A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults

Background: Severe malaria (SM) syndromes caused by Plasmodium falciparum infection result in major morbidity and mortality each year. However, only a fraction of P. falciparum infections develop into SM, implicating host genetic factors as important determinants of disease outcome. Previous studies indicate that tumour necrosis factor (TNF) and lymphotoxin alpha (LT alpha) may be important for the development of cerebral malaria (CM) and other SM syndromes

Normal spirometry, gas transfer and lung volume values in Papua, Indonesia

Spirometry is an efficient and clinically useful tool in the diagnosis and management of chronic lung disease. It relies on an appreciation of normal lung function that can vary between populations. In order to improve the utility of spirometry, gas transfer and lung volume measures for clinical and research use in Papua, Indonesia, we determined lung function in Papuan and non-Papuan Indonesian adults who did not have evidence of lung disease. A cross-sectional survey of Papuan and non-Papuan Indonesians 18 years or older with no history of chronic cough or recent wheeze was made. Spirometry, gas transfer and total lung capacity (TLC) were determined and regression models developed for normal values. The spirometry values were similar but not directly comparable to similar studies in Papua New Guinea populations. Papuan highland residents demonstrated independently greater values of gas transfer and total lung capacity in comparison to lowland Papuans. Values for lung function in apparent respiratory health were shown to differ between Papuan and non-Papuan Indonesian populations and in comparison to reference values de-rived from non-Indonesian populations. Differences in age-related decline in lung function would suggest that simple proportional correction based on values derived from non-Indonesian popula-tions may be inappropriate and would support the development of similar reference values in other populations. Whether differences seen here are innate or occur as a consequence of in-utero and post-partum environmental exposure remains to be accurately elucidated

Pulmonary tuberculosis, impaired lung function, disability and quality of life in a high-burden setting

SETTING: Tuberculosis treatment clinic in Papua, Indonesia. OBJECTIVE: To document the impact of pulmonary tuberculosis (PTB) on lung function, exercise tolerance and quality of life (QOL). DESIGN: A prospective cohort study of 115 patients with smear-positive PTB followed for 6 months. Demographics, disease history, sputum microbiology, spirometry, 6-minute weight.walk distance (6MWWD) and QOL (modified St George's Respiratory Questionnaire) were measured at diagnosis and at 2 and 6 months. Analysis was restricted to the 69/115 (60%) subjects who attended all follow-up visits. RESULTS: Subjects who attended all visits were less likely than the full cohort to be of Papuan ethnicity (P < 0.05), were more likely to be cured (P < 0.001) and had better lung function at diagnosis (P < 0.05). Significant lung function impairment (forced expiratory volume in 1 second [FEV1] <60% predicted) was found in 27/69 (39%) at diagnosis. Although this fell during treatment (P < 0.01), 17/69 (24.6%) had persisting significant lung function impairment at treatment completion. As lung function recovered, exercise tolerance (6MWWD) rose by 12.3% (P < 0.001) and QOL improved (P < 0.001). CONCLUSION: In a high-burden setting, PTB causes prolonged, significant impairment of lung function, exercise tolerance and QOL. Current measures of disease burden are likely to underestimate the true impact of disease. Earlier diagnosis and disease-modifying treatments may reduce the long-term impact of PTB

Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans

Background. Age and host genetics are important determinants of malaria severity. Lymphotoxin-alpha (LT alpha) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LT alpha production contribute to other acute vascular diseases and may contribute to malaria pathogenesis