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Malaria
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Plasmodium falciparum malaria and HIV both cause substantial morbidity and mortality, particularly in sub-Saharan Africa. Given this substantial overlap, even modest interactions between them have public health importance. Early studies failed to identify important interactions between malaria and HIV (1211Chandramohan D, Greenwood BM. Is there an interaction between human immunodeficiency virus and Plasmodium falciparum? Int J Epidemiol 1998;27:296-301., 1212Nguyen-Dinh P, Greenberg AE, Mann JM, et al. Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. Bull World Health Organ 1986;65:607-13.). However, more recent evidence supports the presence of the effect of each infection on the other (1213Slutsker L, Marston BJ. HIV and malaria: interactions and implications. Curr Opin Infect Dis 2007;20:3-10.).

Epidemiology

P. falciparum, P. vivax, P. ovale, and P. malariae, and a recently described species in humans, P. knowlesi, differ in geographic distribution, microscopic appearance, and clinical features. Although P. vivax infections are more common, worldwide, P. falciparum malaria represents the most serious public health problem because of its tendency toward severe or fatal infections.

Malaria is typically transmitted by the bite of an infected female Anopheles sp. mosquito. Nonmosquito-borne routes of infection (congenital, transfusion) occur less frequently (1214Mungai M, Tegtmeier G, Chamberland M, Parise M. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001;344:1973-8., 1215Austin SC, Stolley PD, Lasky T. The history of malariotherapy for neurosyphilis: Modern parallels. JAMA 1992;268:516-9., 1216CDC. Update: self-induced malaria associated with malariotherapy for Lyme diseaseTexas. MMWR 1991;40:665-6.).

Malaria transmission has occurred in 107 countries and territories worldwide (1217World Health Organization. World Malaria Report, 2005. Geneva: World Health Organization and UNICEF; 2005.. Thirty-six percent of the global population lives in areas in which a risk for malaria transmission occurs (1218Snow RW, Craig M, Deichmann U, Marsh K. Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. Bull World Health Organ 1999;77:624-40.). Each year an estimated 300-500 million clinical cases of malaria occur, making it one of the most prevalent infectious diseases (1219World Health Organziation. World malaria situation in 1994: part IPopulation at risk. Wkly Epidemiol Rec 1997;72:269-74.). Approximately 80% of the approximately 1 million deaths attributed to malaria each year occur among African children (1217World Health Organization. World Malaria Report, 2005. Geneva: World Health Organization and UNICEF; 2005.).

The clinical syndromes caused by malaria depend on whether a patient comes from an area with stable endemic malaria transmission or unstable (infrequent or very low) transmission (1220Snow RW, Marsh K. The consequences of reducing transmission of Plasmodium falciparum in Africa. Adv Parasitol 2002:52:235-64.). In stable endemic areas, young children (<5 years) might experience chronic infections with recurrent parasitemia, resulting in severe anemia and often death. Those who survive repeated infections acquire partial immunity by age 5 years and, if they remain in the area where malaria is endemic, maintain this immunity into adulthood. Adults in stable endemic areas usually experience asymptomatic or milder infections. In unstable transmission areas, immunity is not acquired. In these areas, the overwhelming clinical manifestation is acute febrile disease that can be accompanied by cerebral malaria, affecting persons of all ages.

Pregnant women in areas of unstable transmission might experience acute malaria, spontaneous abortion, and stillbirth. In more stable transmission areas, pregnant women might lose some acquired immunity. Although infections might be asymptomatic, women acquire placental malaria that contributes to intrauterine growth retardation, low birthweight, and the concomitant risk for increased infant mortality.

HIV impact on malaria

Parasitemia and clinical severity. HIV disease impairs the acquired immunity to malaria evident in older children and adults in endemic areas. Large cohort studies have demonstrated evidence of increased frequency (with rates one- to twofold higher) of both parasitemia and clinical malaria in HIV-infected adults, with increasing risk and higher density parasitemia associated with more advanced immunosuppression (1221Whitworth J, Morgan D, Quigley M, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000;356:1051-6., 1222Patnaik P, Jere CS, Miller WC, et al. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 2005;192:984-91.). The rates of increased malaria among persons with HIV are not as great as observed with classic OIs like TB and PCP (1223Laufer MK, van Oosterhout JJ, Thesing PC, et al. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. J Infect Dis 2006;193:872-8.).

In a prospective cohort study in an area with unstable malaria transmission, HIV-infected nonimmune adults were at increased risk for severe malaria, and the risk was associated with a low CD4+ count (1224Cohen C, Karstaedt A, Frean J, et al. Increased prevalence of severe malaria in HIV-infected adults in South Africa. Clin Infect Dis 2005;41:1631-7.). Nonimmune HIV-infected patients were substantially more likely to have severe clinical malaria than were nonimmune patients without HIV. In another area of unstable malaria transmission, HIV-infected adults hospitalized for malaria were substantially more likely to die or require an ICU admission than those without HIV (1225Grimwade K, French N, Mbatha DD, et al. HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa. AIDS 2004;18:547-54.). In contrast, HIV infection did not confer an increased risk for these severity measures among partially immune adults from areas with more stable transmission (1221Whitworth J, Morgan D, Quigley M, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000;356:1051-6.).

The situation is more complex in children. Early studies among HIV-infected infants did not suggest an increase in frequency or density of parasitemia associated with HIV infection (1226Greenberg AE, Nsa W, Ryder RW, et al. Plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire: a prospective, longitudinal cohort study of 587 children. N Engl J Med 1991;325:105-9., 1227Kalyesubula I, Musoke-Mudido P, Marum L, et al. Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children. Pediatr Infect Dis J 1997;16:876-81.). More recent data suggest increased rates of parasitemia and higher densities among somewhat older HIV-infected children (up to age 5 years) compared with those without HIV (1228Mermin J, Lule J, Ekwaru JP, et al. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004;364:1428-34.). As with adults, older children with HIV might be at increased risk for clinical malaria because of HIV-induced impairment of acquired anti-malarial immunity. HIV-infected infants in Kenya were at increased risk for severe anemia and for hospitalization because of malaria (1229van Eijk AM, Ayisi JG, Ter Kuile FO, et al. Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, western Kenya. Am J Trop Med Hyg 2002;67:44-53.). Limited data from areas in which malaria is not endemic also suggest HIV is associated with more severe malaria in older children (1230Grimwade K, French N, Mbatha DD, et al. Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence. Pediatr Infect Dis J 2003;22:1057-63.).

Malaria treatment outcomes. Prospective clinical trial data from Kenya indicated that among adults with uncomplicated malaria treated with sulfadoxine-pyrimethamine (SP), the risk for failure 28 days post treatment was substantially higher among HIV-infected adults with low CD4+ counts (<200 cells/µL) than in the HIV-uninfected group (1231Shah SN, Smith EE, Obonyo CO, et al. HIV immunosuppression and antimalarial efficacy: sulfadoxine-pyrimethamine for treatment of uncomplicated malaria in HIV-infected adults in Siaya, Kenya. J Infect Dis 2006;194:1519-28.). In multivariable analysis, the combination of HIV infection with CD4+ count <200 cells/µL and anemia was the only substantial risk factor for treatment failure at 28 days. Similar results were observed in Zambian adults with uncomplicated malaria (1232Van Geertruyden JP, Mulenga M, Mwananyanda L, et al. HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria. J Infect Dis 2006;194:917-25.). Widespread resistance to SP has prompted certain countries to adopt policies calling for use of artemisinin-containing combination therapies (ACTs) for first-line treatment for malaria. Assessing whether HIV-related immunosuppression adversely affects efficacy of ACTs in malaria treatment is important.

Malaria effect on HIV

Viral load and transmission. As occurs with TB and other major OIs, malarial episodes are associated with increased HIV viral load (24Kublin JG, Patnaik P, Jere CS, et al. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet 2005;365:233-40.). Modeling studies have suggested that this increase could affect HIV transmission (25Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science 2006;314:1603-6.). In pregnant women, recent studies have also confirmed that malaria parasitemia was associated with increased HIV concentrations, with a magnitude similar to that observed in asymptomatically infected nonpregnant adults (1233ter Kuile FO, ME P, FH V, et al. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa. Am J Trop Med Hyg 2004;71(Suppl 2):41-54.).

Mother-to-child HIV transmission. Placental malaria also has been associated with increased expression of CCR5 receptors in placental macrophages (1234Tkachuk AN, Moormann AM, Poore JA, et al. Malaria enhances expression of CC chemokine receptor 5 on placental macrophages. J Infect Dis 2001;183:967-72.) and increased viral load (1235Mwapasa V, Rogerson SJ, Molyneux ME, et al. The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women. AIDS 2004;18:1051-9.), raising the possibility of placental malaria leading to increased MTCT of HIV. However, data concerning the effect of malaria during pregnancy on the risk for MTCT of HIV are conflicting. One study in Uganda demonstrated increased MTCT in women with placental malaria (1236Brahmbhatt H, Kigozi G, Wabwire-Mangen F, et al. The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS 2003;17:2539-41.), but studies from Kenya did not demonstrate this association (1237Inion I, Mwanyumba F, Gaillard P, et al. Placental malaria and perinatal transmission of human immunodeficiency virus type 1. J Infect Dis 2003;188:1675-8., 1238Ayisi JG, van Eijk AM, Newman RD, et al. Maternal malaria and perinatal HIV transmission, Western Kenya. Emerg Infect Dis 2004;10:643-52.).

Blood transfusion transmission. Because anemia caused by P. falciparum remains a frequent indication for blood transfusions, malarial anemia can have an important indirect effect on the risk for HIV transmission (1239Greenberg AE, Nguyen-Dinh P, Mann JM, et al. The association between malaria, blood transfusions, and HIV seropositivity in a pediatric population in Kinshasa, Zaire. JAMA 1988;259:545-9.). Improved blood collection and testing practices are leading to improved transfusion safety in Africa (1240Moore A, Herrera G, Nyamongo J, et al. Estimated risk of HIV transmission by blood transfusion in Kenya. Lancet 2001;358:657-60., 1241Heyns Adu P, Benjamin RJ, Swanevelder JP, et al. Prevalence of HIV-1 in blood donations following implementation of a structured blood safety policy in South Africa. JAMA 2006;295:519-26.), but few countries conduct universal screening of blood.

Clinical Manifestations

Patients with malaria can exhibit various symptoms and a broad spectrum of severity depending upon such factors as the infecting species and level of acquired immunity in the host. As noted previously, HIV-immunosuppressed persons in endemic areas might lose acquired malarial immunity, and HIV-immunosuppressed adults with little or no previous malaria exposure such as travelers might be at increased risk for severe outcomes (1242Matteelli A, Casalini C, Bussi G, et al. Imported malaria in an HIV-positive traveler: a case report with a fatal outcome. J Travel Med 2005;12:222-4.).

Among nonimmune persons, typical symptoms of malaria include fever, chills, myalgias and arthralgias, headache, diarrhea, vomiting, and other nonspecific signs. Splenomegaly, anemia, thrombocytopenia, pulmonary or renal dysfunction, and neurologic findings also might be present. Classically, paroxysmal fevers occur every 48 hours for P. falciparum, P. vivax, and P. ovale malaria; those of P. malariae occur every 72 hours. However, this classic presentation is highly variable and might not be present.

Uncomplicated malaria infection can progress to severe disease or death within hours. Malaria with CNS symptoms can be particularly ominous. Cerebral malaria refers to unarousable coma not attributable to any other cause in a patient infected with P. falciparum; in Africa, case fatality rates with cerebral malaria might approach 40% (1243World Health Organization. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1990;84(Suppl 2):1-65., 1244Greenberg AE, Ntumbanzondo M, Ntula N, Mawa L, Howell J. Hospital-based surveillance of malaria-related paediatric morbidity and mortality in Kinshasa, Zaire. Bull World Health Organ 1989;67:189-96., 1245Molyneux ME, Taylor TE, Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 1989;71:441-59.). The risk for severe and complicated illness is increased in patients with high levels of parasitemia and without partial immunity. Metabolic acidosis appears to be an important manifestation of severe malaria and indicator of poor prognosis (1246English M, Sauerwein R, Waruiru C, et al. Acidosis in severe childhood malaria. Q J Med 1997;90:263-70.). Other acute complications include renal failure, hypoglycemia, disseminated intravascular coagulation, shock, and acute pulmonary edema (1247Marsh K, Forster D, Waruiru C, et al. Indicators of life-threatening malaria in African children. N Engl J Med 1995;332:1399-404.). P. falciparum is the species responsible for severe disease and death; severe or fatal malaria rarely results from infections with the other species. A rare exception is spleen rupture, which can occur with acute nonfalciparum malaria (1248Zingman BS, Viner BL. Splenic complications in malaria: case report and review. Clin Infect Dis 1993;16):223-32.).

Diagnosis

The diagnosis of malaria must be considered in all febrile patients who have traveled to or lived in malaria-endemic areas or who have received blood products, tissues, or organs from persons who have been to such areas. Several diagnostic methods are available, including microscopic diagnosis, antigen detection tests, PCR-based assays, and serologic tests. Direct microscopic examination of intracellular parasites on stained blood films is the standard for definitive diagnosis in nearly all settings. In nonimmune persons, symptoms might develop before detectable levels of parasitemia are evident. For this reason, several blood smear examinations taken at 12-24-hour intervals might be needed to positively rule out a diagnosis of malaria in a symptomatic patient. Guidelines for laboratory diagnosis are summarized elsewhere and are available at CDC's malaria website (http://www.cdc.gov/malaria/).

Preventing Exposure

Infection with P. falciparum in HIV-infected persons with low CD4+ counts and in pregnant women regardless of HIV infection status can be more severe than in other persons. Because no chemoprophylactic regimen is completely effective, HIV-infected persons with low CD4+ counts and women who are pregnant or likely to become pregnant should be advised to avoid travel to areas with malaria transmission if possible (AIII). If travel to a malarious area cannot be deferred, use of an effective chemoprophylaxis regimen is essential, along with careful attention to personal protective measures to prevent mosquito bites.

Preventing Disease

In areas where malaria is endemic, strategies to prevent malaria and its consequences include vector control, prophylaxis, and intermittent preventive treatment in pregnancy. For U.S. travelers (including HIV-infected persons) to malarious areas, a combination of chemoprophylaxis and personal protective measures can be highly effective in preventing malaria. One of three drugs is recommended for prophylaxis: atovaquone-proguanil, mefloquine, or doxycycline. Recommendations for prophylaxis are the same for HIV-infected persons as for noninfected persons and are available at CDC's malaria website (AIII) (http://www.cdc.gov/malaria). Malaria incidence has been markedly reduced in African adults with HIV who receive cotrimoxazole (TMP-SMX) prophylaxis (30Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8., 1249Hamel MJ, Greene C, Chiller T, et al. A prospective study of daily cotrimoxazole prophylaxis in Kenyan HIV-Infected Adults and the development of antimicrobial resistance. Am J Trop Med 2004;71:268.). A recent study of HIV-infected persons in Uganda demonstrated that malaria burden was reduced by 70% with cotrimoxazole, was then reduced a further 50% when antiretroviral drugs were provided, and finally a further 50% with provision of insecticide-treated nets (1250Mermin J, Ekwaru JP, Liechty CA, et al. Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet 2006;367:1256-61.). However, cotrimoxazole is not as effective an antimalarial prophylactic regimen as the antimalarials recommended (Table 2). Therefore, HIV-infected travelers on prophylaxis with cotrimoxazole should not rely on it for chemoprophylaxis against malaria (AIII).

Treatment of Disease

Because falciparum malaria can progress within hours to severe disease or death, all HIV-infected persons with confirmed or suspected P. falciparum infections should be admitted to the hospital for evaluation, initiation of treatment, and observation of response to treatment. Ideally, antimalarial treatment should not be initiated until the diagnosis has been confirmed by laboratory investigations. However, treatment should not be delayed when malaria is strongly suspected but laboratory results are pending.

The choice of treatment is guided by the degree of parasitemia and the species of Plasmodium identified, the clinical status of the patient, and the likely drug susceptibility of the infecting species as determined by where the infection was acquired. Although impaired response has been noted in HIV-immunosuppressed persons treated with older antimalarials such as sulfadoxine pyrimethamine (1231Shah SN, Smith EE, Obonyo CO, et al. HIV immunosuppression and antimalarial efficacy: sulfadoxine-pyrimethamine for treatment of uncomplicated malaria in HIV-infected adults in Siaya, Kenya. J Infect Dis 2006;194:1519-28., 1232Van Geertruyden JP, Mulenga M, Mwananyanda L, et al. HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria. J Infect Dis 2006;194:917-25.), no evidence indicates that response in these persons is impaired if currently recommended drugs are used. Therefore, for HIV-infected patients who do acquire Plasmodium infection, treatment recommendations are the same as for HIV-uninfected patients (AIII). Detailed antimalarial treatment recommendations have been reviewed recently (1251Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA 2007;297:2264-77.). CDC posts current treatment recommendations on its website (http://www.cdc.gov/malaria) and has clinicians on call 24 hours to provide advice to clinicians on the diagnosis and treatment of malaria (CDC Malaria Hotline 770-488-7788 M-F 8 AM-4:30 PM ET, 770-488-7100 after hours).

Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome (IRIS)

Several potential drug interactions can occur between antimalarial and HIV drugs, and these have been reviewed recently (1252Khoo S, Back D, Winstanley P. The potential for interactions between antimalarial and antiretroviral drugs. AIDS 2005;19:995-1005.). Atovaquone and doxycycline interactions with antiretroviral drugs and with drugs used to prevent and treat OIs have been summarized previously (37CDC. Guidelines for preventing opportunistic infections among HIV-infected persons-2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR 2002;51(No. RR-8)., 1253CDC. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR 2004;53(No. RR-15).). Mefloquine in repeated doses has been observed to reduce area under the concentration-time curve and maximal plasma concentrations of ritonavir by 31% and 36%, respectively. Sufficient data are not available to suggest that dose adjustments are needed.

Quinine levels might be increased by ritonavir-containing regimens; conversely, nevirapine and efavirenz could reduce plasma quinine levels. Potential interactions can occur between ritonavir with chloroquine; however, the clinical significance of these interactions is unclear and until further data are available, no dose adjustments are recommended. Artemisinin-containing compounds such as artesunate, which are widely used for antimalarial treatment in other parts of the world, are not yet approved in the United States. However, artesunate might soon be available for treatment of severe malaria in the United States through a compassionate use Investigational New Drug application. PIs and NNRTIs have the potential to affect metabolism of artemisinin-containing drugs (1254Parikh S, Gut J, Istvan E, et al. Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother 2005;49:2983-5.), but the overall effect and clinical significance remain unclear. No IRIS has been described in association with malaria.

Management of Treatment Failure

Management of treatment failure for persons with HIV infection should not differ from HIV-positive patients except in terms of drug interactions and drug toxicities as noted above.

Prevention of Recurrence

Not Applicable.

Special Considerations During Pregnancy

Malaria in pregnancy affects both the mother and the fetus. Infection with P. falciparum during pregnancy can increase the mother's risk for having severe disease and anemia and increase the risk for stillbirth, preterm birth, and low birthweight (1255Desai M, ter Kuile FO, Nosten F, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 2007;7:93-104.). The diagnosis of malaria in pregnant women is the same as in nonpregnant women.

For pregnant women with a diagnosis of uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-sensitive P. vivax, and chloroquine-sensitive P. falciparum, prompt treatment with chloroquine is recommended (1251Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA 2007;297:2264-77.). For pregnant women with a diagnosis of chloroquine-resistant P. vivax, treatment with quinine for 7 days is recommended (AIII). For pregnant women with a diagnosis of uncomplicated chloroquine-resistant P. falciparum malaria, prompt treatment with quinine and clindamycin is recommended.

On the basis of extensive experience with its use, chloroquine is considered the drug of choice for prophylaxis and treatment of sensitive strains of malaria in pregnancy. Although quinine at high doses has been associated with an increased risk for birth defects (especially deafness) in some animal species and humans (usually during attempted abortion), use of therapeutic doses in pregnancy is considered safe (1251Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA 2007;297:2264-77., 1256McGready R, Thwai KL, Cho T, et al. The effects of quinine and chloroquine antimalarial treatments in the first trimester of pregnancy. Trans Royal Soc Trop Med Hyg 2002;96:180-4.). Because of the potential for hypoglycemia, pregnant women treated with quinine and their neonates should have monitoring of glucose levels. Clindamycin use has not been associated with birth defects. Because of limited data, atovaquone-proquanil or mefloquine are not recommended for treatment in pregnancy and should be used only if quinine plus clindamycin or quinine monotherapy is not available or not tolerated (1256McGready R, Thwai KL, Cho T, et al. The effects of quinine and chloroquine antimalarial treatments in the first trimester of pregnancy. Trans Royal Soc Trop Med Hyg 2002;96:180-4.). Animal data and human data on use of prophylactic doses of mefloquine do not suggest teratogenicity. Tetracyclines are not recommended in pregnancy because of increased risk for maternal hepatotoxicity and staining of fetal teeth and bones. Primaquine use during pregnancy is not recommended because of limited experience with its use and the potential for fetal G6PD deficiency. Artesunates are not available in the United States.

After treatment, all pregnant women with P. vivax and P. ovale should be administered chloroquine prophylaxis for the duration of the pregnancy to avoid relapses. For pregnant women with P. vivax acquired in an area with chloroquine-resistant strains, once-weekly mefloquine can be used for prophylaxis. Women can be treated with primaquine after delivery if they have a normal G6PD screening test.

Prophylaxis to prevent first episode of opportunistic disease
PathogenIndicationFirst choiceAlternative
MalariaTravel to disease-endemic areaRecommendations are the same for HIV-infected and -uninfected patients. One of the following three drugs is usually recommended depending on location: atovaquone/proguanil, doxycycline, or mefloquine. Refer to the following website for the most recent recommendations based on region and drug susceptibility.

http://www.cdc.gov/malaria/ (AIII)

Drug therapy for treatment and chronic maintenance therapy of AIDS-associated opportunistic infections in adults and adolescents
Opportunistic infectionPreferred therapy, duration of therapy, chronic maintenanceAlternative therapyOther options/issues
Geographic opportunistic infections of specific consideration
Malaria Uncomplicated malaria from Plasmodium falciparum or unknown malaria speciesPreferred therapy for chloroquine-sensitive infection (north of the Panama Canal)
transparent gifgrey bulletChloroquine phosphate 1,000 mg PO (= 600 mg chloroquine base) once, then 500 mg PO (= 300 mg chloroquine base) at 6, 24, and 48 hours
transparent gif
transparent gifgrey bulletTotal dose = chloroquine phosphate 2,500 mg
transparent gif
Preferred therapy for chloroquine-resistant infections (all other malaria areas or unknown region)
transparent gifgrey bulletAtovaquone-proguanil (250 mg/100 mg) -- 4 tablets PO daily x 3 days
transparent gif
Alternative therapy for chloroquine-sensitive infection (north of the Panama Canal)
No alternative listed












Alternative therapy for chloroquine-resistant infections (all other malaria areas or unknown region)
transparent gifgrey bulletMefloquine 750 mg PO x 1, then 500 mg administered 12 hrs later, total dose = 1,250 mg
transparent gif
transparent gifgrey bulletQuinine sulfate 650 mg PO q8h x 3 days (infections acquired outside of southeast Asia) to 7 days (infections acquired in southeast Asia) + (doxycycline 100 mg PO q12h x 7 days or clindamycin 20 mg base/kg/day (in 3 divided doses) PO x 7 days)
transparent gif

Treatment recommendations for HIV-infected patients are the same as HIV non-infected patients.

For most updated treatment recommendations for specific region, clinicians should refer to the following web link: http://www.cdc.gov/malaria/

or call the CDC Malaria Hotline:

770-488-7788 (M-F 8 AM-4:30 PM ET)

770-488-7100 (after hours)

Severe malaria from all regionsPreferred therapy
transparent gifgrey bulletQuinidine gluconate 10 mg/kg IV over 1-2 hours, then 0.02 mg/kg/min infusion (quinidine 6.25 mg base/kg IV over 1-2 hours, then 0.0125 mg/kg/min) for ≥24 hours with cardiac monitoring
transparent gif
+
transparent gifgrey bulletDoxycycline 100 mg PO or IV q12h x 7 days; or
transparent gif
transparent gifgrey bulletClindamycin 20 mg base/kg/day (in 3 divided doses) PO or 10 mg base/kg loading dose IV followed by 5 mg base/kg IV q8h; switch to PO clindamycin (dose as above) as soon as patient can take PO medication - for a total course of 7 days
transparent gif
Alternative therapy
transparent gifgrey bulletArtesunate 2.4 mg/kg IV bolus at 0, 12, and 24 hours, then daily
transparent gif

Duration of therapy: 7 days for Southeast Asia and Oceania and 3 days for other areas

When able to take PO, switch to:
transparent gifgrey bulletAtovaquone-proquanil, mefloquine, or doxycycline (doses as listed above)
transparent gif
Intravenous artesunate is available from CDC quarantine stations (CDC Malaria Hotline 770-488-7788)
Malaria from P. vivax, P. ovale, P. malariaeAll regions use the following regimens (except for Papua New Guinea and Indonesia, in which case treat as for chloroquine-resistant P. falciparum malaria as above)
transparent gifgrey bulletChloroquine phosphate 1000 mg PO x 1, then 500 mg PO at 6, 24, and 48 hours, total dose = 2,500 mg; then
transparent gif
transparent gifgrey bulletAnti-relapse therapy (after checking G6PD status): primaquine 30 mg base PO daily x 14 days
transparent gif
G6PD status should be checked before initiation of primaquine

References

24. Kublin JG, Patnaik P, Jere CS, et al. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet 2005;365:233-40.
25. Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science 2006;314:1603-6.
30. Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8.
37. CDC. Guidelines for preventing opportunistic infections among HIV-infected persons-2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR 2002;51(No. RR-8).
1211. Chandramohan D, Greenwood BM. Is there an interaction between human immunodeficiency virus and Plasmodium falciparum? Int J Epidemiol 1998;27:296-301.
1212. Nguyen-Dinh P, Greenberg AE, Mann JM, et al. Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. Bull World Health Organ 1986;65:607-13.
1213. Slutsker L, Marston BJ. HIV and malaria: interactions and implications. Curr Opin Infect Dis 2007;20:3-10.
1214. Mungai M, Tegtmeier G, Chamberland M, Parise M. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001;344:1973-8.
1215. Austin SC, Stolley PD, Lasky T. The history of malariotherapy for neurosyphilis: Modern parallels. JAMA 1992;268:516-9.
1216. CDC. Update: self-induced malaria associated with malariotherapy for Lyme diseaseTexas. MMWR 1991;40:665-6.
1217. World Health Organization. World Malaria Report, 2005. Geneva: World Health Organization and UNICEF; 2005.
1218. Snow RW, Craig M, Deichmann U, Marsh K. Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. Bull World Health Organ 1999;77:624-40.
1219. World Health Organziation. World malaria situation in 1994: part IPopulation at risk. Wkly Epidemiol Rec 1997;72:269-74.
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