Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls.

Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

ABSTRACT Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

Clinical forms and diagnosis of tuberculosis in children and adolescents during the COVID-19 pandemic.

OBJECTIVE: The present study aimed to describe the clinical forms and the time taken to diagnose new tuberculosis cases and to statistically analyze the isolated and combined forms of the disease in children and adolescents treated at a university hospital in Rio de Janeiro during the first year of the COVID-19 pandemic in Brazil. METHODS: This was a cross-sectional study that used retrospective data on children (0-9 years old) and adolescents (10-18 years old) with pulmonary (PTB), extrapulmonary (EPTB), and combined tuberculosis (PTB + EPTB) followed up at the outpatient clinic from January 2019 to March 2021. Categorical data were analyzed by descriptive statistics and expressed as frequency and proportions. Categorical variables were compared using the Chi-square test, and numerical variables using Student's T-test. RESULTS: A total of 51 cases were included, 63% (32/51) of which comprised patients in the year of the pandemic (group A), while 37% (19/51) were patients attended in previous years (group B). In group A, 19% (6/32) of the patients presented PTB, 59% (16/32) had EPTB, and 31% (10/32) had PTB+EPTB. In group B, 42% (8/19) of the patients presented PTB, 42% (8/19) had EPTB, and 16% (3/19) had PTB+EPTB. CONCLUSION: Our study revealed more tuberculosis cases in the first year of the pandemic than in the same period of the previous year, with greater variation of sites affected by the disease, including rarer and more severe forms.

Clinical Manifestations and Complications of Children With COVID-19 Compared to Other Respiratory Viral Infections: A Cohort Inpatient Study From Rio de Janeiro, Brazil.

Introduction: The coronavirus disease-2019 (COVID-19) clinical manifestations in children and adolescents are diverse, despite the respiratory condition being the main presentation. Factors such as comorbidities and other respiratory infections may play a role in the initial presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aims to describe the epidemiological aspects, clinical, and laboratory manifestations of pediatric patients admitted to a tertiary pediatric hospital in Rio de Janeiro, diagnosed with COVID-19, and compare these with other viral conditions during the first year of the SARS-CoV-2 pandemic. Methods: All patients under 18 years of age that were admitted with upper airway infection were enrolled and followed up for 30 days. The main dependent variable was the laboratorial diagnosis of SARS-CoV-2, and independent variables were studied through logistic regression. Results: A total of 533 patients were recruited, and 105 had confirmed SARS-CoV-2 infection. Detection of other viruses occurred in 34% of 264 tested participants. Six patients died (two in SARS-CoV-2 infected group). The variables independently associated with COVID-19 were older age (OR = 1.1, 95% CI = 1.0-1.1), lower leukocytes count at entry (OR = 0.9, 95% CI = 0.8-0.9), and contact with suspected case (OR = 1.6, 95% CI = 1.0-2.6). Patients with COVID-19 presented higher odds to be admitted in an intensive care unit (OR = 1.99, 95% CI = 1.08-3.66). Conclusions: Even during the SARS-CoV-2 pandemic, several other respiratory viruses were present in admitted pediatric patients. Variables associated with COVID-19 infection were older age, lower leukocytes count at entry, and a domiciliary suspect contact. Although patients with COVID-19 were more frequently admitted to ICU, we did not observe higher mortality in this group.

Neurological Manifestations Associated With SARS-CoV-2 in Children: A Case Series.

Neurological manifestations of COVID-19 may affect both central and peripheral nervous systems. Unlike in adults, in whom majority of severe cases derive from respiratory complications, neurological involvement is one of the main causes of severe COVID-19 in children. This study aimed to detect viral respiratory pathogens, mainly SARS-CoV-2, in nasopharynx and cerebrospinal fluid samples utilizing qRT-PCR (TaqMan) in a pediatric population in Brazil. We evaluated four children with neurological symptoms and laboratory-confirmed SARS-CoV-2 infection: three presenting with meningoencephalitis and one presenting with Guillain-Barré syndrome. All four patients had mild respiratory symptoms. SARS-CoV-2 RNA was identified in two cerebrospinal fluid samples. SARS-CoV-2 involvement should be considered for differential diagnosis in pediatric cases presenting neurological alterations even if symptoms such as headache, anosmia, or dizziness are absent.

Antenatal factors related to congenital toxoplasmosis in Rio De Janeiro, Brazil.

BACKGROUND: Toxoplasmosis is one of the main preventable congenital infections in Brazil. This manuscript aims to describe antenatal factors possibly associated with congenital toxoplasmosis (CT). METHODS: This is a case-control study, with data collected from medical records, from infants admitted under one year of age at the Infectious Diseases Clinic of Instituto de Puericultura e Pediatria Martagão Gesteira, reference center from Rio de Janeiro, exposed to toxoplasmosis during their antenatal period. Patients diagnosed with CT were classified as cases and those exposed without infection as controls. RESULTS: A total of 289 patients were followed up in 10 years. CT was confirmed in 43 (14.9%) of which six (14%) were asymptomatic, five (12%) had the classic triad (retinochoroiditis, hydrocephalus and intracranial calcifications), 27/42 (64.3%) had reactive IgM. Even after adjusted for prematurity, cases were born with lower weight (OR 0.49 - IC95% 0.33-0.73). There was a 13% increase in chance of CT per gestational week of the maternal diagnosis. Maternal fever, consumption of poorly washed vegetables during pregnancy, and diagnosis in the third trimester were associated with CT (OR: 6.43, 6.55, and 2.16, respectively). CONCLUSION: Fever during pregnancy, consumption of poorly washed vegetables and diagnosis in the third trimester were associated with CT. Infants with diagnosis of CT were born with lower weight than the controls.

Clinical forms and diagnosis of tuberculosis in children and adolescents during the COVID-19 pandemic / Formas clínicas e diagnóstico da tuberculose em crianças e adolescentes durante a pandemia de COVID-19

ABSTRACT Objective: The present study aimed to describe the clinical forms and the time taken to diagnose new tuberculosis cases and to statistically analyze the isolated and combined forms of the disease in children and adolescents treated at a university hospital in Rio de Janeiro during the first year of the COVID-19 pandemic in Brazil. Methods: This was a cross-sectional study that used retrospective data on children (0-9 years old) and adolescents (10-18 years old) with pulmonary (PTB), extrapulmonary (EPTB), and combined tuberculosis (PTB + EPTB) followed up at the outpatient clinic from January 2019 to March 2021. Categorical data were analyzed by descriptive statistics and expressed as frequency and proportions. Categorical variables were compared using the Chi-square test, and numerical variables using Student's T-test. Results: A total of 51 cases were included, 63% (32/51) of which comprised patients in the year of the pandemic (group A), while 37% (19/51) were patients attended in previous years (group B). In group A, 19% (6/32) of the patients presented PTB, 59% (16/32) had EPTB, and 31% (10/32) had PTB+EPTB. In group B, 42% (8/19) of the patients presented PTB, 42% (8/19) had EPTB, and 16% (3/19) had PTB+EPTB. Conclusion: Our study revealed more tuberculosis cases in the first year of the pandemic than in the same period of the previous year, with greater variation of sites affected by the disease, including rarer and more severe forms.

RESUMO Objetivo: O presente estudo teve como objetivo descrever as formas clínicas e o tempo de diagnóstico de novos casos de tuberculose e analisar estatisticamente as formas isoladas e combinadas da doença em crianças e adolescentes atendidos em um hospital universitário do Rio de Janeiro durante o primeiro ano da pandemia de COVID-19 no Brasil. Métodos: Este estudo transversal utilizou dados retrospectivos de crianças (0-9 anos) e adolescentes (10-18 anos) com tuberculose pulmonar (TBP), extrapulmonar (TBEP) e combinada (TBP + TBEP) acompanhados no ambulatório de janeiro de 2019 a março de 2021. Os dados categóricos foram analisados por estatística descritiva e expressos em frequência e proporções. As variáveis categóricas foram comparadas pelo teste Qui-quadrado e as variáveis numéricas pelo teste T de Student. Resultados: Foram incluídos 51 casos, sendo 63% (32/51) pacientes no ano da pandemia (grupo A) e 37% (19/51) pacientes atendidos em anos anteriores (grupo B). No grupo A, 19% (6/32) dos pacientes apresentavam TBP, 59% (16/32) TBEP e 31% (10/32) TBP+TBEP. No grupo B, 42% (8/19) dos pacientes apresentavam TBP, 42% (8/19) TBEP e 16% (3/19) TBP+TBEP. Conclusão: Nosso estudo evidenciou mais casos de tuberculose no primeiro ano da pandemia do que no mesmo período do ano anterior, com maior variação de locais acometidos pela doença, incluindo formas mais raras e mais graves.

Serum IgG Titers Against Toxoplasma gondii in Uninfected Infants Exposed In Utero to Toxoplasmosis.

OBJECTIVES: To describe the mean time of decrease of T. gondii IgG titers in uninfected infants exposed in utero to toxoplasmosis. METHODS: A retrospective cohort study was conducted between 2008-2017, among infants under 12 months and exposed in utero to toxoplasmosis. Serial monthly monitoring of serum IgG titers were done till undetectable levels. RESULTS: 240 infants with mean gestational age at diagnosis of 19.2 weeks were included in the study. The mean (range) time for IgG level to become undetectable was 7.9 (0.8-25.0) months. 14 infants became negative between 13-24 months. CONCLUSIONS: Majority of asymptomatic infants exposed in utero to T. gondii become seronegative before 12 months of age.

Personal and Network-Related Factors Associated to Diagnosis Disclosure Reactions for Children and Adolescents Living with HIV.

The process of human immunodeficiency virus (HIV) diagnosis disclosure for vertically infected young people living with HIV has proven decisive for acceptance/adherence to treatment. Herein, we present a cross-sectional study aiming at evaluating how individual and network related variables are associated with reactions to HIV disclosure among them. We used the egocentric approach with a structured questionnaire applied to individuals aged 15-25 years in an HIV referral center in Rio de Janeiro, Brazil. Outcome variable referred to adoption or not of risk behavior after diagnostic disclosure, was classified as "good"/"bad" reactions. Results showed that, of the 80 study participants, 25% reported a "bad reaction" to diagnostic disclosure, an outcome that was more common for patients with at least one friend in their social support network (OR 4.81; 95%CI [1.05-22.07]). In conclusion, a "bad reaction" to HIV serological disclosure may be associated with inadequate structure of the individual's social support network.

RESUMEN: El proceso de divulgación del diagnóstico del virus de inmunodeficiencia humana (VIH) es decisivo para la aceptación/adhesión a tratamiento de los jóvenes infectados verticalmente que viven con VIH. Presentamos un estudio transversal con el objetivo de evaluar cómo variables individuales y de red están asociadas con reacciones a la divulgación del VIH entre ellos. Utilizamos el enfoque egocéntrico por medio de un cuestionario estructurado aplicado a personas de 15-25 años en un Centro de Referencia para VIH en Río de Janeiro, Brasil. La variable de resultado se refiere a la adopción o no de comportamiento de riesgo después de la divulgación del diagnóstico, clasificadas como reacciones "buena"/"mala". Los resultados mostraron que, de los 80 participantes del estudio, el 25% reportó una "mala reacción" a la divulgación diagnóstica. Este resultado fue más común en pacientes con al menos un amigo en su red de apoyo social (OR:4.81; IC95% [1.05-22.07]). Como conclusión, una "mala reacción" a la divulgación serológica del VIH puede estar asociada con una estructura inadecuada de la red de apoyo social del individuo.

Congenital Toxoplasmosis: Missed Opportunities for Diagnosis and Prevention.

OBJECTIVES: Identify missed opportunities for the prevention and early diagnosis of congenital toxoplasmosis (CT) in infants followed up in a reference center for pediatric infectious diseases (PID) in Rio de Janeiro between January 2007 and December 2016. METHODS: Descriptive study including infants with CT, diagnosis established based on Brazil's Ministry of Health's criteria. All data regarding the infants and their mother's prenatal care were collected from the medical records of the Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG)-a tertiary public pediatric university hospital. The study enrolled infants aged between 0 and 12 months followed up in the PID department of IPPMG and with confirmed infection by Toxoplasma gondii in the period between January 2007 and December 2016. All patients with diagnosis of CT registered in the PID database of the IPPMG and admitted in the above-mentioned period were included in the study. Patients whose records were not available, or who went to just one clinic appointment were excluded. RESULTS: The obstetric history of all 44 women, whose infants (45) were diagnosed with CT, was analyzed. Their median age was 22 years. None had undergone preconception serological testing for toxoplasmosis. Only 20 (45%) of them started antenatal care during the first trimester of gestation, a total of 24 (55%) had more than six antenatal care visits, and 16% of those did not undergo serological testing for toxoplasmosis. None were adequately informed of preventive measures. The diagnosis of acute toxoplasmosis was made in 50% of these pregnancies but 32% of the women were not treated. Only 10 children of these mothers were adequately screened and treated at birth. CONCLUSION: Despite the existence of national recommendations, several opportunities were missed to prevent CT during the antenatal period and to diagnose and treat this condition in the neonatal period.

Calvarial tuberculosis: two cases in children.

Tuberculosis of the skull or calvarial tuberculosis (CTB) is rare. The literature until 2019 reported less than 60 cases of CTB in childhood. The authors describe two patients with CTB associated with other manifestations of TB, such as: spine and rib injuries, peripheral adenopathy, hepatic and splenic involvement who improved with chemotherapy. The patients were a four-year-old and an eight-year-old child, whose diagnoses were confirmed by histopathological, bacteriological or molecular investigation. Both were not infected with the human immunodeficiency virus (HIV) and did not need orthopedic treatment.

Factors associated with the development of Congenital Zika Syndrome: a case-control study.

BACKGROUND: We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS: This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12 days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS: Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21 years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio = 0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS: Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.

HIV Vertical transmission in Rio de Janeiro, Brazil - does the distance matter?

Mother-to-child transmission (MTCT) is the main route of transmission for HIV among under 5 children in Brazil. National data indicate that missed opportunities for HIV prevention of MTCT are still common in antenatal care (ANC). We studied variables related to target process indicators in a cohort of HIV exposed children. We used data from 1996 to 2013 related to HIV exposed uninfected and HIV-infected children attended in an HIV reference hospital in Rio de Janeiro, Brazil. Data were collected from baseline questionnaires applied to all children followed-up in the hospital. Gestational and perinatal history were extracted from the mother's ANC card. Infants were categorized according to dates of first HIV care at the unit (1996-2000, 2001-2006 and 2007-2013). Distances between recorded addresses and the nearest maternity/hospital were measured by Euclidean distance, the shortest car route calculated in Google Maps and the route of the available bus line. Of the 599 children who fulfilled the inclusion criteria, 178 (29.7%) were HIV-infected. Approximately 70% of infants exposed to the virus from 1996-2000 were infected, dropping to 15.2% from 2001-2006 and rebounding to 30.1% from 2007-2013. Birth cohort was associated with ANC, and mothers from 2007-2013 had a lower chance of attending ANC (OR = 0.16; 95%CI 0.08-0.30). In addition, when the distance home-birthplace was higher than 9.5 km, there was a lower chance that the mother had attended ANC (OR = 0.35; 95%CI 0.18-0.68). Birth cohort was associated to HIV and ANC, and our data showed that a reduction of ANC might be related to rebound in HIV cases. There seems to have an association between larger distances from home to the birthplace and absence of ANC, which suggests that ANC was being performed in the tertiary units instead of in the primary care facilities as recommended.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus / Persistência de anticorpos seguida de vacina conjugada meningocócica C em crianças e adolescentes infectados por vírus da imunodeficiência humana

Abstract Objective: HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU), aged 2-18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4) at baseline and at 12-18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02). 85 HIVI (44%) had undetectable viral load (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months after immunization (p = 0.14). Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12-18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

Resumo Objetivo: As pessoas infectadas pelo HIV (HIVI) estão sujeitas a infecção meningocócica e apresentam menor resposta a vacinas. São escassos os dados a respeito da persistência de longo prazo do anticorpo bactericida no soro humano (hSBA) após vacina conjugada meningocócica C (MCC) em HIVI jovens e visamos a descrever essa persistência em HIVI. Métodos: Foram recrutadas pessoas HIVI e pessoas não infectadas por HIV (HIVU), entre 2 e 18 anos, CD4 > 15%. A seroproteção (hSBA ≥ 1:4) basal aos 12-18 meses após a imunização foi avaliada e a associação dos diferentes fatores com a persistência de longo prazo foi calculada com a regressão logística. Resultados: Foram recrutados 145 HIVI e 50 HIVU e imunizados e sua idade média foi determinada em 11 anos (12 no grupo HIVI e 10 no grupo HIVU, valor de p = 0,02); 85 HIVI (44%) apresentaram carga viral indetectável (CVI). A taxa de seroproteção foi 27,2%: 24,1% no grupo HIVI e 36% no grupo HIVU 12-18 meses após imunização (p = 0,14). A imunidade basal [razão de chance (RC) = 7070, IC: 65,2-7666]; CVI no momento da participação (RC: 2,87, IC de 95%: 0,96-8,62) e renda familiar mais baixa (RC: 0,09, IC de 95%: 0,01-0,69) foram associadas a seroproteção entre as pessoas HIVI. Conclusão: A seroproteção aos 12-18 meses após única dose de MCC mostrou-se baixa em ambos os grupos e mais elevada entre as pessoas que apresentaram imunidade basal. Entre as pessoas HIVI, as vacinas devem ser administradas após a CVI ser atingida.

The cascade of care to prevent mother-to-child transmission in Rio de Janeiro, Brazil, 1996-2013: improving but still some way to go.

OBJECTIVE: To describe the cascade of care to HIV mother-to-child transmission (PMTCT) in a Rio de Janeiro reference paediatric clinic and evaluate the main factors possibly associated with HIV transmission. METHODS: Data on antenatal care (ANC), perinatal and neonatal assistance to HIV-infected and HIV-exposed but uninfected children assisted in the clinic from 1996 to 2013 were collected. The cascade of care was graphically demonstrated, and possible factors associated with HIV infection were described using regression models for bivariate and multivariate analysis. We imputed missing values of explanatory variables for the final model. RESULTS: A total of 989 children were included in the analysis: 211 were HIV and 778 HEU. Graphically, the HIV PMTCT cascade of care improved from 1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main factor independently associated with the HIV infection over time was breastfeeding. In the period 1996/2000, the lack of antiretroviral use during labour was associated HIV transmission. While in 2001/2007, other modes of delivery but elective Caesarean section, and lack of maternal antiretroviral use during ANC were associated with HIV transmission. In the last period, the main factor associated with transmission was the lack of maternal ANC. CONCLUSIONS: The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a problem, and better access to ANC is needed.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. METHODS: HIVI and HIV uninfected individuals (HIVU), aged 2-18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4) at baseline and at 12-18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. RESULTS: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value=0.02). 85 HIVI (44%) had undetectable viral load (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months after immunization (p=0.14). Baseline immunity (odds ratio [OR]=70.70, 95% CI: 65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI. CONCLUSION: Seroprotection at 12-18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil.

BACKGROUND: There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV-exposed but uninfected (HEU) children. The aim of this study was to evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first 2 years of life. METHODS: This cohort study was conducted among HEU infants born between 1996 and 2010 in Tertiary children's hospital in Rio de Janeiro, Brazil. Weight was measured by mechanical scale, and height was measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. RESULTS: A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared with infants exposed later: adjusted differences were -0.52 (95% confidence interval [CI]: -0.99 to -0.04, P = 0.02) at birth and -0.22 (95% CI: -0.47 to 0.04, P = 0.10) during follow-up. LAZ were lower during follow-up: -0.35 (95% CI: -0.63 to -0.08, P = 0.01). There were no differences in weight-for-length scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. CONCLUSIONS: In HEU children, early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

Healthcare-associated infections among neonates in Brazil.

OBJECTIVE: To describe the epidemiology of healthcare-associated infections (HAIs) among neonates. DESIGN: Prospective surveillance of HAIs was conducted during 2 years. Infections beginning within 48 hours of birth were defined as HAIs of maternal origin. Death occurring during an active episode of HAI was considered related to HAI. SETTING: Seven neonatal units located in three Brazilian cities. PATIENTS: All admitted neonates were included and observed until discharge. RESULTS: Twenty-two percent of 4,878 neonates had at least one HAI. The overall incidence density was 24.9 per 1,000 patient-days, and 28.1% of all HAIs were maternally acquired. HAI rates ranged from 12.3% in the group with a birth weight (BW) of more than 2,500 g to 51.9% in the group with a BW of 1,000 g or less. The main HAIs were bloodstream infection (BSI) and pneumonia. Coagulase-negative staphylococci, Enterobacter species, Staphylococcus aureus, and Klebsiella pneumoniae were the main pathogens. Forty percent of all deaths were related to HAI. Central venous catheter (CVC)-associated BSIs per 1,000 CVC-days ranged from 17.3 (BW, 1,501 to 2,500 g; device utilization [DU], 0.11) to 34.9 (BW, < or = 1,000 g; DU, 34.92). Ventilator-associated pneumonia per 1,000 ventilator-days ranged from 7.0 (BW, < or = 1,000 g; DU, 0.34) to 9.2 (BW, 1,001 to 1,500 g; DU, 0.14). CONCLUSIONS: The high proportion of HAIs of maternal origin highlights perinatal care issues in Brazil and the need to improve the diagnosis of neonatal HAIs. The very low BW group and device-associated infections should be priorities for prevention strategies in this population.

Nosocomial infection among children with symptomatic human immunodeficiency virus infection.

A prospective cohort study was conducted during a 15-month period to compare nosocomial infections (NIs) among pediatric patients without (n = 989 and with (n = 50) symptomatic human immunodeficiency virus (HIV) infection. Patients with symptomatic HIV infection presented higher overall NI incidence density rates (relative risk, 1.65; P= .0001), and may represent a population at high risk for the acquisition of NI.

Infection due to extended-spectrum beta-lactamase-producing Salmonella enterica subsp. enterica serotype infantis in a neonatal unit.

OBJECTIVE: To describe the investigation and control of an outbreak of extended-spectrum beta-lactamase producing Salmonella enterica subsp. enterica serotype Infantis in a neonatal unit in Brazil. METHODS: A case-control study for risk factors for Salmonella Infantis systemic infection, environmental cultures, and evaluation of staffing and overcrowding and an assessment of infection control practices were performed. RESULTS: During July 1998 to June 1999, 140 Salmonella Infantis culture-positive patients were identified in the neonatal unit. Presence of a peripheral intravascular catheter was identified as an independent risk factor (odds ratio = 4.98; 95% CI = 1.59-19.31; P =.01) and each 250-g increase in birth weight as a protective factor (odds ratio = 0.76; 95% CI = 0.57-0.95; P =.03). Hospital stay was significantly longer and costs higher in case patients than in control patients. Salmonella Infantis was isolated from multiple environmental sources. Neonatal unit personnel were observed to make several breaks in infection control practices. The unit was understaffed and overcrowded. Prompt case identification, cohorting of patients, enhanced staff hand hygiene, and environmental cleaning terminated the outbreak. CONCLUSIONS: Inadequate infection control practices, nursery overcrowding, and understaffing can have an adverse effect on patient morbidity, mortality rates, and hospital cost.