Showing papers by "Makerere University published in 2010"

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study

Abstract: Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6–50·4], 48·2 years [47·3–49·2], 46·8 years [46·6–48·1], and 55·5 years [54·9–56·1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agencia de Gestio d'Ajuts Universitaris i de Recerca, Marato de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.

Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology

Abstract: Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml. Killing studies showed that the assay's buffer decreased M. tuberculosis viability by at least 8 logs, substantially reducing biohazards. Tests of 23 different commonly occurring rifampin resistance mutations demonstrated that all 23 (100%) would be identified as rifampin resistant. An analysis of 20 nontuberculosis mycobacteria species confirmed high assay specificity. A small clinical validation study of 107 clinical sputum samples from suspected tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture-positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive cases, as determined by growth on solid medium or on both solid and liquid media, respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture-negative samples. A study of 64 smear-positive culture-positive sputa from retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after correcting for a conventional susceptibility test error. In conclusion, this highly sensitive and simple-to-use system can detect M. tuberculosis directly from sputum in less than 2 h.

Prosocial Spending and Well-Being: Cross-Cultural Evidence for a Psychological Universal

Abstract: This research provides the first support for a possible psychological universal: human beings around the world derive emotional benefits from using their financial resources to help others (prosocial spending). Analyzing survey data from 136 countries, we show that prosocial spending is consistently associated with greater happiness. To test for causality, we conduct experiments within two very different countries (Canada and Uganda) and show that spending money on others has a consistent, causal impact on happiness. In contrast to traditional economic thought--which places self-interest as the guiding principle of human motivation--our findings suggest that the reward experienced from helping others may be deeply ingrained in human nature, emerging in diverse cultural and economic contexts.

Cancer survival in Africa, Asia, and Central America: a population-based study

Abstract: Summary Background Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions. Methods Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined. Findings For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76–82% for breast cancer, 63–79% for cervical cancer, 71–78% for bladder cancer, and 44–60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services. Interpretation The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources. Funding Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

Abstract: per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. Conclusions Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log 10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Cerebral Malaria: Mechanisms of Brain Injury and Strategies for Improved Neurocognitive Outcome

Abstract: Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum. With >575,000 cases annually, children in sub-Saharan Africa are the most affected. Surviving patients have an increased risk of neurological and cognitive deficits, behavioral difficulties, and epilepsy making cerebral malaria a leading cause of childhood neurodisability in the region. The pathogenesis of neurocognitive sequelae is poorly understood: coma develops through multiple mechanisms and there may be several mechanisms of brain injury. It is unclear how an intravascular parasite causes such brain injury. Understanding these mechanisms is important to develop appropriate neuroprotective interventions. This article examines possible mechanisms of brain injury in cerebral malaria, relating this to the pathogenesis of the disease, and explores prospects for improved neurocognitive outcome.

Assessment of heavy metal pollution in the urban stream sediments and its tributaries

Abstract: Globally, aquatic ecosystems are highly polluted with heavy metals arising from anthropogenic and terrigenous sources. The objective of this study was to investigate the pollution of stream sediments and possible sources of pollutants in Nakivubo Channel Kampala, Uganda. Stream sediments were collected and analysed for heavy metal concentration using flame atomic absorption spectrophotometer. The degree of pollution in Nakivubo channelized stream sediments for lead, cadmium, copper, zinc, manganese and iron was assessed using enrichment factor, geo- accumulation index and pollution load index. The results indicated that (1) the sediments have been polluted with lead, cadmium and zinc and have high anthropogenic influences; (2) the calculation of geo-accumulation index suggest that Nakivubo stream sediments have background concentration for copper, manganese and Fe (I geo < 0); (3) factor analysis results reveal three sources of pollutants as explained by three factors (75.0 %); (i) mixed origin or retention phenomena of industrial and vehicular emissions; (ii) terrigenous and (iii) dual origin of zinc (vehicular and industrial). In conclusion, the co-precipitation (inclusion, occlusion and adsorption) of lead, cadmium and zinc with manganese and iron hydroxides, scavenging ability of other metals, very low dissolved oxygen and slightly acidic to slightly alkaline pH in stream water could account for the active accumulation of heavy metals in Nakivubo stream sediments. These phenomena may pose a risk of secondary water pollution under sediment disturbance and/or changes in the geo-chemistry of sediments.

Indigenous climate knowledge in southern Uganda: the multiple components of a dynamic regional system

Abstract: Farmers in southern Uganda seek information to anticipate the interannual variability in the timing and amount of precipitation, a matter of great importance to them since they rely on rain-fed agriculture for food supplies and income. The four major components of their knowledge system are: (1) longstanding familiarity with the seasonal patterns of precipitation and temperature, (2) a set of local traditional climate indicators, (3) observation of meteorological events, (4) information about the progress of the seasons elsewhere in the region. We examine these components and show the connections among them. We discuss the social contexts in which this information is perceived, evaluated, discussed and applied, and we consider the cultural frameworks that support the use of this information. This system of indigenous knowledge leads farmers to participate as agents as well as consumers in programs that use modern climate science to plan for and adapt to climate variability and climate change.

Cost-Effectiveness of Serum Cryptococcal Antigen Screening to Prevent Deaths among HIV-Infected Persons with a CD4+ Cell Count ≤100 Cells/μL Who Start HIV Therapy in Resource-Limited Settings

Abstract: died within 2 months of ART initiation. The number needed to test and treat with CRAG screening and fluconazole to prevent 1 CM case is 11.3 (95% CI, 7.9‐17.1) at costs of $190 (95% CI, $132‐$287). The number needed to test and treat to save 1 life is 15.9 (95% CI, 11.1‐24.0) at costs of $266 (95% CI, $185‐$402). The cost per disability-adjusted life year saved is $21 (95% CI, $15‐$32). Conclusions. Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4 + cell count 100 cells/mL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.

Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions

Abstract: Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement.

Identification of Staphylococcus aureus : DNase and Mannitol salt agar improve the efficiency of the tube coagulase test

Abstract: Background: The ideal identification of Staphylococcus aureus clinical isolates requires a battery of tests and this is costly in resource limited settings. In many developing countries, the tube coagulase test is usually confirmatory for S. aureus and is routinely done using either human or sheep plasma. This study evaluated Mannitol salt agar and the deoxyribonuclease (DNase) test for improving the efficiency of the tube coagulase test in resource limited settings. The efficiency of human and sheep plasma with tube coagulase tests was also evaluated. Methods: One hundred and eighty Gram positive, Catalase positive cocci occurring in pairs, short chains or clusters were subjected to growth on Mannitol salt agar, deoxyribonuclease and tube coagulase tests. Of these, isolates that were positive for at least two of the three tests (n = 60) were used to evaluate the performance of the tube coagulase test for identification of S. aureus, using PCR-amplification of the nuc gene as a gold standard. Results: Human plasma was more sensitive than sheep plasma for the tube coagulase test (sensitivity of 91% vs. 81% respectively), but both plasmas had very low specificity (11% and 7% respectively). The sensitivity and specificity of the tube coagulase test (human plasma) was markedly improved when Mannitol salt agar and DNase were introduced as a tri-combination test for routine identification of Staphylococcus aureus (100% specificity and 75% sensitivity). The specificity and sensitivity of Mannitol salt agar/DNase/tube coagulase (sheep plasma) combination was 100% and 67%, respectively. Conclusion: The efficiency of the tube coagulase test can be markedly improved by sequel testing of the isolates with Mannitol salt agar, DNase and Tube coagulase. There is no single phenotypic test (including tube coagulase) that can guarantee reliable results in the identification of Staphylococcus aureus.

Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study.

Abstract: Background: Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible. Methods and Findings: We prospectively followed 101 ART-naive Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR=2.3, 95% CI 1.1-5.1, p=0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p=0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-a, granulocyte colony-stimulating factor (G- CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve (AUC)=0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p#0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level .32 mg/l (highest quartile). Pre-ART CRP level .32 mg/l alone was associated with future death (OR=8.3, 95% CI 2.7-25.6, p,0.001). Conclusions: Pre-ART increases in Th17 and Th2 responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-a, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions. Please see later in the article for the Editors' Summary.

Using the three delays model to understand why newborn babies die in eastern Uganda

Abstract: Summary Objectives To investigate causes of and contributors to newborn deaths in eastern Uganda using a three delays audit approach. Methods Data collected on 64 neonatal deaths from a demographic surveillance site were coded for causes of deaths using a hierarchical model and analysed using a modified three delays model to determine contributing delays. A survey was conducted in 16 health facilities to determine capacity for newborn care. Results Of the newborn babies, 33% died in a hospital/health centre, 13% in a private clinic and 54% died away from a health facility. 47% of the deaths occurred on the day of birth and 78% in the first week. Major contributing delays to newborn death were caretaker delay in problem recognition or in deciding to seek care (50%, 32/64); delay to receive quality care at a health facility (30%; 19/64); and transport delay (20%; 13/64). The median time to seeking care outside the home was 3 days from onset of illness (IQR 1–6). The leading causes of death were sepsis or pneumonia (31%), birth asphyxia (30%) and preterm birth (25%). Health facilities did not have capacity for newborn care, and health workers had correct knowledge on only 31% of the survey questions related to newborn care. Conclusions Household and health facility-related delays were the major contributors to newborn deaths, and efforts to improve newborn survival need to address both concurrently. Understanding why newborn babies die can be improved by using the three delays model, originally developed for understanding maternal death.

An overview of Uganda's mental health care system: results from an assessment using the world health organization's assessment instrument for mental health systems (WHO-AIMS).

Abstract: The Ugandan government recognizes mental health as a serious public health and development concern, and has of recent implemented a number of reforms aimed at strengthening the country's mental health system. The aim of this study was to provide a profile of the current mental health policy, legislation and services in Uganda. A survey was conducted of public sector mental health policy and legislation, and service resources and utilisation in Uganda, in the year 2005, using the World Health Organization's Assessment Instrument for Mental Health Systems (WHO-AIMS) Version 2.2. Uganda's draft mental health policy encompasses many positive reforms, including decentralization and integration of mental health services into Primary Health Care (PHC). The mental health legislation is however outdated and offensive. Services are still significantly underfunded (with only 1% of the health expenditure going to mental health), and skewed towards urban areas. Per 100,000 population, there were 1.83 beds in mental hospitals, 1.4 beds in community based psychiatric inpatient units, and 0.42 beds in forensic facilities. The total personnel working in mental health facilities were 310 (1.13 per 100,000 population). Only 0.8% of the medical doctors and 4% of the nurses had specialized in psychiatry. Although there have been important developments in Uganda's mental health policy and services, there remains a number of shortcomings, especially in terms of resources and service delivery. There is an urgent need for more research on the current burden of mental disorders and the functioning of mental health programs and services in Uganda.

Determinants of male involvement in the prevention of mother-to-child transmission of HIV programme in Eastern Uganda: a cross-sectional survey

Abstract: Mother-to-child transmission of HIV (MTCT) accounts for over 95% of all paediatric HIV infections worldwide. Several studies have shown that male participation in the antenatal care of their spouses together with couple counselling and testing for HIV, increases use of the interventions for HIV prevention. The prevention programme of MTCT (PMTCT) was launched in Uganda in 2000 and Mbale in 2002. Less than 10% of the pregnant women accepted antenatal HIV testing at Mbale Regional Referral Hospital in 2003; couple counselling and testing for HIV was low. Therefore, we conducted the study to determine the level of male involvement and identify its determinants in the PMTCT programme. A cross-sectional survey of 388 men aged 18 years or more, whose spouses were attending antenatal care at Mbale Regional Referral Hospital, was conducted in Mbale district, Eastern Uganda. A male involvement index was constructed based on 6 questions. The survey was complemented by eight focus group discussions and five in-depth interviews. The respondents had a median age of 32 years (inter-quartile range, IQR: 28-37). The majority (74%) had a low male involvement index and only 5% of men accompanied their spouses to the antenatal clinic. Men who had attained secondary education were more likely to have a high male involvement index (OR: 1.9, 95% CI: 1.1-3.3) than those who had primary or no formal education. The respondents, whose occupation was driver (OR: 0.3, 95% CI: 0.1-0.7) or those who had fear of disclosure of their HIV sero-status results to their spouses (OR: 0.4, 95% CI: 0.2-0.8), were less likely to have a high male involvement index. Barriers to male involvement in the PMTCT programme were related to both the poor health system, to socio-economic factors and to cultural beliefs. Structural and cultural barriers to men's involvement in the PMTCT programme in Mbale district were complex and interrelated. Community sensitization of men about the benefits of antenatal care and PMTCT and improving client-friendliness in the clinics needs to be prioritised in order to improve low male participation and mitigate the effect of socio-economic and cultural factors.

The Effects of Circumcision on the Penis Microbiome

Abstract: Background Circumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners. Methodology/Principal Findings We assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3–V4 hypervariable regions. Taxonomic classification was performed using the RDP Naive Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significant decrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families—Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)—were uniquely abundant before circumcision. Within these families we identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. Conclusions/Significance The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

On the diversity of malaria parasites in African apes and the origin of Plasmodium falciparum from Bonobos.

Abstract: The origin of Plasmodium falciparum, the etiological agent of the most dangerous forms of human malaria, remains controversial. Although investigations of homologous parasites in African Apes are crucial to resolve this issue, studies have been restricted to a chimpanzee parasite related to P. falciparum, P. reichenowi, for which a single isolate was available until very recently. Using PCR amplification, we detected Plasmodium parasites in blood samples from 18 of 91 individuals of the genus Pan, including six chimpanzees (three Pan troglodytes troglodytes, three Pan t. schweinfurthii) and twelve bonobos (Pan paniscus). We obtained sequences of the parasites' mitochondrial genomes and/or from two nuclear genes from 14 samples. In addition to P. reichenowi, three other hitherto unknown lineages were found in the chimpanzees. One is related to P. vivax and two to P. falciparum that are likely to belong to distinct species. In the bonobos we found P. falciparum parasites whose mitochondrial genomes indicated that they were distinct from those present in humans, and another parasite lineage related to P. malariae. Phylogenetic analyses based on this diverse set of Plasmodium parasites in African Apes shed new light on the evolutionary history of P. falciparum. The data suggested that P. falciparum did not originate from P. reichenowi of chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it subsequently colonized humans by a host-switch. Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria.

Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure

Abstract: Background Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety ...

Changing cancer incidence in Kampala, Uganda, 1991-2006.

Abstract: Incidence rates of different cancers have been calculated for the population of Kyadondo County (Kampala, Uganda) for a 16-year period (1991-2006). This period coincides with continuing social and lifestyle changes and the peak and subsequent wane of the epidemic of HIV-AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with the incidence rates of cancers of the breast and prostate showing particularly marked increases (4.5% annually). Prostate cancer is now the most common cancer in men. The incidence of cancer of the esophagus, formerly the most common cancer in men and second in frequency in women, has remained relatively constant, whereas the incidence of cancer of the cervix, the most common malignancy in women, continues to increase. Since the early 1990s the incidence of Kaposi sarcoma (KS) in men has declined, and while remaining relatively constant in women, it has been diagnosed at progressively later ages. The rates of pediatric KS have declined by about 1/3rd. The incidence of squamous cell cancers of the conjunctiva has also declined since the mid 1990s. Cancer control in Uganda, as elsewhere in sub-Saharan Africa, involves meeting the challenge of emerging cancers associated with westernization of lifestyles (large bowel, breast and prostate); although the incidence of cancers associated with poverty and infection (liver, cervix, esophagus) shows little decline, the residual burden of the AIDS-associated cancers remains a major burden.

Male Circumcision Decreases Acquisition and Increases Clearance of High-Risk Human Papillomavirus in HIV-Negative Men: A Randomized Trial in Rakai, Uganda

Abstract: P p .006 HPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28‐0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60‐ 1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17‐1.64). Conclusions. Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men. Trial Registration. ClinicalTrials.gov identifier: NCT00425984.

Male partner attendance of skilled antenatal care in peri-urban Gulu district, Northern Uganda

Abstract: Male partner attendance of skilled Antenatal Care (ANC) is beneficial to improving maternal outcomes. This study investigated the level, perceived benefits and factors associated with male partner attendance of skilled ANC in a peri-urban community recovering from two decades of civil conflict. This cross-sectional survey used multi-stage sampling in 12 villages of Omoro county to select 331 married male respondents aged 18 years or more, whose female spouses had childbirth within 24 months prior to the survey. A structured questionnaire elicited responses about male partner attendance of ANC during pregnancy at a public health facility as the main outcome variable. Analysis used Generalized Linear Model (GLM) in Stata version 10.0 to obtain Prevalence Risk Ratios (PRR) for association between the binary outcome and independent factors. All factors significant at p < 0.15 and potential confounders were included in the multivariable model. Overall, 65.4% (95%CI; 60.3, 70.5) male partners attended at least one skilled ANC visit. Mean age was 31.9 years [SD 8.2]. Perceived benefits of attending ANC were: HIV screening (74.5%), monitoring foetal growth (34%) and identifying complications during pregnancy (18.9%). Factors independently associated with higher ANC attendance were: knowledge of 3 or more ANC services (adj.PRR 2.77; 95%CI 2.24, 3.42), obtaining health information from facility health workers (adj.PRR 1.14; 95%CI 1.01, 1.29) and if spouse had skilled attendance at last childbirth (adj.PRR 1.31; 95%CI 1.04-1.64). However, factors for low attendance were: male partners intending their spouse to carry another pregnancy (adj.PRR 0.83; 95%CI 0.71, 0.97) and living more than 5 Km from a health facility (adj.PRR 0.83, 95%CI 0.70, 0.98). Men who were knowledgeable of ANC services, obtained health information from a health worker and whose spouses utilised skilled delivery at last pregnancy were more likely to accompany their spouses at ANC, unlike those who wanted to have more children and lived more than 5 km from the health facility. These findings suggest that empowering male partners with knowledge about ANC services may increase their ANC participation and in turn increase skilled delivery. This strategy may improve maternal health care in post conflict and resource-limited settings.

Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome

Abstract: Background Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20–40% of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown.

Validation of a core outcome measure for palliative care in Africa: the APCA African Palliative Outcome Scale

Abstract: Despite the burden of progressive incurable disease in Africa, there is almost no evidence on patient care or outcomes. A primary reason has been the lack of appropriate locally-validated outcome tools. This study aimed to validate a multidimensional scale (the APCA African Palliative Outcome Scale) in a multi-centred international study. Validation was conducted across 5 African services and in 3 phases: Phase 1. Face validity: content analysis of qualitative interviews and cognitive interviewing of POS; Phase 2. Construct validity: correlation of POS with Missoula-Vitas Quality of Life Index (Spearman's rank tests); Phase 3. Internal consistency (Cronbach's alpha calculated twice using 2 datasets), test-retest reliability (intraclass correlation coefficients calculated for 2 time points) and time to complete (calculated twice using 2 datasets). The validation involved 682 patients and 437 family carers, interviewed in 8 different languages. Phase 1. Qualitative interviews (N = 90 patients; N = 38 carers) showed POS items mapped well onto identified needs; cognitive interviews (N = 73 patients; N = 29 carers) demonstrated good interpretation; Phase 2. POS-MVQoLI Spearman's rank correlations were low-moderate as expected (N = 285); Phase 3. (N = 307, 2nd assessment mean 21.2 hours after first, SD 7.2) Cronbach's Alpha was 0.6 on both datasets, indicating expected moderate internal consistency; test-retest found high intra-class correlation coefficients for all items (0.78-0.89); median time to complete 7 mins, reducing to 5 mins at second visit. The APCA African POS has sound psychometric properties, is well comprehended and brief to use. Application of this tool offers the opportunity to at last address the omissions of palliative care research in Africa.

Intellectual capital and performance: testing interaction effects

Abstract: Purpose – The purpose of this paper is to examine the interaction effect of intellectual capital elements and how they fuse to affect financial performance in microfinance institutions. The major purpose is to explore the appropriate blend or mix of intellectual capital elements that explains the source of value creation – hence performance – in microfinance institutions.Design/methodology/approach – The paper adopts the ModGraph program (Excel version) along with the Kenny and Boran approach to test conditional hypotheses.Findings – The magnitude effect of human capital on performance depends on any of structural or relational capital; hence the assumption of nonadditivity is met. However, no significant interaction effects were established between relational and structural capital.Research limitations/implications – Only a single research methodological approach was employed and future research through interviews could be undertaken to triangulate. Furthermore, the findings from the present study are cr...

Hormonal contraception and HIV acquisition: reanalysis using marginal structural modeling.

Abstract: During the HC-HIV Study more than 30% of participants switched their contraceptive method. The decision to switch contraceptive use was found to be associated with participants’ use of condoms, their sexual behavioral risk, and their partners’ behavioral risks – all risk factors for HIV acquisition in the HC-HIV Study dataset. Furthermore, these HIV risk factors changed over time and may both predict subsequent hormonal contraceptive use and be predicted by past hormonal contraceptive exposure and thus were found to be time-dependent confounders. Use of conventional Cox proportional hazard regression modeling as applied in the original analysis [1] cannot satisfactorily adjust for