Tetrahydrofolate Dehydrogenase

Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin-derivative combination therapies (ACT) are highly efficacious against multidrug-resistant Plasmodium falciparum malaria. Few efficacy data, however, are available for vivax malaria. With high rates of chloroquine (CQ) resistance in both vivax and falciparum malaria in Papua Province, Indonesia, new combination therapies are required for both species. We recently found artesunate plus sulfadoxine-pyrimethamine (ART-SP) to be highly effective (96%) in the treatment of falciparum malaria in Papua Province.

Author(s): 
Tjitra, Emiliana
Baker, Joanne
Suprianto, Sri
Cheng, Qin
Anstey, Nicholas M.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

We have analyzed artemisinin sensitivity in Plasmodium falciparum isolates obtained from patients in South Vietnam and show that artemisinin sensitivity does not differ before and after drug treatment. There was an increase in the level of mefloquine resistance in the isolates after drug treatment that was concomitant with a decrease in chloroquine resistance, suggesting that treatment with artemisinin has selected for increased mefloquine resistance. Mutations in the pfmdr1 gene, previously shown to be associated with sensitivity to mefloquine, were selected against.

Author(s): 
Ngo, Thanh
Duraisingh, Manoj
Reed, Michael
Hipgrave, David
Biggs, Beverley
Cowman, Alan F.
Publication Title: 
The Journal of Infectious Diseases

Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment.

Author(s): 
Dorsey, Grant
Vlahos, Jonathan
Kamya, Moses R.
Staedke, Sarah G.
Rosenthal, Philip J.
Publication Title: 
Tropical medicine & international health: TM & IH

In Congo, urgent efforts are needed to help with the revision of the national antimalarial drug policy. Despite its high resistance level, chloroquine (CQ) is still extensively used as the first-line treatment for uncomplicated Plasmodium falciparum malaria. The study was conducted in children under 5 years with uncomplicated malaria in Pointe-Noire and Brazzaville, the two largest cities that contain approximately 60% of the population of Congo.

Author(s): 
Nsimba, Basile
Jafari-Guemouri, Sayeh
Malonga, David A.
Mouata, André M.
Kiori, Jeannine
Louya, Frédéric
Yocka, Dominique
Malanda, Maurice
Durand, Rémy
Le Bras, Jacques
Publication Title: 
Malaria Journal

BACKGROUND: In Tanzania, drug-resistant malaria parasites are an increasing public health concern. Because of widespread chloroquine (CQ) resistance Tanzania changed its first line treatment recommendations for uncomplicated malaria from CQ to sulfadoxine-pyrimethamine (SP) in 2001. Loss of SP sensitivity is progressing rapidly. SP resistance is associated with mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes.

Author(s): 
Schönfeld, Mirjam
Barreto Miranda, Isabel
Schunk, Mirjam
Maduhu, Ibrahim
Maboko, Leonard
Hoelscher, Michael
Berens-Riha, Nicole
Kitua, Andrew
Löscher, Thomas
Publication Title: 
Malaria Journal

BACKGROUND: Plasmodium falciparum is the predominant human malaria species in Mozambique and a lead cause of mortality among children and pregnant women nationwide. Sulphadoxine/pyrimethamine (S/P) is used as first line antimalarial treatment as a partner drug in combination with artesunate. METHODS: A total of 92 P.

Author(s): 
Fernandes, Natercia
Figueiredo, Paula
do Rosario, Virgilio E.
Cravo, Pedro
Publication Title: 
Malaria Journal

BACKGROUND: In the last five years, countries have been faced with changing their malaria treatment policy to an artemisinin-based combination therapy (ACT), many with no national data on which to base their decision. This is particularly true for a number of West African countries, including Guinea, where these studies were performed. Two studies were conducted in 2004/2005 in programmes supported by Medecins Sans Frontieres, when chloroquine was still national policy, but artesunate (AS)/sulphadoxine-pyrimethamine (SP) had been used in refugee camps for two years.

Author(s): 
Bonnet, Maryline
Roper, Cally
Félix, Martine
Coulibaly, Léonie
Kankolongo, Gabriel Mufuta
Guthmann, Jean Paul
Publication Title: 
Malaria Journal

BACKGROUND: In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs.

Author(s): 
Mkulama, Mtawa A. P.
Chishimba, Sandra
Sikalima, Jay
Rouse, Petrica
Thuma, Philip E.
Mharakurwa, Sungano
Publication Title: 
Malaria Journal

BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases.

Author(s): 
Enosse, Sónia
Magnussen, Pascal
Abacassamo, Fatima
Gómez-Olivé, Xavier
Rønn, Anita M.
Thompson, Ricardo
Alifrangis, Michael
Publication Title: 
Antimicrobial Agents and Chemotherapy

The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target of pyrimethamine, a component of the antimalarial pyrimethamine-sulfadoxine. Resistance to this drug is associated primarily with mutations in the Pfdhfr gene. The I164L mutant allele is of particular interest, because strains possessing this mutation are highly resistant to pyrimethamine and to chlorproguanil, a component of chlorproguanil-dapsone.

Author(s): 
Ochong, Edwin
Bell, David J.
Johnson, David J.
D'Alessandro, Umberto
Mulenga, Modest
Muangnoicharoen, Sant
Van Geertruyden, Jean-Pierre
Winstanley, Peter A.
Bray, Patrick G.
Ward, Stephen A.
Owen, Andrew

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