New Recommendations Issued for Treatment of Malaria in the United States

May 22, 2007 — A systemic review of treatment of malaria in the United States, published in the May 23/30 issue of JAMA, provides recommendations to minimize morbidity and mortality of this disease.

"Even though endemic malaria has been eliminated from the United States, it remains a leading infectious disease worldwide," write Kevin S. Griffith, MD, MPH, from the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and colleagues. "As a consequence, every year in the United States an average 1200 cases of malaria are reported, almost all imported, resulting in up to 13 deaths per year. The unfamiliarity of US clinicians and laboratory personnel with malaria and drug resistance patterns has contributed to delays in diagnosis and treatment, at times with adverse outcomes."

To address this issue, the authors set forth practical recommendations for the diagnosis and treatment of malaria in the United States, based on published evidence; the CDC experience in assisting US clinicians; and the available drugs and diagnostic modalities used in this country.

The investigators performed a systematic MEDLINE search from 1966 to 2006 using the search term "malaria," with subheadings of "congenital," "diagnosis," "drug therapy," "epidemiology," and "therapy." They also obtained additional references from the bibliographies of pertinent articles and by reviewing articles suggested by experts in the treatment of malaria in North America.

To reduce morbidity and mortality from malaria in the United States, the authors recommend obtaining a travel history, considering malaria in the differential diagnosis of fever based on the travel history, and prompt and accurate diagnosis and treatment.

Successful management of malaria requires that treating clinicians answer the following 5 questions:

What is the species?

What is the density of parasitemia?

What is the drug-resistant pattern where the infection was acquired?

Are there signs of severe malaria?

Can the patient tolerate oral medication?
Because Plasmodium falciparum infections can rapidly progress to severe illness or death in as little as 1 to 2 days, patients with malaria should be treated immediately.

In the absence of continued antigen exposure, immunity decreases. Therefore, semi-immune persons who have left an endemic area for an extended period and then return are susceptible to severe disease and death.

Unidentified species should be presumed to be P falciparum pending further identification. The travel history provides useful information about risk for drug resistance.

The need for initial hospital admission for all patients with P falciparum malaria remains controversial. Some authors have tried to define triage criteria for which patients need to be admitted and which can be followed as outpatients.

"However, since these patients can deteriorate rapidly and progress to death within 1 to 2 days, and many centers do not have the expertise to adequately triage (eg, to accurately quantify the parasite density), the CDC advises that patients infected with P falciparum or an unidentified Plasmodium species should be initially admitted to ensure that the medication is tolerated and the patient is improving clinically and parasitologically," the authors write. "Blood films should be repeated to ensure clearance of P falciparum parasitemia. Patients who are not responding clinically (with defervescence within 72 hours) need follow-up malaria blood films and may also require a search for other causes of fever."

For P falciparum acquired in areas without chloroquine-resistant strains, chloroquine remains the treatment of choice. The best treatment options for P falciparum acquired in areas with chloroquine resistance are a combination of atovaquone and proguanil; oral quinine plus tetracycline, doxycycline, or clindamycin; or mefloquine.

Chloroquine remains the treatment of choice for all other malaria species, except for Plasmodium vivax acquired in Indonesia or Papua New Guinea. In these cases, atovaquone-proguanil is recommended, with mefloquine or quinine plus tetracycline or doxycycline as suitable alternatives.

Severe malaria occurs when a patient with asexual malaria parasitemia, and no other confirmed cause of symptoms, has at least 1 designated clinical or laboratory finding. Because artemisinin drugs are not yet available in the United States, quinidine is currently the recommended treatment of severe malaria in this country. Exchange transfusion is the only adjunctive measure recommended for severe malaria.

"Malaria remains a diagnostic and treatment challenge for US clinicians as increasing numbers of persons travel to and emigrate from malarious areas," the authors write. "A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and minimize the major mortality and morbidity burdens caused by this disease."

The CDC posts current treatment recommendations on its Web site (http://www.cdc.gov/malaria) and has clinicians available 24 hours daily to assist clinicians with malaria diagnosis and treatment. Malaria is a nationally notifiable disease. All cases should be reported to the appropriate state health department to facilitate monitoring of trends in disease acquisition and to provide recommendations for malaria chemoprophylaxis and treatment.

"Malaria will remain a diagnostic and treatment challenge for US clinicians as increasing numbers of persons travel to and emigrate from malarious areas," the authors conclude. "In a review of all malaria deaths in the US from 1963-2001, failure to diagnose malaria on initial presentation, promptly initiate treatment after diagnosis, and/or prescribe an appropriate antimalarial drug, were substantial contributing factors in malaria deaths. Clinicians must remain alert to the possibility of this disease and take immediate measures toward prompt accurate diagnosis and treatment."

The authors have disclosed no relevant financial relationships.

JAMA. 2007;297:2264-2277.

Source: http://www.medscape.com/viewarticle/557050?src=mp