Infectious Disease Research Collaboration

Kampala, Uganda

Infectious Disease Research Collaboration

Kampala, Uganda
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Lumu W.,Mengo Hospital | Kampiire L.,Infectious Disease Research Collaboration | Akabwai G.P.,Baylor College of Medicine | Kiggundu D.S.,Mulago National Referral and Teaching Hospital | Kibirige D.,Uganda Martyrs Hospital Lubaga
Therapeutics and Clinical Risk Management | Year: 2017

Background: Hypertension is one of the recognized risk factors of cardiovascular diseases in adult diabetic patients. High prevalence of suboptimal blood pressure (BP) control has been well documented in the majority of studies assessing BP control in diabetic patients in sub-Saharan Africa. In Uganda, there is a dearth of similar studies. This study evaluated the prevalence and correlates of suboptimal BP control in an adult diabetic population in Uganda. Patients and methods: This was a cross-sectional study that enrolled 425 eligible ambulatory adult diabetic patients attending three urban diabetic outpatient clinics over 11 months. Data about their sociodemographic characteristics and clinical history were collected using pre-tested questionnaires. Suboptimal BP control was defined according to the 2015 American Diabetes Association standards of diabetes care guideline as BP levels ≥140/90 mmHg. Results: The mean age of the study participants was 52.2±14.4 years, with the majority being females (283, 66.9%). Suboptimal BP control was documented in 192 (45.3%) study participants and was independently associated with the study site (private hospitals; odds ratio 2.01, 95% confidence interval 1.18–3.43, P=0.01) and use of statin therapy (odds ratio 0.5, 95% confidence interval 0.26–0.96, P=0.037). Conclusion: Suboptimal BP control was highly prevalent in this study population. Strategies to improve optimal BP control, especially in the private hospitals, and the use of statin therapy should be encouraged in adult diabetic patients. © 2017 Lumu et al.

Sangare L.R.,University of Washington | Weiss N.S.,University of Washington | Brentlinger P.E.,University of Washington | Richardson B.A.,University of Washington | And 4 more authors.
Malaria Journal | Year: 2011

Background: Prompt use of an effective anti-malarial drug is essential for controlling malaria and its adverse effects in pregnancy. The World Health Organization recommends an artemisinin-based combination therapy as the first-line treatment of uncomplicated malaria in the second and third trimesters of pregnancy. The study objective was to determine the degree to which presumed episodes of uncomplicated symptomatic malaria in pregnancy were treated with a recommended anti-malarial regimen in a region of Uganda. Methods. Utilizing a population-based random sample, we interviewed women living in Jinja, Uganda who had been pregnant in the past year. Results: Self-reported malaria during the index pregnancy was reported among 67% (n = 334) of the 500 participants. Among the 637 self-reported episodes of malaria, an anti-malarial drug was used for treatment in 85% of the episodes. Use of a currently recommended treatment in the first trimester was uncommon (5.6%). A contraindicated anti-malarial drug (sulphadoxine-pyrimethamine and/or artemether-lumefantrine) was involved in 70% of first trimester episodes. Recommended anti-malarials were used according to the guidelines in only 30.1% of all second and third trimester episodes. Conclusions: Self-reported malaria was extremely common in this population and adherence to treatment guidelines for the management of malaria in pregnancy was poor. Use of artemether-lumefantrine combined with non-recommended anti-malarials was common practice. Overuse of anti-malarial drugs, especially ones that are no longer recommended, undermines malaria control efforts by fueling the spread of drug resistance and delaying appropriate treatment of non-malarial febrile illnesses. Improved diagnostic capacity is essential to ultimately improving the management of malaria-like symptoms during pregnancy and appropriate use of currently available anti-malarials. © 2011 Sangaré et al; licensee BioMed Central Ltd.

Sangare L.R.,University of Washington | Stergachis A.,University of Washington | Brentlinger P.E.,University of Washington | Richardson B.A.,University of Washington | And 4 more authors.
PLoS ONE | Year: 2010

Background: Maternal malaria is associated with serious adverse pregnancy outcomes. One recommended means of preventing malaria during pregnancy is intermittent preventive therapy (IPTp) with sulfadoxine/pyrimethamine (SP). We sought to identify determinants of preventive use of SP during pregnancy among recently pregnant women in Uganda. Additionally, we characterized the timing of and indications for the administration of SP at antenatal care (ANC) visits and missed opportunities for SP administration. Methodology/Principal Findings: Utilizing a population-based random sample, we interviewed 500 women living in Jinja, Uganda who had been pregnant in the past year. Thirty-eight percent (192/500) of women received SP for the treatment of malaria and were excluded from the analysis of IPTp-SP. Of the remaining women, 275 (89.3%) reported at least two ANC visits after the first trimester and had an opportunity to receive IPTp-SP according to the Ugandan guidelines, but only 86 (31.3%) of these women received a full two-dose course of IPTp. The remaining 189 (68.7%) women missed one or more doses of IPTp-SP. Among the 168 women that were offered IPTp, 164 (97.6%) of them took the dose of SP. Conclusions/Significance: Use of IPTp in Uganda was found to be far below target levels. Our results suggest that women will take SP for IPTp if it is offered during an ANC visit. Missed opportunities to administer IPTp-SP during ANC were common in our study, suggesting provider-level improvements are needed. © 2010 Sangaré et al.

Banek K.,Infectious Disease Research Collaboration | Banek K.,London School of Hygiene and Tropical Medicine | Nankabirwa J.,Infectious Disease Research Collaboration | Nankabirwa J.,Makerere University | And 6 more authors.
Health Policy and Planning | Year: 2015

Background In Uganda, community services for febrile children are expanding from presumptive treatment of fever with anti-malarials through the home-based management of fever (HBMF) programme, to include treatment for malaria, diarrhoea and pneumonia through Integrated Community Case Management (ICCM). To understand the level of support available, and the capacity and motivation of community health workers to deliver these expanded services, we interviewed community medicine distributors (CMDs), who had been involved in the HBMF programme in Tororo district, shortly before ICCM was adopted. Methods Between October 2009 and April 2010, 100 CMDs were recruited to participate by convenience sampling. The survey included questionnaires to gather information about the CMDs' work experience and to assess knowledge of fever case management, and in-depth interviews to discuss experiences as CMDs including motivation, supervision and relationships with the community. All questionnaires and knowledge assessments were analysed. Summary contact sheets were made for each of the 100 interviews and 35 were chosen for full transcription and analysis. Results CMDs faced multiple challenges including high patient load, limited knowledge and supervision, lack of compensation, limited drugs and supplies, and unrealistic expectations of community members. CMDs described being motivated to volunteer for altruistic reasons; however, the main benefits of their work appeared related to 'becoming someone important', with the potential for social mobility for self and family, including building relationships with health workers. At the time of the survey, over half of CMDs felt demotivated due to limited support from communities and the health system. Conclusions Community health worker programmes rely on the support of communities and health systems to operate sustainably. When this support falls short, motivation of volunteers can wane. If community interventions, in increasingly complex forms, are to become the solution to improving access to primary health care, greater attention to what motivates individuals, and ways to strengthen health system support are required. © 2014 Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014.

Staedke S.G.,London School of Hygiene and Tropical Medicine | Staedke S.G.,Infectious Disease Research Collaboration | Chandler C.I.R.,London School of Hygiene and Tropical Medicine | DiLiberto D.,London School of Hygiene and Tropical Medicine | And 6 more authors.
Implementation Science | Year: 2013

Background: In Africa, inadequate health services contribute to the lack of progress on malaria control. Evidence of the impact of interventions to improve health services on population-level malaria indicators is needed. We are conducting a cluster-randomised trial to assess whether a complex intervention delivered at public health centres in Uganda improves health outcomes of children and treatment of malaria, as compared to the current standard of care.Methods/Design: Twenty public health centres (level II and III) in Tororo district will be included; 10 will be randomly assigned to the intervention and 10 to control. Clusters will include households located within 2 km of health centres. The trial statistician will generate the random allocation sequence and assign clusters. Health centres will be stratified by level, and restricted randomisation will be employed to ensure balance on cluster location and size. Allocation will not be blinded. The intervention includes training in health centre management, fever case management with use of rapid diagnostic tests (RDTs) for malaria, and patient-centered services, and provision of artemether-lumefantrine (AL) and RDTs when stocks run low. The impact of the intervention on population-level health indicators will be assessed through community surveys conducted at baseline in randomly selected children from each cluster, and repeated annually for two years. The impact on individuals over time will be assessed in a cohort study of children recruited from households randomly selected per cluster. The impact on health centres will be assessed using patient exit interviews, monthly surveillance, and assessment of health worker knowledge and skills. The primary outcome is the prevalence of anaemia (haemoglobin <11.0 g/dL) in individual children under five measured in the annual community surveys. The primary analysis will be based on the cluster-level results.Discussion: The PRIME trial findings will be supplemented by the PROCESS study, an evaluation of the process, context, and wider impact of the PRIME intervention which will be conducted alongside the main trial, together providing evidence of the health impact of a public sector intervention in Uganda. Trial registration and funding: This trial is registered at (NCT01024426) and is supported by the ACT Consortium. © 2013 Staedke et al.; licensee BioMed Central Ltd.

Kim L.H.,University of California at San Francisco | Cohan D.L.,University of California at San Francisco | Sparks T.N.,Brigham and Women's Hospital | Pilliod R.A.,Brigham and Women's Hospital | And 2 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2013

Objective: To estimate the cost-effectiveness of HIV screening strategies for the prevention of perinatal transmission in Uganda, a resource-limited country with high HIV prevalence and incidence. Study Design: We designed a decision analytic model from a health care system perspective to assess the vertical transmission rates and cost-effectiveness of 4 different HIV screening strategies in pregnancy: (1) rapid HIV antibody (Ab) test at initial visit (current standard of care), (2) strategy 1 + HIV RNA at initial visit (adds detection of acute HIV), (3) strategy 1 + repeat HIV Ab at delivery (adds detection of incident HIV), and (4) strategy 3 + HIV RNA at delivery (adds detection of acute HIV at delivery). Model estimates were derived from the literature and local sources, and life years saved were discounted at a rate of 3% per year. Based on World Health Organization guidelines, we defined our cost-effectiveness threshold as #3 times the gross domestic product per capita, which for Uganda was US$3300 in 2008. Results: Using base case estimates of 10% HIV prevalence among women entering prenatal care and 3% incidence during pregnancy, strategy 3 was incrementally the cost-effective option that led to the greatest total life years. Conclusions: Repeat rapid HIV Ab testing at the time of labor is a costeffective strategy even in a resource-limited setting such as Uganda. Copyright © 2013 by Lippincott Williams & Wilkins.

Nankabirwa J.,Makerere University | Nankabirwa J.,Infectious Disease Research Collaboration | Wandera B.,Makerere University | Kiwanuka N.,Makerere University | And 6 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2013

Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] -0.6, 95% confidence interval [CI] -1.01 to -0.21) and sustained attention (AMD -1.6 95% CI -2.40 to -0.81) compared with uninfected children. There was also evidence for a dose-response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.

Eziefula A.C.,London School of Hygiene and Tropical Medicine | Bousema T.,London School of Hygiene and Tropical Medicine | Bousema T.,Radboud University Nijmegen | Yeung S.,London School of Hygiene and Tropical Medicine | And 14 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: Primaquine is the only available drug that clears mature Plasmodium falciparum gametocytes in infected human hosts, thereby preventing transmission of malaria to mosquitoes. However, concerns about dose-dependent haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiencies have limited its use. We assessed the dose-response association of single-dose primaquine for gametocyte clearance and for safety in P falciparum malaria. Methods: We undertook this randomised, double-blind, placebo-controlled trial with four parallel groups in Jinja district, eastern Uganda. We randomly allocated Ugandan children aged 1-10 years with uncomplicated falciparum malaria and normal G6PD enzyme function to receive artemether-lumefantrine, combined with either placebo or with 0·1 mg/kg, 0·4 mg/kg, or 0·75 mg/kg (WHO reference dose) primaquine base. Randomisation was done with computer-generated four-digit treatment assignment codes allocated to random dose groups in block sizes of 16. Study staff who provided care or assessed outcomes and the participants remained masked to the intervention group after assignment. The primary efficacy endpoint was the non-inferiority of the mean duration of gametocyte carriage in the test doses compared with the reference group of 0·75 mg primaquine per kg, with a non-inferiority margin of 2·5 days. The primary safety endpoint was the superiority of the arithmetic mean maximum decrease in haemoglobin concentration from enrolment to day 28 of follow-up in the primaquine treatment groups compared with placebo, with use of significance testing of pairwise comparisons with a cutoff of p=0·05. The trial is registered with, number NCT01365598. Findings: We randomly allocated 468 participants to receive artemether-lumefantrine combined with placebo (119 children) or with 0·1 mg/kg (116), 0·4 mg/kg (116), or 0·75 mg/kg (117) primaquine base. The mean duration of gametocyte carriage was 6·6 days (95% CI 5·3-7·8) in the 0·75 mg/kg reference group, 6·3 days (5·1-7·5) in the 0·4 mg/kg primaquine group (p=0·74), 8·0 days (6·6-9·4) in the 0·1 mg/kg primaquine group (p=0·14), and 12·4 days (9·9-15·0) in the placebo group (p<0·0001). No children showed evidence of treatment-related haemolysis, and the mean maximum decrease in haemoglobin concentration was not associated with the dose of primaquine received-it did not differ significantly compared with placebo (10·7 g/L, SD 11·1) in the 0·1 mg/kg (11·4 g/L, 9·4; p=0·61), 0·4 mg/kg (11·3 g/L, 10·0; p=0·67), or 0·75 mg/kg (12·7 g/L, 8·2; p=0·11) primaquine groups. Interpretation: We conclude that 0·4 mg/kg primaquine has similar gametocytocidal efficacy to the reference 0·75 mg/kg primaquine dose, but a dose of 0·1 mg/kg was inconclusive for non-inferiority. Our findings call for the prioritisation of further trials into the efficacy and safety of doses of primaquine between 0·1 mg/kg and 0·4 mg/kg (including the dose of 0·25 mg/kg recently recommended by WHO), in view of the potential for widespread use of the drug to block malaria transmission. Funding: Wellcome Trust and the Bill & Melinda Gates Foundation. © 2014 Eziefula et al. Open Access article distributed under the terms of CC BY-NC-ND.

PubMed | University of science, Centers for Disease Control and Prevention, University of Liverpool, University of Ouagadougou and 7 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted.Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02).The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

PubMed | Centers for Disease Control and Prevention, University of California at San Francisco, London School of Hygiene and Tropical Medicine and Infectious Disease Research Collaboration
Type: | Journal: Malaria journal | Year: 2016

Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria.To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia.Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria.These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria.

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