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Background: Pneumonia is the largest cause of child deaths in low-income countries. Lack of availability of oxygen in small rural hospitals results in avoidable deaths and unnecessary and unsafe referrals., Method: We evaluated a programme for improving reliable oxygen therapy using oxygen concentrators, pulse oximeters and sustainable solar power in 38 remote health facilities in nine provinces in Papua New Guinea. The programme included a quality improvement approach with training, identification of gaps, problem solving and corrective measures. Admissions and deaths from pneumonia and overall paediatric admissions, deaths and referrals were recorded using routine health information data for 2-4 years prior to the intervention and 2-4 years after. Using Poisson regression we calculated incidence rates (IRs) preintervention and postintervention, and incidence rate ratios (IRR)., Results: There were 18 933 pneumonia admissions and 530 pneumonia deaths. Pneumonia admission numbers were significantly lower in the postintervention era than in the preintervention era. The IRs for pneumonia deaths preintervention and postintervention were 2.83 (1.98-4.06) and 1.17 (0.48-1.86) per 100 pneumonia admissions: the IRR for pneumonia deaths was 0.41 (0.24-0.71, p<0.005). There were 58 324 paediatric admissions and 2259 paediatric deaths. The IR for child deaths preintervention and postintervention were 3.22 (2.42-4.28) and 1.94 (1.23-2.65) per 100 paediatric admissions: IRR 0.60 (0.45-0.81, p<0.005). In the years postintervention period, an estimated 348 lives were saved, at a cost of US$6435 per life saved and over 1500 referrals were avoided., Conclusions: Solar-powered oxygen systems supported by continuous quality improvement can be achieved at large scale in rural and remote hospitals and health care facilities, and was associated with reduced child deaths and reduced referrals. Variability of effectiveness in different contexts calls for strengthening of quality improvement in rural health facilities., Trial Registration Number: ACTRN12616001469404., Competing Interests: Competing interests: Apart from being funded through the Bill & Melinda Gates Foundation for the conduct of this work, none of the authors have any competing interests in regard to this manuscript., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Pneumonia and meningitis are common causes of severe childhood illness in Papua New Guinea (PNG). The etiology of both clinical conditions in PNG has not been recently assessed. Changes in lifestyle, provision and access to healthcare, antimicrobial utilization and resistance, and the national childhood vaccination schedule necessitate reassessment., Methods: A prospective case-control study was undertaken, enrolling children <5 years of age to determine the contemporary etiology of clinically defined moderate or severe pneumonia or suspected meningitis. Cases were identified following presentation for inpatient or outpatient care in Goroka town, the major population centre in the Eastern Highlands Province. Following enrolment, routine diagnostic specimens including blood, nasopharyngeal swabs, urine and (if required) cerebrospinal fluid, were obtained. Cases residing within one hour's drive of Goroka were followed up, and recruitment of healthy contemporaneous controls was undertaken in the cases' communities., Results: 998 cases and 978 controls were enrolled over 3 years. This included 784 cases (78.6%) with moderate pneumonia, 187 (18.7%) with severe pneumonia and 75 (7.5%) with suspected meningitis, of whom 48 (4.8%) had concurrent pneumonia. The median age of cases was 7.8 months (Interquartile range [IQR] 3.9-14.3), significantly lower than community controls, which was 20.8 months (IQR 8.2-36.4). Half the cases were admitted to hospital (500/998; 50.1%). Recruitment of cases and controls and successful collection of diagnostic specimens improved throughout the study, with blood volume increasing and rates of blood culture contamination decreasing. The overall case fatality rate was 18/998 (1.8%). Of cases eligible for follow-up, outcome data was available from 76.7%. Low but increasing coverage of Haemophilus influenzae type B conjugate vaccines on the national schedule was observed during the study period: three dose DTPw-HepB-Hib coverage in children >3 months increased from 14.9 to 43.0% and 29.0 to 47.7% in cases and controls (both p  < 0.001). Despite inclusion in the national immunization program in 2014, 2015 PCV13 three-dose coverage in cases and controls >3 months was only 4.0 and 6.5%., Conclusions: Recruitment of large numbers of pediatric pneumonia and meningitis cases and community controls in a third-world setting presents unique challenges. Successful enrolment of 998 cases and 978 controls with comprehensive clinical data, biological specimens and follow up was achieved. Increased vaccine coverage remains an ongoing health priority.

Although the WHO recommends all countries use International Classification of Diseases (ICD)-10 coding for reporting health data, accurate health facility data are rarely available in developing or low and middle income countries. Compliance with ICD-10 is extremely resource intensive, and the lack of real data seriously undermines evidence-based approaches to improving quality of care and to clinical and public health programme management. We developed a simple tool for the collection of accurate admission and outcome data and implemented it in 16 provincial hospitals in Papua New Guinea over 6 years. The programme was low cost and easy to use by ward clerks and nurses. Over 6 years, it gathered data on the causes of 96,998 admissions of children and 7128 deaths. National reports on child morbidity and mortality were produced each year summarising the incidence and mortality rates for 21 common conditions of children and newborns, and the lessons learned for policy and practice. These data informed the National Policy and Plan for Child Health, triggered the implementation of a process of clinical quality improvement and other interventions to reduce mortality in the neediest areas, focusing on diseases with the highest burdens. It is possible to collect large-scale data on paediatric morbidity and mortality, to be used locally by health workers who gather it, and nationally for improving policy and practice, even in very resource-limited settings where ICD-10 coding systems such as those that exist in some high-income countries are not feasible or affordable., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

With a mortality rate in the under-5 s of 93 per 1000 live births reported in the 1996 Demographic and Health Survey (DHS), Papua New Guinea (PNG) was at the time one of only four countries with stalled progress in child survival, and seemed destined to fail its national Millennium Development Goal (MDG) 4 target. However, accurate estimates have shown reductions in under-5 and infant mortality rates of 19% and 17% respectively, over 10 years from 1996 to 2006. In that period PNG adopted an integrated and coordinated approach to child health that includes all the essential interventions outlined in the Lancet's child survival series, under a framework consistent with the Western Pacific Regional Child Survival Strategy, associated with significant improvements in leadership and coordination of child health services by paediatricians at the provincial and national level. The reduction in child mortality since the mid-1990s is strong encouragement that such an approach can translate to real improvements. This paper outlines the recent advances in child health in PNG, identifying successful areas, and the challenges that lie ahead. There has been increased immunization coverage, introduction of vitamin A supplementation, bed-nets to prevent malaria, interventions to reduce mortality from acute respiratory infection, and improvements in the education of girls. These and improved leadership and coordination help to explain the recent significant gains in child survival.

We report three cases of meningo-encephalitis caused by Cryptococcous neoformans var. gattii in apparently immunocompetent children presenting to a provincial hospital in Papua New Guinea (PNG) over a nine-month period. After a postmortem diagnosis was made in the first case, a further two were identified quickly using Indian ink staining of cerebrospinal fluid (CSF). The second case had a complicated course and recovered after relapse. The third made a full recovery with appropriate antifungal therapy. Despite the fact that an environmental reservoir has not been established, cryptococcal meningo-encephalitis occurs regularly in PNG. In developing countries such as PNG, a lack of laboratory resources and limited therapeutic options can complicate the management of severe infections such as cryptococcosis. Nevertheless, with inexpensive diagnostic tests (such as Indian ink staining of CSF), a high index of suspicion and a pragmatic approach to antifungal therapy, good therapeutic outcomes can be achieved.

The colonization of Oceania occurred in two waves. By 32,000 BP, humans had reached New Guinea and settled all intervisible islands east to the Solomon Islands. Around 3,500 BP, a distinct intrusive group from Southeast Asia reached coastal New Guinea, integrated their components with indigenous resources, and gave rise to the Lapita Cultural Complex. Within 2,500 years, Lapita and its descendant cultures colonized the Pacific. To uncover the origin of the Lapita Cultural Complex, we analyzed the hypervariable region I of the mitochondrial deoxyribonucleic acid (mtDNA) in 219 individuals from eight East Sepik Province villages: two villages in each of four environmental zones. Same-zone villages spoke different languages: one Austronesian and three Papuan (Arapesh, Abelam, and Boiken). Our analysis examined whether language or geography better predicted gene flow. In general, language better predicted genetic affinities. Boiken villages across all four zones showed no significant genetic difference (F(ST) P value > 0.05). In contrast, the Austronesian village was significantly different to most other villages (P < 0.05). Only the mountains and coast showed zonal gene flow (P > 0.05). We interpret the data to reflect limited gene flow inland by Austronesians overshadowed by a regional displacement by inland Boiken speakers migrating seaward. These results are consistent with oral histories and ethnographic accounts.

To overcome the declining efficacy of the 4-aminoquinolines in Papua New Guinea, sulfadoxine/pyrimethamine (SP) was combined with the 4-aminoquinolines as the first line treatment for falciparum malaria since 2000. To assess how this change had affected SP resistant gene polymorphisms, we determined allele frequencies of dhfr and dhps in 113 Plasmodium falciparum isolates from Wewak, East Sepik of Papua New Guinea in 2002 and 2003. In dhfr, double mutant (ACNRNVI) was the predominant allele with a prevalence of 91%. We found a significant decrease of wild dhfr allele prevalence (7%) compared with that reported in the adjacent area of East Sepik called the Wosera region (57%), before the drug policy changed in 1990-1993. Between 2002 and 2003, the prevalence of this allele decreased from 15% to 3% (P=0.02). Two distinct microsatellite haplotypes flanking dhfr were found in isolates with dhfr double mutant, suggesting the selection of preexisting SP resistant parasites rather than a frequent occurrence of dhfr mutations. The dhfr/dhps quartet mutations (ACNRNVI in dhfr and SGEAA in dhps) were identified in six of the isolates (8%) from 2003. This genotype, which is associated with in vivo resistance to SP, has not been reported before in Papua New Guinea. These findings suggest that isolates resistant to SP were rapidly selected despite the use of the SP combination therapy, probably because of their preexisting high level of resistance to the 4-aminoquinoline partner drug.

The N86Y mutation in pfmdr1 is reported to play an additional role for the chloroquine resistance in Plasmodium falciparum isolates. However, not much has been done to clarify whether this mutation augments the level of chloroquine resistance in the isolates harboring pfcrt K76T mutation. We compared the in vitro chloroquine efficacy between pfcrt K76T mutant parasites with or without N86Y mutation from Papua New Guinea. A total of 57 isolates (4% sensitive, 14% borderline, and 82% resistant) were successfully tested in vitro for chloroquine sensitivity. We found a slightly higher effective concentration of chloroquine needed to inhibit P. falciparum by 50% (mean EC50=107 nM) in isolates with the pfcrt K76T+pfmdr1 N86Y than that in isolates with the pfcrt K76T+pfmdr1 N86 (EC50=88 nM), but this difference was not statistically significant. A significant non-random association was observed between the pfcrt K76T and pfmdr1 N86Y alleles. Our results suggest that the pfmdr1 N86Y mutation plays a compensatory role to chloroquine-resistant isolates under a chloroquine pressure while it may also augment the level of chloroquine resistance in the K76T parasites to a small extent.

The 27-bp deletion in the erythrocyte band 3 gene (B3Delta27) constitutes a genetic basis for Southeast Asian and Melanesian ovalocytosis. The distribution of B3Delta27 has been interpreted to reflect malaria selection or dispersal of the recent expansion of Austronesian-speaking populations. To explore these two hypotheses, we examined eight malarious populations of the East Sepik Province of Papua New Guinea (PNG) that speak both the Austronesian and Papuan languages. The B3Delta27 allele frequencies within populations were not positively correlated with malaria endemicities. In contrast, statistically significant geographical variations in the B3Delta27 allele distribution were observed. B3Delta27 was high (0.06-0.07) in the islands, intermediate (0.02-0.03) in coastal regions, but was absent or rare (0.00-0.01) in inland populations. Furthermore, the prevalence of the mitochondrial DNA region V 9-bp deletion, associated with the Austronesian expansion, was significantly correlated with that of B3Delta27. These results suggest that B3Delta27 was introduced by Austronesian-speaking people within the past 3,500 years and subsequently expanded to populations along the coasts and islands of PNG. This study highlights the contribution of population origins, patterns of gene flow, disease selection and genetic drift in determining the genetic compositions of present populations.

Aims: We assessed the disposition of oral amodiaquine (AQ) and CYP2C8 polymorphism in 20 children with falciparum malaria., Methods: AQ and DEAQ concentrations were determined with SPE-HPLC method. CYP2C8 genotypes were assessed by PCR-RFLP method., Results: AQ was not detectable beyond day 3 postdose. Cmax for DEAQ was reached in 3.0 days. The mean values for t1/2, MRT, and AUCtotal were 10.1 days, 15.5 days and 4512.6 microg l(-1) day, respectively. All the children were CYP2C8* homozygous., Conclusion: Our data are consistent with those previously reported, and the AQ regimen seems pharmacokinetically adequate in the absence of CYP2C8 polymorphism.

Aims: To investigate the epidemiology of illness among young infants at remote health clinics in a rural developing country, and to determine risk factors for mortality that might be used as triggers for emergency treatment or referral., Methods: Multi-site 12 month observational study of consecutive presentations of infants less than 2 months, and an investigation of neonates who died in one district without accessing health care., Results: Forty per cent of 511 young infant presentations occurred in the first week of life and most of these in the first 24 hours. Twenty five deaths were recorded: 18 in the health facilities and seven in villages. In addition there were eight stillbirths. Clinical signs predicting death were: not able to feed, fast respiratory rate, apnoea, cyanosis, "too small", "skin-cold", and severe abdominal distension. Signs indicating severe respiratory compromise were present in 25% of young infants; failure to give oxygen therapy was a modifiable factor in 27% of deaths within health facilities. A high proportion of seriously ill young infants were discharged from health facilities early without adequate follow up. A common reason for not seeking care for fatally ill neonates was the perception by parents that health staff would respond negatively to their social circumstances., Conclusions: Clinical signs with moderate positive predictive value for death may be useful triggers for emergency treatment and longer observation or urgent referral. The results of this study may be useful in planning strategies to address high neonatal mortality rates in developing countries.

The cytochrome P450 (CYP) isozyme CYP2C19 metabolizes clinically important drugs, including the anti-malarial proguanil currently used for multi-drug resistant Plasmodium falciparum malaria. CYP2C19 activity varies among geographical regions due to high frequencies of two null alleles (CYP2C19*2/*3) in Asian and especially Pacific populations. Previously, we reported an unprecedentedly high frequency of CYP2C19 poor metabolizers (PM) within populations of Vanuatu, which suggested even higher PM frequencies in Papua New Guinea. We examined CYP2C19 allele frequencies of three malarious populations from inland East Sepik Province, Papua New Guinea to evaluate this prediction and the use of proguanil in malaria treatment programs. These Papua New Guinean populations have PM frequencies intermediate between island South-east Asia and Vanuatu, most likely resulting from genetic drift during the settlement of the Pacific. This study highlights the medical consequences of population origins and the need for a better understanding of the genetic diversity of our global species., (Copyright 2003 Lippincott Williams & Wilkins)

Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a possible change of the current first-line treatment of uncomplicated malaria with chloroquine alone (amodiaquine for children under five years) to chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the therapeutic efficacy of the new drug combination in Papua New Guinea, a study was carried out in 1998-1999 at five hospital outpatient departments. From the 513 patients enrolled for the study, 95 defaulted from follow-up. Of the remaining 418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients who did not have an ACR, 3 (0.7% of the total) developed severe signs in the first 24 hours and were treated in hospital; they were regarded as early treatment failures. The remaining 16 did not complete the study on the basis of various exclusion criteria but were not excluded from the analysis. From these results it was concluded that the combination was effective and a decision was taken in May 2000 to introduce the two-drug combination regimens as the standard first-line treatment of uncomplicated malaria, including falciparum malaria, in Papua New Guinea.

We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.