Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient developed eosinophilic peripheral pulmonary infiltrates while receiving malaria prophylaxis with sulfadoxine-pyrimethamine (Fansidar). Withdrawal of Fansidar and treatment with corticosteroids led to rapid recovery. No exacerbation occurred after cessation of corticosteroids. Lymphocyte transformation testing gave a positive result in the presence of sulfadoxine but not pyrimethamine. It is concluded that drug hypersensitivity to sulfadoxine was the cause of the eosinophilic pneumonia in this patient.
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PMID:Sulfadoxine specific lymphocyte transformation in a patient with eosinophilic pneumonia induced by sulfadoxine-pyrimethamine (Fansidar). 276 33

A 47-year-old woman developed pulmonary eosinophilia from the use of maloprim as malaria prophylaxis. The diagnosis was confirmed by bronchoalveolar lavage (BAL) and transbronchial lung biopsy. Her condition improved with drug withdrawal and steroid therapy. With the increased use of pyrimethamine and dapsone in the treatment of human immunodeficiency syndrome (HIV) infection, this form of drug allergy may become more common.
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PMID:Maloprim-induced pulmonary eosinophilia. 841 12

Mutations in the Plasmodium falciparum 'chloroquine resistance transporter' (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transport these drugs away from their targets within the parasite's digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite's hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite's survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite's hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite's sensitivity to this antimalarial. These insights provide a foundation for understanding clinically-relevant observations of inverse drug susceptibilities in the malaria parasite.
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PMID:Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite's Chloroquine Resistance Transporter. 2744 71