospectively recorded into a standardized form. Statistical analyses, including multivariable logistic regression, were performed in Stata version 9.1. There were 765 eligible admissions. Health care-associated pneumonia occurred in 51 (6.7%) patients with an incidence density of 13.1 episodes/1,000 patient-days. There were 366 (47.8%) patients on mechanical ventilation, of whom 39 (10.7%) presented with ventilator-associated pneumonia with an incidence density of 27.1/1,000 days on ventilation. Longer stay on ventilation (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.08), use of gastric tube (OR, 2.88; 95% CI, 1.41–5.87), and of sedatives/analgesics (OR, 2.45; 95% CI, 1.27–4.72) were identified as independent risk factors for healthcare-associated pneumonia. Conclusion:Identification of independent predictors of health care-associated pneumonia may inform preventive measures. Strategies to optimize use of sedatives/analgesics, reduce the use of gastric tubes, and reduce the time on ventilation should be considered for inclusion in future intervention studies.

Incidence and risk factors of corneal epithelial defects in mechanically ventilated children

Objective:To determine the incidence of corneal defects and the main risk factors in children exposed to mechanical ventilation (MV) in the pediatric intensive care unit between March 28 and November 4, 2001. Methods:A cohort study where characteristics of 53 children exposed to MV were evaluated and risk factors relating to the occurrence of corneal defects were identified. Patients’ corneas were evaluated on a daily basis using a fluorescein test and a portable slit lamp. Risk ratios and 95% confidence intervals were calculated. A multiple logistic regression analysis was performed using a nonconditional model. The model selects variables that maintain associations with corneal defects at a 5% level of significance. The variables with the highest predictive value were identified. Results:Twenty-five percent of children exposed to MV developed corneal defects. From this percent, almost 54% of the defects occurred in both eyes, and 46% in the left eye alone. Most defects (69%) were detected within the first week of MV, and a large number were detected within the first 48 hours (46% of cases). In those children who exhibited failure of at least one organ in addition to the lungs, 43% developed defects. Among the children who died, 44% showed corneal defects. After adjusting for potential confounding variables in the multivariate analysis, the maintenance of opened eyes and sepsis remained as prognostic factors for corneal defects. Conclusions:A high incidence (25%) of corneal defects was found in children exposed to MV, as is also observed with adult patients. The main risk factors associated with corneal defects were the maintenance of opened eyes and the presence of sepsis.