Genetic host factors play a substantial role in susceptibility to and severity of malaria, which continues to cause at least one million deaths per year. Recently, members of the toll-like receptor (TLR) family have been shown to be involved in recognition of the etiologic organism Plasmodium falciparum: The glycosylphosphatidylinositol anchor induces signaling in host cells via TLR-2 and -4, whereas hemozoin-induced immune activation involves TLR-9. Binding of microbial ligands to the respective TLRs triggers the release of proinflammatory cytokines via the TLR͞IL-1 receptor (TIR) domain and may contribute to the host response in malaria, including cytokine induction and fever. In a case-control study among 870 Ghanaian children, we examined the influence of TLR-2, -4, and -9 polymorphisms in susceptibility to severe malaria. TLR-2 variants common in Caucasians and Asians were completely absent. However, we found a rare previously undescribed mutation (Leu658Pro), which impairs signaling via TLR-2. We failed to detect any polymorphisms within the TLR-9 Toll͞IL-1 receptor domain. Two frequent TLR-9 promoter polymorphisms did not show a clear association with malaria severity. In contrast, the TLR-4-Asp299Gly variant occurred at a high rate of 17.6% in healthy controls and was even more frequent in severe malaria patients (24.1%, P < 0.05). Likewise, TLR-4-Thr399Ile was seen in 2.4% of healthy children and in 6.2% of patients (P ‫؍‬ 0.02). TLR-4-Asp299Gly and TLR-4-Thr399Ile conferred 1.5-and 2.6-fold increased risks of severe malaria, respectively. These findings suggest TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation.single-nucleotide polymorphisms ͉ innate immunity ͉ Plasmodium falciparum

For frequency counts, the situation of extra zeros often arises in biomedical applications. This is demonstrated with count data from a dental epidemiological study in Belo Horizonte (the Belo Horizonte caries prevention study) which evaluated various programmes for reducing caries. Extra zeros, however, violate the variance±mean relationship of the Poisson error structure. This extra-Poisson variation can easily be explained by a special mixture model, the zero-in¯ated Poisson (ZIP) model. On the basis of the ZIP model, a graphical device is presented which not only summarizes the mixing distribution but also provides visual information about the overall mean. This device can be exploited to evaluate and compare various groups. Ways are discussed to include covariates and to develop an extension of the conventional Poisson regression. Finally, a method to evaluate intervention effects on the basis of the ZIP regression model is described and applied to the data of the Belo Horizonte caries prevention study.

Background Sub-Saharan Africa faces a rapid spread of diabetes mellitus type 2 (DM2) but its potentially specific characteristics are inadequately defined. In this hospital-based study in Kumasi, Ghana, we aimed at characterizing clinical, anthropometric, socio-economic, nutritional and behavioural parameters of DM2 patients and at identifying associated factors. Methods Between August 2007 and June 2008, 1466 individuals were recruited from diabetes and hypertension clinics, outpatients, community, and hospital staff. Fasting plasma glucose (FPG), serum lipids and urinary albumin were measured. Physical examination, anthropometry, and interviews on medical history, socio-economic status (SES), physical activity and nutritional behaviour were performed. Results The majority of the 675 DM2 patients (mean FPG, 8.31 mmol/L) was female (75%) and aged 40-60 years (mean, 55 years). DM2 was known in 97% of patients, almost all were on medication. Many had hypertension (63%) and microalbuminuria (43%); diabetic complications occurred in 20%. Overweight (body mass index > 25 kg/m 2 ), increased body fat (> 20% (male), > 33% (female)), and central adiposity (waist-to-hip ratio > 0.90 (male), > 0.85 (female)) were frequent occurring in 53%, 56%, and 75%, respectively. Triglycerides were increased (≥ 1.695 mmol/L) in 31% and cholesterol (≥ 5.17 mmol/L) in 65%. Illiteracy (46%) was high and SES indicators generally low. Factors independently associated with DM2 included a diabetes family history (adjusted odds ratio (aOR), 3.8; 95% confidence interval (95%CI), 2.6-5.5), abdominal adiposity (aOR, 2.6; 95%CI, 1.8-3.9), increased triglycerides (aOR, 1.8; 95%CI, 1.1-3.0), and also several indicators of low SES. Conclusions In this study from urban Ghana, DM2 affects predominantly obese patients of rather low socio-economic status and frequently is accompanied by hypertension and hyperlipidaemia. Prevention and management need to account for a specific risk profile in this population.

Acinetobacter spp. have frequently been reported to be the causative agents of hospital outbreaks. The circumstances of some outbreaks demonstrated the long survival of Acinetobacter in a dry, inanimate environment. In laboratory experiments, we compared the abilities of five Acinetobacter baumannii strains, three Acinetobacter sp. strains from the American Type Culture Collection (ATCC), one Escherichia coli ATCC strain, and one Enterococcus faecium ATCC strain to survive under dry conditions. Bacterial solutions of the 10 strains were inoculated onto four different material samples (ceramic, polyvinyl chloride, rubber, and stainless steel) and stored under defined conditions. We investigated the bacterial counts of the material samples immediately after inoculation, after drying, and after 4 h, 1 day, and 1, 2, 4, 8, and 16 weeks of storage. A statistical model was used to distribute the 40 resulting curves among four types of survival curves. The type of survival curve was significantly associated with the bacterial strain but not with the material. The ability of the A. baumannii strains to survive under dry conditions varied greatly and correlated well with the source of the strain. Strains isolated from dry sources survived better than those isolated from wet sources. An outbreak strain that had caused hospital-acquired respiratory tract infections survived better than the strains from wet sources, but not as well as strains from dry sources. Resistance to dry conditions may promote the transmissibility of a strain, but it is not sufficient to make a strain an epidemic one. However, in the case of an outbreak, sources of Acinetobacter must be expected in the dry environment.

The symptoms of severe malaria and their contribution to mortality were assessed in 290 children in northern Ghana. Common symptoms were severe anemia (55%), prostration (33%), respiratory distress (23%), convulsions (20%), and impaired consciousness (19%). Age influenced this pattern. The fatality rate was 11.2%. In multivariate analysis, circulatory collapse, impaired consciousness, hypoglycemia, and malnutrition independently predicted death. Children with severe malaria by the current World Health Organization (WHO) classification, but not by the previous one (1990), showed relatively mild clinical manifestations and a low case fatality rate (3.2%). In hospitalized children with severe malaria in northern Ghana, severe anemia is the leading manifestation, but itself does not contribute to mortality. In this region, malnutrition and circulatory collapse were important predictors of fatal malaria. The current WHO criteria serve well in identifying life-threatening disease, but also include rather mild cases that may complicate the allocation of immediate care in settings with limited resources.

The high frequency of ␣ ؉ -thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, ␣ ؉ -thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous ␣ ؉ -thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [ IntroductionSevere Plasmodium falciparum malaria is a major cause of death in sub-Saharan Africa, particularly in children younger than 5 years of age. 1 Interindividual variation in susceptibility and manifestation can be attributed partially to innate host factors such as the sickle cell trait. [2][3][4] According to Haldane's "malaria hypothesis," 5 these factors are subject to selection in endemic regions because of the resistance they confer against malaria. Another hemoglobin disorder, ␣ ϩ -thalassemia, reaches a prevalence of more than 80% in parts of Southeast Asia and Melanesia. [6][7][8] Heterozygosity is characterized by the commonly deletional loss of one of the duplicated ␣-globin genes (Ϫ␣/␣␣) and slight hematologic changes. Homozygous individuals (Ϫ␣/Ϫ␣) have mild microcytic anemia. 9 In Melanesia, the geographic correlation between the prevalence of ␣ ϩ -thalassemia and malarial endemicity suggests natural selection. 6 In one case-control study in Papua New Guinea, the risk of severe malaria was reduced by 60% and 34% in homozygous and heterozygous children, respectively. 7 In sub-Saharan Africa, ␣ ϩ -thalassemia affects up to 50% of the population, but protection against uncomplicated or severe malaria could not be demonstrated so far. 3,9,10 We examined whether ␣ ϩ -thalassemia confers protection from severe falciparum malaria in Ghana. Study design Patients and controlsWe conducted an unmatched case-control study in the city of Tamale and its vicinity, northern Ghana, during the rainy season 2002 (August to November). In the study area, malaria is hyperendemic (F.P.M., unpublished observations, December 1, 2003). Ethical clearance was obtained from the Ethics Committee, University for Development Studies, Tamale, and informed consent, from the participants' parents. We recruited 290 children with severe malaria according to WHO definition at Tamale Teaching Hospital. 1,11 An additional 11 children with severe malaria were detected during the survey mentioned later in this paragraph and classified as cases. In the 301 index patients, symptoms defining severe malaria were as follows: severe anemia, 57%; prostration, 32%; respiratory distress, 22%; multiple convulsions, 20%; impaired consciousness, 19%; jaundice, 11%; circulatory collapse, 3%; and hemoglobinuria, 3%. Controls were 2107 children from Tamale and the surrounding districts who were recruited following a 2-stage cluster sampling st...

Aitken acceleration, boundary problem, mixtures, asymptotic distribution of likelihood ratio,

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