Treatment of Uncomplicated Malaria
Oral quinine sulfate is used for the treatment of uncomplicated malaria caused by Plasmodium falciparum. Oral quinine sulfate also is used for the treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax and for the treatment of uncomplicated malaria when the plasmodial species has not been identified.
Oral quinine sulfate is designated an orphan drug by the US Food and Drug Administration (FDA) for the treatment of malaria. Since malaria is a life-threatening infection, the FDA states that the potential benefits of the drug outweigh the associated risks and justify its use for the treatment of malaria.
For the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or the treatment of uncomplicated malaria when the plasmodial species has not been identified, the US Centers for Disease Control and Prevention (CDC) recommends the fixed combination of atovaquone and proguanil (atovaquone/proguanil), the fixed combination of artemether and lumefantrine (artemether/lumefantrine), or a regimen that includes quinine sulfate in conjunction with doxycycline, tetracycline, or clindamycin. Although mefloquine is another option for treatment in these patients, the CDC recommends that it be used only when other recommended treatment regimens cannot be used. If a quinine regimen is used, concomitant doxycycline or tetracycline generally is preferred instead of concomitant clindamycin since more efficacy data exist regarding antimalarial regimens that include tetracyclines.
For the treatment of uncomplicated malaria caused by chloroquine-susceptible P. falciparum, P. malariae, or P. knowlesi or the treatment of uncomplicated malaria when the plasmodial species has not been identified and the infection was acquired in areas where chloroquine resistance has not been reported, the CDC recommends chloroquine (or hydroxychloroquine). Alternatively, the CDC states that any of the regimens recommended for the treatment of uncomplicated chloroquine-resistant P. falciparum malaria may be used if preferred, more readily available, or more convenient.
For the treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax, the CDC recommends a regimen of quinine sulfate and doxycycline (or tetracycline) given in conjunction with primaquine, atovaquone/proguanil given in conjunction with primaquine, or mefloquine given in conjunction with primaquine. Because quinine sulfate, doxycycline (or tetracycline), atovaquone/proguanil, and mefloquine are active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), a 14-day regimen of primaquine is indicated to prevent delayed primary attacks or relapse and provide a radical cure whenever any of these drugs is used for treatment of P. vivax or P. ovale malaria.
Pediatric patients with uncomplicated malaria generally can receive the same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages. For the treatment of uncomplicated chloroquine-resistant P. falciparum in children younger than 8 years of age, the CDC recommends atovaquone/proguanil or artemether/lumefantrine; mefloquine can be considered if no other options are available. Because children younger than 8 years of age generally should not receive tetracyclines, the CDC states that if a quinine-based regimen is used for the treatment of uncomplicated malaria in such children, a 7-day regimen of quinine sulfate alone can be used (regardless of where the infection was acquired) or quinine sulfate can be given in conjunction with clindamycin. In rare instances, doxycycline or tetracycline can be used in conjunction with quinine sulfate in children younger than 8 years of age if other treatment options are not available or not tolerated and if potential benefits of using a tetracycline outweigh risks. For the treatment of chloroquine-resistant P. vivax malaria in children younger than 8 years of age who should not receive tetracyclines, the CDC recommends mefloquine given in conjunction with primaquine. Alternatively, if mefloquine is not available or not tolerated and if potential benefits outweigh risks, atovaquone/proguanil or artemether/lumefantrine can be used for treatment of chloroquine-resistant P. vivax in this age group.
Pregnant women with uncomplicated malaria caused by P. malariae, P. vivax, P. ovale, or chloroquine-susceptible P. falciparum should receive prompt treatment with chloroquine (or hydroxychloroquine). The CDC recommends that pregnant women with uncomplicated malaria caused by chloroquine-resistant P. falciparum receive prompt treatment with either mefloquine or a regimen of quinine sulfate and clindamycin; mefloquine is recommended for those with uncomplicated malaria caused by chloroquine-resistant P. vivax. Alternatively, atovaquone/proguanil or artemether/lumefantrine can be considered for the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum in pregnant women when other treatment options are not available or not tolerated and if potential benefits outweigh risks. Although tetracyclines generally are contraindicated in pregnant women, in rare circumstances when other treatment options are not available or not tolerated and if potential benefits outweigh risks, the CDC states that quinine sulfate may be used in conjunction with doxycycline (or tetracycline) for the treatment of uncomplicated malaria in pregnant women.
(See Pregnancy under Cautions: Pregnancy, Fertility, and Lactation.)
Assistance with diagnosis or treatment of malaria is available by contacting the CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or the CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.
Quinine has been used for centuries for the treatment of malaria worldwide, and has been effective in geographic regions where chloroquine resistance has been documented. Oral quinine used alone or in conjunction with other antimalarial agents for the treatment of uncomplicated P. falciparum malaria has been evaluated in at least 21 randomized, active-controlled studies in more than 2900 patients from malaria-endemic areas; over 1400 such patients received treatment with oral quinine. Review of data from these trials indicates that a regimen containing oral quinine is effective for the treatment of uncomplicated P. falciparum malaria. In areas of increasing multidrug-resistant P. falciparum (e.g., Southeast Asia), cure rates (cure defined as initial clearing of parasitemia within 7 days after initiation of treatment without recrudescence by day 28) were at least 80% following a 7-day regimen of oral quinine monotherapy and greater than 90% following a 7-day regimen of oral quinine in conjunction with either tetracycline or clindamycin. In areas with less widespread multidrug-resistant P. falciparum, cure rates ranged from 86-100% following 7 days of quinine monotherapy.
Intolerance to quinine may prevent completion of a full 7-day regimen of oral quinine and a shorter regimen (e.g., 3 days) of oral quinine in conjunction with another antimalarial (tetracycline, doxycycline, or clindamycin) has been used. However, data from randomized, controlled clinical trials evaluating these shorter regimens for the treatment of uncomplicated P. falciparum malaria are limited and such regimens may be less effective than the usual 7-day regimen.
P. falciparum malaria that is clinically resistant to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh; quinine treatment may be less effective in these areas.
Treatment of Severe Malaria
Although quinine sulfate is not approved by the FDA for the treatment of severe or complicated malaria, the CDC states that oral quinine sulfate can be used in conjunction with doxycycline, tetracycline, or clindamycin for follow-up treatment after an appropriate initial parenteral regimen.
For the treatment of severe malaria in adults or children, the CDC recommends an initial regimen of IV quinidine gluconate in conjunction with doxycycline, tetracycline, or clindamycin initiated as soon as possible after the diagnosis. The CDC states that after parasitemia is reduced to less than 1% and oral therapy is tolerated, IV quinidine gluconate therapy can be discontinued and oral quinine sulfate initiated to complete 7 or 3 days of total quinidine and quinine therapy as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).
In the past, IV quinine dihydrochloride was considered the drug of choice for the treatment of severe malaria (e.g., cerebral malaria) caused by chloroquine-susceptible or -resistant P. falciparum; however, delivery of emergency supplies for specific patient needs frequently required 24-36 hours because the drug was available in the US only from the Parasitic Diseases Drug Service of the CDC. Because severe P. falciparum malaria can be fatal if therapy is not initiated promptly, IV quinidine gluconate became the drug of choice for initial parenteral treatment of severe malaria in the US since it is more readily available. IV quinine dihydrochloride is no longer available for use in the US, either commercially or from CDC.
If IV quinidine gluconate cannot be used for initial treatment because of adverse effects or contraindications or because it is unavailable locally and cannot be obtained quickly, parenteral artesunate is available from the CDC under an investigational new drug (IND) protocol for emergency initial treatment of severe malaria.
Assistance with diagnosis or treatment of malaria or assistance obtaining quinidine gluconate or artesunate for treatment of severe malaria is available by contacting the CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or the CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.
Presumptive Self-treatment of Malaria
Although some clinicians have suggested that a regimen of oral quinine sulfate in conjunction with oral doxycycline may be used for presumptive self-treatment of malaria in travelers, quinine sulfate is not approved by the FDA for presumptive self-treatment of malaria and is not recommended by CDC for such treatment.
For presumptive self-treatment of malaria in travelers, the CDC and other experts recommend atovaquone/proguanil or artemether/lumefantrine.
Prevention of Malaria
Quinine sulfate is not approved by the FDA for prevention of malaria. The CDC and other clinicians usually recommend use of other antimalarial agents (e.g., chloroquine [or hydroxychloroquine], atovaquone/proguanil, doxycycline, mefloquine) for prevention or chemoprophylaxis of malaria caused by susceptible plasmodia.
Information on the risk of malaria transmission in specific countries, information on mosquito avoidance measures, recommendations regarding whether chemoprophylaxis of malaria is indicated, and information on the choice of antimalarials for prevention are available from the CDC at http://wwwnc.cdc.gov/travel and http://www.cdc.gov/malaria.
Oral quinine sulfate is used in conjunction with IV or oral clindamycin for the treatment of babesiosis caused by Babesia microti.
Although several species of Babesia can infect humans, B. microti is the most common cause of babesiosis in the US.B. microti is transmitted by Ixodes scapularis ticks, which also may be simultaneously infected with and transmit Borrelia burgdorferi (causative agent of Lyme disease) and Anaplasma phagocytophilum (causative agent of human granulocytotropic anaplasmosis [HGA, formerly known as human granulocytic ehrlichiosis]). Therefore, the possibility of coinfection with B. burgdorferi and/or A. phagocytophilum should be considered in patients who have severe or persistent symptoms despite appropriate anti-infective treatment for babesiosis.
The Infectious Diseases Society of America (IDSA) states that all patients with active babesiosis (i.e., symptoms of viral-like infection and identification of babesial parasites in blood smears or by polymerase chain reaction [PCR] amplification of babesial DNA) should receive anti-infective treatment because of the risk of complications; however, symptomatic patients whose serum contains antibody to babesia but whose blood lacks identifiable babesial parasites on smear or babesial DNA by PCR should not receive treatment. In addition, treatment is not recommended initially for asymptomatic individuals, regardless of the results of serologic examination, blood smears, or PCR, but should be considered if parasitemia persists for longer than 3 months.
When anti-infective treatment of babesiosis is indicated, the IDSA and other clinicians recommend that either a regimen of quinine and clindamycin or a regimen of atovaquone and azithromycin be used. The quinine and clindamycin regimen may be preferred in those with severe babesiosis. However, there is some evidence that, in patients with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the quinine and clindamycin regimen. Patients with moderate to severe babesiosis should be monitored closely during treatment to ensure clinical improvement. Exchange transfusions have been used successfully in asplenic patients with life-threatening babesiosis and should be considered, especially in severely ill patients with high levels of parasitemia (10% or more), significant hemolysis, or compromised renal, hepatic, or pulmonary function.
Nocturnal Recumbency Leg Muscle Cramps
Quinine sulfate is not approved by the FDA for the treatment or prevention of nocturnal leg cramps, and the drug should not be used in the management of this or related conditions (e.g., restless legs syndrome).
Although quinine sulfate has been used in the past for the prevention and treatment of nocturnal recumbency leg muscle cramps (night cramps) and results of some uncontrolled or placebo-controlled studies suggest the drug may provide relief of cramps in some patients, there are no adequate and well-controlled studies evaluating efficacy and safety for this use.
Quinine sulfate has a narrow margin of safety and may cause unpredictable serious and life-threatening hypersensitivity reactions, QT interval prolongation, serious cardiac arrhythmias (including torsades de pointes), serious hematologic reactions (including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura [HUS/TTP]), and other serious adverse events (e.g., blindness, deafness) requiring medical intervention and hospitalization. Fatalities associated with use of the drug have been reported. The known risks associated with the use of quinine sulfate, in the absence of evidence of safety and efficacy of the drug for the treatment or prevention of nocturnal leg cramps, outweigh any potential benefits for this benign, self-limiting condition.
The FDA has determined that quinine preparations (including preparations containing any quinine salt alone or in fixed combination with vitamin E) are not generally recognized as safe and effective for treatment or prevention of nocturnal leg muscle cramps. Promotion of quinine for self-medication of nocturnal leg cramps has been prohibited in the US since February 1995 because of safety concerns. In addition, the FDA ordered firms involved in the marketing of unapproved quinine preparations to discontinue marketing such preparations on December 11, 2006.