16 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. 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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5. 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, and Swedberg, Göte
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PLASMODIUM falciparum ,TREATMENT effectiveness ,MALARIA ,GENETIC variation ,INFECTIOUS disease transmission - Abstract
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 RO33 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 correlation between MOI and ACPR. However, a borderline significant correlation was observed between day 2 parasitaemia and MOI. [ABSTRACT FROM AUTHOR]
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- 2022
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6. 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, and Swedberg, Gote
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MALARIA ,ONLINE databases ,TREATMENT effectiveness ,PLASMODIUM falciparum ,ARTEMISININ derivatives ,META-analysis - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes.
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Moser, Kara A., Madebe, Rashid A., Aydemir, Ozkan, Chiduo, Mercy G., Mandara, Celine I., Rumisha, Susan F., Chaky, Frank, Denton, Madeline, Marsh, Patrick W., Verity, Robert, Watson, Oliver J., Ngasala, Billy, Mkude, Sigsbert, Molteni, Fabrizio, Njau, Ritha, Warsame, Marian, Mandike, Renata, Kabanywanyi, Abdunoor M., Mahende, Muhidin K., and Kamugisha, Erasmus
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MOLECULAR probes ,PLASMODIUM falciparum ,DRUG resistance ,PLASMODIUM vivax ,POPULATION dynamics ,POPULATION ,PLASMODIUM - Abstract
High‐throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up‐to‐date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high‐burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome‐wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13‐R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region‐level complexity‐of‐infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared. [ABSTRACT FROM AUTHOR]
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- 2021
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8. 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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MALARIA transmission ,DISEASE susceptibility ,MALARIA treatment ,ENDEMIC diseases ,PARASITEMIA - Abstract
Background: Passive 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. Methods: Surveillance 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. Results: During 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 <5 children and 9.9% to 20.7% of all OPD visits among the ≥5 patients were due to malaria. Moreover, survey of all registered causes of admission in hospitals found 47% of admissions were due to malaria. The disease was a major cause of admission in epidemic prone setting where 63.4% of the <5 children and 62.8% of the ≥5 patients were admitted due to malaria (p>0.05) and 40% of all malaria admissions were school age children. Malaria related death rate was highest among <5 years at the hyperendemic site, that is 60.9 death per 1000 malaria <5 admissions. Conversely, the epidemic prone setting experienced highest malaria related death among ≥15 years (18.6 death per 1000 admissions) than the < 15 years (5.7 death per 1000 admissions of the <15 years) (p< 0.001). Surveillance of severe form of the disease found that hyperpyrexia, hyperparastemia, prostration and convulsions as common presentations of severe disease. Conclusion: Malaria is still the major cause of hospital consultations in Western Kenya with an alarming number of severe forms of the disease among the school aged children at the epidemic prone setting. Mortalities were higher among <5 children years in high infection transmission setting and among ≥15 years in low and moderate transmission settings. Surveillance of asymptomatic and symptomatic malaria along with evaluation of current interventions in different age groups should be implemented in Kenya. [ABSTRACT FROM AUTHOR]
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- 2018
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9. 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, Guofa Zhou, Githeko, Andrew K., and Yan, Guiyun
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MALARIA ,MALARIA treatment ,INSECTICIDE resistance ,DELTAMETHRIN ,ANOPHELES gambiae ,PLASMODIUM - Abstract
Background: In 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. Methods: The 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. Results: Areas 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]
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- 2017
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10. 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, and Swedberg, Göte
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PLASMODIUM falciparum , *MALARIA , *DRUG resistance , *ANTIMALARIALS , *ARTEMISININ , *GENETIC markers , *POLYMERASE chain reaction , *PROTOZOA - 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 transmission intensity as compared to high transmission intensity and large variations in Tanzania. [ABSTRACT FROM AUTHOR]
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- 2015
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11. 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, and SWEDBERG, GÖTE
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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. [ABSTRACT FROM AUTHOR]
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- 2014
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12. Malaria among adult inpatients in two Tanzanian referral hospitals: A prospective study.
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Kilonzo, Semvua B., Kamugisha, Erasmus, Downs, Jennifer A., Kataraihya, Johannes, Onesmo, Rwakyendela, Mheta, Koy, Jeong, Jiyeon M., Verweij, Jaco J., Fitzgerald, Daniel W., and Peck, Robert N.
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MALARIA , *MOSQUITO vectors , *HOSPITAL care , *LONGITUDINAL method , *MEDICAL errors - Abstract
Highlights: [•] Malaria is commonly misdiagnosed in Tanzania. [•] More than 80% of adults with suspected malaria did not have malaria. [•] The agreement between routine malaria BS and RDT was only fair. [•] Malaria PCR generally agreed with rapid malaria diagnostic tests. [•] HIV infection was associated with delayed malaria parasite clearance. [Copyright &y& Elsevier]
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- 2014
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13. Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda—A reflection of differences in policies regarding withdrawal of chloroquine?
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Kamugisha, Erasmus, Bujila, Ioana, Lahdo, Mona, Pello-Esso, Samtou, Minde, Mercy, Kongola, Gilbert, Naiwumbwe, Halima, Kiwuwa, Steven, Kaddumukasa, Mark, Kironde, Fred, and Swedberg, Göte
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CHLOROQUINE , *DRUG resistance , *GENETIC mutation , *DISEASE prevalence , *PUBLIC health , *PHARMACEUTICAL policy , *MALARIA treatment - Abstract
Abstract: Background: Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine–pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women. Methods: Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products. Results: The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates. Conclusions: The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down. [Copyright &y& Elsevier]
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- 2012
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14. 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, and Martin, Troy
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POWDERY mildew diseases ,MALARIA - Abstract
Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440–600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631 [ABSTRACT FROM AUTHOR]
- Published
- 2019
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15. 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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HIGH performance liquid chromatography , *PLASMODIUM falciparum , *MALARIA , *DRUG monitoring , *DRUG efficacy - Abstract
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). 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 200ng/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 associated 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). Lumefantrine plasma concentrations below cut-off points (175ng/ml and 200ng/ml) on day 3 and 7 did not influence treatment outcomes. [ABSTRACT FROM AUTHOR]
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- 2022
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16. 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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TREATMENT effectiveness , *MALARIA , *PLASMODIUM falciparum , *TREATMENT failure , *DRUG utilization - Abstract
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 Igombe, 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 was108 (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 corrected efficacies greater than 95% implying a failure rate less than 5% which is below the WHO minimum threshold requirement for recommendation of a change in the treatment policy. Both drugs were well tolerated with no major adverse events reported. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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