The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype −261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52–0.84, Pnominal 0.0009, Pcorrected 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70–1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49–0.81, Pnominal 0.0004, Pcorrected 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants −261C and −261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM −261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.

Background: The Home Management of Malaria (HMM) strategy was developed using chloroquine, a now obsolete drug, which has been replaced by artemisinin-based combination therapy (ACT) in health facility settings. Incorporation of ACT in HMM would greatly expand access to effective antimalarial therapy by the populations living in underserved areas in malaria endemic countries. The feasibility and acceptability of incorporating ACT in HMM needs to be evaluated.

This paper estimates the total cost to women and their families associated with a spontaneous vaginal delivery and five types of 'near-miss' obstetric complication in Benin and Ghana, and assesses affordability in relation to household cash expenditure. A retrospective evaluation of costs was carried out among 121 mothers in three hospitals in Ghana. A prospective evaluation of costs was undertaken among 420 pregnant women in two hospitals in Benin. Information was collected on the cost of travel to the facilities and of direct medical and non-medical costs incurred during their stay in hospital. In Benin, costs ranged from an average of 15 US dollars for a spontaneous delivery to 256 US dollars for a near-miss complication caused by dystocia. In Ghana, average costs ranged from 18 US dollars for a spontaneous vaginal delivery to 115 US dollars for a near-miss complication caused by haemorrhage. Medical costs accounted for the largest share of total costs, mainly drugs and medical supplies in Ghana and costs of the delivery and any surgical intervention in Benin. Payments associated with a spontaneous vaginal delivery amounted to at least 2% of annual household cash expenditure in both countries. In the case of severe obstetric complications, costs incurred reached a high of 34% of annual household cash expenditure in Benin. The economic burden of hospital-based delivery care in Ghana and Benin is likely to deter or delay women's use of health services. Should a woman develop severe obstetric complications while in labour, the relatively high costs of hospital care could have a potentially catastrophic impact on the household budget.

This paper outlines the practical steps involved in setting up and running multi-professional, in-depth case reviews of 'near miss' obstetrical complications. It draws on lessons learned in 12 referral hospitals in Benin, Côte d'Ivoire, Ghana and Morocco. A range of feasibility indicators are presented which measured the implementation and frequency of audit activities, the quality of participation, adherence to the planned protocol for the near-miss audits, the quality of audit discussions and the sustainability of the project. Although the principles of the audit approach were well accepted and implemented everywhere, near-miss audits appeared most successful in first referral level hospitals. Contextual factors that determine the successful implementation of near-miss audit include staff finding adequate time for audit activities, financial incentives to groups rather than individuals, involvement of senior staff and hospital managers, the ease of communication in smaller units, the employment of social workers for the incorporation of women's views at audits, and the strength of external support provided by the research team. The poor quality of information recorded in case notes was recognized everywhere as a deficiency, but did not present a major obstacle to effective case reviews. Ownership and leadership within the hospital, more easily achieved in the first-level referral hospitals, were probably the most important determinants of successful implementation. Sustainability requires a commitment to audit from policy makers and managers at higher levels of the health system and some devolution of resources for implementing recommendations.

Current endeavour focuses on human genetic factors that contribute to susceptibility to or protection from tuberculosis (TB). Monocytes are crucial in containing Mycobacterium tuberculosis infection, and the monocyte chemoattractant protein-1 (MCP-1) cytokine plays a role in their recruitment to the site of infection. The G allele of the MCP-1 promoter polymorphism at position -2581 relative to the ATG transcription start codon has been described to be associated in Mexican and Korean TB patients with increased susceptibility to TB. We genotyped this and additional MCP-1 variants in sample collections comprising more than 2000 cases with pulmonary TB and more than 2300 healthy controls and 332 affected nuclear families from Ghana, West Africa, and more than 1400 TB patients and more than 1500 controls from Russia. In striking contrast to previous reports, MCP-1 -2581G was significantly associated with resistance to TB in cases versus controls [odds ratio (OR) 0.81, corrected P-value (P(corr)) = 0.0012] and nuclear families (OR 0.72, P(corr) = 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P = 0.86). Our and other results do not support an association of MCP-1 -2581 with TB. In the Ghanaian population, eight additional MCP-1 polymorphisms were genotyped. MCP-1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, P(corr) = 0.00017) and in the affected families (OR 0.7, P(corr) = 0.004). Linkage disequilibrium (LD) and logistic regression analyses indicate that, in Ghanaians, the effect results exclusively from the MCP-1 -362 variant, whereas the effect of -2581 may in part be explained by its LD with -362.