Etiology of child mortality in Goroka, Papua New Guinea: a prospective two-year study.

OBJECTIVE: To collect accurate data on disease- and microbial-specific causes and avoidable factors in child deaths in a developing country. METHODS: A systematic prospective audit of deaths of children seen at Goroka Hospital in the highlands of Papua New Guinea was carried out. Over a 24-month period, we studied 353 consecutive deaths of children: 126 neonates, 186 children aged 1-59 months, and 41 children aged 5-12 years. FINDINGS: The most frequent age-specific clinical diagnoses were as follows: for neonates--very low birth weight, septicaemia, birth asphyxia and congenital syphilis; for children aged 1-59 months--pneumonia, septicaemia, marasmus and meningitis; and for children aged 5-12 years--malignancies and septicaemia. At least one microbial cause of death was identified for 179 (50.7%) children and two or more were identified for 37 (10.5%). Nine microbial pathogens accounted for 41% of all childhood deaths and 76% of all deaths that had any infective component. Potentially avoidable factors were identified for 177 (50%) of deaths. The most frequently occurring factors were as follows: no antenatal care in high-risk pregnancies (8.8% of all deaths), very delayed presentation (7.9%), vaccine-preventable diseases (7.9%), informal adoption or child abandonment leading to severe malnutrition (5.7%), and lack of screening for maternal syphilis (5.4%). Sepsis due to enteric Gram-negative bacilli occurred in 87 (24.6%). The strongest associations with death from Gram- negative sepsis were adoption/abandonment leading to severe malnutrition, village births, and prolonged hospital stay. CONCLUSIONS: Reductions in child mortality will depend on addressing the commonest causes of death, which include disease states, microbial pathogens, adverse social circumstances and health service failures. Systematic mortality audits in selected regions where child mortality is high may be useful for setting priorities, estimating the potential benefit of specific and non-specific interventions, and providing continuous feedback on the quality of care provided and the outcome of health reforms.

Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial.

BACKGROUND: Pneumonia is the most frequent cause of child mortality in less-developed countries. We aimed to establish whether the combination of benzylpenicillin and gentamicin or chloramphenicol would be better as first-line treatment in children with severe pneumonia in Papua New Guinea. METHODS: We did an open randomised trial in which we enrolled children aged 1 month to 5 years of age who fulfilled the WHO criteria for very severe pneumonia and who presented to hospitals in two provinces. Children were randomly assigned to receive chloramphenicol (25 mg/kg 6 hourly) or benzylpenicillin (50 mg/kg 6 hourly) plus gentamicin (7.5 mg/kg daily) by intramuscular injection. The primary outcome measure was a good or an adverse outcome. FINDINGS: 1116 children were enrolled; 559 children were treated with chloramphenicol and 557 with benzylpenicillin and gentamicin. At presentation the median haemoglobin oxygen saturation was 71% (IQR 57-77) for those allocated chloramphenicol and 69% (55-77) for those allocated penicillin and gentamicin. 147 (26%) children treated with chloramphenicol and 123 (22%) treated with penicillin and gentamicin had adverse outcomes (p=0.11). 36 children treated with chloramphenicol and 29 treated with penicillin and gentamicin died. More children treated with chloramphenicol than penicillin and gentamicin represented with severe pneumonia within 1 month of hospital discharge (p=0.03). INTERPRETATION: For children with severe pneumonia in less-developed countries the probability of a good outcome is similar if treated with chloramphenicol or with the combination of benzylpenicillin and gentamicin.

Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial.

A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinal fluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used.

Clinical presentation of subacute sclerosing panencephalitis in Papua New Guinea.

Eighty-three children presented at Goroka Base Hospital in the Eastern Highlands Province (EHP) of Papua New Guinea over a period of 3 years and 9 months between February 1997 and November 2000 were confirmed to have subacute sclerosing panencephalitis (SSPE). Confirmation of the diagnosis was based on the demonstration of high titres of measles antibodies in the cerebrospinal fluid and/or serum in association with clinical features supportive of SSPE, including characteristic electroencephalographic changes and amplification of measles virus genome by reverse transcriptase polymerase chain reaction in some cases. The mean cerebrospinal fluid and serum enzyme immunoassay antibody levels among the SSPE patients were 38 250 and 860 580, respectively. The mean age of onset of SSPE was 7.9 +/- 2.6 years and ranged between 2 and 14 years. The overall male to female ratio was 1.2:1 and 1.4:1 for EHP.

Molecular analysis of measles virus genome derived from SSPE and acute measles patients in Papua, New Guinea.

A very high annual incidence of 56 per million population below the age of 20 years for subacute sclerosing panencephalitis (SSPE) has been reported from Papua New Guinea (PNG). In a more recent study, we have confirmed this unusual high incidence for Eastern Highlands Province (EHP) of PNG. In the study, it was observed that the vaccination rate among SSPE patients registered at Goroka Base General Hospital (GBGH) in EHP was higher than that of other infants in the province in recent years. To identify the measles virus (MV) responsible for SSPE in EHP, sequence analysis of hypervariable region of the N gene was performed from 13 MV genomes: 2 amplified from clinical specimens of SSPE patients and 11 from acute measles patients. In 2 cases among the 11 with acute measles, nucleotide sequence of the entire H gene derived from isolated viruses was determined. Both nucleotide sequence and phylogenetic tree analyses showed that the amplified MV cDNAs were closely related to one another and belonged to the D3 genotype though they were different from any previously reported MV sequences. No genome sequences of vaccine strains were detected. These findings suggest that the MV strains prevailing in the highlands of PNG belong to genotype D3 of the MV and this wild-type MV rather than the vaccine strains was likely to be responsible for SSPE in these patients.