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      Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia

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          Summary

          To determine the level of antimalarial drug resistance in southern Papua, Indonesia, we assessed the therapeutic efficacy of chloroquine plus sulfadoxine–pyrimethamine (CQ+SP) for Plasmodium falciparum infections as well as CQ monotherapy for P. vivax infections. Patients with P. falciparum failing therapy were re-treated with unsupervised quinine ± doxycycline therapy and those with P. vivax with either unsupervised quinine ± doxycycline or amodiaquine. In total, 143 patients were enrolled in the study (103 treated with CQ+SP and 40 with CQ). Early treatment failures occurred in four patients (4%) with P. falciparum and six patients (15%) with P. vivax. The failure rate by Day 28 for P. vivax was 65% (95% CI 49–81). After PCR correction for re-infections, the Day 42 recrudescence rate for P. falciparum infections was 48% (95% CI 31–65). Re-treatment with unsupervised quinine ± doxycycline resulted in further recurrence of malaria in 48% (95% CI 31–65) of P. falciparum infections and 70% (95% CI 37–100) of P. vivax infections. Eleven patients with recurrent P. vivax were re-treated with amodiaquine; there were no early or late treatment failures. In southern Papua, a high prevalence of drug resistance of P. falciparum and P. vivax exists both to first- and second-line therapies. Preliminary data indicate that amodiaquine retains superior efficacy compared with CQ for CQ-resistant P. vivax.

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          The global distribution of clinical episodes of Plasmodium falciparum malaria.

          Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.
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            Chloroquine resistance in Plasmodium vivax.

            J. Baird (2004)
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              Therapeutic responses to different antimalarial drugs in vivax malaria.

              The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for > or =28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action.
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                Author and article information

                Journal
                Trans R Soc Trop Med Hyg
                Trans. R. Soc. Trop. Med. Hyg
                Transactions of the Royal Society of Tropical Medicine and Hygiene
                Elsevier
                0035-9203
                1878-3503
                April 2007
                April 2007
                : 101
                : 4-4
                : 351-359
                Affiliations
                [a ]International Health Program, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
                [b ]National Institute of Health Research and Development, Jakarta, Indonesia
                [c ]MSHR-NIHRD Malaria Research Program, Timika, Papua, Indonesia
                [d ]Dinas Kesehatan Kabupaten, Timika, Papua, Indonesia
                [e ]Lembarga Pengembangan Masyarakat Amungme Kamoro, Timika, Papua, Indonesia
                [f ]Public Health & Malaria Control Department, PT Freeport Indonesia, Tembagapura, Papua, Indonesia
                [g ]Australian Army Malaria Institute, Brisbane, QLD, Australia
                [h ]Directorate General of Disease Control and Environment Health, Ministry of Health, Jakarta, Indonesia
                [i ]International SOS, Tembagapura, Papua, Indonesia
                [j ]Centre for Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK
                Author notes
                [* ]Corresponding author. Present address: Menzies School of Health Research, P.O. Box 41096, Casuarina, NT 0811, Australia. Tel.: +61 8 8922 8197; fax: +61 8 8922 8429. rnp@ 123456menzies.edu.au
                Article
                TRSTMH512
                10.1016/j.trstmh.2006.06.008
                2080856
                17028048
                5a0ff789-7e7a-4704-a733-f3b36cd0ef48
                © 2007 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 24 April 2006
                : 16 May 2006
                : 9 June 2006
                Categories
                Article

                Medicine
                drug resistance,plasmodium falciparum,sulfadoxine–pyrimethamine,papua,indonesia,plasmodium vivax,malaria,chloroquine

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