Browsing by Author "Biraro, Samuel"
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Item Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda.(The American journal of tropical medicine and hygiene., 2004) Fogg, Carole; Bajunirwe, Francis; Piola, Patrice; Biraro, Samuel; Checchi, Francesco; Kiguli, James; Namiiro, Proscovia; Musabe, Joy; Kyomugisha, Agnes; Guthmann, Jean-PaulMeasuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations.Item Herpes simplex virus type 2: a key role in HIV incidence(Aids, 2009) Glynn, Judith R.; Biraro, Samuel; Weiss, Helen A.Many epidemiological studies have found a strong association between HSV-2 infection and HIV infection, including longitudinal studies in which it was known that the HSV-2 infection preceded the HIV infection [1]. However, two recent trials of suppressive therapy of HSV-2 with acyclovir (400 mg b.i.d) showed no reduction in HIV incidence [2,3]. Although this may simply reflect the difficulty of adequately suppressing HSV-2 reactivations with the drug regimen used, the results have led some to challenge the importance of HSV-2 infection as a risk factor for HIV [4]. In this issue, Tobian et al.[5] use data from the Rakai male circumcision trial to assess the effect of prevalent and incident HSV-2 infection on HIV incidence. They found that prevalent HSV-2 infection increased HIV incidence three-fold, and that men who acquired HSV-2 during follow-up had a six-fold risk of HIV incidence, in analyses adjusted for sexual behaviour. These results are very similar to those found in a systematic review [1]. This included cohort and nested case–control studies up to 2004, and identified 18 that were adjusted for age and sexual behaviour. We have re-run the meta-analysis including more recent studies that fit the same criteria (Fig. 1). Six additional studies, as well as that by Tobian et al.[5], are included: one in men from the circumcision trial in South Africa [6]; two in women in the general population, in Uganda and Zimbabwe [7]; two in female sex workers in Kenya [8] and Tanzania [9]; and one in men who have sex with men (MSM) in the US [10]. Summary estimates of the relative risk (RR) show a strong and consistent association of prevalent HSV-2 and incident HIV after adjusting for age and measures of sexual behaviour [RRwomen = 3.4, 95% confidence interval (CI) 2.4–4.8; RRmen = 2.8, 2.1–3.7; RRsex workers = 1.5, 0.75–3.0; RRMSM = 1.6, 1.2–2.0). In addition, a cohort study in Uganda found an adjusted rate ratio of 8.7 (1.1–67.2) for men and women combinedItem Performance of Commercial Herpes Simplex Virus Type-2 Antibody Tests Using SerumSamples From Sub-Saharan Africa: A Systematic Review and Meta-analysis(Biraro, S., Mayaud, P., Morrow, R. A., Grosskurth, H., & Weiss, H. A. (2011). Performance of commercial herpes simplex virus type-2 antibody tests using serum samples from Sub-Saharan Africa: a systematic review and meta-analysis. Sexually transmitted diseases, 140-147., 2011) Biraro, Samuel; Mayaud, Philippe; Morrow, Rhoda Ashley; Grosskurth, Heiner; Weiss, Helen A.Several commercial type-specific serologic tests are available for herpes simplex virus type 2 (HSV-2). Poor specificity of some tests has been reported on samples from sub-Saharan Africa. Methods: To summarize the performance of the tests using samples from sub-Saharan Africa, we conducted a systematic review of publi- cations reporting performance of commercially available HSV-2 tests against a gold standard (Western Blot or monoclonal antibody-blocking EIA). We used random-effects meta-analyses to summarize sensitivity and specificity of the 2 most commonly evaluated tests, Kalon gG2 enzyme-linked immunosorbent assay (ELISA), and Focus HerpeSelect HSV-2 ELISA. Results: We identified 10 eligible articles that included 21 studies of the performance of Focus, and 12 of Kalon. The primary analyses included studies using the manufacturers' cut-offs (index value = 1.1). Focus had high sensitivity (random effects summary estimate 99%, 95% confidence interval [CI]: 99%-100%) but low specificity (69%, 95% CI: 59%- 80%). Kalon had sensitivity of 95% (95% CI: 93%- 97%) and specificity of 91% (95% CI: 86%-95%). Specificity of Focus was significantly lower ( P = 0.002) among HIV-positive (54%, 95% CI: 40%- 68%) than HIV-negative individuals (69%, 95% CI: 56%- 82%). When the cut-off optical density index was increased above the recommended value of 1.1 to between 2.2 and 3.5, the specificity of Focus increased to 85% (95% CI: 77%-92%). Conclusions: Sensitivity and specificity of HSV-2 tests used in sub-Saharan Africa vary by setting, and are lower than reported from studies in the United States and Europe. Increasing the cut-off optical density index may improve test performance. Evaluation of test per- formance in a given setting may help deciding which test is most appropriate.Item Supervised Versus Unsupervised Intake Of Six-Dose Artemether-Lumefantrine For Treatment Of Acute, Uncomplicated Plasmodium Falciparum Malaria In Mbarara, Uganda: A Randomised Trial(The Lancet, 2005) Piola, Patrice; Fogg, Carole; Bajunirwe, Francis; Biraro, Samuel; Grandesso, Francesco; Ruzagira, Eugene; Babigumira, Joseph; Kigozi, Isaac; Kiguli, James; Kyomuhendo, Juliet; Ferradini, Laurent; Taylor, Walter; Checchi, Francesco; Guthmann, Jean-PaulThe six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria.We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis.38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97·7% (296 of 303) and 98·0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved.Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.