Browsing by Author "Talisuna, Ambrose O."

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    Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial
    (PLoS clinical trials, 2007) Kamya, Moses R.; Yeka, Adoke; Bukirwa, Hasifa; Lugemwa, Myers; Rwakimari, John B.; Staedke, Sarah G.; Talisuna, Ambrose O.; Mangen, Fred Wabwire
    To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Randomized single-blinded clinical trial.Apac, Uganda, an area of very high malaria transmission intensity.Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%–26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%–19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%–12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%–16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.
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    Ebola Hemorrhagic Fever Associated with Novel Virus Strain, Uganda, 2007–2008
    (Emerging infectious diseases, 2010) Wamala, Joseph F.; Lukwago, Luswa; Malimbo, Mugagga; Nguku, Patrick; Yoti, Zabulon; Musenero, Monica; Amone, Jackson; Mbabazi, William; Nanyunja, Miriam; Zaramba, Sam; Opio, Alex; Lutwama, Julius J.; Talisuna, Ambrose O.; Okware, Sam I.
    During August 2007–February 2008, the novel Bundibugyo ebola virus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a caseseries investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebola virus was less fatal (case fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78–8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions.
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    Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial
    (Bmj, 2009) Achan, Jane; Tibenderana, James K.; Kyabayinze, Daniel; Wabwire Mangen, Fred; Kamya, Moses R.; Dorsey, Grant; D’Alessandro, Umberto; Rosenthal, Philip J.; Talisuna, Ambrose O.
    Objective To compare the effectiveness of oral quininewith that of artemether-lumefantrine in treatinguncomplicated malaria in children.Design Randomised, open label effectiveness study.Setting Outpatient clinic of Uganda’s national referral hospital in Kampala.Participants 175 children aged 6 to 59 months withuncomplicated malaria.Interventions Participants were randomised to receiveoral quinine or artemether-lumefantrine administered bycare givers at home.Main outcome measures Primary outcomes wereparasitological cure rates after 28 days of follow-upunadjusted and adjusted by genotyping to distinguishrecrudescence from new infections. Secondary outcomeswere adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles.Results Using survival analysis the cure rate unadjustedby genotyping was 96% for the artemether-lumefantrinegroup compared with 64% for the quinine group (hazardratio10.7, 95% confidence interval 3.3 to 35.5, P=0.001).In the quinine group 69% (18/26) of parasitologicalfailures were due to recrudescence compared with none inthe artemether-lumefantrine group. The mean adherenceto artemether-lumefantrine was 94.5% compared with85.4% to quinine (P=0.0008). Having adherence levels of80% or more was associated with a decreased risk oftreatment failure (0.44, 0.19 to 1.02, P=0.06). Adverseevents did not differ between the two groups.ConclusionsThe effectiveness of a seven day course ofquinine for the treatment of uncomplicated malariainUgandanchildren was significantly lower than that ofartemether-lumefantrine. These findings question theadvisability of the recommendation for quinine therapyfor uncomplicated malaria in Africa.Trial registration ClinicalTrials.gov NCT00540202.
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    Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
    (BMC infectious diseases, 2017) Byakika-Kibwika, Pauline; Achan, Jane; Lamorde, Mohammed; Karera-Gonahasa, Carine; Kiragga, Agnes N.; Mayanja-Kizza, Harriet; Kiwanuka, Noah; Nsobya, Sam; Talisuna, Ambrose O.; Merry, Concepta
    Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral arte
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    Quinine monotherapy for treating uncomplicated malaria in the era of artemisinin-based combination therapy: an appropriate public health policy?
    (The Lancet infectious diseases, 2009) Yeka, Adoke; Achan, Jane; D’Alessandro, Umberto; Talisuna, Ambrose O.
    Several African countries that have adopted artemisinin-based combination therapy (ACT) as fi rst-line treatment of uncomplicated Plasmodium falciparum malaria also use quinine monotherapy as second-line therapy. This policy goes against WHO recommendations for combination therapy and could be considered an inappropriate public health policy. Adherence to a 7-day quinine treatment schedule is likely to be poor and may increase the risk of selecting resistant parasites. Furthermore, because quinine has limited post-treatment prophylaxis, it will not prevent, in areas of intense transmission, recurrent malaria infections, which can lead to additional morbidity, including anaemia. Therefore, ACTs and not quinine should be used as second-line treatment, because these are well tolerated, highly effi cacious, and have the advantage of reducing gametocyte carriage and consequently malaria transmissibility, particularly in areas of less intense transmission.
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    Quinine, an old anti-malarial drug in a Modern world: role in the treatment of Malaria
    (Malaria journal, 2011) Achan, Jane; Talisuna, Ambrose O.; Erhart, Annette; Yeka, Adoke; Tibenderana, James K.; Baliraine, Frederick N.; Rosenthal, Philip J.; D’Alessandro, Umberto;
    Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented.However, itscontinued use is challenged by its poor tolerability, poor compliance with complex dosing regimens,and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine,considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In lightof recent research findings intravenous artesunate should be thefirst-line drug for severe malaria, with quinine asan alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored,but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the managementof malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives becomeavailable. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option thanquinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapidwithdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions toACT stock-outs, maintain quinine in case ofACT stock-outs, and evaluate strategies for improving quininetreatment outcomes by combining it with antibiotics. In HIV andTB infected populations, concerns about potentialinteractions between quinine and antiretroviral and antituberculosis drugs exist, andthese will need furtherresearch and pharmacovigilance.
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    Role of the pfcrt codon 76 mutation as a molecular marker for population-based surveillance of chloroquine (CC&resistant Plasmodium falciparum malaria in Ugandan sentinel sites with high CQ resistance
    (Transactions of the Royal Society of Tropical Medicine and Hygiene, 2002) Talisuna, Ambrose O.; Kyosiimire-Lugemwa, Jackie; Langi, Peter; Mutabingwa, Theonest K.; Watkins, William; Marck, Eric Van; Egwang, Thomas; D'Alessandro, Umberto
    The mutant genotype at codon 76 of the pfcrt gene (T76) has been proposed as a molecular marker for surveillance of chloroquine (CQ)-resistant Plasmodium falciparum malaria but this proposal has not been validated by population-based surveys. In 1998–1999, in 6 Ugandan sentinel sites, the prevalence of P. falciparum infections with the T76 genotype and the level of CQ use were measured by community surveys, and CQ resistance was determined by in-vivo tests on 6–59-month-old children with clinical malaria. The prevalence of T76 was not related to the overall clinical (early and late treatment failure: ETF+LTF; r = 0 · 14, P = 0 · 78) or parasitological (RI+RII+RIII; r = 0 · 17, P = 0 · 73) CQ resistance. However, the percentage of individuals carrying only infections with the T76 genotype (T76 alone) increased with increasing ETF (r = 0 · 76, P = 0 · 07) and type RIII parasitological failure (r = 0 · 69, P = 0 · 12). Similarly, the ratio between T76 and K76 (the wild type) prevalences () was strongly and positively correlated with ETF (r = 0 · 85, P = 0 · 03) and RIII (r = 0 · 82, P = 0 · 04). Moreover, T76 alone (r = 0 · 90, P = 0 · 01) as well as (r = 0 · 90, P = 0 · 01) significantly increased with increasing community CQ use. T76 alone and can be useful markers to estimate the ETF and RIII prevalence as well as the amount of CQ use in the community.
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    Uganda’s Experience in Ebola Virus Disease Outbreak Preparedness, 2018–2019
    (Globalization and health, 2020) Aceng, Jane Ruth; Ario, Alex R.; Muruta, Allan N.; Nanyunja, Miriam; N. Bakainaga, Andrew; Talisuna, Ambrose O.
    Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda’s experience in EVD preparedness.On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significantand verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a “fire-fighting” approach during public health emergencies.