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At the end of the year 2002, Cameroon switched from chloroquine to amodiaquine as first-line therapy for of uncomplicated malaria.
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This study aims to evaluate the safety and efficacy of a standard chloroquine drug regimen administration supplemented with dehydroepiandrosterone sulfate against drug-resistant malaria.
Worldwide progression of Plasmodium falciparum chloroquine (CQ), amodiaquine and sulfadoxine-pyrimethamine resistance leaves few alternative for the control of malaria, particularly in Africa. For some strains of P. falciparum and P. berghei, the resistance to CQ and AQ is linked to an increase in reduced glutathione (GSH) levels and GSH-related enzyme activity, such as glucose 6-phosphate deshydrogenase (G6PD). The pro-hormone dehydroepiandrosterone sulphate can be used to potentiate the antimalarial action of CQ on drug resistant P. falciparum strains, by inhibiting parasite G6PD activity. This hormone has a second advantage: it is metabolised in human into a series of potent immunomodulatory steroids which may be in the causal pathway that allowed the induction of protective immune responses against several infections, included malaria. This first study evaluated the tolerance and efficacy of a standard CQ regimen supplemented with dehydroepiandrosterone sulphate for the treatment of drug resistant uncomplicated falciparum malaria.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| chloroquine | Drug | |||
| dehydroepiandrosterone sulphate | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Development of any adverse event; | ||
| Rate of clinical and/or parasitological failure during the 14 days of follow up. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with positive blood smear during follow-u; | ||
| Mean parasitemia during follow-up; | ||
| Proportion of patients with clinical symptoms on day 3. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michel LE BRAS, Professor | Université Victor Segalen Bordeaux 2, Centre René Labusquière (Santé et Développement) | Study Director |
| Pascal MILLET, Doctor | Université Victor Segalen Bordeaux 2, Pôle des Maladies Tropicale, CHU de Bordeaux | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Medical Research and study of Medicinal Plants, Medical Research Center | Yaoundé | Cameroon |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16846568 | Background | Libonati RM, de Mendonca BB, Maues JA, Quaresma JA, de Souza JM. Some aspects of the behavior of the hypothalamus-pituitary-adrenal axis in patients with uncomplicated Plasmodium falciparum malaria: Cortisol and dehydroepiandrosterone levels. Acta Trop. 2006 Jul;98(3):270-6. doi: 10.1016/j.actatropica.2006.05.008. Epub 2006 Jul 17. | |
| 16699290 |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D003687 | Dehydroepiandrosterone |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Libonati RM, Cunha MG, Souza JM, Santos MV, Oliveira SG, Daniel-Ribeiro CT, Carvalho LJ, do Nascimento JL. Estradiol, but not dehydroepiandrosterone, decreases parasitemia and increases the incidence of cerebral malaria and the mortality in plasmodium berghei ANKA-infected CBA mice. Neuroimmunomodulation. 2006;13(1):28-35. doi: 10.1159/000093271. Epub 2006 May 12. |
| 15476661 | Background | Safeukui I, Mangou F, Malvy D, Vincendeau P, Mossalayi D, Haumont G, Vatan R, Olliaro P, Millet P. Plasmodium berghei: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway. Biochem Pharmacol. 2004 Nov 15;68(10):1903-10. doi: 10.1016/j.bcp.2004.05.049. |
| 12854087 | Background | Leenstra T, ter Kuile FO, Kariuki SK, Nixon CP, Oloo AJ, Kager PA, Kurtis JD. Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya. J Infect Dis. 2003 Jul 15;188(2):297-304. doi: 10.1086/376508. Epub 2003 Jul 1. |
| 12234842 | Background | Ayi K, Giribaldi G, Skorokhod A, Schwarzer E, Prendergast PT, Arese P. 16alpha-bromoepiandrosterone, an antimalarial analogue of the hormone dehydroepiandrosterone, enhances phagocytosis of ring stage parasitized erythrocytes: a novel mechanism for antimalarial activity. Antimicrob Agents Chemother. 2002 Oct;46(10):3180-4. doi: 10.1128/AAC.46.10.3180-3184.2002. |
| 11119497 | Background | Kurtis JD, Mtalib R, Onyango FK, Duffy PE. Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels. Infect Immun. 2001 Jan;69(1):123-8. doi: 10.1128/IAI.69.1.123-128.2001. |
| D000079426 |
| Vector Borne Diseases |
| D006571 | Heterocyclic Compounds |
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015068 | 17-Ketosteroids |
| D007664 | Ketosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |