Showing papers by "Makerere University published in 2009"

Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis

Abstract: Background Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. Methods We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2–seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup ...

Perceptions of aging across 26 cultures and their culture-level associates.

Abstract: College students (N=3,435) in 26 cultures reported their perceptions of age-related changes in physical, cognitive, and socioemotional areas of functioning and rated societal views of aging within their culture. There was widespread cross-cultural consensus regarding the expected direction of aging trajectories with (a) perceived declines in societal views of aging, physical attractiveness, the ability to perform everyday tasks, and new learning; (b) perceived increases in wisdom, knowledge, and received respect; and (c) perceived stability in family authority and life satisfaction. Cross-cultural variations in aging perceptions were associated with culture-level indicators of population aging, education levels, values, and national character stereotypes. These associations were stronger for societal views on aging and perceptions of socioemotional changes than for perceptions of physical and cognitive changes. A consideration of culture-level variables also suggested that previously reported differences in aging perceptions between Asian and Western countries may be related to differences in population structure.

A systematic review of factors influencing fertility desires and intentions among people living with HIV/AIDS: implications for policy and service delivery.

Abstract: With availability of antiretroviral treatments, HIV is increasingly recognised as a chronic disease people live with for many years. This paper critically reviews the current literature on fertility desires and reproductive intentions among people living with HIV/AIDS (PLHIV) and critiques the theoretical frameworks and methodologies used. A systematic review was conducted using electronic databases: ISI Web of Knowledge, Science Direct, Proquest, Jstor and CINAHL for articles published between 1990 and 2008. The search terms used were fertility desire, pregnancy, HIV, reproductive decision making, reproductive intentions, motherhood, fatherhood and parenthood. Twenty-nine studies were reviewed. Fertility desires were influenced by a myriad of demographic, health, stigma-associated and psychosocial factors. Cultural factors were also important, particularly in Sub-Saharan Africa and Asia. Future research that examines fertility desires among PLHIV should include cultural beliefs and practices in the theoretical framework in order to provide a holistic understanding and to enable development of services that meet the reproductive needs of PLHIV.

Community health workers for ART in sub-Saharan Africa: learning from experience--capitalizing on new opportunities.

Abstract: Low-income countries with high HIV/AIDS burdens in sub-Saharan Africa must deal with severe shortages of qualified human resources for health. This situation has triggered the renewed interest in community health workers, as they may play an important role in scaling-up antiretroviral treatment for HIV/AIDS by taking over a number of tasks from the professional health workers. Currently, a wide variety of community health workers are active in many antiretroviral treatment delivery sites. This article investigates whether present community health worker programmes for antiretroviral treatment are taking into account the lessons learnt from past experiences with community health worker programmes in primary health care and to what extent they are seizing the new antiretroviral treatment-specific opportunities. Based on a desk review of multi-purpose community health worker programmes for primary health care and of recent experiences with antiretroviral treatment-related community health workers, we developed an analytic framework of 10 criteria: eight conditions for successful large-scale antiretroviral treatment-related community health worker programmes and two antiretroviral treatment-specific opportunities. Our appraisal of six community health worker programmes, which we identified during field work in Ethiopia, Malawi and Uganda in 2007, shows that while some lessons from the past have been learnt, others are not being sufficiently considered and antiretroviral treatment-specific opportunities are not being sufficiently seized. In particular, all programmes have learnt the lesson that without adequate remuneration, community health workers cannot be retained in the long term. Yet we contend that the apparently insufficient attention to issues such as quality supervision and continuous training will lead to decreasing quality of the programmes over time. The life experience of people living with HIV/AIDS is still a relatively neglected asset, even though it may give antiretroviral treatment-related community health worker programmes better chances of success than their predecessors and may be crucially important for adherence and retention in large-scale antiretroviral treatment programmes. Community health workers as a community-based extension of health services are essential for antiretroviral treatment scale-up and comprehensive primary health care. The renewed attention to community health workers is thus very welcome, but the scale-up of community health worker programmes runs a high risk of neglecting the necessary quality criteria if it is not aligned with broader health systems strengthening. To achieve universal access to antiretroviral treatment, this is of paramount importance and should receive urgent attention.

Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda.

Abstract: OBJECTIVE: Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second-line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring. DESIGN: Observational cohort. METHODS: Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year and every 6 months thereafter. HIV-1 viral loads were performed every 6 months. RESULTS: A total of 1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4-29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load more than 400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 viral load > 400 copies/ml) during follow-up. CONCLUSION: Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 viral load being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting.

Application of Superabsorbent Polymers for Improving the Ecological Chemistry of Degraded or Polluted Lands

Abstract: About 3.5 billion ha of land, which amounts to almost 30% of the total solid land of the world, has been degraded by human activities. The ecological restoration of these lands is a major challenge for mankind since they are the only option left for increasing the amount of arable land and producing food for the ever growing worldwide population. One common feature of these degraded lands is the fact that their organic soil matter is degraded also. Rainfall therefore, changes from a blessing to a menace since it is not kept in the soil and therefore causes erosion. A solution for the restoration of these lands could be the application of superabsorbent polymers (SAPs) to these soils. These substances are like ‘artificial humus’ as they are hydrophilic and contain carboxylic groups. This enables them to bind cations and water. They have the following advantages for the restoration of degraded lands. They increase the plant available water in the soil which enables the plants to survive longer under water stress. SAP amendment to soils reduces the evapotranspiration rate of the plants. They induce a significantly higher growth rate in plants growing on SAP amended soil. They bind heavy metals and mitigate their action on plants. They mitigate the effects of salinity. The benefits of SAP amendment to soils substantially outweigh their costs.

Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children.

Abstract: Background Limited tools exist to identify which individuals infected with Plasmodium falciparum are at risk of developing serious complications such as cerebral malaria (CM). The objective of this study was to assess serum biomarkers that differentiate between CM and non-CM, with the long-term goal of developing a clinically informative prognostic test for severe malaria.

The dilemma of safe sex and having children: challenges facing HIV sero-discordant couples in Uganda.

Abstract: Background: Sixty percent of new HIV infections in Uganda occur in stable relationships between HIV discordant couples. Given the importance of fertility in Uganda, we hypothesized that unsafe sexual practices may be used to found a family/replace a dead child. Thus, we explored sexual practices to understand to what extent these are influenced by the desire to have children and the implications for HIV transmission among discordant couples. Methods: A cross-sectional survey of 114 HIV discordant couples in Kampala, and in-depth interviews with 15 purposively selected couples. Quantitative data were analysed using STATA. Multivariate logistic regression analysis done to identify factors associated with consistent condom use. Thematic content analysis of qualitative data was done using NVIVO 2. Results: Participants wanting children and those with multiple sexual partners were less likely to use condoms (Adj OR 0.51, and 0.36 respectively). Three of the five types of sexual practices used by couples do not allow pregnancy to occur. Main reasons for wanting a child included: ensuring lineage continuity and posterity, securing relationships and pressure from relatives to reproduce. Challenges included: risk of HIV transmission to partner and child, lack of negotiating power for safer sex, failure of health systems to offer safe methods of reproduction Conclusions: HIV sero-discordant couples with strong desire for childbearing have a dilemma of risking HIV infection or infecting their spouse. Some risk transmission of HIV infection to reproduce. We need to address gender issues, risky behaviour and reproductive

Direct susceptibility testing for multi drug resistant tuberculosis: a meta-analysis.

Abstract: One of the challenges facing the tuberculosis (TB) control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB). Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples are needed. This study compared the sensitivity, specificity and time to results of four direct drug susceptibility testing tests with the conventional indirect testing for detection of resistance to rifampicin and isoniazid in M. tuberculosis. The four direct tests included two in-house phenotypic assays – Nitrate Reductase Assay (NRA) and Microscopic Observation Drug Susceptibility (MODS), and two commercially available tests – Genotype® MTBDR and Genotype® MTBDRplus (Hain Life Sciences, Nehren, Germany). A literature review and meta-analysis of study reports was performed. The Meta-Disc software was used to analyse the reports and tests for sensitivity, specificity, and area under the summary receiver operating characteristic (sROC) curves. Heterogeneity in accuracy estimates was tested with the Spearman correlation coefficient and Chi-square. Eighteen direct DST reports were analysed: NRA – 4, MODS- 6, Genotype MTBDR® – 3 and Genotype® MTBDRplus – 5. The pooled sensitivity and specificity for detection of resistance to rifampicin were 99% and 100% with NRA, 96% and 96% with MODS, 99% and 98% with Genotype® MTBDR, and 99% and 99% with the new Genotype® MTBDRplus, respectively. For isoniazid it was 94% and 100% for NRA, 92% and 96% for MODS, 71% and 100% for Genotype® MTBDR, and 96% and 100% with the Genotype® MTBDRplus, respectively. The area under the summary receiver operating characteristic (sROC) curves was in ranges of 0.98 to 1.00 for all the four tests. Molecular tests were completed in 1 – 2 days and also the phenotypic assays were much more rapid than conventional testing. Direct testing of rifampicin and isoniazid resistance in M. tuberculosis was found to be highly sensitive and specific, and allows prompt detection of MDR TB.

Temporal rainfall variability in the Lake Victoria Basin in East Africa during the twentieth century

Abstract: Water resources systems are designed and operated on assumption of stationary hydrology. Existence of trends and other changes in the data invalidates this assumption, and detection of the changes in hydrological time series should help us revise the approaches used in assessing, designing and operating our systems. In addition, trend and step change studies help us understand the impact of man’s activities (e.g. urbanisation, deforestation, dam construction, agricultural activities, etc.) on the hydrological cycle. Trends and step changes in the seasonal and annual total rainfall for 20 stations in the Lake Victoria basin were analysed. The seasonal rainfall for any station in a given year was defined in two ways: (1) fixed time period where the rainy seasons were taken as occurring from March–May (long rains) and from October–December (short rains); and (2) variable periods where the rainy seasons were taken as the three consecutive months with maximum total rainfall covering the period of January–June (long rains) and July–December (short rains), to take into account the fact that the onset of rainy seasons within the basin varies from year to year and from one station to the next. For each station, sub datasets were derived covering different periods (all available data at the station, 1941–1980, 1961–1990, 1971–end of each station’s time series). The trends were analysed using the Mann-Kendall method, while the step changes were analysed using the Worsley Likelihood method. The results show that positive trends predominate, with most stations showing trend being located in the northern part of the basin, though this pattern is not conclusive. In all, 17% of the cases have trends, of which 67% are positive. The 1960s represent a significant upward jump in the basin rainfall. Seasonal rainfall analysis shows that the short rains tend to have more trends than the long rains. The impact of the varying month of onset of the rainy season is that the results from analyzing the fixed-period and variable-period time series are rarely the same, meaning the two series have different characteristics. It may be argued that the variable-period time series are more reliable as a basis for analysing trends and step changes, since these time series reflect more closely the actual variability in rainy seasons from one year to the next. The fixed-period analysis would, on the other hand, find more practical use in planning.

Longitudinal Antiretroviral Adherence in HIV+ Ugandan Parents and Their Children Initiating HAART in the MTCT-Plus Family Treatment Model: Role of Depression in Declining Adherence Over Time

Abstract: We conducted a study to assess the effect of family-based treatment on adherence amongst HIV-infected parents and their HIV-infected children attending the Mother-To-Child-Transmission Plus program in Kampala, Uganda. Adherence was assessed using home-based pill counts and self-report. Mean adherence was over 94%. Depression was associated with incomplete adherence on multivariable analysis. Adherence declined over time. Qualitative interviews revealed lack of transportation money, stigma, clinical response to therapy, drug packaging, and cost of therapy may impact adherence. Our results indicate that providing ART to all eligible HIV-infected members in a household is associated with excellent adherence in both parents and children. Adherence to ART among new parents declines over time, even when patients receive treatment at no cost. Depression should be addressed as a potential barrier to adherence. Further study is necessary to assess the long-term impact of this family treatment model on adherence to ART in resource-limited settings.

Rainfall intensity and groundwater recharge: empirical evidence from the Upper Nile Basin

Abstract: Changes in the intensity of precipitation as a result of global warming are expected to be especially pronounced in the tropics. The impact of changing rainfall intensities on groundwater recharge remains, however, unclear. Analysis of a recently compiled data set of coincidental, daily observations of rainfall and groundwater levels remote from abstraction for four stations in the Upper Nile Basin over the period 1999?2008 shows that the magnitude of observed recharge events is better related to the sum of heavy rainfalls, exceeding a threshold of 10?mm?day?1, than to that of all daily rainfall events. Consequently, projected increases in rainfall intensities as a result of global warming may promote rather than restrict groundwater recharge in similar environments of the tropics. Further monitoring and research are required to test the robustness of these findings, but the evidence presented is consistent with recent modelling highlighting the importance of explicitly considering changing rainfall intensities in the assessment of climate change impacts on groundwater recharge.

Production and evaluation of some physicochemical parameters of peanut milk yoghurt

Abstract: The peanut milk for yoghurt production was prepared by fortifying peanut milk (∼12 g/100 g total solids) with 4 g/100 g skimmed milk powder. The final product was subjected to physicochemical analysis using cow milk yoghurt (CMY) as a control throughout the study. Peanut milk yoghurt (PMY) had higher protein content, fat, water holding capacity and lower susceptibility to Syneresis than CMY. PMY had lower lactose level (1.73 g/100 ml) compared to CMY (4.93 g/100 ml). Generally both PMY and CMY had high mineral composition and contained high amounts of essential amino acids. PMY also contained a higher proportion of unsaturated fatty acids than saturated fatty acids as compared to CMY. Therefore, in terms of fatty acid composition, PMY could be considered to be more health promoting than CMY. Sensory evaluation revealed that though PMY had better sensory texture scores than CMY, its sensory appearance, flavor and overall acceptability scores were lower than those of CMY.

Complex population structure in African village dogs and its implications for inferring dog domestication history

Abstract: High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication.

Increasing access to surgical services in sub-saharan Africa: priorities for national and international agencies recommended by the Bellagio Essential Surgery Group.

Abstract: In this Policy Forum, the Bellagio Essential Surgery Group, which was formed to advocate for increased access to surgery in Africa, recommends four priority areas for national and international agencies to target in order to address the surgical burden of disease in sub-Saharan Africa.

Utilization of public or private health care providers by febrile children after user fee removal in Uganda.

Abstract: Background Despite investments in providing free government health services in Uganda, many caretakers still seek treatment from the drug shops/private clinics. The study aimed to assess determinants for use of government facilities or drug shops/private clinics for febrile illnesses in children under five.

First things first: effectiveness and scalability of a basic prehospital trauma care program for lay first-responders in Kampala, Uganda.

Abstract: Author(s): Jayaraman, Sudha; Mabweijano, Jacqueline R; Lipnick, Michael S; Caldwell, Nolan; Miyamoto, Justin; Wangoda, Robert; Mijumbi, Cephas; Hsia, Renee; Dicker, Rochelle; Ozgediz, Doruk | Abstract: BackgroundWe previously showed that in the absence of a formal emergency system, lay people face a heavy burden of injuries in Kampala, Uganda, and we demonstrated the feasibility of a basic prehospital trauma course for lay people. This study tests the effectiveness of this course and estimates the costs and cost-effectiveness of scaling up this training.Methods and findingsFor six months, we prospectively followed 307 trainees (police, taxi drivers, and community leaders) who completed a one-day basic prehospital trauma care program in 2008. Cross-sectional surveys and fund of knowledge tests were used to measure their frequency of skill and supply use, reasons for not providing aid, perceived utility of the course and kit, confidence in using skills, and knowledge of first-aid. We then estimated the cost-effectiveness of scaling up the program. At six months, 188 (62%) of the trainees were followed up. Their knowledge retention remained high or increased. The mean correct score on a basic fund of knowledge test was 92%, up from 86% after initial training (n = 146 pairs, p = 0.0016). 97% of participants had used at least one skill from the course: most commonly haemorrhage control, recovery position and lifting/moving and 96% had used at least one first-aid item. Lack of knowledge was less of a barrier and trainees were significantly more confident in providing first-aid. Based on cost estimates from the World Health Organization, local injury data, and modelling from previous studies, the projected cost of scaling up this program was $0.12 per capita or $25-75 per life year saved. Key limitations of the study include small sample size, possible reporter bias, preliminary local validation of study instruments, and an indirect estimate of mortality reduction.ConclusionsLay first-responders effectively retained knowledge on prehospital trauma care and confidently used their first-aid skills and supplies for at least six months. The costs of scaling up this intervention to cover Kampala are very modest. This may be a cost-effective first step toward developing formal emergency services in Uganda other resource-constrained settings. Further research is needed in this critical area of trauma care in low-income countries.

Immunogenicity of novel DosR regulon-encoded candidate antigens of Mycobacterium tuberculosis in three high-burden populations in Africa.

Abstract: Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in >75% of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity.

Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity

Abstract: The understanding of the epidemiology of severe malaria in African children remains incomplete across the spectrum of Plasmodium falciparum transmission intensities through which communities might expect to transition, as intervention coverage expands. Paediatric admission data were assembled from 13 hospitals serving 17 communities between 1990 and 2007. Estimates of Plasmodium falciparum transmission intensity in these communities were assembled to be spatially and temporally congruent to the clinical admission data. The analysis focused on the relationships between community derived parasite prevalence and the age and clinical presentation of paediatric malaria in children aged 0–9 years admitted to hospital. As transmission intensity declined a greater proportion of malaria admissions were in older children. There was a strong linear relationship between increasing transmission intensity and the proportion of paediatric malaria admissions that were infants (R2 = 0.73, p < 0.001). Cerebral malaria was reported among 4% and severe malaria anaemia among 17% of all malaria admissions. At higher transmission intensity cerebral malaria was a less common presentation compared to lower transmission sites. There was no obvious relationship between the proportions of children with severe malaria anaemia and transmission intensity. As the intensity of malaria transmission declines in Africa through the scaling up of insecticide-treated nets and other vector control measures a focus of disease prevention among very young children becomes less appropriate. The understanding of the relationship between parasite exposure and patterns of disease risk should be used to adapt malaria control strategies in different epidemiological settings.

Determinants of delay in care-seeking for febrile children in eastern Uganda.

Abstract: OBJECTIVE To explore factors associated with delay in seeking treatment outside the home for febrile children under five. METHODS Using a pre-tested structured questionnaire, all 9176 children below 5 years in Iganga-Mayuge Demographic Surveillance Site were enumerated. Caretakers of children who had been ill within the previous 2 weeks were asked about presenting symptoms, type of home treatment used, timing of seeking treatment and distance to provider. Children who sought care latest after one night were compared with those who sought care later. RESULTS Those likely to delay came from the lowest socio-economic quintile (OR 1.45; 95% CI 1.06-1.97) or had presented with pallor (OR 1.58; 95% CI 1.10-2.25). Children less likely to delay had gone to drug shops (OR 0.70; 95% CI 0.59-0.84) or community medicine distributors (CMDs) (OR 0.33; 95% CI 0.15-0.74), had presented with fast breathing (OR 0.75; 95% CI 0.60-0.87), used tepid sponging at home (OR 0.43; 95% CI 0.27-0.68), or perceived the distance to the provider to be short (OR 0.72; 95% CI 0.60-0.87). CONCLUSION Even in the presence of 'free services', poverty is associated with delay to seek care. Drug shops and CMDs may complement government efforts to deliver timely treatment. Health workers need to sensitize caretakers to take children for care promptly. Methods to elucidate time in population-surveys in African settings need to be evaluated.

A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.

Abstract: AIMS Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using nonmem.

Severe Sepsis in Two Ugandan Hospitals: a Prospective Observational Study of Management and Outcomes in a Predominantly HIV-1 Infected Population

Abstract: Background Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality. Methodology/Results Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm3 (IQR, 16–131 cells/mm3). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250–1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01–3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19–327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia. Conclusion Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings.

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Abstract: Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon's role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.

Genetically distinct strains of Cassava brown streak virus in the Lake Victoria basin and the Indian Ocean coastal area of East Africa.

Abstract: Six isolates of Cassava brown streak virus (CBSV, genus Ipomovirus; Potyviridae) from the Lake Victoria basin in Uganda and Tanzania were characterized. Virus particles were 650 nm long. The complete coat protein (CP)-encoding sequences (1,101 nucleotides, nt) were 90.7–99.5 and 93.7–99.5% identical at the nt and amino acid (aa) levels, respectively. The 3′ untranslated region was 225, 226 or 227 nt long. These eight isolates were only 75.8–77.5% (nt) and 87.0–89.9% (aa) identical when compared to the partial CP sequences (714 nt) of six CBSV isolates characterized previously from the costal lowlands of Tanzania and Mozambique. Hence, two genetically different and geographically separated populations of CSBV exist in East Africa.

Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi

Abstract: Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.