Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.

Association Between Antenatal Exposure to Zika Virus and Anatomical and Neurodevelopmental Abnormalities in Children.

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

Cardiac findings in infants with in utero exposure to Zika virus- a cross sectional study.

BACKGROUND: Antenatal exposure to Zika virus (ZIKV) is related to severe neurological manifestations. A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the mother or infant. The objective of this study is to report echocardiographic (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV. METHODOLOGY: Cross sectional study of cardiologic assessments of infants born between November 2015 and January 2017 with confirmed vertical exposure to ZIKV in Rio de Janeiro, Brazil. RESULTS: The study enrolled 120 children with a median age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97 children (80,8%) through positive maternal polymerase chain reaction (PCR) results during pregnancy or a positive PCR result at birth; 23 additional children (19.2%) had maternal positive PCR results during pregnancy and postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO. Thirteen infants (10.8%) had major cardiac defects (atrial septal defect, ventricular septal defect, patent ductus arteriosus). None of the defects were severe. The frequency of major defects was higher in infants whose mothers had a rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System (CNS) imaging postnatally or were preterm. CONCLUSIONS: Infants with in utero ZIKV exposure have a higher prevalence of major cardiac defects, however none were severe enough to require immediate intervention. For this reason, guidelines for performance of postnatal ECHO in this population should follow general newborn screening guidelines, which significantly reduces the burden of performing emergent fetal or neonatal ECHOs in a setting where resources are not available, such as most Brazilian municipalities.

Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.

Neurosurgical implications of Pott's puffy tumor in children and adolescents.

INTRODUCTION: Pott's puffy tumor (PPT) is rare and usually seen as a complication of frontal sinusitis resulting in subperiosteal abscess of the frontal bone with underlying osteomyelitis. PPT is potentially severe and can lead to life-threatening intracranial complications. PATIENTS AND METHODS: The authors present a series of six pediatric patients diagnosed with PPT and intracranial complications between 1999 and 2012. There were five boys and one girl, and the mean age at diagnosis was 11.8 years. All patients presented with frontal swelling, headache, and fever. Two patients had lowered level of consciousness and severe hemodynamic instability. RESULTS: All patients had epidural abscess, and one also presented subdural empyema. Five patients underwent drainage of all associated abscesses, bone resection, and sinusitis treatment. One was treated conservatively with broad-spectrum antibiotics, and no surgical intervention was required. All patients fully recovered their neurologic status, without further complications.

Lipodystrophy syndrome and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy.

OBJECTIVE: To describe lipid profile, body shape changes, and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy. METHODS: We investigated 43 children and adolescents being treated with this therapy at the outpatient clinic of pediatric infectious diseases of Instituto Fernandes Figueira/Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Values of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were determined. We also performed glucose tolerance test and analyzed body fat distribution, nutritional status, dietary intake, and family history of cardiovascular risk. The statistical analysis was performed using Student's t test. Significance level of p-value was lower than 0.05. RESULTS: We found lipid abnormality in 88.3% and body shape change in 13.9% of the cases. Nutritional status was adequate (81.3%) in most of the study population. Cholesterol intake in children older than 9 years was above the recommended value. CONCLUSION: Prevalence of dyslipidemia and, therefore, risk for cardiovascular diseases were high during the use of highly active antiretroviral therapy.

Síndrome da lipodistrofia e fatores de risco cardiovasculares em crianças e adolescentes infectados pelo HIV/AIDS em uso de terapia antirretroviral de alta potência / Lipodystrophy syndrome and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy

Objetivo: Descrever o perfil lipídico, alterações da conformação corporal e fatores de risco cardiovasculares em crianças e adolescentes infectados pelo HIV/AIDS, tratados com terapia antirretroviral de alta potência. Métodos: Foram estudadas 43 crianças e adolescentes em uso dessa terapia atendidas no ambulatório de doenças infecciosas em Pediatria do Instituto Fernandes Figueira/Fundação Oswaldo Cruz, Rio de Janeiro (RJ). Foram realizadas dosagens de colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade, triglicerídeos, teste de tolerância à glicose e avaliada a distribuição de gordura corporal, estado nutricional, ingestão dietética e história familiar de risco cardiovascular. As análises estatísticas foram realizadas com o teste t de Student. O nível de significância estatístico do p foi menor que 0,05. Resultados: Observou-se alteração lipídica em 88,3 por cento e de conformação corporal em 13,9 por cento dos casos. O estado nutricional foi adequado na maioria (81,3 por cento) da população do estudo. A ingestão de colesterol em crianças com mais de 9 anos foi acima do recomendado. Conclusão: A prevalência de dislipidemia e, consequentemente, o risco para doenças cardiovasculares foram altos durante o uso de terapia antirretroviral de alta potência.

Objective: To describe lipid profile, body shape changes, and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy. Methods: We investigated 43 children and adolescents being treated with this therapy at the outpatient clinic of pediatric infectious diseases of Instituto Fernandes Figueira/Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Values of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were determined. We also performed glucose tolerance test and analyzed body fat distribution, nutritional status, dietary intake, and family history of cardiovascular risk. The statistical analysis was performed using Student’s t test. Significance level of p-value was lower than 0.05. Results: We found lipid abnormality in 88.3 percent and body shape change in 13.9 percent of the cases. Nutritional status was adequate (81.3 percent) in most of the study population. Cholesterol intake in children older than 9 years was above the recommended value. Conclusion: Prevalence of dyslipidemia and, therefore, risk for cardiovascular diseases were high during the use of highly active antiretroviral therapy.

Positive reaction for cysticercosis and multicentric anaplastic oligoastrocytoma.

INTRODUCTION: An unusual case of positive immunological testing for cysticercosis in the cystic fluid obtained from an anaplastic oligoastrocytoma is presented. CASE REPORT: A 15-year-old boy was admitted with multiple brain lesions. The biggest was a cyst with a mural node and neurocysticercosis was suspected. In order to relieve intracranial pressure, the cyst was punctured and the immunological testing for cysticercosis was positive, reinforcing the clinical suspicion and leading to a clinical trial with albendazole and steroids. As the patient deteriorated the cystic lesion was removed and the diagnosis of anaplastic oligoastrocytoma was established. A second lesion was eventually approached and the histopathological diagnosis of both specimens concurred. DISCUSSION: Although some authors believe that chronic inflammatory changes following neurocysticercosis could induce the formation of brain tumors, this association may be a mere coincidence. In our case no clinical evidence of a prior infestation by Cysticercus was found. In fact, an exhaustive examination of the specimens did not reveal any areas of inflammatory reaction. We believe that the similarity of the glioma and cysticercosis antigens may be the cause of the positive reactions in the cystic fluid.