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Weak preservation of local neutral substitution rates across mammalian genomes
No full textBACKGROUND: The rate at which neutral (non-functional) bases undergo substitution is highly dependent on their location within a genome. However, it is not clear how fast these location-dependent rates change, or to what extent the substitution rate patterns are conserved between lineages. To address this question, which is critical not only for understanding the substitution process but also for evaluating phylogenetic footprinting algorithms, we examine ancestral repeats: a predominantly neutral dataset with a significantly higher genomic density than other datasets commonly used to study substitution rate variation. Using this repeat data, we measure the extent to which orthologous ancestral repeat sequences exhibit similar substitution patterns in separate mammalian lineages, allowing us to ascertain how well local substitution rates have been preserved across species. RESULTS: We calculated substitution rates for each ancestral repeat in each of three independent mammalian lineages (primate - from human/macaque alignments, rodent - from mouse/rat alignments, and laurasiatheria - from dog/cow alignments). We then measured the correlation of local substitution rates among these lineages. Overall we found the correlations between lineages to be statistically significant, but too weak to have much predictive power (r2 <5%). These correlations were found to be primarily driven by regional effects at the scale of several hundred kb or larger. A few repeat classes (e.g. 7SK, Charlie8, and MER121) also exhibited stronger conservation of rate patterns, likely due to the effect of repeat-specific purifying selection. These classes should be excluded when estimating local neutral substitution rates. CONCLUSION: Although local neutral substitution rates have some correlations among mammalian species, these correlations have little predictive power on the scale of individual repeats. This indicates that local substitution rates have changed significantly among the lineages we have studied, and are likely to have changed even more for more diverged lineages. The correlations that do persist are too weak to be responsible for many of the highly conserved elements found by phylogenetic footprinting algorithms, leading us to conclude that such elements must be conserved due to selective forces
Venezuela en het socialisme van de 21e eeuw; de moeizame opbouw van de "partij van de revolutie"
No full textClinical presentation and aetiologies of acute or complicated headache among HIV-seropositive patients in a Ugandan clinic
No full textABSTRACT: BACKGROUND: We set out to define the relative prevalence and common presentations of the various aetiologies of headache within an ambulant HIV-seropositive adult population in Kampala, Uganda. METHODS: We conducted a prospective study of adult HIV-1-seropositive ambulatory patients consecutively presenting with new onset headaches. Patients were classified as focal-febrile, focal-afebrile, non-focal-febrile or non-focal-afebrile, depending on presence or absence of fever and localizing neurological signs. Further management followed along a pre-defined diagnostic algorithm to an endpoint of a diagnosis. We assessed outcomes during four months of follow up. RESULTS: One hundred and eighty patients were enrolled (72% women). Most subjects presented at WHO clinical stages III and IV of HIV disease, with a median Karnofsky performance rating of 70% (IQR 60-80).The most common diagnoses were cryptococcal meningitis (28%, n = 50) and bacterial sinusitis (31%, n = 56). Less frequent diagnoses included cerebral toxoplasmosis (4%, n = 7), and tuberculous meningitis (4%, n = 7). Thirty-two (18%) had other diagnoses (malaria, bacteraemia, etc.). No aetiology could be elucidated in 28 persons (15%). Overall mortality was 13.3% (24 of 180) after four months of follow up. Those without an established headache aetiology had good clinical outcomes, with only one death (4% mortality), and 86% were ambulatory at four months. CONCLUSION: In an African HIV-infected ambulatory population presenting with new onset headache, aetiology was found in at least 70%. Cryptococcal meningitis and sinusitis accounted for more than half of the cases
Ranking malaria risk factors to guide malaria control efforts in African highlands
No full textINTRODUCTION: Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies. METHODS AND FINDINGS: A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through "classification and regression trees", an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density. CONCLUSIONS: In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors
Risk factors for obstetric fistula in the Far North Province of Cameroon
No full textOBJECTIVE: To describe the circumstances of occurrence and identify potential risk factors for obstetric fistula in northern Cameroon. METHODS: A case series study of 42 obstetric fistula patients seeking services at the Provincial Hospital of Maroua, Cameroon, between May 2005 and August 2007. Structured interviews were conducted prior to surgical intervention. RESULTS: Among obstetric fistula patients, 60% had lived with obstetric fistula for more than 5 years at the time of surgery. Eighty-one percent of patients had received no formal education and 86% were teenagers at their first delivery. Regarding the pregnancy and delivery preceding the occurrence of the fistula, 50% of women reported that they had received no prenatal care and 76% were in labor for more than 12 hours. The majority (83%) of women delivered a stillborn baby. CONCLUSIONS: Obstetric fistula patients in the Far North Province of Cameroon had a low level of education, were married at a young age, and had poor access to quality maternal healthcare services
Molecular diagnostics of intestinal parasites in returning travellers
No full textA new diagnostic strategy was assessed for the routine diagnosis of intestinal parasites in returning travellers and immigrants. Over a period of 13 months, unpreserved stool samples, patient characteristics and clinical data were collected from those attending a travel clinic. Stool samples were analysed on a daily basis by microscopic examination and antigen detection (i.e. care as usual), and compared with a weekly performed multiplex real-time polymerase chain reaction (PCR) analysis on Entamoeba histolytica, Giardia lamblia, Cryptosporidium and Strongyloides stercoralis. Microscopy and antigen assays of 2,591 stool samples showed E. histolytica, G. lamblia, Cryptosporidium and S. stercoralis in 0.3, 4.7, 0.5 and 0.1% of the cases, respectively. These detection rates were increased using real-time PCR to 0.5, 6.0, 1.3 and 0.8%, respectively. The prevalence of ten additional pathogenic parasite species identified with microscopy was, at most, 0.5%. A pre-selective decision tree based on travel history or gastro-intestinal complaints could not be made. With increased detection rates at a lower workload and the potential to extend with additional parasite targets combined with fully automated DNA isolation, molecular high-throughput screening could eventually replace microscopy to a large extent
Specific detection and identification of African trypanosomes in bovine peripheral blood by means of a PCR-ELISA assay
No full textThe aim of the present study was to develop a PCR-ELISA assay for the detection and differentiation of the main African pathogen trypanosomal species present in peripheral blood of cattle. The proposed methodology allows to specifically differentiate Trypanosoma congolense, Trypanosoma vivax and the subgenus Trypanozoon, by means of a sensitive universal PCR amplifying trypanosome DNA followed by an ELISA-based hybridization with three highly specific probes. The semi-nested PCR had a sensitivity of 15 fg, 15 fg, and 0.15 fg of DNA from T. vivax, T. congolense, and Trypanosoma brucei brucei, respectively that is sufficient to detect parasites in blood during the chronic phase of the disease. Biotinylated second round asymmetric PCR amplification products were used in an ELISA set up using three species-specific probes for the diagnosis of T. congolense (type Riverine, Kilifi or Savannah), T. vivax and T. brucei brucei. A factor O.D. of 0.082 was determined on blood samples from bovines (n=18) from a non-endemic area in Africa. In a pilot study of blood samples of naturally and experimentally Trypanosoma infected cattle previously characterized by PCR-RFLP (n=42), a high rate of concordance (93.3%) was found between PCR-RFLP and PCR-ELISA. There is a good ratio between positive and negative O.D. values (3.00 vs. 0.1) and the technique can also be used to distinguish mixed infections
Mosquito vectors of disease: spatial biodiversity, drivers of change, and risk; final report
No full textMortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo
No full textOBJECTIVE:: We aimed to describe factors associated with mortality among children receiving antiretroviral treatment (ART) at a pediatric hospital in Kinshasa, Democratic Republic of the Congo. RESULTS:: Two hundred ninety-nine children, /=2 opportunistic infections before ART initiation, severe immunosuppression as defined by age-specific CD4 count or percentage criteria, hemoglobin <9 g/dL, oral candidiasis, and severe malnutrition. In multivariate analysis, weight for age z-score [hazard ratio (HR): 0.39; 95% CI: 0.27-0.61; P < 0.001] and oral candidiasis (HR: 5.86; 95% CI: 2.34-14.65; P = 0.0002) were independent predictors of mortality. Suspected septic shock was the most common cause of death (n = 12/31, 38.7%). CONCLUSIONS:: Children receiving ART in this resource-poor setting were at the highest risk of dying in the first 2 months of ART, particularly when they presented with malnutrition or oral candidiasis. Optimal timing of ART initiation during nutritional rehabilitation should be determined. Promotion of early care seeking, strengthened health care, and prevention services are important to further improve outcome of pediatric ART in resource-poor settings
Improvement of the patient flow in a large urban clinic with high HIV seroprevalence in Kampala, Uganda
No full textAntiretroviral treatment roll-out programmes in Africa often have difficulties to cope with the increasing number of clients. Based on the findings of a survey carried out in 2005 that showed long waiting times, innovative organizational changes (nurse visits and pharmacy-only refill visits) were introduced in our clinic. In August 2007, the survey was repeated to evaluate the impact of these changes. During both surveys we used the same standardized questionnaire. In 2007, 400 patients visited the clinic on the study day compared to 250 in 2005. The median time spent at the clinic decreased from 157 minutes in 2005 (range 22-426) to 124 minutes (15-314). All the waiting times for different services decreased except the time between the visit to the triage nurse and the doctors' visit. A similar methodology could be used by other health services to evaluate and compare different models of care