251 results on '"Kamugisha, Erasmus"'
Search Results
2. Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania
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Ishengoma, Deus S., Mandara, Celine I., Madebe, Rashid A., Warsame, Marian, Ngasala, Billy, Kabanywanyi, Abdunoor M., Mahende, Muhidin K., Kamugisha, Erasmus, Kavishe, Reginald A., Muro, Florida, Mandike, Renata, Mkude, Sigsbert, Chacky, Frank, Njau, Ritha, Martin, Troy, Mohamed, Ally, Bailey, Jeffrey A., and Fola, Abebe A.
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- 2024
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3. Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
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Bakari, Catherine, Mandara, Celine I., Madebe, Rashid A., Seth, Misago D., Ngasala, Billy, Kamugisha, Erasmus, Ahmed, Maimuna, Francis, Filbert, Bushukatale, Samwel, Chiduo, Mercy, Makene, Twilumba, Kabanywanyi, Abdunoor M., Mahende, Muhidin K., Kavishe, Reginald A., Muro, Florida, Mkude, Sigsbert, Mandike, Renata, Molteni, Fabrizio, Chacky, Frank, Bishanga, Dunstan R., Njau, Ritha J. A., Warsame, Marian, Kabula, Bilali, Nyinondi, Ssanyu S., Lucchi, Naomi W., Talundzic, Eldin, Venkatesan, Meera, Moriarty, Leah F., Serbantez, Naomi, Kitojo, Chonge, Reaves, Erik J., Halsey, Eric S., Mohamed, Ally, Udhayakumar, Venkatachalam, and Ishengoma, Deus S.
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- 2024
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4. Lumefantrine plasma concentrations in uncontrolled conditions among patients treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in Mwanza, Tanzania
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Marwa, Karol J, Liwa, Anthony C, Konje, Eveline T, Mwita, Stanley, Kamugisha, Erasmus, and Swedberg, Göte
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- 2022
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5. Utility of passive malaria surveillance in hospitals as a surrogate to community infection transmission dynamics in western Kenya
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Kapesa, Anthony, Kweka, Eliningaya J, Zhou, Guofa, Atieli, Harrysone Etemesi, Kamugisha, Erasmus, Mazigo, Humphrey D, Ngallaba, Sospatro E, Githeko, Andrew K, and Yan, Guiyun
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Epidemiology ,Midwifery ,Public Health ,Health Sciences ,Infectious Diseases ,Rare Diseases ,Clinical Trials and Supportive Activities ,Malaria ,Vector-Borne Diseases ,Clinical Research ,Infection ,Good Health and Well Being ,Malaria blood slide positivity ,Outpatient department ,School age children ,Public Health and Health Services ,Public health - Abstract
BackgroundMalaria continued to be the major public health concern in sub-Sahara Africa, thus for better planning of control activities, periodic surveillance of both clinical and asymptomatic cases remains important. However, the usability of routinely collected malaria data in Kenyan hospitals as a predictor of the asymptomatic malaria infection in the community amidst rapid infection resurgence or reduction in different areas of disease endemicities remains widely unstudied. This study was therefore aimed to evaluate the utility of passive surveillance of malaria in health facilities as a proxy of infection transmission of the surrounding community in different transmission intensities.MethodsProspective multiple cross-sectional surveys were done in three villages in western Kenya. Monthly asymptomatic malaria positivity among school children, number of outpatient (OPD) confirmed malaria cases and abundancy of indoor resting malaria vectors were surveyed from June 2015 to August 2016. Community surveys on antimalarial drug use among adults and children were also done. Detection of malaria parasitaemia was done using thick and thin Giemsa stained blood slide microscopy for both clinical and school participants. A questionnaire was used to collect information on self-use of antimalarial drugs from randomly selected households.ResultsThe overall OPD blood slide positivity from all study sites was 26.6% (95%CI 26.2-27.0) and highest being among the 5-14 years (41.2% (95% CI 40.1-42.3). Asymptomatic malaria positivity among the school children were 6.4% (95%CI 5.3-7.5) and 38.3% (95%CI 36.1-40.5) in low and high transmission settings respectively. A strong correlation between overall monthly OPD positivity and the school age children positivity was evident at Marani (low transmission) (rho = 0.78, p = 0.001) and at Iguhu (Moderate transmission) (rho = 0.61, p = 0.02). The high transmission setting (Kombewa) showed no significant correlation (rho = - 0.039, p = 0.89).ConclusionHospital malaria data from low and moderate malaria transmission predicted the infection transmission dynamics of the surrounding community. In endemic sites, hospital based passive surveillance didn't predict the asymptomatic infection dynamics in the respective community.
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- 2018
6. The current malaria morbidity and mortality in different transmission settings in Western Kenya
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Kapesa, Anthony, Kweka, Eliningaya J, Atieli, Harrysone, Afrane, Yaw A, Kamugisha, Erasmus, Lee, Ming-Chieh, Zhou, Guofa, Githeko, Andrew K, and Yan, Guiyun
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Infectious Diseases ,Malaria ,Vector-Borne Diseases ,Rare Diseases ,Clinical Research ,Aetiology ,2.4 Surveillance and distribution ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Antimalarials ,Child ,Child ,Preschool ,Communicable Disease Control ,Female ,Hospitalization ,Humans ,Kenya ,Male ,Outpatients ,Parasitemia ,Patient Discharge ,Population Surveillance ,Prevalence ,Prospective Studies ,Public Health ,Seasons ,Young Adult ,General Science & Technology - Abstract
BackgroundPassive surveillance of malaria in health facilities remains vital for implementation of control and elimination programs. It is therefore essential understanding current age profile of clinical malaria morbidity, mortality and presentations in areas with variant infection susceptibility. This study aimed at understanding the current malaria morbidity and mortality in Western Kenya.MethodsSurveillance of clinical and asymptomatic parasitological positivity rates of all malaria suspected patients and school children were respectively determined from June 2015 to August 2016. From 2014 to 2016, register books in hospitals were referred and the confirmed malaria cases in conjunction with total number of monthly outpatient visits (OPD) counted. All registered malaria admissions were counted together with other causes of admissions. Moreover, outcome of malaria admissions in terms of discharge or death was recorded using inpatient charts within the same time frame. Prospective surveillance of severe malaria collected information on clinical features of the disease. Giemsa stained blood slides confirmed existence of malaria parasitemia. Chi-square and analysis of variance tests were used, respectively, to compute proportions and means; then a comparison was made between different age groups, periods, and study areas.ResultsDuring the survey of asymptomatic infections among school children, overall blood slide positivity ranged from 6.4% at the epidemic prone site to 38.3% at the hyperendemic site. During the clinical malaria survey, school age children (5-14) presented with overall the highest (45%) blood slide positivity rate among those suspected to have the infection at the epidemic prone study site. The survey of all malaria confirmed and registered cases at OPD found 17% to 27% of all consultations among 0.05) and 40% of all malaria admissions were school age children. Malaria related death rate was highest among
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- 2018
7. Why some sites are responding better to anti-malarial interventions? A case study from western Kenya.
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Kapesa, Anthony, Kweka, Eliningaya J, Atieli, Harrysone, Kamugisha, Erasmus, Zhou, Guofa, Githeko, Andrew K, and Yan, Guiyun
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Animals ,Humans ,Plasmodium falciparum ,Malaria ,Bites and Stings ,Pyrethrins ,Nitriles ,Antimalarials ,Insecticides ,Cross-Sectional Studies ,Disease Vectors ,Population Density ,Mosquito Control ,Insecticide Resistance ,Geography ,Kenya ,Insecticide-Treated Bednets ,Climate Change ,Early Medical Intervention ,Mosquito Vectors ,Climate variability ,Insecticide resistance ,Malaria intervention ,Species shift ,Western Kenya ,Tropical Medicine ,Medical Microbiology ,Public Health and Health Services ,Microbiology - Abstract
BackgroundIn sub-Saharan Africa, malaria interventions over the last decades have been successful in reducing both mortality and morbidity. In western Kenya however some areas experience contrasting outcomes of the ongoing interventions while the causes for this observation remains not yet clearly known.MethodsThe WHO insecticide (deltamethrin) susceptibility test of the common malaria vectors was studied. Multiple surveys on household use and hospital prescriptions of antimalarial drugs from 2003 to 2015 were done. Along with this, cross sectional surveys on their availability in the local drug dispensing outlets were also done in 2015. Monthly precipitations and air temperature data was collected along with systematic review on abundance and composition of common malaria vectors in the study area before and during interventions. The above factors were used to explain the possible causes of contrasting outcome of malaria interventions between the three study sites.ResultsAreas with malaria resurgence or sustained high transmission (Kombewa and Marani) showed higher composition of Anopheles funestus sensu lato (s.l.) than the previously abundant Anopheles gambiae sensu stricto (s.s.) and the later had higher composition to an area with a sustained infection decline (Iguhu). Anopheles gambiae s.l. from Kombewa showed highest resistance (50% mortality) upon exposure to WHO deltamethrin discriminating dosage of 0.75% while those from Marani and Iguhu had reduced resistance status (both had a mean mortality of 91%). Sampled An. funestus s.l. from Marani were also highly resistant to deltamethrin as 57% of the exposed vectors survived. An increasing of mean air temperature by 2 °C was noted for Marani and Iguhu from 2013 to 2015 and was accompanied by an increased rainfall at Marani. Community drug use and availability in selling outlets along with prescription in hospitals were not linked to the struggling control of the disease.ConclusionsThe malaria vector species composition shift, insecticide resistance and climatic warming were the likely cause of the contrasting outcome of malaria intervention in western Kenya. Surveillance of malaria parasite and vector dynamics along with insecticide resistance and vector biting behaviour monitoring are highly recommended in these areas.
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- 2017
8. Surveillance for sickle cell disease, United Republic of Tanzania/Surveillance de la drepanocytose en Republique-Unie de Tanzanie/Vigilancia de la drepanocitosis en la Republica Unida de Tanzania
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Ambrose, Emmanuela E., Smart, Luke R., Charles, Mwesige, Hernandez, Arielle G., Latham, Teresa, Hokororo, Adolfine, Beyanga, Medard, Howard, Thad A., Kamugisha, Erasmus, McElhinney, Kathryn E., Tebuka, Erius, and Ware, Russell E.
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Sickle cell anemia -- Analysis ,HIV (Viruses) -- Analysis ,Hemoglobin -- Analysis ,Medical policy -- Analysis ,Phosphates -- Analysis ,Medical screening -- Analysis ,Health - Abstract
Objective To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. Methods We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of [alpha]-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. Findings We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion [alpha]-thalassaemia trait. We documented G6PD [A.sup.-] deficiency in 19.2% (14/73) of males. Conclusion Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available. Objectif Determiner la prevalence de la drepanocytose et du trait drepanocytaire chez les nouveau-nes, ainsi que la prevalence de variants d'hemoglobine et de modificateurs genetiques de la drepanocytose dans les neufregions du nord-ouest de la Republique-Unie de Tanzanie. Methodes Nous avons reutilise des echantillons de gouttes de sang seche provenant d'enfants (ages de 0 a 24 mois) nes de meres atteintes du virus de l'immunodeficience humaine (VIH), preleves dans le cadre du programme de diagnostic precoce de l'infection a VIH chez le nourrisson pour detecter une eventuelle drepanocytose. Nous avons procede a une focalisation isoelectrique pour savoir si les echantillons presentaient une hemoglobine normale, un trait drepanocytaire, une drepanocytose ou un variant d'hemoglobine rare. Ensuite, nous avons envoye les echantillons identifies comme porteurs de la maladie ou d'un variant a l'hopital pour enfants de Cincinnati, aux Etats-Unis, afin d'analyser l'acide desoxyribonucleique et de mesurer la prevalence d'une [alpha]-thalassemie, d'un deficit en glucose-6-phosphate deshydrogenase (G6PD) ou de modificateurs genetiques de l'hemoglobine foetale. Resultats Nous avons etudie 17 200 specimens au total entre fevrier 2017 et mai 2018. Nous avons observe une prevalence de 20,3% (3492/17 200) pour la drepanocytose, et de 1,2% (210/17 200) pour le trait drepanocytaire. D'un district a l'autre, la presence du trait variait de 8,6% (5/58) a 28,1% (77/274). Nous avons constate que 42,7% (61/143) des specimens chez qui une drepanocytose avait ete confirmee etaient prives d'un gene, et 14,7% (21/143) de deux genes du trait [alpha]-thalassemique. Enfin, nous avons repertorie un deficit en G6PD [A.sup.-] chez 19,2% (14/73) des males. Conclusion La prevalence que nous avons calculee est deux fois superieure aux chiffres mentionnes precedemment, et souligne la necessite d'instaurer de meilleurs services de diagnostic de la drepanocytose. Nos donnees reparties par district fourniront des informations en matiere de politique de sante publique, afin que le depistage et le traitement modificateur de la maladie, a base d'hydroxyuree, se concentrent sur les zones de forte prevalence jusqu'a ce qu'un depistage universel des nouveau-nes soit disponible. Objetivo Determinar la prevalence de la enfermedad y del rasgo de las celulas falciformes en los recien nacidos a nivel regional y de distrito, y la prevalencia de las variantes de hemoglobina y de los modificadores geneticos de la drepanocitosis en las nueve regiones del noroeste de la Republica Unida de Tanzania. Metodos Se reutilizaron las muestras de las manchas de sangre seca de los ninos (de 0 a 24 meses de edad) nacidos de madres que padecian el virus de la inmunodeficiencia humana (VIH); estas muestras se obtuvieron a traves del programa de Diagnostico precoz del VIH en ninos para diagnosticar las celulas falciformes. Se aplico la tecnica del enfoque isoelectrico para determinar si las muestras tenian hemoglobina, rasgos de celulas falciformes, drepanocitosis normales o una variante de hemoglobina poco frecuente. Se enviaron muestras diagnosticadas como enfermedad o variante al Hospital Infantil de Cincinnati (Cincinnati Children's Hospital) en los Estados Unidos de America para analizarlas a base de acido desoxirribonucleico y asi determinar la prevalencia de talasemia a, de deficiencia de glucosa-6-fosfato deshidrogenasa (G6PD, por sus siglas en ingles) o de modificadores geneticos de hemoglobina fetal. Resultados Se analizaron un total de 17 200 muestras entre febrero de 2017 y mayo de 2018. Se observo una prevalencia del rasgo de las celulas falciformes y de la drepanocitosis del 20,3 % (3492/17 200) y del 1,2 % (210/17 200), respectivamente. El rasgo a nivel de distrito vario del 8,6 % (5/58) al 28,1 % (77/274). Se observo que en las muestras de drepanocitosis confirmadas, el 42,7 % (61/143) presentaba la eliminacion de un gen y el 14,7 % (21/143) la eliminacion de dos genes en el rasgo de talasemia a. Se registro una deficiencia de G6PD [A.sup.-] en el 19,2 % (14/73) de los varones. Conclusion La prevalencia que se calcula aqui es el doble de la que se notifico anteriormente y refuerza la necesidad de mejorar los servicios para el diagnostico de la drepanocitosis. Estos datos a nivel de distrito contribuiran a la politica de salud publica, ya que permitiran que los cribados y la terapia con hidroxicarbamida que modifica la enfermedad se centren en las zonas de alta prevalencia, hasta que se disponga de un cribado universal de los recien nacidos. [phrase omitted], Introduction Sickle cell disease is an inherited disorder of haemoglobin, caused by a mutation in the [beta]-globin subunit of adult haemoglobin. In classic autosomal recessive fashion, inheritance of one abnormal [...]
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- 2020
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9. Artemether–lumefantrine and dihydroartemisinin–piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza, Tanzania
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Marwa, Karol J., Konje, Eveline T., Kapesa, Anthony, Kamugisha, Erasmus, Mwita, Stanley, and Swedberg, Göte
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- 2021
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10. The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review
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Marwa, Karol J, primary, Kapesa, Anthony, additional, Kamugisha, Erasmus, additional, and Swedberg, Göte, additional
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- 2023
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11. The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa : A Systematic Review
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Marwa, Karol J., Kapesa, Anthony, Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol J., Kapesa, Anthony, Kamugisha, Erasmus, and Swedberg, Göte
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Background: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations. Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies. Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles. Conclusion: This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among P. falciparum malaria patients.
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- 2023
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12. The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review
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Marwa,Karol J, Kapesa,Anthony, Kamugisha,Erasmus, Swedberg,Göte, Marwa,Karol J, Kapesa,Anthony, Kamugisha,Erasmus, and Swedberg,Göte
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Karol J Marwa,1 Anthony Kapesa,2 Erasmus Kamugisha,3 Göte Swedberg4 1Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Department of Community Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 3Department of Biochemistry, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 4Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SwedenCorrespondence: Karol J Marwa, Department of Pharmacology, Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania, Tel +255769861421, Email carol_maro@yahoo.com; karoljuliusmarwa@gmail.comBackground: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.Conclusion: This review reports lack of influence of
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- 2023
13. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania
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Ishengoma, Deus S., Mandara, Celine I., Francis, Filbert, Talundzic, Eldin, Lucchi, Naomi W., Ngasala, Billy, Kabanywanyi, Abdunoor M., Mahende, Muhidin K., Kamugisha, Erasmus, Kavishe, Reginald A., Muro, Florida, Mohamed, Ally, Mandike, Renata, Mkude, Sigsbert, Chacky, Frank, Paxton, Lynn, Greer, George, Kitojo, Chonge A., Njau, Ritha, Martin, Troy, Venkatesan, Meera, Warsame, Marian, Halsey, Eric S., and Udhayakumar, Venkatachalam
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- 2019
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14. Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania
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Kakolwa, Mwaka A., Mahende, Muhidin K., Ishengoma, Deus S., Mandara, Celine I., Ngasala, Billy, Kamugisha, Erasmus, Kataraihya, Johannes B., Mandike, Renata, Mkude, Sigsbert, Chacky, Frank, Njau, Ritha, Premji, Zul, Lemnge, Martha M., Warsame, Marian, Menard, Didier, and Kabanywanyi, Abdunoor M.
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- 2018
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15. Plasmodium falciparum Merozoite Surface Proteins Polymorphisms and Treatment Outcomes among Patients with Uncomplicated Malaria in Mwanza, Tanzania
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Marwa, Karol J., primary, Lyimo, Eric, additional, Konje, Eveline T., additional, Kapesa, Anthony, additional, Kamugisha, Erasmus, additional, and Swedberg, Göte, additional
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- 2022
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16. Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
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Mansoor, Rashid, Commons, Robert J, Douglas, Nicholas M, Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O, Adjuik, Martin, Alemayehu, Bereket H, Allan, Richard, Allen, Elizabeth N, Anvikar, Anupkumar R, Arinaitwe, Emmanuel, Ashley, Elizabeth A, Ashurst, Hazel, Asih, Puji BS, Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J, Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy ME, Desai, Meghna, Djimde, Abdoulaye A, Dondorp, Arjen M, Dorsey, Grant, Drakeley, Chris J, Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F, Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S, Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S Patrick, Kager, Piet A, Kamugisha, Erasmus, Kamya, Moses R, Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G, Lalloo, David G, Laman, Moses, Lee, Sue J, Lell, Bertrand, Maiga, Amelia W, Martensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R, Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N, Ngasala, Billy E, Nikiema, Frederic, Nji, Akindeh M, Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R, Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K, Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L, Rombo, Lars, Rosenthal, Philip J, Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B, Smithuis, Frank M, Some, Fabrice A, Staedke, Sarah G, Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D, Syafruddin, Din, Talisuna, Ambrose O, Taylor, Walter R, Temu, Emmanuel A, Thwing, Julie I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A, Tran, T Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A, Were, Vincent, White, Nicholas J, Woodrow, Charles J, Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A, Guerin, Philippe J, Stepniewska, Kasia, Price, Ric N, Roper, Cally, Resistance, WorldWide Antimalarial, WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Group, WorldWide Antimalarial Resistance Network Falciparum Haematology Study, Mansoor, R, Ashley, EA, Ashurst, H, Burrow, R, Carrara, VI, Das, D, Dondorp, AM, Humphreys, GS, Lee, SJ, Mayxay, M, McGready, R, Newton, PN, Nosten, F, Richmond, CL, Sibley, C, Smithuis, FM, Taylor, WR, Tran, TH, von Seidlein, L, White, NJ, Woodrow, CJ, Guerin, PJ, Stepniewska, K, Price, RN, AII - Infectious diseases, Intensive Care Medicine, Infectious diseases, APH - Global Health, and APH - Quality of Care
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Infectious Medicine ,Plasmodium falciparum ,wh_120 ,Infektionsmedicin ,Severe anaemia ,Parasitemia ,wa_530 ,Antimalarials ,Non-artemisinin-based therapy ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,parasitic diseases ,qv_256 ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Malaria, Falciparum ,Child ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Pooled analysis of individual patient data ,Anemia ,Public Health, Global Health, Social Medicine and Epidemiology ,General Medicine ,Artemisinin-based therapy ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Malaria ,wc_750 ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Haemoglobin - Abstract
Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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- 2022
17. Therapeutic efficacy of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa : A systematic review and meta-analysis
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Marwa, Karol, Kapesa, Anthony, Baraka, Vito, Konje, Evelyne, Kidenya, Benson, Mukonzo, Jackson, Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol, Kapesa, Anthony, Baraka, Vito, Konje, Evelyne, Kidenya, Benson, Mukonzo, Jackson, Kamugisha, Erasmus, and Swedberg, Göte
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Background Sub-Saharan Africa has the highest burden of malaria in the world. Artemisinin-based combination therapies (ACTs) have been the cornerstone in the efforts to reduce the global burden of malaria. In the effort to facilitate early detection of resistance for artemisinin derivatives and partner drugs, WHO recommends monitoring of ACT's efficacy in the malaria endemic countries. The present systematic meta-analysis study summarises the evidence of therapeutic efficacy of the commonly used artemisinin-based combinations for the treatment of uncomplicated P. falciparum malaria in Sub-Saharan Africa after more than a decade since the introduction of the drugs. Methods Fifty two studies carried out from 2010 to 2020 on the efficacy of artemether-lumefantrine or dihydro-artemisinin piperaquine or artesunate amodiaquine in patients with uncomplicated P. falciparum malaria in Sub-Saharan Africa were searched for using the Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. Data was extracted by two independent reviewers. Random analysis effect was performed in STATA 13. Heterogeneity was established using I-2 statistics. Results Based on per protocol analysis, unadjusted cure rates in malaria infected patients treated with artemether-lumefantrine (ALU), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DHP) were 89%, 94% and 91% respectively. However, the cure rates after PCR correction were 98% for ALU, 99% for ASAQ and 99% for DHP. Conclusion The present meta-analysis reports the overall high malaria treatment success for artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine above the WHO threshold value in Sub-Saharan Africa.
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- 2022
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18. Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
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Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Bassat, Quique, Borrmann, Steffen, Bousema, Teun, Bukirwa, Hasifa, Carrara, Verena, I, Corsi, Marco, D'Alessandro, Umberto, Davis, Timothy M. E., Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Gilayeneh, Julius, Greenwood, Brian, Grivoyannis, Anastasia, Hien, Tran Tinh, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy, Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Ogutu, Bernhards R., Olliaro, Piero L., Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher, V, Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Vitare, Primum, Rombo, Lars, Rosenthal, Philip J., Sibley, Carol, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala, Thuy-Nhien, Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan D., van Herp, Michel, van Lenthe, Marit, van Vugt, Michele, William, Yavo, Winnips, Cornelis, Zaloumis, Sophie, Zongo, Issaka, White, Nick J., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Arinaitwe, Emmanuel, Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Bassat, Quique, Borrmann, Steffen, Bousema, Teun, Bukirwa, Hasifa, Carrara, Verena, I, Corsi, Marco, D'Alessandro, Umberto, Davis, Timothy M. E., Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Gilayeneh, Julius, Greenwood, Brian, Grivoyannis, Anastasia, Hien, Tran Tinh, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy, Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Ogutu, Bernhards R., Olliaro, Piero L., Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher, V, Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Vitare, Primum, Rombo, Lars, Rosenthal, Philip J., Sibley, Carol, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala, Thuy-Nhien, Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan D., van Herp, Michel, van Lenthe, Marit, van Vugt, Michele, William, Yavo, Winnips, Cornelis, Zaloumis, Sophie, Zongo, Issaka, White, Nick J., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Arinaitwe, Emmanuel
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Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days
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- 2022
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19. Plasmodium falciparum Merozoite Surface Proteins Polymorphisms and Treatment Outcomes among Patients with Uncomplicated Malaria in Mwanza, Tanzania
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Marwa, Karol J., Lyimo, Eric, Konje, Eveline T., Kapesa, Anthony, Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol J., Lyimo, Eric, Konje, Eveline T., Kapesa, Anthony, Kamugisha, Erasmus, and Swedberg, Göte
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Background. The severity of malaria infection depends on the host, parasite and environmental factors. Merozoite surface protein (msp) diversity determines transmission dynamics, P. falciparum immunity evasion, and pathogenesis or virulence. There is limited updated information on P. falciparum msp polymorphisms and their impact on artemether-lumefantrine treatment outcomes in Tanzania. Therefore, this study is aimed at examining msp genetic diversity and multiplicity of infection (MOI) among P. falciparum malaria patients. The influence of MOI on peripheral parasite clearance and adequate clinical and parasitological response (ACPR) was also assessed. Methods. Parasite DNA was extracted from dried blood spots according to the manufacture's protocol. Primary and nested PCR were performed. The PCR products for both the block 2 region of msp1 and the block 3 regions of msp2 genes and their specific allelic families were visualized on a 2.5% agarose gel. Results. The majority of the isolates, 58/102 (58.8%) for msp1 and 69/115 (60.1%) for msp2, harboured more than one parasite genotypes. For the msp1 gene, K1 was the predominant allele observed (75.64%), whereas R033 occurred at the lowest frequency (43.6%). For the msp2 gene, the 3D7 allele was observed at a higher frequency (81.7%) than the FC27 allele (76.9%). The MOIs were 2.44 for msp1 and 2.27 for msp2 (p = 0.669). A significant correlation between age and multiplicity of infection (MOI) for msp1 or MOI for msp2 was not established in this study (rho = 0.074, p = 0.521 and rho = -0.129, p = 0.261, respectively). Similarly, there was no positive correlation between parasite density at day 1 and MOI for both msp1 (rho = 0.113, p = 0.244) and msp2 (rho = 0.043, p = 0.712). The association between MOI and ACPR was not observed for either msp1 or mps2 (p = 0.776 and 0.296, respectively). Conclusions. This study reports high polyclonal infections, MOI and allelic frequencies for both msp1 and msp2. There was a lack of
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- 2022
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20. Lumefantrine plasma concentrations in uncontrolled conditions among patients treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in Mwanza, Tanzania
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Marwa, Karol J., Liwa, Anthony C., Konje, Eveline, Mwita, Stanley, Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol J., Liwa, Anthony C., Konje, Eveline, Mwita, Stanley, Kamugisha, Erasmus, and Swedberg, Göte
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Background: Therapeutic efficacy of artemether-lumefantrine is highly dependent on adequate systemic exposure to the partner drug lumefantrine particularly day 7 lumefantrine plasma concentration. There has been contradicting findings on the role of the cut-off values in predicting treatment outcomes among malaria patients in malaria endemic regions. This study assesses the day 3 and 7 lumefantrine plasma concentrations including related determinant factors and their influence on treatment outcomes among treated Tanzanian children and adults in uncontrolled conditions (real life condition). Methods: Data was nested from an efficacy study employing the WHO protocol, 2015 for monitoring antimalarial drug efficacy. Lumefantrine plasma concentration was measured by high performance liquid chromatography with ultraviolet (HPLC-UV). Results: Lumefantrine plasma concentrations below 175ng/ml and 20 0ng/ml on day 3 and 7 did not affect adequate clinical and parasitological response (ACPR) and recurrence of infection ( p = 0.428 and 0.239 respectively). Age and baseline parasitemia were not as-sociated to day 3 median lumefantrine plasma concentrations (p = 0.08 and 0.31 respectively) and day 7 lumefantrine plasma concentrations (p = 0.07 and 0.41 respectively). However, the day 3 and day 7 lumefantrine plasma concentrations were significantly higher in males compared to females ( p = 0.03 and 0.042 respectively). Conclusion: Lumefantrine plasma concentrations below cut-off points (175ng/ml and 20 0ng/ml) on day 3 and 7 did not influence treatment outcomes.
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- 2022
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21. Therapeutic efficacy of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa: A systematic review and meta-analysis
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Marwa, Karol, primary, Kapesa, Anthony, additional, Baraka, Vito, additional, Konje, Evelyne, additional, Kidenya, Benson, additional, Mukonzo, Jackson, additional, Kamugisha, Erasmus, additional, and Swedberg, Gote, additional
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- 2022
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22. Artemether-lumefantrine and dihydroartemisinin-piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza,Tanzania
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Marwa, Karol J., Konje, Eveline T., Kapesa, Anthony, Kamugisha, Erasmus, Mwita, Stanley, Swedberg, Göte, Marwa, Karol J., Konje, Eveline T., Kapesa, Anthony, Kamugisha, Erasmus, Mwita, Stanley, and Swedberg, Göte
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Background: Artemisinin based combination therapies (ACTs) have been a cornerstone in the treatment of malaria in the world. A rapid decline in dihydroartemisinin piperaquine (DHP) and artemether lumefantrine (ALU) efficacies has been reported in some parts of South East Asia, the historical epicenter for the antimalarial drug resistance. Prolonged drug use is associated with selection of resistant parasites due to exposure to inadequate drug levels hence effects on treatment outcomes in malaria. ALU and DHP are used as first line and alternative first line, respectively, in Tanzania. This study was carried in lgombe, Tanzania to assess the efficacies of ALU and DHP in routine treatment of uncomplicated malaria among children. Methods: This was a prospective study involving children up to 10 years and followed up for 28 and 35 days as per the WHO protocol, 2015 for monitoring antimalarial drug efficacy. The primary end points were crude and adjusted Adequate Clinical and Parasitological Response (ACPR), parasite clearance rate and reported adverse events. Results: A total of 205 children with uncomplicated malaria were enrolled. One hundred and sixteen participants were treated with ALU, while 89 participants were treated with DHP. Two participants in the ALU group were lost within the 24 h of follow-up. The PCR unadjusted ACPR was 108 (94.7%) for ALU and 88 (98.9%) for DHP, while the PCR adjusted ACPR was 109(95.6%) and 88(98.9%) for ALU and DHP, respectively, at 28 day follow-up. No treatment failure was observed in both groups. Cumulative risk of recurrent parasitemia was similar in both groups (p = 0.32). Age and parasite density were strong predictors for persistent day 1 parasitemia (p = 0.034 and 0.026, respectively). Nausea and vomiting, abdominal pain and headache were the most clinical adverse events reported in both groups of patients. Conclusion: The present study shows that ALU and DHP are still efficacious after more than a decade of use with PCR corre
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- 2021
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23. Genetic Analysis in the Tanzania Sickle Surveillance Study (TS3): Modifiers of Sickle Cell Disease and Identification of Hemoglobin Variants
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Smart, Luke R., primary, Ambrose, Emmanuela E., primary, Charles, Mwesige, primary, Hernandez, Arielle G., primary, Latham, Teresa S., primary, Hokororo, Adolfine, primary, Beyanga, Medard, primary, Kamugisha, Erasmus, primary, Tebuka, Erius, primary, Howard, Thad A., primary, and Ware, Russell E., primary
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- 2019
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24. Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
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Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., Stepniewska, Kasia, Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., and Stepniewska, Kasia
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Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold
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- 2019
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25. Relationship between Non-Hodgkin’s lymphoma and blood levels of Epstein-Barr Virus in children in north-western Tanzania: a case control study
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Kabyemera Rogatus, Masalu Nestory, Rambau Peter, Kamugisha Erasmus, Kidenya Benson, De Rossi Anita, Petrara Maria, and Mwizamuholya Damas
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Non-Hodgkin’s Lymphoma ,Children ,HIV ,EBV ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Non-Hodgkin’s Lymphomas (NHL) are common in African children, with endemic Burkitt’s lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. Methods A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). Results A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 – 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). Conclusions BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children.
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- 2013
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26. Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania
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Kamugisha Erasmus, Jing Sun, Minde Mercy, Kataraihya Johaness, Kongola Gilbert, Kironde Fred, and Swedberg Göte
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pfcrt ,pfmdr1 ,pfdhfr ,pfdhps ,pfatp6 ,Mutations ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. Methods A prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously. Results A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/μl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites. Conclusion The efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.
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- 2012
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27. Supply chain management of laboratory supportive services and its potential implications on the quality of HIV diagnostic services in Tanzania
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Kagaruki, Gibson B., Kamugisha, Mathias L., Kilale, Andrew M., Kamugisha, Erasmus, Rutta, Acleus S.M, Baraka, Vito, Mandara, Celine I., Magesa, Stephen M., Materu, Godlisten, Kahwa, Amos M., Madebe, Rashid, Massaga, Julius J., Lemnge, Martha M., Mboera, Leonard E.G., Ishengoma, Deus I., and Global Fund for AIDS, Tuberculosis and Malaria (Grant Number 2013/20).
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laboratory services, supply chain, diagnosis, HIV/AIDS, Tanzania - Abstract
Background: Reliable supply of laboratory supportive services contributes significantly to the quality of HIV diagnostic services. This study assessed the status of supply chain management of laboratory supportive services and its potential implications on the quality of HIV diagnostic services in selected districts of Tanzania.Methods: The study was conducted in 39 health facilities (HFs) from eight districts in four regions of Tanzania, namely Iringa, Mtwara, Tabora and Tanga. Facilities with care and treatment centres for HIV/AIDS patients were purposively selected for the study. The study utilized a quantitative method of data collection. A questionnaire was administered to heads of laboratories to obtain information on laboratory supply chain management.Results: A total of 39 health facilities (HF) were included in the study. This included 23 public and 16 private facilities. In 82% of the HFs, ordering of supplies was performed by the laboratory departments. The information commonly used to forecast requirements of the laboratories included the number of tests done (74.4%; n=29), current stock levels (69.2%; n=27), average monthly consumption (64.1%, n=25) and minimum and maximum stock levels (10.2%, n=4). Emergency orders were significantly common in public than private facilities (73.9% vs. 56.3%, p=0.004). Delivery of ordered supplies took 1 to 180 days with a significantly longer period for public than private facilities (32.5 vs. 13.1 days, p=0.044). Most of the public HFs ordered supplies from diverse sources compared to private facilities (68.2% vs. 31.8%).Conclusion: There was a weak inventory management system and delays in delivery of supplies in the majority of HFs, which are likely to impede quality of HIV care and treatment. Strengthening capacity for data management and ensure constant supply will potentially improve the quality of HIV diagnostic services.
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- 2018
28. Geospatial Mapping of Sickle Cell Disease in Northwest Tanzania: The Tanzania Sickle Surveillance Study (TS3)
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Ambrose, Emmanuela E., primary, Smart, Luke R., additional, Charles, Mwesige, additional, Hernandez, Arielle G., additional, Hokororo, Adolfine, additional, Latham, Teresa, additional, Beyanga, Medard, additional, Tebuka, Erius, additional, Kamugisha, Erasmus, additional, Howard, Thad A., additional, and Ware, Russell E., additional
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- 2018
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29. Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania
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Jeremiah Seni, Mwizamholya Damas L, Kamugisha Erasmus, Kayange Neema, and Mshana Stephen E
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Pediatrics ,RJ1-570 - Abstract
Abstract Background Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. Methods This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Results Among 770 neonates admitted during the study period; 300 (38.9%) neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40%) and 179(60%) had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1%) and 92 (51.4%) among neonates with early and late onset neonatal sepsis respectively (p = 0.466). Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA). Deaths occurred in 57 (19%) of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001), gram negative sepsis (p = 0.0001) and infection with ESBL (p = 0.008) or MRSA (p = 0.008) isolates. Conclusion Our findings suggest that lethargy, convulsion, inability to feed, cyanosis, PROM and meconium stained liquor are significantly associated with positive blood culture in both early and late onset disease. Mortality and morbidity on neonatal sepsis is high at our setting and is significantly contributed by positive blood culture with multi-resistant gram negative bacteria.
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- 2010
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30. Prevalence of multiresistant gram-negative organisms in a tertiary hospital in Mwanza, Tanzania
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Chakraborty Trinad, Mirambo Mariam, Kamugisha Erasmus, Mshana Stephen E, and Lyamuya Eligius F
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Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background Antimicrobial resistance is fast becoming a global concern with rapid increases in multidrug-resistant Gram negative organisms. The prevalence of extended spectrum beta-lactamase (ESBL)-producing clinical isolates increases the burden on implementing infectious disease management in low socio-economic regions. As incidence can vary widely between regions, this study was done to determine resistance patterns of Gram-negative organisms at Bugando Medical Center, a tertiary hospital in Mwanza, Tanzania. Methods A total of 800 clinical samples (urine, wound swab, pus, blood, aspirate, sputum etc) were processed over a period of 6 months. Gram-negative bacteria were identified using conventional in-house biochemical tests and susceptibility to common antibiotics done using disc diffusion methods. The disc approximation method was used to identify ESBL producers. Results A total of 377 Gram-negative bacteria (GNB) recovered from 377 clinical specimens were analyzed of which 76.9% were Enterobacteriaceae. Among all GNB, 110/377 (29.2%) were found to be ESBL producers. Species specific ESBLs rate among Klebsiella pneumoniae, Escherichia coli, Acinetobacter spp, Proteus spp and other enterobacteria were 63.7%, 24.4%, 17.7%, 6.4% and 27.9% respectively. A statistically significant higher number of inpatients 100/283 (35.3%) compared to 10/94 (10.6%) of outpatients had ESBL-producing organisms (p = 0.000023). Rates of resistances to gentamicin, tetracycline, sulphamethaxazole/trimethoprim and ciprofloxacin were significantly higher among ESBLs isolates than non-ESBL isolates (p = 0.000001). Conclusion ESBL producing organisms are common at BMC (Bugando Medical Center) and pose a challenge to antibiotic therapy. Successful implementation of a routine detection of ESBL production is essential in designing appropriate antibiotic prescribing policies and infection control intervention programmes.
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- 2009
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31. Self-medication among pregnant women attending antenatal clinic at Makongoro health centre in Mwanza, Tanzania: a challenge to health systems
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Marwa, Karol J., primary, Njalika, Agnes, additional, Ruganuza, Deodatus, additional, Katabalo, Deogratias, additional, and Kamugisha, Erasmus, additional
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- 2018
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32. Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study
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Gunda, Daniel W., primary, Kilonzo, Semvua B., additional, Kamugisha, Erasmus, additional, Rauya, Engelbert Z., additional, and Mpondo, Bonaventura C., additional
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- 2017
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33. Performance of health laboratories in provision of HIV diagnostic and supportive services in selected districts of Tanzania
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Ishengoma, Deus S., primary, Kamugisha, Mathias L., additional, Rutta, Acleus S. M., additional, Kagaruki, Gibson B., additional, Kilale, Andrew M., additional, Kahwa, Amos, additional, Kamugisha, Erasmus, additional, Baraka, Vito, additional, Mandara, Celine I., additional, Materu, Godlisten S., additional, Massaga, Julius J., additional, Magesa, Stephen M., additional, Lemnge, Martha M., additional, and Mboera, Leonard E. G., additional
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- 2017
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34. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data
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Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., Zongo, Issaka, and WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group
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parasitic diseases - Abstract
BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P 37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
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- 2015
35. High Prevalence of Plasmodium Falciparum pfcrt K76T Mutation in Children with Sickle cel Disease at a Tertiary Hospital in North-western Tanzania
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MONGELA, STELA, ENWEJI, NIZAR, MNONG’ONE, NAIZIHIJWA, MINDE, MERCY, KAMUGISHA, ERASMUS, and SWEDBERG, GÖTE
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parasitic diseases ,Diagnosis & treatment - Abstract
The high prevalence of sickle cel disease (SCD) and trait in Sub-Saharan Africa coincides with the distribution of Plasmodium falciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as an antimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQ for uncomplicated malaria, except its use as prophylaxis in patients with sickle cel disease. This study investigated the prevalence of malaria in SCD patients and mutations asociated with CQ resistance. Children diagnosed with sickle cel disease atending both outpatient clinic and those admited at Bugando Medical Centre in north-western Tanzania were screned for malaria using thick blod smear. A dried blod spot on Whatman filter paper was also taken for polymerase chain reaction (PCR) and restriction fragment length polymorphism. Among 123 known patients with sickle cel disease, the prevalence of malaria by blod smear microscopy was 3.2% and by PCR was 13.8%. The prevalence of K76T mutation among the patients was 81.3%. The majority of the patients (72.4%) were using chloroquine prophylaxis. In conclusion, the prevalence of malaria parasitaemia among children with sickle cel disease atending BMC is low (3.2%) by microscopy but several children maintain sub patent infection detectable by PCR. The prevalence of chloroquine resistant P. falciparum in these children was higher than that previously sen in normal population in Tanzania. We recommend special atention to be paid to patients with sickle cel disease while studying the dynamics of drug resistant parasites.
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- 2014
36. Prevalence of undernutrition and risk factors of severe undernutrition among children admitted to Bugando Medical Centre in Mwanza, Tanzania
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Ahmed, Maimuna M., primary, Hokororo, Adolfine, additional, Kidenya, Benson R., additional, Kabyemera, Rogatus, additional, and Kamugisha, Erasmus, additional
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- 2016
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37. Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania
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Golassa, Lemu, Kamugisha, Erasmus, Ishengoma, Deus S., Baraka, Vito, Shayo, Alex, Baliraine, Frederick N., Enweji, Nizar, Erko, Berhanu, Aseffa, Abraham, Choy, Angel, Swedberg, Göte, Golassa, Lemu, Kamugisha, Erasmus, Ishengoma, Deus S., Baraka, Vito, Shayo, Alex, Baliraine, Frederick N., Enweji, Nizar, Erko, Berhanu, Aseffa, Abraham, Choy, Angel, and Swedberg, Göte
- Abstract
Background: Plasmodium falciparum resistance to anti-malarials is a major drawback in effective malaria control and elimination globally. Artemisinin-combination therapy (ACT) is currently the key first-line treatment for uncomplicated falciparum malaria. Plasmodium falciparum genetic signatures at pfmdr-1, pfcrt, and pfubp-1 loci are known to modulate in vivo and in vitro parasite response to ACT. The objective of this study was to assess the distribution of these resistance gene markers in isolates collected from different malaria transmission intensity in Ethiopia and Tanzania. Methods: Plasmodium falciparum clinical isolates were collected from different regions of Ethiopia and Tanzania. Genetic polymorphisms in the genes pfcrt, pfmdr-1 and pfubp-1 were analysed by PCR and sequencing. Frequencies of the different alleles in the three genes were compared within and between regions, and between the two countries. Results: The majority of the isolates from Ethiopia were mutant for the pfcrt 76 and wild-type for pfmdr-1 86. In contrast, the majority of the Tanzanian samples were wild-type for both pfcrt and pfmdr-1 loci. Analysis of a variable linker region in pfmdr-1 showed substantial variation in isolates from Tanzania as compared to Ethiopian isolates that had minimal variation. Direct sequencing of the pfubp-1 region showed that 92.8% (26/28) of the Ethiopian isolates had identical genome sequence with the wild type reference P. falciparum strain 3D7. Of 42 isolates from Tanzania, only 13 (30.9%) had identical genome sequences with 3D7. In the Tanzanian samples, 10 variant haplotypes were identified. Conclusion: The majority of Ethiopian isolates carried the main marker for chloroquine (CQ) resistance, while the majority of the samples from Tanzania carried markers for CQ susceptibility. Polymorphic genes showed substantially more variation in Tanzanian isolates. The low variability in the polymorphic region of pfmdr-1 in Ethiopia may be a consequence of low tr, Medical Research Council UK G0600718, Swedish Research Link Grant
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- 2015
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38. High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania
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MONGELLA, STELLA, ENWEJI, NIZAR, MNONG’ONE, NAIZIHIJWA, MINDE, MERCY, KAMUGISHA, ERASMUS, SWEDBERG, GÖTE, MONGELLA, STELLA, ENWEJI, NIZAR, MNONG’ONE, NAIZIHIJWA, MINDE, MERCY, KAMUGISHA, ERASMUS, and SWEDBERG, GÖTE
- Abstract
The high prevalence of sickle cell disease (SCD) and trait in Sub-Saharan Africa coincides with the distribution of Plasmodium falciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as an antimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQ for uncomplicated malaria, except its use as prophylaxis in patients with sickle cell disease. This study investigated the prevalence of malaria in SCD patients and mutations associated with CQ resistance. Children diagnosed with sickle cell disease attending both outpatient clinic and those admitted at Bugando Medical Centre in north-western Tanzania were screened for malaria using thick blood smear. A dried blood spot on Whatman filter paper was also taken for polymerase chain reaction (PCR) and restriction fragment length polymorphism. Among 123 known patients with sickle cell disease, the prevalence of malaria by blood smear microscopy was 3.2% and by PCR was 13.8%. The prevalence of K76T mutation among the patients was 81.3%. The majority of the patients (72.4%) were using chloroquine prophylaxis. In conclusion, the prevalence of malaria parasitaemia among children with sickle cell disease attending BMC is low (3.2%) by microscopy but several children maintain sub patent infection detectable by PCR. The prevalence of chloroquine resistant P. falciparum in these children was higher than that previously seen in normal population in Tanzania. We recommend special attention to be paid to patients with sickle cell disease while studying the dynamics of drug resistant parasites.
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- 2015
39. Prevalence and factors associated with severe anaemia amongst under-five children hospitalized at Bugando Medical Centre, Mwanza, Tanzania
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Simbauranga, Rehema H., primary, Kamugisha, Erasmus, additional, Hokororo, Adolfine, additional, Kidenya, Benson R., additional, and Makani, Julie, additional
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- 2015
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40. Detecting adenosine triphosphatase 6 point mutations that may be associated with Plasmodium falciparum resistance to artemisinin : prevalence at baseline, before policy change in Uganda
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Kamugisha, Erasmus, Sendagire, Hakim, KadduMukasa, Mark, Enweji, Nizar, Gheysari, Fatheme, Swedberg, Göte, and Kironde, Fred
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PfATP5 ,resistance ,artemisinin ,SERCA ,parasitic diseases ,Plasmodium falciparum ,Uganda - Abstract
The artemisinin based combination therapy (ACT) of artemether and lumefantrine (Co-artem) has recently replaced chloroquine and fansidar as the first line treatment policy drug in Uganda. It is necessary to develop practical procedures to monitor the likely emergence and spread of artemisinin resistant P. falciparum strains. We have analyzed the genotypes of PfATP6 in parasites from 300 stored filter paper samples from malaria patients who were diagnosed and treated in the years 1999 to 2004 at three field sites in Uganda. This is a period just prior to introduction of Co-artem. In order to develop a simple molecular procedure for mutation detection, regions of PfATP6 encoding protein domains important in artemisinin binding was amplified by nested PCR. Three DNA products, which together contain most of the coding region of amino acids located within the putative active site of pfATP6 were readily amplified. The amplified DNA was digested by restriction enzymes and the fragments sized by agarose gel electrophoresis. For the important codons 260, 263 and 769, methods using engineered restriction sites were employed. We did not find mutations at codons for the key residues Lys 260, Leu263, Gln266, Ser769 and Asn1039. Nucleotide sequencing of pfATPase6 gene DNA from at least 15 clinical isolates confirmed the above findings and suggested that mutations at these amino acid residues have not emerged in our study sites.
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- 2011
41. Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania
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Golassa, Lemu, primary, Kamugisha, Erasmus, additional, Ishengoma, Deus S, additional, Baraka, Vito, additional, Shayo, Alex, additional, Baliraine, Frederick N, additional, Enweji, Nizar, additional, Erko, Berhanu, additional, Aseffa, Abraham, additional, Choy, Angel, additional, and Swedberg, Göte, additional
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- 2015
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42. The readiness of the national health laboratory system in supporting care and treatment of HIV/AIDS in Tanzania
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Mboera, Leonard E.G., primary, Ishengoma, Deus S., additional, Kilale, Andrew M., additional, Massawe, Isolide S., additional, Rutta, Acleus S.M., additional, Kagaruki, Gibson B., additional, Kamugisha, Erasmus, additional, Baraka, Vito, additional, Mandara, Celine I., additional, Materu, Godlisten S., additional, and Magesa, Stephen M., additional
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- 2015
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43. Multi-resistant gram negative enteric bacteria causing urinary tract infection among malnourished underfives admitted at a tertiary hospital, northwestern, Tanzania
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Ahmed, Maimuna, primary, Moremi, Nyambura, additional, Mirambo, Mariam M., additional, Hokororo, Adolfine, additional, Mushi, Martha F., additional, Seni, Jeremiah, additional, Kamugisha, Erasmus, additional, and Mshana, Stephen E., additional
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- 2015
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44. Predictors of Positive Blood Culture and Deaths Among Neonates with Suspected Neonatal Sepsis in a Tertiary Hospital, Mwanza-Tanzania
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Kayange, Neema, Kamugisha, Erasmus, Mwizamholya, Damas L, Jeremiah, Seni, and Mshana, Stephen E
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Neonatal Health - Abstract
Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Among 770 neonates admitted during the study period; 300 (38.9%) neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40%) and 179(60%) had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1%) and 92 (51.4%) among neonates with early and late onset neonatal sepsis respectively (p = 0.466). Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA). Deaths occurred in 57 (19%) of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001), gram negative sepsis (p = 0.0001) and infection with ESBL (p = 0.008) or MRSA (p = 0.008) isolates. Our findings suggest that lethargy, convulsion, inability to feed, cyanosis, PROM and meconium stained liquor are significantly associated with positive blood culture in both early and late onset disease. Mortality and morbidity on neonatal sepsis is high at our setting and is significantly contributed by positive blood culture with multi-resistant gram negative bacteria.
- Published
- 2010
45. Predictors of Outcome among patients with Obstructive jaundice at Bugando Medical Centre in north-western Tanzania
- Author
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MABULA, JOSEPH B., GILYOMA, JAPHET M., MCHEMBE, MABULA D., JAKA, HYASINTA, KAMUGISHA, ERASMUS, KIDENYA, BENSON, RAMBAU, PETER F., CHALYA, PHILLIPO L., MABULA, JOSEPH B., GILYOMA, JAPHET M., MCHEMBE, MABULA D., JAKA, HYASINTA, KAMUGISHA, ERASMUS, KIDENYA, BENSON, RAMBAU, PETER F., and CHALYA, PHILLIPO L.
- Abstract
Despite recent advances both in preoperative diagnosis and postoperative care, obstructive jaundice still contributes significantly to high morbidity and mortality. A prospective study was undertaken to identify predictors of outcome among patients with obstructive jaundice at Bugando Medical Centre in north-western Tanzania. A total of 138 patients were studied. The male to female ratio was 1:1.6. The median age of patients was 58 years. Patients with malignant obstructive jaundice were older than those of benign type (P < 0.001). Ca head of pancreas (65.1%) was the commonest malignant cause of jaundice where as choledocholithiasis (51.9%) was the commonest benign cause. Twelve (9.7%) patients were HIV positive with a median CD 4+ count of 342 cells/μl. A total of 130 (94.2%) patients underwent surgical treatment and the remaining 8 (5.8%) patients were unfit for surgery. The complication rate was 30.4% mainly due to surgical site infections and it was significantly influenced by malignant causes, WBC count > 10 X 109/l and HIV infection with low CD4 (≤ 200 cells/μl) (p < 0.0001). The median hospital stay and mortality rate were 18 days and 20.3%, respectively. A low haematocrit and presence of postoperative complications were the main predictors of the hospital stay (P < 0.001), whereas age > 60 years, prolonged duration of jaundice, malignant causes, high bilirubin levels, HIV infection with low CD4+ count (≤ 200 cells/μl) and presence of postoperative complications significantly predicted mortality (P< 0.001). In conclusion, our study highlighted the important factors that predict the outcome of patients presenting with obstructive jaundice at BMC; therefore attention should be focused to these factors so as to improve the outcome of these patients.
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- 2014
46. Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population : a concern about the metabolism of artemisinin-based combinations
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Marwa, Karol J., Schmidt, Theresa, Sjögren, Maria, Minzi, Omary M. S., Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol J., Schmidt, Theresa, Sjögren, Maria, Minzi, Omary M. S., Kamugisha, Erasmus, and Swedberg, Göte
- Abstract
Background: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. Methods: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET (TM) Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). Results: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. Conclusion: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/ subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.
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- 2014
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47. High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania
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Mongella, Stella, Enweji, Nizar, Mnongone, Naizihijwa, Minde, Mercy, Kamugisha, Erasmus, Swedberg, Göte, Mongella, Stella, Enweji, Nizar, Mnongone, Naizihijwa, Minde, Mercy, Kamugisha, Erasmus, and Swedberg, Göte
- Abstract
The high prevalence of sickle cell disease (SCD) and trait in Sub-Saharan Africa coincides with thedistribution of Plasmodium falciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as anantimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQfor uncomplicated malaria, except its use as prophylaxis in patients with sickle cell disease. This studyinvestigated the prevalence of malaria in SCD patients and mutations associated with CQ resistance.Children diagnosed with sickle cell disease attending both outpatient clinic and those admitted at BugandoMedical Centre in north-western Tanzania were screened for malaria using thick blood smear. A driedblood spot on Whatman filter paper was also taken for polymerase chain reaction (PCR) and restrictionfragment length polymorphism. Among 123 known patients with sickle cell disease, the prevalence ofmalaria by blood smear microscopy was 3.2% and by PCR was 13.8%. The prevalence of K76T mutationamong the patients was 81.3%. The majority of the patients (72.4%) were using chloroquine prophylaxis. Inconclusion, the prevalence of malaria parasitaemia among children with sickle cell disease attending BMC islow (3.2%) by microscopy but several children maintain sub patent infection detectable by PCR. Theprevalence of chloroquine resistant P. falciparum in these children was higher than that previously seen innormal population in Tanzania. We recommend special attention to be paid to patients with sickle celldisease while studying the dynamics of drug resistant parasites.
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- 2014
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48. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
- Author
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Venkatesan, Meera, Gadalla, Nahla B, Stepniewska, Kasia, Dahal, Prabin, Nsanzabana, Christian, Moriera, Clarissa, Price, Ric N, Mårtensson, Andreas, Rosenthal, Philip J, Dorsey, Grant, Sutherland, Colin J, Guérin, Philippe, Davis, Timothy M E, Ménard, Didier, Adam, Ishag, Ademowo, George, Arze, Cesar, Baliraine, Frederick N, Berens-Riha, Nicole, Björkman, Anders, Borrmann, Steffen, Checchi, Francesco, Desai, Meghna, Dhorda, Mehul, Djimdé, Abdoulaye A, El-Sayed, Badria B, Eshetu, Teferi, Eyase, Frederick, Falade, Catherine, Faucher, Jean-François, Fröberg, Gabrielle, Grivoyannis, Anastasia, Hamour, Sally, Houzé, Sandrine, Johnson, Jacob, Kamugisha, Erasmus, Kariuki, Simon, Kiechel, Jean-René, Kironde, Fred, Kofoed, Poul-Erik, LeBras, Jacques, Malmberg, Maja, Mwai, Leah, Ngasala, Billy, Nosten, Francois, Nsobya, Samuel L, Nzila, Alexis, Oguike, Mary, Otienoburu, Sabina Dahlström, Ogutu, Bernhards, Ouédraogo, Jean-Bosco, Piola, Patrice, Rombo, Lars, Schramm, Birgit, Somé, A Fabrice, Thwing, Julie, Ursing, Johan, Wong, Rina P M, Zeynudin, Ahmed, Zongo, Issaka, Plowe, Christopher V, Sibley, Carol Hopkins, Venkatesan, Meera, Gadalla, Nahla B, Stepniewska, Kasia, Dahal, Prabin, Nsanzabana, Christian, Moriera, Clarissa, Price, Ric N, Mårtensson, Andreas, Rosenthal, Philip J, Dorsey, Grant, Sutherland, Colin J, Guérin, Philippe, Davis, Timothy M E, Ménard, Didier, Adam, Ishag, Ademowo, George, Arze, Cesar, Baliraine, Frederick N, Berens-Riha, Nicole, Björkman, Anders, Borrmann, Steffen, Checchi, Francesco, Desai, Meghna, Dhorda, Mehul, Djimdé, Abdoulaye A, El-Sayed, Badria B, Eshetu, Teferi, Eyase, Frederick, Falade, Catherine, Faucher, Jean-François, Fröberg, Gabrielle, Grivoyannis, Anastasia, Hamour, Sally, Houzé, Sandrine, Johnson, Jacob, Kamugisha, Erasmus, Kariuki, Simon, Kiechel, Jean-René, Kironde, Fred, Kofoed, Poul-Erik, LeBras, Jacques, Malmberg, Maja, Mwai, Leah, Ngasala, Billy, Nosten, Francois, Nsobya, Samuel L, Nzila, Alexis, Oguike, Mary, Otienoburu, Sabina Dahlström, Ogutu, Bernhards, Ouédraogo, Jean-Bosco, Piola, Patrice, Rombo, Lars, Schramm, Birgit, Somé, A Fabrice, Thwing, Julie, Ursing, Johan, Wong, Rina P M, Zeynudin, Ahmed, Zongo, Issaka, Plowe, Christopher V, and Sibley, Carol Hopkins
- Abstract
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
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- 2014
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49. Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations
- Author
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Marwa, Karol J, primary, Schmidt, Theresa, additional, Sjögren, Maria, additional, Minzi, Omary MS, additional, Kamugisha, Erasmus, additional, and Swedberg, Göte, additional
- Published
- 2014
- Full Text
- View/download PDF
50. High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania
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Mongella, Stella, primary, Enweji, Nizar, additional, Mnong'one, Naizihjwa, additional, Minde, Mercy, additional, Kamugisha, Erasmus, additional, and Swedberg, Göte, additional
- Published
- 2014
- Full Text
- View/download PDF
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