The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria.

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4.

A learning health systems approach to improving the quality of care for patients in South Asia.

Poor quality of care is a leading cause of excess morbidity and mortality in low- and middle- income countries (LMICs). Improving the quality of healthcare is complex, and requires an interdisciplinary team equipped with the skills to design, implement and analyse setting-relevant improvement interventions. Such capacity is limited in many LMICs. However, training for healthcare workers in quality improvement (QI) methodology without buy-in from multidisciplinary stakeholders and without identifying setting-specific priorities is unlikely to be successful. The Care Quality Improvement Network (CQIN) was established between Network for Improving Critical care Systems and Training (NICST) and University College London Centre for Perioperative Medicine, with the aim of building capacity for research and QI. A two-day international workshop, in collaboration with the College of Surgeons of Sri Lanka, was conducted to address the above deficits. Innovatively, the CQIN adopts a learning health systems (LHS) approach to improving care by leveraging information captured through the NICST electronic multi-centre acute and critical care surveillance platform. Fifty-two delegates from across the CQIN representing clinical, civic and academic healthcare stakeholders from six countries attended the workshop. Mapping of care processes enabled identification of barriers and drivers to the delivery of care and facilitated the selection of feasible QI methods and matrices. Six projects, reflecting key priorities for improving the delivery of acute care in Asia, were collaboratively developed: improving assessment of postoperative pain; optimising sedation in critical care; refining referral of deteriorating patients; reducing surgical site infection after caesarean section; reducing surgical site infection after elective general surgery; and improving provision of timely electrocardiogram recording for patients presenting with signs of acute myocardial infarction. Future project implementation and evaluation will be supported with resources and expertise from the CQIN partners. This LHS approach to building capacity for QI may be of interest to others seeing to improve care in LMICs.

Malaria in southeast Bangladesh: a descriptive study.

Malaria in Asia is thought to be grossly under-reported and this is evident from previously published statistics from Bangladesh. Malaria screening data from four Upazillas was analysed alongside census data to assess the trends in malaria incidence over time and distribution of malaria by age and gender. Malaria incidence in this area has decreased by around two thirds since 2003, although control measures were not significantly increased until 2005. Malaria occurred in people of all ages with the highest incidence being in young adults. This is consistent with higher occupational exposure in this group. The probability of being screened for malaria decreased with age suggesting significant numbers of adults with malaria may be being missed.

Activation of the cytokine network in a patient with AIDS and the recalcitrant erythematous desquamating disorder.

An AIDS patient with the recalcitrant erythematous desquamating (RED) disorder, a presumed variant of the Staphylococcus aureus toxic shock syndrome that is characterized by relapses, skin involvement, and variable multiple-organ involvement, is described. A strain of S. aureus producing toxic shock syndrome toxin 1 was isolated from the patient, but no antibodies to this exotoxin were detectable before and during the most severe episode of the RED disorder. Levels of cytokines were measured during episodes and at other times. Tumor necrosis factor and interleukin 6 were detectable only during the most severe exacerbation of the disorder; this finding suggests a pathogenetic role for these cytokines.