Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania.
Richard Mwaiswelo,Richard Mwaiswelo,Billy Ngasala,Billy Ngasala,Irina Jovel,Weiping Xu,Erik Larsson,Maja Malmberg,José Pedro Gil,José Pedro Gil,Zul Premji,Bruno P. Mmbando,Andreas Mårtensson +12 more
TLDR
Day 3 PCR-determined P. falciparum positivity remained common in patients treated before and after implementation of artemether–lumefantrine in Bagamoyo district, Tanzania, and its presence was associated with pretreatment characteristics.Abstract:
Prevalence of and risk factors associated with polymerase chain reaction (PCR)-determined Plasmodium falciparum positivity were assessed on day 3 after initiation of treatment, pre-implementation and up to 8 years post-deployment of artemether-lumefantrine as first-line treatment for uncomplicated malaria in Bagamoyo district, Tanzania. Samples originated from previously reported trials conducted between 2006 and 2014. Cytochrome b-nested PCR was used to detect malaria parasites from blood samples collected on a filter paper on day 3. Chi-square and McNemar chi-squared tests, logistic regression models, and analysis of variance were used as appropriate. Primary outcome was based on the proportion of patients with day 3 PCR-determined P. falciparum positivity. Overall, 256/584 (43.8%) of screened patients had day 3 PCR-determined positivity, whereas only 2/584 (0.3%) had microscopy-determined asexual parasitemia. Day 3 PCR-determined positivity increased from 28.0% (14/50) in 2006 to 74.2% (132/178) in 2007-2008 and declined, thereafter, to 36.0% (50/139) in 2012-2013 and 27.6% (60/217) in 2014. When data were pooled, pretreatment microscopy-determined asexual parasitemia ≥ 100,000/µL, hemoglobin < 10 g/dL, age < 5 years, temperature ≥ 37.5°C, and year of study 2007-2008 and 2012-2013 were significantly associated with PCR-determined positivity on day 3. Significant increases in P. falciparum multidrug resistance gene 1 N86 and P. falciparum chloroquine resistant transporter K76 across years were not associated with PCR-determined positivity on day 3. No statistically significant association was observed between day 3 PCR-determined positivity and PCR-adjusted recrudescence. Day 3 PCR-determined P. falciparum positivity remained common in patients treated before and after implementation of artemether-lumefantrine in Bagamoyo district, Tanzania. However, its presence was associated with pretreatment characteristics. Trials registration numbers: NCT00336375, ISRCTN69189899, NCT01998295, and NCT02090036.read more
Citations
More filters
Journal ArticleDOI
Evaluation of residual submicroscopic Plasmodium falciparum parasites 3 days after initiation of treatment with artemisinin-based combination therapy
TL;DR: Robust techniques should be used to evaluate if the residual submicroscopic parasites detected on day 3 after ACT are viable asexual parasites, or gametocytes, or the DNA of the dead parasites waiting to be cleared from the circulation.
Journal ArticleDOI
Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether-lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania: a randomized controlled trial.
Lwidiko E. Mhamilawa,Lwidiko E. Mhamilawa,Billy Ngasala,Billy Ngasala,Ulrika Morris,Eliford Ngaimisi Kitabi,Rory Barnes,Aung Paing Soe,Aung Paing Soe,Bruno P. Mmbando,Anders Björkman,Andreas Mårtensson +11 more
TL;DR: Extended 6-day artemether–lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe.
Journal ArticleDOI
Detection of Plasmodium falciparum by Light Microscopy, Loop-Mediated Isothermal Amplification, and Polymerase Chain Reaction on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania: A Comparative Trial.
Lwidiko E. Mhamilawa,Lwidiko E. Mhamilawa,Berit Aydin-Schmidt,Bruno P. Mmbando,Billy Ngasala,Billy Ngasala,Ulrika Morris +6 more
TL;DR: Loop-mediated isothermal amplification had comparable diagnostic accuracy to PCR and could potentially represent a field-friendly tool for determining day 3 positivity rates, however, what day 3 P. falciparum positivity determined using molecular methods represents needs to be further elucidated.
Journal ArticleDOI
Persistence of Residual Submicroscopic P. falciparum Parasitemia following Treatment of Artemether-Lumefantrine in Ethio-Sudan Border, Western Ethiopia
Geletta Tadele,Fatou Jaiteh,Mary Aigbiremo Oboh,Eniyou Oriero,Sisay Dugassa,Alfred Amambua-Ngwa,Lemu Golassa +6 more
TL;DR: Assessment of artemether-lumefantrine (AL) efficacy in western Ethiopia finds that AL remains efficacious for the treatment of uncomplicated falciparum malaria in the study area, however, the persistence of PCR-detected residual submicroscopic parasitemia following AL might compromise this treatment and need careful monitoring.
Journal ArticleDOI
Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania
Hillary M. Topazian,Kara A. Moser,Billy Ngasala,Peter O Oluoch,Catherine Forconi,Lwidiko E. Mhamilawa,Ozkan Aydemir,Oksana Kharabora,Molly Deutsch-Feldman,Andrew F. Read,Madeline Denton,A. Lorenzo,Nicole Mideo,Bernhards Ogutu,Ann M. Moormann,Andreas Mårtensson,Boaz Odwar,Jeffrey A. Bailey,Hoseah M. Akala,John M. Ong’echa,Jonathan J. Juliano +20 more
TL;DR: Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.
References
More filters
Journal ArticleDOI
Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
Elizabeth A. Ashley,Mehul Dhorda,Rick M. Fairhurst,Chanaki Amaratunga,Pharath Lim,Seila Suon,Sokunthea Sreng,Jennifer M. Anderson,Mao S,Sam B,Chantha Sopha,Char Meng Chuor,Chea Nguon,Siv Sovannaroth,Sasithon Pukrittayakamee,Podjanee Jittamala,Kesinee Chotivanich,K Chutasmit,C Suchatsoonthorn,R Runcharoen,Tran Tinh Hien,Nguyen Thuy-Nhien,Thanh Nv,Nguyen Hoan Phu,Ye Htut,Han Kt,Kyin Hla Aye,Olugbenga A. Mokuolu,Rasaq Olaosebikan,Olaleke Oluwasegun Folaranmi,Mayfong Mayxay,Maniphone Khanthavong,Bouasy Hongvanthong,Paul N. Newton,M A Onyamboko,Caterina I. Fanello,Antoinette Tshefu,Neelima Mishra,Neena Valecha,Aung Pyae Phyo,François Nosten,Yi P,Rupam Tripura,Steffen Borrmann,Mahfudh Bashraheil,Judy Peshu,M A Faiz,Aniruddha Ghose,M A Hossain,Rasheda Samad,M. R. Rahman,Manal Hasan,Ashraful Islam,Olivo Miotto,Roberto Amato,Bronwyn MacInnis,Jim Stalker,Dominic P. Kwiatkowski,Zbynek Bozdech,Atthanee Jeeyapant,Phaik Yeong Cheah,Tharisara Sakulthaew,Jeremy Chalk,Benjamas Intharabut,Kamolrat Silamut,Lee Sj,Benchawan Vihokhern,Chanon Kunasol,Mallika Imwong,Joel Tarning,Taylor Wj,Shunmay Yeung,Charles J. Woodrow,Jennifer A. Flegg,Debashish Das,Jennifer L. Smith,Meera Venkatesan,Christopher V. Plowe,Kasia Stepniewska,Philippe J Guerin,Arjen M. Dondorp,Nicholas P. J. Day,Nicholas J. White +82 more
TL;DR: Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing, and the incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission.
Journal ArticleDOI
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Frédéric Ariey,Benoit Witkowski,Chanaki Amaratunga,Johann Beghain,Anne-Claire Langlois,Nimol Khim,Saorin Kim,Valentine Duru,Christiane Bouchier,Laurence Ma,Pharath Lim,Rithea Leang,Socheat Duong,Sokunthea Sreng,Seila Suon,Char Meng Chuor,Denis Mey Bout,Sandie Menard,William O. Rogers,Blaise Genton,Thierry Fandeur,Olivo Miotto,Pascal Ringwald,Jacques Le Bras,Antoine Berry,Jean Christophe Barale,Rick M. Fairhurst,Françoise Benoit-Vical,Odile Mercereau-Puijalon,Didier Menard +29 more
TL;DR: Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance.
Journal ArticleDOI
A molecular marker for chloroquine-resistant falciparum malaria.
Abdoulaye A. Djimde,Ogobara K. Doumbo,Joseph F. Cortese,Kassoum Kayentao,Safi N. Doumbo,Yacouba Diourte,Drissa Coulibaly,Alassane Dicko,Xin-zhuan Su,Takashi Nomura,David A. Fidock,Thomas E. Wellems,Christopher V. Plowe +12 more
TL;DR: This study shows an association between the pfcrt T76 mutation in P. falciparum and the development of chloroquine resistance during the treatment of malaria, and this mutation can be used as a marker in surveillance forchloroquine-resistant falcIParum malaria.
Journal ArticleDOI
Qinghaosu (artemisinin): the price of success.
TL;DR: Artemisinin combination treatments are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries and a global subsidy would make these drugs more affordable and available.
Journal ArticleDOI
Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand
Georges Snounou,Xinping Zhu,Napaporn Siripoon,William Jarra,Sodsri Thaithong,K. N. Brown,S. Viriyakosol +6 more
TL;DR: Although a high degree of diversity characterized these isolates, the overall population structure of the parasites associated with patent malaria infections was observed to remain relatively stable over time and two interesting exceptions to the random distribution were observed.