Dr Jean Bertin Kabuya
| Call | Career Development Fellowship (CDF) |
| Programme | EDCTP2 |
| Start Date | 2018-07-01 |
| End Date | 2021-06-30 |
| Project Code | TMA2016CDF1584 |
| Status | Active |
Title
Safety and Efficacy of Intermittent Presumptive Treatment with Sulfadoxine-Pyrimethamine using Rapid Diagnostic Test Screening And Treatment at First Antenatal Care Visit
Objectives
Primary Objective: To evaluate the impact of adding, at first ANC, mRDT screening and treatment with DHA-PPQ to the current IPTp-SP (IPTp-SP+) on IPT-SP efficacy at clearing maternal peripheral parasitemia and at preventing maternal anemia, LBW and neonatal mortality. Specific Objectives: To compare: • IPTp-SP+ and IPTp-SP PCR treatment failure rates at Days 28, 42, 63 and at delivery • IPTp-SP+ and IPTp-SP maternal anemia and low birth weight rates at delivery • IPTp-SP+ and IPTp-SP neonatal mortality rates at 28 post delivery • Proportion of pregnancy losses between the groups • PCR median time to recrudescence between the two groups • PCR re-infection rates between the two groups • Incidences of post-treatment clinical malaria during pregnancy between the two groups • Prevalence of asymptomatic malaria during pregnancy between the two groups • Prevalence of malaria at delivery between the two groups • Prevalence of congenital malaria and anaemia between the two groups • Overtime SP resistance prevalence and mutant haplotypes types between the two groups • Placental infection rates between the two groups • Proportions of Acute infection, Chronic infection /Past infection between the two groups, using placental biopsies Describe the Incidence of adverse events until one year post-partum Determine the overtime prevalence of asymptomatic malaria and their impact on birth outcomes Exploratory objectives: Assess the impact of screen and treat with one dose DHA-PQ on antimalarial drug resistance development To determine the relationship between the prevalence of infections with mutant transporter genotypes and the plasma concentration of PQ
Host Organisation
| Institution | Country |
|---|---|
| Tropical Diseases Research Centre | Zambia |
Participants
| Name | Institution | Country |
|---|---|---|
| Dr. Christine Manyando | Tropical Diseases Research Centre | Zambia |
Study Design
A phase IIIB open-label, two arms randomized controlled superiority trial will be carried out to assess the safety and efficacy of adding to the current IPTp-SP, at first ANC visit, mRDT screening and treatment of positive mothers with Dihydroartemisinin-Piperaquine (DHA-PQ)). After obtaining the informed consent and assessing for eligibility criteria. HIV-negative mothers will be randomly allocated to IPTp-SP+ or to the standard of care IPTp-SP upon provision of a voluntary informed consent. Mothers in IPTp-SP+ group will be tested with mRDT at first ANC visit; If they test positive they will be treated with DHA-PQ followed with 2 doses of SP given at days 35 and 63; if negative they will be given three doses of SP at enrollment, days 35 and 63. Mothers in the IPTp-SP group will receive 3 doses of SP at enrollment, day 35 and day 63. All mothers will be followed up to day 63 and thereafter at delivery. Their babies will be followed up to one year after delivery.
Sites
| Nchelenge, Zambia |
Results & Outcomes
392 mothers out of 850 screened were recruited. Dats analysis is underway. Data collection and laboratory analysis have been completed. Data analysis is underway.
Publications
| Kabuya et al. Trials (2021) 22:820 |
Current Organisation
Tropical Diseases research Centre
Current Job Title
Senior Scientific Officer
Awards
| 2016 | Career Development Fellowship |
Education
| Institution | Degree | Year |
|---|---|---|
| Institute of Tropical Medicine, Belgium | Master of Science in Public Health | 2012-07-05 |
| University of Kinshasa, The Democratic Republic of The Congo | 2001-08-31 |
Areas Of Specialisation
Malaria
Publications
Authors:
Jonathan J. Juliano
, Juliano JJ
Date:
2021-03-14
Journal:
Current Epidemiology Reports
Content:
Purpose of Review: Five years have passed since the World Health Organization released its Global Technical Strategy for Malaria (GTS). In that time, progress against malaria has plateaued. This review focuses on the implications of antimalarial drug resistance for the GTS and how interim progress in parasite genomics and antimalarial pharmacology offers a bulwark against it.
Recent Findings: For the first time, drug resistance–conferring genes have been identified and validated before their global expansion in malaria parasite populations. More efficient methods for their detection and elaboration have been developed, although low-density infections and polyclonality remain a nuisance to be solved. Clinical trials of alternative regimens for multidrug-resistant malaria have delivered promising results. New agents continue down the development pipeline, while a nascent infrastructure in sub-Saharan Africa for conducting phase I trials and trials of transmission-blocking agents has come to fruition after years of preparation.
Summary: These and other developments can help inform the GTS as the world looks ahead to the next two decades of its implementation. To remain ahead of the threat that drug resistance poses, wider application of genomic-based surveillance and optimization of existing and forthcoming antimalarial drugs are essential.
Identifiers:
Authors:
Michael Nambozi
, Tropical Diseases Research Centre, Ndola, Zambia
Jean‑Bertin Bukasa Kabuya , Tropical Diseases Research Centre, Ndola, Zambia
Sebastian Hachizovu , Tropical Diseases Research Centre, Ndola, Zambia
David Mwakazanga , Tropical Diseases Research Centre, Ndola, Zambia
Joyce Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
Webster Kasongo , Tropical Diseases Research Centre, Ndola, Zambia
Jozefien Buyze , Institute of Tropical Medicine, Antwerp, Belgium
Modest Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
Jean‑Pierre Van Geertruyden , University of Antwerp, Antwerp, Belgium
Umberto D’Alessandro , London School of Hygiene and Tropical Medicine, London, UK.
Jean‑Bertin Bukasa Kabuya , Tropical Diseases Research Centre, Ndola, Zambia
Sebastian Hachizovu , Tropical Diseases Research Centre, Ndola, Zambia
David Mwakazanga , Tropical Diseases Research Centre, Ndola, Zambia
Joyce Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
Webster Kasongo , Tropical Diseases Research Centre, Ndola, Zambia
Jozefien Buyze , Institute of Tropical Medicine, Antwerp, Belgium
Modest Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
Jean‑Pierre Van Geertruyden , University of Antwerp, Antwerp, Belgium
Umberto D’Alessandro , London School of Hygiene and Tropical Medicine, London, UK.
Date:
2017-05-16
Journal:
Malaria Journal
Content:
Background: In Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, the World Health Organization recommends the use of artemisininbased combination therapy (ACT) in the second and third trimester of pregnancy. In a context of limited information on ACT, the safety and efficacy of three combinations, namely artemether–lumefantrine (AL), mefloquine–artesunate (MQAS) and dihydroartemisinin–piperaquine (DHAPQ) were assessed in pregnant women with malaria.
Methods: The trial was carried out between July 2010 and August 2013 in Nchelenge district, Luapula Province, an area of high transmission, as part of a multi-centre trial. Women in the second or third trimester of pregnancy and with malaria were recruited and randomized to one of the three study arms. Women were actively followed up for 63 days, and then at delivery and 1 year post-delivery.
Results: Nine hundred pregnant women were included, 300 per arm. PCR-adjusted treatment failure was 4.7% (12/258) (95% CI 2.7–8.0) for AL, 1.3% (3/235) (95% CI 0.4–3.7) for MQAS and 0.8% (2/236) (95% CI 0.2–3.0) for DHAPQ, with significant risk difference between AL and DHAPQ (p = 0.01) and between AL and MQAS (p = 0.03) treatments. Re-infections during follow up were more frequent in the AL (HR: 4.71; 95% CI 3.10–7.2; p < 0.01) and MQAS (HR: 1.59; 95% CI 1.02–2.46; p = 0.04) arms compared to the DHAPQ arm. PCR-adjusted treatment failure was significantly associated with women under 20 years [Hazard Ratio (HR) 5.35 (95% CI 1.07–26.73; p = 0.04)] and higher malaria parasite density [3.23 (95% CI 1.03–10.10; p = 0.04)], and still women under 20 years [1.78, (95% CI 1.26–2.52; p < 0.01)] had a
significantly higher risk of re-infection. The three treatments were generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as adverse events (AEs) were more common in MQAS than in AL or DHAPQ (p < 0.001). Birth outcomes were not significantly different between treatment arms.
Conclusion: As new infections can be prevented by a long acting partner drug to the artemisinins, DHAPQ should be preferred in places as Nchelenge district where transmission is intense while in areas of low transmission intensity AK or MQAS may be used.
Identifiers:
Authors:
Pregact Study Group
, Pregact Consortium
Pekwi D , Center for Global Health Research, Kumasi, Ghana.
Amprmfi AA , Center for Global Health Research, Kumasi, Ghana.
Tinto H , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Valea I , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Mwapasa V , College of Medicine, University of Malawi, Blantyre, Malawi
Kalilani-Phiri L , College of Medicine, University of Malawi, Blantyre, Malawi
Kalanda G , College of Medicine, University of Malawi, Blantyre, Malawi
Madanitsa M , College of Medicine, University of Malawi, Blantyre, Malawi
Ravinetto R , Department of Pharmaceutical and Pharmacologic Sciences, KU Leuven, Leuven, Belgium; Institute of Tropical Medicine, Antwerp, Belgium.
Mutabingwa T , Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
Gbekor P , Juaben Government Hospital, Juaben, Ghana.
Tagbor H , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Antwi G , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Menten J , Institute of Tropical Medicine, Antwerp, Belgium.
De Crop M , Institute of Tropical Medicine, Antwerp, Belgium.
Claeys Y , Institute of Tropical Medicine, Antwerp, Belgium.
Schurmans C , Institute of Tropical Medicine, Antwerp, Belgium.
Van Overmeir C , Institute of Tropical Medicine, Antwerp, Belgium.
Thriemer K , Institute of Tropical Medicine, Antwerp, Belgium; Menzies School of Health Research, Darwin, NT, Australia
Van Geertruyden JP , International Health Unit, University of Antwerp, Antwerp, Belgium.
D’Alessandro U , Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nambozi M , Tropical Diseases Research Center, Ndola, Zambia
Mulenga M , Tropical Diseases Research Center, Ndola, Zambia
Hachizovu S , Tropical Diseases Research Center, Ndola, Zambia
Kabuya JB , Tropical Diseases Research Center, Ndola, Zambia
Mulenga J , Tropical Diseases Research Center, Ndola, Zambia
Pekwi D , Center for Global Health Research, Kumasi, Ghana.
Amprmfi AA , Center for Global Health Research, Kumasi, Ghana.
Tinto H , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Valea I , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Mwapasa V , College of Medicine, University of Malawi, Blantyre, Malawi
Kalilani-Phiri L , College of Medicine, University of Malawi, Blantyre, Malawi
Kalanda G , College of Medicine, University of Malawi, Blantyre, Malawi
Madanitsa M , College of Medicine, University of Malawi, Blantyre, Malawi
Ravinetto R , Department of Pharmaceutical and Pharmacologic Sciences, KU Leuven, Leuven, Belgium; Institute of Tropical Medicine, Antwerp, Belgium.
Mutabingwa T , Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
Gbekor P , Juaben Government Hospital, Juaben, Ghana.
Tagbor H , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Antwi G , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Menten J , Institute of Tropical Medicine, Antwerp, Belgium.
De Crop M , Institute of Tropical Medicine, Antwerp, Belgium.
Claeys Y , Institute of Tropical Medicine, Antwerp, Belgium.
Schurmans C , Institute of Tropical Medicine, Antwerp, Belgium.
Van Overmeir C , Institute of Tropical Medicine, Antwerp, Belgium.
Thriemer K , Institute of Tropical Medicine, Antwerp, Belgium; Menzies School of Health Research, Darwin, NT, Australia
Van Geertruyden JP , International Health Unit, University of Antwerp, Antwerp, Belgium.
D’Alessandro U , Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nambozi M , Tropical Diseases Research Center, Ndola, Zambia
Mulenga M , Tropical Diseases Research Center, Ndola, Zambia
Hachizovu S , Tropical Diseases Research Center, Ndola, Zambia
Kabuya JB , Tropical Diseases Research Center, Ndola, Zambia
Mulenga J , Tropical Diseases Research Center, Ndola, Zambia
Date:
2016-03-10
Journal:
The new England journal o f medicine
Content:
BACKGROUND:
Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa.
METHODS:
We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chain-reaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes.
RESULTS:
The PCR-adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin-piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-adjusted cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin-piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine-artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups).
CONCLUSIONS:
Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile.
Identifiers:
Authors:
Christine Manyando1
, Manyando C
Date:
2021-11-20
Journal:
Trals
Content:
Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high-burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed.
Methods: This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday.
Discussion: A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP-resistant parasites.
Identifiers:
PMC8605457: not informed
Authors:
PREGACT Study Group
, PREGACT Consortium
Pekwi D , Center for Global Health Research, Kumasi, Ghana.
Amprmfi AA , Center for Global Health Research, Kumasi, Ghana.
Tinto H , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Traoré-Coulibaly M , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Tahita MC , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso.
Valea I , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso.
Mwampasa V , College of Medicine, University of Malawi, Blantyre, Malawi.
Kalilani-Phiri L , College of Medicine, University of Malawi, Blantyre, Malawi
Kalanda G , College of Medicine, University of Malawi, Blantyre, Malawi.
Madanitsa M , College of Medicine, University of Malawi, Blantyre, Malawi.
Ravinetto R , Department of Pharmaceutical and Pharmacologic Sciences, KU Leuven, Leuven, Belgium; Institute of Tropical Medicine, Antwerp, Belgium
Mutabingwa T , Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
Gbekor P , Juaben Government Hospital, Juaben, Ghana
Tagbor H , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Antwi G , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Menten J , Institute of Tropical Medicine, Antwerp, Belgium
De Crop M , Institute of Tropical Medicine, Antwerp, Belgium
Claeys Y , Institute of Tropical Medicine, Antwerp, Belgium
Schurmans C , Institute of Tropical Medicine, Antwerp, Belgium
Van Overmeir C , Institute of Tropical Medicine, Antwerp, Belgium
Thriemer K , Institute of Tropical Medicine, Antwerp, Belgium; Menzies School of Health Research, Darwin, NT, Australia
Van Geertruyden JP , International Health Unit, University of Antwerp, Antwerp, Belgium
D'Alessandro U , Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nambozi M , Tropical Diseases Research Center, Ndola, Zambia
Mulenga M , Tropical Diseases Research Center, Ndola, Zambia
Hachizovu S , Tropical Diseases Research Center, Ndola, Zambia
Kabuya JB , Tropical Diseases Research Center, Ndola, Zambia
Mulenga J , Tropical Diseases Research Center, Ndola, Zambia
Pekwi D , Center for Global Health Research, Kumasi, Ghana.
Amprmfi AA , Center for Global Health Research, Kumasi, Ghana.
Tinto H , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Traoré-Coulibaly M , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso
Tahita MC , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso.
Valea I , Clinical Trial Unit Nanoro, Nanoro, Burkina Faso.
Mwampasa V , College of Medicine, University of Malawi, Blantyre, Malawi.
Kalilani-Phiri L , College of Medicine, University of Malawi, Blantyre, Malawi
Kalanda G , College of Medicine, University of Malawi, Blantyre, Malawi.
Madanitsa M , College of Medicine, University of Malawi, Blantyre, Malawi.
Ravinetto R , Department of Pharmaceutical and Pharmacologic Sciences, KU Leuven, Leuven, Belgium; Institute of Tropical Medicine, Antwerp, Belgium
Mutabingwa T , Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
Gbekor P , Juaben Government Hospital, Juaben, Ghana
Tagbor H , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Antwi G , Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Menten J , Institute of Tropical Medicine, Antwerp, Belgium
De Crop M , Institute of Tropical Medicine, Antwerp, Belgium
Claeys Y , Institute of Tropical Medicine, Antwerp, Belgium
Schurmans C , Institute of Tropical Medicine, Antwerp, Belgium
Van Overmeir C , Institute of Tropical Medicine, Antwerp, Belgium
Thriemer K , Institute of Tropical Medicine, Antwerp, Belgium; Menzies School of Health Research, Darwin, NT, Australia
Van Geertruyden JP , International Health Unit, University of Antwerp, Antwerp, Belgium
D'Alessandro U , Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nambozi M , Tropical Diseases Research Center, Ndola, Zambia
Mulenga M , Tropical Diseases Research Center, Ndola, Zambia
Hachizovu S , Tropical Diseases Research Center, Ndola, Zambia
Kabuya JB , Tropical Diseases Research Center, Ndola, Zambia
Mulenga J , Tropical Diseases Research Center, Ndola, Zambia
Date:
2016-09-28
Journal:
Malawi Medical Journal
Content:
BACKGROUND:
Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa.
METHODS:
We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chain-reaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes.
RESULTS:
The PCR-adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin-piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-adjusted cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin-piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine-artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups).
CONCLUSIONS:
Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile.
Identifiers:
Authors:
Matthew M. Ippolito
, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2Malaria Research Institute
Luc K. Kamavu , Saint Paul’s General Hospital, Nchelenge
Jean-Bertin Kabuya , Tropical Diseases Research Centre, Ndola, Zambia
Catherine Tente , Saint Paul’s General Hospital, Nchelenge
Edward Chileshe , Saint Paul’s General Hospital, Nchelenge
McBerth Wapachole , Ministry of Health, Nchelenge, Zambia
Philip E. Thuma , Macha Research Trust, Macha, Zambia
Mbanga Muleba , Tropical Diseases Research Centre, Ndola, Zambia
Mike Chaponda , Tropical Diseases Research Centre, Ndola, Zambia
Modest Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
William J. Moss , Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Luc K. Kamavu , Saint Paul’s General Hospital, Nchelenge
Jean-Bertin Kabuya , Tropical Diseases Research Centre, Ndola, Zambia
Catherine Tente , Saint Paul’s General Hospital, Nchelenge
Edward Chileshe , Saint Paul’s General Hospital, Nchelenge
McBerth Wapachole , Ministry of Health, Nchelenge, Zambia
Philip E. Thuma , Macha Research Trust, Macha, Zambia
Mbanga Muleba , Tropical Diseases Research Centre, Ndola, Zambia
Mike Chaponda , Tropical Diseases Research Centre, Ndola, Zambia
Modest Mulenga , Tropical Diseases Research Centre, Ndola, Zambia
William J. Moss , Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Date:
2018-06-30
Journal:
American Journal of Tropical of Medicine and Hygiene
Content:
Malaria remains a public health crisis in areas where it has resisted control efforts. In Nchelenge District, a high-transmission area in northern Zambia, malaria accounts for more than one-third of pediatric hospitalizations and nearly one-half of hospital deaths in children. To identify risk factors for death due to malaria, we conducted a retrospective, time-matched case-control study of 126 children hospitalized with malaria who died (cases) and 126 children who survived (controls). There were no differences in age, gender, hemoglobin concentration, or prevalence of severe anemia between cases and controls. Children who died were more likely to come from villages located at greater distances from the hospital than children who survived (median 13.5 versus 3.2 km). Each additional kilometer of distance from the hospital increased the odds of death by4%(odds ratio 1.04,95%confidence interval 1.01–1.07,P < 0.01). Extent of anemia and admission during periods when blood was unavailable for transfusion were associated with early death (P £ 0.03). Delays in initiation of treatment of severe malaria contribute to the increased odds of death in children referred from more distant health centers, and might be mitigated by transportation improvements, capacity at rural health posts to administer treatment before transfer, hospital triage systems that minimize time to treatment, and reliable blood product stores at referral hospitals.
Identifiers:
Authors:
Sydney Mwanza
, Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Sudhaunshu Joshi , Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201‑1509, USA
Michael Nambozi , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Justin Chileshe , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Phidelis Malunga , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Jean‑Bertin Bukasa Kabuya , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Sebastian Hachizovu , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Christine Manyando , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Modest Mulenga , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Miriam Laufer , Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201‑1509, USA
Sudhaunshu Joshi , Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201‑1509, USA
Michael Nambozi , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Justin Chileshe , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Phidelis Malunga , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Jean‑Bertin Bukasa Kabuya , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Sebastian Hachizovu , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Christine Manyando , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Modest Mulenga , Tropical Diseases Research Centre (TDRC), 6th and 7th Floors, Ndola Central Hospital Building, P.O. Box 71769, Ndola, Zambia
Miriam Laufer , Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201‑1509, USA
Date:
2016-10-05
Journal:
Malaria Journal
Content:
Background: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy. Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use. In Zambia, chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003. Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued.
Methods: Parasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial. The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter, the gene that is associated with CQ resistance.
Results: Three-hundred and two specimens were successfully analysed. No chloroquine-resistant genotypes were detected.
Conclusion: The study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure. Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future.
Identifiers:
Projects
Fellow:
Jean Bertin Kabuya
Collaborators:
| Name | Country | Institution |
|---|---|---|
| Prof. William J. Moss | United States | Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA |
| Dr, Matthew M. Ippolito | United States | Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA |
| Dr. Modest Mulenga | Zambia | Tropical Diseases Research Centre |
| Dr. Mike Chaponda | Zambia | Tropical Diseases Research Centre |
Objectives:
Objective 1:
Measure spatial and temporal changes in malaria parasitemia, gametocytemia and serological responses to help guide targeted, risk-based combinations of malaria control strategies that are cost-effective and acceptable to the community in three regions of Southern Africa with different levels of malaria transmission and control.
Objective 2:
Characterize the bionomics, seasonal entomological inoculation rate, and the feeding and resting behavior of Anopheles arabiensis; measure insecticide susceptibility and identify mechanisms of insecticide resistance; and determine the population genetic structure of An. arabiensis in three regions of Southern Africa with different levels of malaria transmission and control.
Objective 3:
Obtain a high-resolution profile of the genetic diversity of Plasmodium falciparum isolates and establish how genetic diversity is impacted by intervention history, vector differences, climate differences and other factors; establish and monitor changes in parasite population genetics over time; and determine the level and distribution of parasite clonal diversity within individuals residing in three regions of Southern Africa with different levels of malaria transmission and control
Sites:
Zambia, Zimbabwe and DRC
Study Design:
Study participants will include hospitalized in-patients with malaria, clinic outpatients with malaria and residents of randomly selected households. Children and adults, both male and female, are eligible for study participation. Based on an estimated 150 households per site per year for six years, and five persons per household, we plan to enroll approximately 13,500 persons in the community-based surveys and approximately 500 persons in the hospital and clinic-based studies of parasite genomics. Subject duration will range from a single study visit to follow-up for up to six years.
Subjects:
13,500
Start Date:
2016-07-04
End Date:
2023-06-30
Fellow:
Jean Bertin Kabuya
Collaborators:
| Name | Country | Institution |
|---|---|---|
| William J. Moss | United States | Johns Hopkins University Bloomberg School of Public Health, Baltimore |
| Mike Chaponda | Zambia | Tropical Disease Research Centre |
| Matthew M. Ippolito | United States | Johns Hopkins University Bloomberg School of Public Health |
| Philip E. Thuma | Zambia | Macha Research Trust |
| Theresa A. Shapiro | Zambia | Johns Hopkins University School of Medicine |
Objectives:
To model the pharmacokinetic and pharmacodynamic (PK/PD) profiles of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for gametocyte clearance.
To model the PK/PD profiles of AL and DP for post-treatment protection against malaria re-infection.
To study the selective pressures of AL and DP on drug-resistant parasite genotypes.
Sites:
Nchelenge, Zambia.
Study Design:
An open-label single-center single-blinded randomized trial to elucidate the PK/PD of two ACTs among children in Zambia with uncomplicated falciparum malaria, designed according to modified WHO guidelines for drug efficacy studies of antimalarial agents.
Subjects:
182
Start Date:
2018-09-04
End Date:
2019-07-28
Fellow:
Jean Bertin Kabuya
Collaborators:
| Name | Country | Institution |
|---|---|---|
| Dr. Victor Mwapasa | Malawi | Division of Community Health, College of Medicine |
| Dr. Modest Mulenga | Zambia | Tropical Diseases Research Centre |
| Dr. Esperança Sevene | Mozambique | Centro de Investigaçao em Saude |
| Dr. Mike Chaponda | Zambia | Tropical Diseases Research Centre |
| Dr, Sebastian Hachizovu | Zambia | Tropical Diseases Research Centre |
Objectives:
To assess the efficacy and safety of ACTs in HIV+ malaria infected patients receiving different types of ART.
To determine the day 42 PCR-corrected Adequate Clinical and Parasitological Response (ACPR) of ACTs (AL, AS-AQ and DHA-PPQ) in HIV+ patients with clinical malaria who are taking EFV or NVP-based ART.
Sites:
Zamia, Malawi and Mozambique
Study Design:
A single arm (non-comparative) open-label efficacy and safety clinical trials for each ACT (AL, AS-AQ and DHA-PPQ) in people taking NVP-based and EFV-based ART.
Subjects:
457
Start Date:
2014-06-02
End Date:
2019-04-30