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Treatment of Malaria in the United States a Systematic Review

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Treatment of Malaria in the United States a Systematic Review CLINICAL REVIEW CLINICIAN’S CORNER Treatment of Malaria in the United States A Systematic Review Kevin S. Griffith, MD, MPH Context Many US clinicians and laboratory personnel are unfamiliar with the diag- Linda S. Lewis, DVM, MPVM nosis and treatment of malaria. Sonja Mali, MPH Objectives To examine the evidence base for management of uncomplicated and severe malaria and to provide clinicians with practical recommendations for the diag- Monica E. Parise, MD nosis and treatment of malaria in the United States. VEN THOUGH ENDEMIC MALARIA Evidence Acquisition Systematic MEDLINE search from 1966 to 2006 using the has been eliminated from the search term malaria (with the subheadings congenital, diagnosis, drug therapy, epi- United States, it remains a lead- demiology, and therapy). Additional references were obtained from searching the bib- ing infectious disease world- liographies of pertinent articles and by reviewing articles suggested by experts in the Ewide. As a consequence, every year in treatment of malaria in North America. the United States an average 1200 cases Evidence Synthesis Important measures to reduce morbidity and mortality from of malaria are reported, almost all im- malaria in the United States include the following: obtaining a travel history, consid- ported, resulting in up to 13 deaths per ering malaria in the differential diagnosis of fever based on the travel history, and year.1 The unfamiliarity of US clini- prompt and accurate diagnosis and treatment. Chloroquine remains the treatment cians and laboratory personnel with ma- of choice for Plasmodium falciparum acquired in areas without chloroquine- resistant strains. In areas with chloroquine resistance, a combination of atovaquone laria and drug resistance patterns has and proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best contributed to delays in diagnosis and treatment options. Chloroquine remains the treatment of choice for all other treatment, at times with adverse out- malaria species, with the exception of P vivax acquired in Indonesia or Papua New comes.2 Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine To address this problem, we pro- plus tetracycline or doxycycline as alternatives. Quinidine is currently the recom- vide clinicians with practical recom- mended treatment for severe malaria in the United States because the artemisinins mendations for the diagnosis and treat- are not yet available. Severe malaria occurs when a patient with asexual malaria ment of malaria in the United States, parasitemia, and no other confirmed cause of symptoms, has 1 or more designated clinical or laboratory findings. The only adjunctive measure recommended in severe based on published evidence; the Cen- malaria is exchange transfusion. ters for Disease Control and Preven- tion (CDC) experience in assisting US Conclusions Malaria remains a diagnostic and treatment challenge for US clinicians clinicians; and the available drugs and as increasing numbers of persons travel to and emigrate from malarious areas. A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and mini- diagnostic modalities used in this mize the major mortality and morbidity burdens caused by this disease. country. JAMA. 2007;297:2264-2277 www.jama.com METHODS evance to this article, hand searched America. Recommendations are based We performed a systematic MEDLINE bibliographies of pertinent articles, and on randomized controlled trials, ob- search from 1966 to 2006 using the reviewed articles suggested by experts servational studies, and consensus ex- search term malaria (with the subhead- in the treatment of malaria in North pert opinion. ings congenital, diagnosis, drug therapy, epidemiology, and therapy). This search Author Affiliations: Malaria Branch, Division of Parasitic National Center for Zoonotic, Vector-Borne and Enteric Diseases, National Center for Zoonotic, Vector-Borne and Diseases, Centers for Disease Control and Prevention. was conducted on August 1, 2006, and Enteric Diseases, Coordinating Center for Infectious Dis- Corresponding Author: Monica E. Parise, MD, Para- resulted in 5588 potentially relevant ar- eases, Centers for Disease Control and Prevention, At- sitic Diseases Branch, Division of Parasitic Diseases, Na- ticles. We reviewed titles and/or ab- lanta, Ga (Drs Griffith and Parise and Ms Mali); and Butte tional Center for Zoonotic, Vector-Borne and Enteric County Department of Public Health, Oroville, Calif (Dr Diseases, Centers for Disease Control and Preven- stracts of all articles to determine rel- Lewis). Dr Griffith is now with the Bacterial Diseases Branch, tion, 4770 Buford Hwy NE MS F22, Atlanta, GA 30341 DivisionofVector-BorneInfectiousDiseases,NationalCen- ([email protected]). ter for Zoonotic, Vector-Borne and Enteric Diseases, Co- Clinical Review Section Editor: Michael S. Lauer, MD. CME available online at ordinating Center for Infectious Diseases, Centers for Dis- We encourage authors to submit papers for consid- www.jama.com ease Control and Prevention. Dr Parise is now with the eration as a Clinical Review. Please contact Michael Parasitic Diseases Branch, Division of Parasitic Diseases, S. Lauer, MD, at [email protected]. 2264 JAMA, May 23/30, 2007—Vol 297, No. 20 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 TREATMENT OF MALARIA IN THE UNITED STATES BIOLOGICAL AND Plasmodium ovale may reactivate weeks Plasmodium ovale occurs mostly in West EPIDEMIOLOGIC or months after the initial infection, pro- Africa and is occasionally encountered CONSIDERATIONS ducing relapses. in Southeast Asia and Papua New In the Plasmodium life cycle (FIGURE 1), Of the 4 Plasmodium species that in- Guinea. Plasmodium malariae occurs at the asexual blood stages (rings, tropho- fect humans, Plasmodium falciparum is low frequency in a patchy distribution zoites, schizonts) are responsible for the the one with potential to rapidly progress worldwide. Plasmodium falciparum ac- symptoms of malaria, and thus are the to severe illness or death. It predomi- counts for slightly more than 50% and main target of chemotherapy. The nates in sub-Saharan Africa, Hispani- P vivax approximately 25% of reported sexual blood stages (gametocytes) do ola, and Papua New Guinea. Among the cases in the United States.1,2 not cause any known pathology and other species, P vivax is the most com- Chloroquine-resistant strains of P fal- thus are not a primary target of treat- mon3 and predominates in South Asia, ciparum occur in all endemic areas ex- ment. Dormant liver stage parasites Eastern Europe and Northern Asia, and cept Central America west of the Panama (hypnozoites) of Plasmodium vivax and Central and most of South America.4 Canal, Mexico, Hispaniola, and parts of Figure 1. Plasmodium Life Cycle Mosquito Stages Human Liver Stages Human Blood Stages Exo-Erythrocytic Schizont Mosquito Injects Sporozoites Erythrocyte Immature Ruptured Merozoites Trophozoite Exo-Erythrocytic Sporozoites Infected (Ring Stage) Schizont Migrate to Hepatocyte Salivary Glands Ruptured Schizont Ruptured Oocyst ASEXUAL STAGES Hypnozoite Hypnozoites (Dormant Stage; Can Reactivate, P vivax, P ovale) Causing Relapses Oocyst in Midgut Mature Trophozoite Schizont Ookinete (Motile Zygote) Amplification of Infection Zygote SEXUAL STAGE Gametes Gametocytes Mosquito Ingests Gametocytes The morphology of Plasmodium life cycle stages varies between species. Those shown in the illustration are Plasmodium falciparum, except for the hypnozoite, which occurs only in Plasmodium vivax and Plasmodium ovale. In P falciparum, the mature asexual stages (eg, schizonts) are sequestered in the microvasculature of vital organs due to cytoadherence of infected erythrocytes to the capillary endothelium and are rarely seen circulating in the peripheral blood. (Blood film photomicrograph insets: Giemsa stain; source: Division of Parasitic Diseases/Centers for Disease Control and Prevention). ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, May 23/30, 2007—Vol 297, No. 20 2265 Downloaded From: https://jamanetwork.com/ on 09/25/2021 TREATMENT OF MALARIA IN THE UNITED STATES the disease. The typical incubation pe- Diagnostic confirmation is ob- Box. Manifestations riod usually varies between 9 and 18 days tained by microscopic demonstration of Severe Malaria* for P falciparum, P vivax, and P ovale12; of malaria parasites on Giemsa- Prostration it is longer (18-40 days) for P malariae stained thick and thin blood films, and may be as short as 7 days for P fal- which should be examined as soon as Impaired consciousness/coma ciparum.13 However, symptoms may oc- possible but within 12 hours of the pre- Respiratory distress (acidotic cur weeks or even months after expo- sentation of any patient with sus- breathing) sure as a result of inadequate prophylaxis pected malaria. Institutions unfamil- Multiple convulsions or treatment, immune response, or re- iar with malaria diagnosis should not Circulatory shock lapses. Some temperate strains of P vivax, delay microscopic diagnosis (eg, by Pulmonary edema such as the North Indian and North Ko- sending the films out to a laboratory Acute respiratory distress syndrome rean strains, can exhibit delayed pri- that cannot provide same-day re- Abnormal bleeding mary attacks, occurring 12 to 18 months sults), but should promptly refer the pa- after an infected mosquito bite.14 Of cases tient to a more experienced institu-
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