Identification of polymorphic motifs using probabilistic search algorithms. (33/208)

The problem of identifying motifs comprising nucleotides at a set of polymorphic DNA sites, not necessarily contiguous, arises in many human genetic problems. However, when the sites are not contiguous, no efficient algorithm exists for polymorphic motif identification. A search based on complete enumeration is computationally inefficient. We have developed probabilistic search algorithms to discover motifs of known or unknown lengths. We have developed statistical tests of significance for assessing a motif discovery, and a statistical criterion for simultaneously estimating motif length and discovering it. We have tested these algorithms on various synthetic data sets and have shown that they are very efficient, in the sense that the "true" motifs can be detected in the vast majority of replications and in a small number of iterations. Additionally, we have applied them to some real data sets and have shown that they are able to identify known motifs. In certain applications, it is pertinent to find motifs that contain contrasting nucleotides at the sites included in the motif (e.g., motifs identified in case-control association studies). For this, we have suggested appropriate modifications. Using simulations, we have discovered that the success rate of identification of the correct motif is high in case-control studies except when relative risks are small. Our analyses of evolutionary data sets resulted in the identification of some motifs that appear to have important implications on human evolutionary inference. These algorithms can easily be implemented to discover motifs from multilocus genotype data by simple numerical recoding of genotypes.  (+info)

MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. (34/208)

Major histocompatibility complex (MHC) variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or frequency-dependent selection. However, empirical support for these hypotheses under natural conditions is rare. In this study, we investigated the genetic constitution of the functionally important MHC class II gene (DRB exon 2) and the parasite load in a population of the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Fifty-eight individuals were genetically examined and the endoparasite load was quantified by counting fecal helminth eggs by using a modified McMaster technique. Thirty-four animals (58.6%) were infected. We identified 20 different MHC alleles with high levels of sequence divergence between alleles. Particularly, the antigen-binding sites revealed a significant higher rate of nonsynonymous substitutions (d(N)) than synonymous substitutions (d(S)), giving strong evidence of balancing selection. Heterozygosity did influence the infection status (being infected or not) and the individual fecal egg count (FEC) value with significantly higher values observed in homozygous individuals. Furthermore, a positive relationship was found between specific alleles and parasite load. The allele Rhpu-DRB*1 significantly occurred more frequently in infected individuals and in individuals with high FEC values (high parasite load). Individuals with the allele Rhpu-DRB*1 had a 1.5-fold higher chance of being infected than individuals without this allele (odds ratio test, P < 0.05). Contrarily, the allele Rhpu-DRB*8 significantly occurred more frequent in individuals with low FEC values. Our results support the hypotheses that MHC polymorphism in R. pumilio is maintained through pathogen-driven selection acting by both heterozygosity advantage and frequency-dependent selection.  (+info)

Adherence to management guidelines in acute respiratory infections and diarrhoea in children under 5 years old in primary health care in Botswana. (35/208)

OBJECTIVE: To evaluate health care providers' adherence to management guidelines for acute respiratory infection and diarrhoea in children under 5 years old in Botswana primary health care. DESIGN: Cross-sectional prospective field survey. Data collection was carried out through observation of consecutive consultations at 30 randomly assigned clinics and health posts in three purposely chosen districts. STUDY PARTICIPANTS: This study comprises 185 cases of acute respiratory infection and 85 cases of diarrhoea. MAIN MEASURE: Criteria for acceptable standards of history taking and physical examination for acute respiratory infection and diarrhoea were defined as well as criteria for categorizing the appropriateness of antibiotic prescription. The percentage of oral dehydration salts provided in cases of diarrhoea was calculated. RESULTS: Acute respiratory infection and diarrhoea accounted for 270 (including 15 missing cases) of all main diagnoses (n = 539). In 262 cases (97%) health care providers were nurses or enrolled nurses; in 3% family welfare educators. Acceptable history taking, physical examination, and both combined in acute respiratory infection was found in 113 (63%), 32 (18%), and 28 (16%), and in diarrhoea in 45 (58%), 26 (34%) and 20 (26%) cases, respectively. Antibiotics were prescribed in 76 of 255 (30%) cases. Prescription was assessed as inappropriate in 56 of 76 (74%) of all cases; in 41 of 52 (79%) cases with acute respiratory infection, in none of the pneumonia cases, and in all 15 cases of diarrhoea. Oral rehydration salts were prescribed in 74 (87%) of the diarrhoea cases. CONCLUSIONS: Health care providers' adherence to guidelines on history taking was suboptimal in acute respiratory infection and diarrhoea but poor on examination in both conditions. A high level of inappropriate antibiotic prescription was found in acute respiratory infection and diarrhoea. Overall, there is considerable scope for improving diagnostic and therapeutic management of these major childhood diseases in Botswana primary health care.  (+info)

Public-private partnerships and antiretroviral drugs for HIV/AIDS: lessons from Botswana. (36/208)

The African Comprehensive HIV/AIDS Partnerships (ACHAP) played a major role in initiating Botswana's antiretroviral (ARV) program in 2001. ACHAP is a prominent public-private partnership involving Merck and its foundation, the Bill and Melinda Gates Foundation, and the government of Botswana. This paper analyzes ACHAP's efforts to assist Botswana with its ARV program, the first and most advanced in sub-Saharan Africa. It identifies five features of the model and shows how they contributed to the ARV program. It also raises questions about ACHAP's role in scaling up and sustaining the program, as Botswana faces the challenges of treating growing numbers of HIV-infected people.  (+info)

Establishment of a public antiretroviral treatment clinic for adults in urban Botswana: lessons learned. (37/208)

Countries in sub-Saharan Africa are under significant pressure to open large-scale, public antiretroviral treatment clinics. Many lessons have been learned in Botswana, where the first public antiretroviral treatment clinic in Africa was established. The availability of core, well-trained medical staff will be the primary factor that limits a rapid scale-up of antiretroviral treatment programs.  (+info)

Use of rainfall and sea surface temperature monitoring for malaria early warning in Botswana. (38/208)

Improved prediction, prevention, and control of epidemics is a key technical element of the Roll Back Malaria partnership. We report a methodology for assessing the importance of climate as a driver of inter-annual variability in malaria in Botswana, and provide the evidence base for inclusion of climate information in a national malaria early warning system. The relationships of variability in rainfall and sea surface temperatures (SSTs) to malaria incidence are assessed at the national level after removing the impact of non-climatic trends and a major policy intervention. Variability in rainfall totals for the period December-February accounts for more than two-thirds of the inter-annual variability in standardized malaria incidence in Botswana (January-May). Both rainfall and annual malaria anomalies in December-February are significantly related to SSTs in the eastern Pacific, suggesting they may be predictable months in advance using seasonal climate forecasting methodologies.  (+info)

Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. (39/208)

BACKGROUND: We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum. METHODS: Adults participated if they had a history of cough > or =2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for >7 days. Observed maximum serum concentrations were compared with published normal ranges. RESULTS. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have >4 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels (P<.05 for all). The associations with noncavitary pulmonary disease (P=.12) and HIV infection (P=.07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin. CONCLUSIONS: These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.  (+info)

Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk. (40/208)

BACKGROUND: The ability of highly active antiretroviral therapy (HAART) to reduce human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described. METHODS: We compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART (nevirapine, lamivudine, and zidovudine) and women who did not receive HAART. RESULTS: Women in the HAART group received treatment for a median of 98 days (range, 67-222 days) at the time of breast-milk sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with 9 (36%) of 25 women who did not receive HAART (P=.0001). This finding remained significant in a multivariate logistic-regression model (P = .0006). The whole-milk HIV-1 DNA load was unaffected by HAART. Of women who received HAART, 13 (50%) of 26 had HIV-1 DNA loads <10 copies/10(6) cells, compared with 15 (65%) of 23 who did not receive HAART (P = .39). CONCLUSIONS: HAART suppressed cell-free HIV-1 RNA in breast milk and may therefore reduce mother-to-child transmission (MTCT) of HIV-1 via breast-feeding. However, HAART initiated during pregnancy or early after delivery had no apparent effect on cell-associated HIV-1 DNA loads in breast milk. Clinical trials to determine MTCT among breast-feeding women receiving HAART are needed.  (+info)