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.

Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed.

No abstract

BackgroundPneumonia 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.MethodWe 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).ResultsThere 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.ConclusionsSolar-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 numberACTRN12616001469404.

BackgroundPneumonia is the largest cause of child deaths in Papua New Guinea (PNG), and hypoxaemia is the major complication causing death in childhood pneumonia, and hypoxaemia is a major factor in deaths from many other common conditions, including bronchiolitis, asthma, sepsis, malaria, trauma, perinatal problems, and obstetric emergencies. A reliable source of oxygen therapy can reduce mortality from pneumonia by up to 35%. However, in low and middle income countries throughout the world, improved oxygen systems have not been implemented at large scale in remote, difficult to access health care settings, and oxygen is often unavailable at smaller rural hospitals or district health centers which serve as the first point of referral for childhood illnesses. These hospitals are hampered by lack of reliable power, staff training and other basic services.MethodsWe report the methodology of a large implementation effectiveness trial involving sustainable and renewable oxygen and power systems in 36 health facilities in remote rural areas of PNG. The methodology is a before–and after evaluation involving continuous quality improvement, and a health systems approach. We describe this model of implementation as the considerations and steps involved have wider implications in health systems in other countries.ResultsThe implementation steps include: defining the criteria for where such an intervention is appropriate, assessment of power supplies and power requirements, the optimal design of a solar power system, specifications for oxygen concentrators and other oxygen equipment that will function in remote environments, installation logistics in remote settings, the role of oxygen analyzers in monitoring oxygen concentrator performance, the engineering capacity required to sustain a program at scale, clinical guidelines and training on oxygen equipment and the treatment of children with severe respiratory infection and other critical illnesses, program costs, and measurement of processes and outcomes to support continuous quality improvement.ConclusionsThis study will evaluate the feasibility and sustainability issues in improving oxygen systems and providing reliable power on a large scale in remote rural settings in PNG, and the impact of this on child mortality from pneumonia over 3 years post–intervention. Taking a continuous quality improvement approach can be transformational for remote health services.