Guideline sources The following summarized guidelines for the evaluation and management of malaria infection are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2023; 2013), the World Health Organization (WHO 2022), the British Society for Haematology (BSH 2022), the Royal College of Ophthalmologists (RCOphth 2020), the Committee to Advise on Tropical Medicine and Travel (CATMAT 2014), and the Royal College of Obstetricians and Gynaecologists (RCOG 2010). 1 2 3 4 5 6 7 8 9 9 9 10 11 12 Definition Malaria is mosquito-borne parasitic disease that is endemic to tropical and subtropical countries. 9 Epidemiology https://web.pathway.md/diseases/recGqIJ7Dentek44q 1/10 6/29/23, 6:18 AM Malaria infection Pathway Malaria is caused by single-celled microorganisms of the Plasmodium group, predominantly P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The parasite is most commonly spread by an infected female Anopheles mosquito. 9 Pathophysiology In the United States, the incidence of malaria requiring hospitalization is estimated at 0.5 per 100,000 population. 10 Disease course Replication of parasites cause the infectious syndrome associated with malaria. Severe complications of malaria include respiratory failure, severe anemia, increased risk of abortion in pregnant women, confusion, convulsions, shock, jaundice, pulmonary edema, AKI, and death. 9 Prognosis and risk of recurrence Malaria, when treated with standard artemisin-based therapy, is associated with a disease-specific mortality rate of 0.32%. Infection with P. vivax can relapse weeks to months following an initial infection in up to 50-80% of cases. 11 12 Guidelines 1. Screening and diagnosis Indications for screening: do not obtain mass testing and treatment to reduce transmission of malaria, D including in patients with an increased risk of infection relative to the general population. D 2. Classification and risk stratification Severity grading: Classify patients as having severe malaria in the presence of 1 of the following criteria: prostration/impaired consciousness multiple convulsions respiratory distress pulmonary edema circulatory collapse abnormal bleeding jaundice hgburia. https://web.pathway.md/diseases/recGqIJ7Dentek44q 2/10 6/29/23, 6:18 AM Malaria infection Pathway 3. Diagnostic investigations Laboratory tests: As per BSH 2022 guidelines, assess good-quality thick and thin films for diagnosis of malaria. Stain thin films with a Giemsa stain and thick films with either a Giemsa or a Field stain. Use Giemsa at pH 7.2. A Show 4 more As per WHO 2022 guidelines, obtain a parasitological test (microscopy or rapid diagnostic test) in all patients with suspected malaria, in order to confirm the diagnosis. A 4. Medical management Management of uncomplicated P. falciparum malaria: Administer any of the following artemisinin-based combination therapies for 3 days for the treatment of adult patients with uncomplicated P. falciparum malaria: artemether-lumefantrine artesunate-amodiaquine artesunate-mefloquine dihydroartemisinin-piperaquine artesunate plus sulfadoxine-pyrimethamine artesunate-pyronaridine. A Show 2 more Management of uncomplicated P. vivax, P. ovale, P. malariae, or P. knowlesi malaria: treat patients with malaria as uncomplicated if the malaria species is not known with certainty. A Show 7 more Management of severe malaria (antimalarial treatment): administer IV or IM artesunate for at least 24 hours for the treatment of adult patients with severe malaria (including infants, pregnant patients in all trimesters, and lactating patients) until they can tolerate oral medication. Complete treatment with 3 days of artemisinin-based combination therapy once the patient has received at least 24 hours of parenteral therapy and can tolerate oral therapy. A Show 3 more Management of severe malaria (corticosteroids): do not use corticosteroids for the treatment of severe malaria or cerebral malaria, as they have been associated with worse outcomes. D 5. Therapeutic procedures Exchange transfusion: consider administering exchange transfusion in patients with hyperparasitemic P. falciparum malaria. C https://web.pathway.md/diseases/recGqIJ7Dentek44q 3/10 6/29/23, 6:18 AM Malaria infection Pathway 6. Specific circumstances Pediatric patients (prevention): offer RTS, S/AS01 malaria vaccination to prevent P. falciparum malaria in children living in regions with moderate-to-high transmission, as defined by the WHO. A Show 4 more Pediatric patients (management of uncomplicated P. falciparum malaria): Administer any of the following artemisinin-based combination therapies for 3 days for the treatment of pediatric patients with uncomplicated P. falciparum malaria: artemether-lumefantrine artesunate-amodiaquine artesunate-mefloquine dihydroartemisinin-piperaquine artesunate plus sulfadoxine-pyrimethamine artesunate-pyronaridine. A Show 4 more Pediatric patients (management of uncomplicated P. vivax, P. ovale, P. malariae or P. knowlesi malaria): administer either artemisinin-based combination therapy or chloroquine in pediatric patients with uncomplicated P. vivax, P. ovale, P. malariae, or P. knowlesi malaria in areas with chloroquine-susceptible infections. Administer artemisinin-based combination therapy in pediatric patients in areas with chloroquine-resistant infections. A Show 2 more Pediatric patients (management of severe malaria): administer IV or IM artesunate for at least 24 hours for the treatment of pediatric patients with severe malaria (including infants, pregnant patients in all trimesters, and lactating patients) until they can tolerate oral medication. Complete treatment with 3 days of artemisinin-based combination therapy once the patient has received at least 24 hours of parenteral therapy and can tolerate oral therapy. A Show 3 more Pregnant patients (diagnosis): recognize that there are no specific symptoms or signs, and malaria infection may present with a flu-like illness. B Show 4 more Pregnant patients (counseling): recognize that malaria infection during pregnancy carries significant risks to the mother and baby B and may result in reduced birth weight. B Show 2 more Pregnant patients (primary chemoprevention): administer antimalarial therapy at predetermined intervals to reduce disease burden and adverse pregnancy and birth outcomes in pregnant females (of all gravidities) in malaria-endemic areas. B Pregnant patients (general principles of management): treat malaria in pregnancy as an emergency. B Admit pregnant patients with uncomplicated malaria to the hospital and pregnant patients with severe/complicated malaria to an ICU. A https://web.pathway.md/diseases/recGqIJ7Dentek44q 4/10 6/29/23, 6:18 AM Malaria infection Pathway Show 5 more Pregnant patients, antimalarial treatment: As per WHO 2022 guidelines: Administer artemether-lumefantrine during the first trimester in pregnant patients with uncomplicated P. falciparum malaria. B Consider administering weekly chemoprophylaxis with chloroquine in pregnant or breastfeeding patients until delivery and breastfeeding are completed, and then treat with primaquine (based on G6PD status) to prevent future relapse. C As per RCOG 2010 guidelines, initiate IV artesunate in patients with severe P. falciparum malaria. Initiate IV quinine if artesunate is not available. A Show 3 more Pregnant patients (management of complications): obtain regular monitoring for hypoglycemia, as it can be profound and persistent in pregnant patients and can be exacerbated by quinine. B Show 3 more Pregnant patients (obstetric care): recognize that preterm labor, fetal growth restriction, and fetal HR abnormalities can occur in malaria during pregnancy. B Show 11 more Patients with HIV (primary prevention): advise human immunodeficiency virus-positive patients with a low CD4 cell count and pregnant patients with human immunodeficiency virus to avoid travel to areas with malaria transmission, if possible, because no chemoprophylactic regimen is completely effective. Do not rely on prophylaxis with cotrimoxazole for chemoprophylaxis against malaria in travelers with human immunodeficiency virus. (AIII). B Show 4 more Patients with HIV (antimalarial treatment): avoid using artesunate plus sulfadoxine- pyrimethamine in patients with human immunodeficiency virus/AIDS and uncomplicated P. falciparum malaria receiving cotrimoxazole. Avoid using artesunate plus amodiaquine in patients receiving with efavirenz or zidovudine. D Patients with HIV (pediatric patients): provide pre-travel counseling, including information on insecticide-treated bed nets, DEET, and country-specific antimalarial prophylaxis, in families traveling to malaria-endemic countries. B Show 10 more Patients returning from travel: administer artemisinin-based combination therapy for the treatment of travelers with uncomplicated P. falciparum malaria returning to non-endemic settings. A 7. Preventative measures Insecticide-treated nets: deploy pyrethroid-only long-lasting insecticidal nets for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission. A Show 6 more https://web.pathway.md/diseases/recGqIJ7Dentek44q 5/10 6/29/23, 6:18 AM Malaria infection Pathway Insecticide-treated cloths: do not use insecticide-treated clothing for the prevention and control of malaria at the community level in areas with ongoing malaria transmission. Consider using insecticide-treated clothing to provide personal protection against malaria in specific population groups. D Indoor residual spraying: perform indoor residual spraying for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission. B Show 4 more Space spraying: do not perform space spraying for the prevention and control of malaria in children and adults in areas with ongoing malaria transmission. Prioritize indoor residual spraying or use of insecticide-treated nets. D Insect repellents: Do not use topical repellents for the prevention and control of malaria at the community level in areas with ongoing malaria transmission. D Insufficient evidence to support the use of spatial/airborne repellents for the prevention and control of malaria. I Environmental measures: consider applying insecticides regularly to water bodies (larviciding) as a supplementary intervention to insecticide-treated nets or indoor residual spraying for the prevention and control of malaria in children and adults in areas with ongoing malaria transmission where aquatic habitats are few, fixed, and findable. C Show 2 more House screening: consider screening residential houses for the prevention and control of malaria in children and adults in areas with ongoing malaria transmission. C Immunization: offer RTS, S/AS01 malaria vaccination to prevent P. falciparum malaria in children living in regions with moderate-to-high transmission, as defined by the WHO. A Mass drug administration: consider administering antimalarial therapy as chemoprevention through mass drug administration to achieve short-term reductions in disease burden in areas of moderate-to-high transmission of P. falciparum. C Show 5 more Primary chemoprevention (family relatives): consider administering antimalarial therapy as chemoprevention in patients with increased risk of infection relative to the general population to reduce transmission in areas with very low-to-low transmission or post-elimination settings preventing re-establishment of transmission. C Primary chemoprevention (pediatric patients): consider administering antimalarial therapy at predefined intervals to reduce disease burden in children of age groups at high risk of severe malaria in areas of moderate-to-high perennial malaria transmission. C Show 3 more Primary chemoprevention (pregnant patients): administer antimalarial therapy at predetermined intervals to reduce disease burden and adverse pregnancy and birth outcomes in pregnant patients (of all gravidities) in malaria-endemic areas. B https://web.pathway.md/diseases/recGqIJ7Dentek44q 6/10 6/29/23, 6:18 AM Malaria infection Pathway 8. Follow-up and surveillance Monitoring for chloroquine/hydroxychloroquine retinopathy: obtain annual monitoring for retinopathy in all patients receiving hydroxychloroquine for > 5 years or chloroquine for > 1 year. B Show 17 more 9. Quality improvement Elimination programs: do not obtain routine malaria testing and treatment in persons arriving at points of entry (land, sea, or air) to reduce importation. D Show 4 more National/regional quality control: ensure (by national drug and regulatory authorities) that antimalarial drugs provided in both the public and the private sectors are of acceptable quality, through regulation, inspection and law enforcement. A Show 4 more Laboratory quality control: Ensure that laboratory personnel is alert to the possibility of malaria even when examination for parasites was not requested. A Ensure that laboratory personnel is aware of the differential diagnosis of babesiosis, particularly when intra-erythrocytic parasites are seen but travel history and/or rapid diagnostic tests results do not indicate a diagnosis of malaria. Clinical findings Symptoms Past medical history Chills Blood transfusion Fatigue Human immunodeficiency virus infection Fever Headache Social history Loss of appetite Malaise Exposure to anopheles mosquitoes Myalgia Nausea Neurological exam Seizure Sweating Altered mental status Vomiting Coma Past events Abdominal exam Recent travel Hepatomegaly Splenomegaly https://web.pathway.md/diseases/recGqIJ7Dentek44q 7/10 6/29/23, 6:18 AM Malaria infection Pathway Vital signs Lab findings Signs of shock serum TBIL Ocular exam serum creatinine blood glucose Retinal abnormalities blood histidine-rich protein 2 Retinal hemorrhage blood parasite LDH Retinal whitening malaria deoxyRNA Integument exam Microbiological findings Jaundice Blood malaria parasites Pallor Hematological findings Anemia WBC count blood leukocyte count blood platelet count hematocrit Likelihood Ratios Pertinent positives The following findings increase the probability of malaria infection in adults. 12 Finding LR+ Value Increased serum TBIL 7.3 (5.5-9.6) Presence of splenomegaly 6.5 (3.9-11.0) Decreased blood platelet count 5.6 (4.1-7.5) History of fever 5.1 (4.9-5.3) Show 5 more Pertinent negatives The following findings decrease the probability of malaria infection in adults. 12 Finding LR- Value No history of fever 0.12 (0.10-0.15) blood platelet count not decreased 0.32 (0.26-0.41) No history of headache 0.40 (0.32-0.49) No history of chills 0.47 (0.38-0.59) Show 5 more https://web.pathway.md/diseases/recGqIJ7Dentek44q 8/10 6/29/23, 6:18 AM Malaria infection Pathway References 1. 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