RESUMO
Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%). On the Thailand-Myanmar border we investigated the contribution of genetic risk factors to high bilirubin levels in the first month of life in 1596 neonates enrolled in a prospective observational birth cohort study. Lower gestational age (<38 weeks), mutations in the genes encoding glucose-6-phosphate dehydrogenase (G6PD) and uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1 were identified as the main independent risk factors for NH in the first week, and for prolonged jaundice in the first month of life. Population attributable risks (PAR%) were 61.7% for lower gestational age, 22.9% for hemi or homozygous and 9.9% for heterozygous G6PD deficiency respectively, and 6.3% for UGT1A1*6 homozygosity. In neonates with an estimated gestational age ≥ 38 weeks, G6PD mutations contributed PARs of 38.1% and 23.6% for "early" (≤ 48 hours) and "late" (49-168 hours) NH respectively. For late NH, the PAR for UGT1A1*6 homozygosity was 7.7%. Maternal excess weight was also a significant risk factor for "early" NH while maternal mutations on the beta-globin gene, prolonged rupture of membranes, large haematomas and neonatal sepsis were risk factors for "late" NH. For prolonged jaundice during the first month of life, G6PD mutations and UGT1A1*6 mutation, together with lower gestational age at birth and presence of haematoma were significant risk factors. In this population, genetic factors contribute considerably to the high risk of NH. Diagnostic tools to identify G6PD deficiency at birth would facilitate early recognition of high risk cases.
RESUMO
BACKGROUND: Pneumonia is a significant cause of morbidity and mortality in the developing world. Viruses contribute significantly to pneumonia burden, although data for low-income and tropical countries are scarce. The aim of this laboratory-enhanced, hospital-based surveillance was to characterise the epidemiology of respiratory virus infections among refugees living on the Thailand-Myanmar border. METHODS: Maela camp provides shelter for ~45,000 refugees. Inside the camp, a humanitarian organisation provides free hospital care in a 158-bed inpatient department (IPD). Between 1st April 2009 and 30th September 2011, all patients admitted to the IPD with a clinical diagnosis of pneumonia were invited to participate. Clinical symptoms and signs were recorded and a nasopharyngeal aspirate (NPA) collected. NPAs were tested for adenoviruses, human metapneumovirus (hMPV), influenza A & B, and RSV by PCR. RESULTS: Seven hundred eight patient episodes (698 patients) diagnosed as pneumonia during the enhanced surveillance period were included in this analysis. The median patient age was 1 year (range: < 1-70), and 90.4% were aged < 5 years. At least one virus was detected in 53.7% (380/708) of episodes. Virus detection was more common in children aged < 5 years old (<1 year: OR 2.0, 95% CI 1.2-3.4, p = 0.01; 1-4 years: OR 1.4, 95% CI 0.8-2.3, p = 0.2). RSV was detected in 176/708 (24.9%); an adenovirus in 133/708 (18.8%); an influenza virus in 68/708 (9.6%); and hMPV in 33/708 (4.7%). Twenty-eight episodes of multiple viral infections were identified, most commonly adenovirus plus another virus. RSV was more likely to be detected in children <5 years (OR 12.3, 95% CI 3.0-50.8, p = 0.001) and influenza viruses in patients ≥5 years (OR 2.8, 95% CI 1.5-5.4, p = 0.002). IPD treatment was documented in 702/708 cases; all but one patient received antimicrobials, most commonly a beta-lactam (amoxicillin/ampicillin +/-gentamicin in 664/701, 94.7%). CONCLUSIONS: Viral nucleic acid was identified in the nasopharynx in half the patients admitted with clinically diagnosed pneumonia. Development of immunisations targeting common respiratory viruses is likely to reduce the incidence of pneumonia in children living refugee camps and similar settings.
