eMedicine Specialties > Emergency Medicine > Infectious Diseases

Malaria: Differential Diagnoses & Workup

Author: Miguel C Fernández, MD, FAAEM, FACEP, FACMT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Contributor Information and Disclosures

Updated: May 29, 2009

Differential Diagnoses

Acute HIV
Mononucleosis
Babesiosis
Otitis Media
CBRNE - Plague
Pelvic Inflammatory Disease
CBRNE - Q Fever
Pharyngitis
CBRNE - Viral Hemorrhagic Fevers
Pneumonia, Bacterial
Dengue Fever
Pneumonia, Immunocompromised
Encephalitis
Pneumonia, Mycoplasma
Endocarditis
Pneumonia, Viral
Gastroenteritis
Salmonella Infection
Giardiasis
Sinusitis
Heat Exhaustion and Heatstroke
Tetanus
Hepatitis
Toxic Shock Syndrome
Hypothermia
Toxoplasmosis
Leishmaniasis
Yellow Fever
Meningitis

Other Problems to Be Considered

African trypanosomiasis
Amebiasis and amebic liver abscess
Brucellosis
Cholera
Collagen vascular disease
Enteric fever
Epidemic or louse-borne typhus
Food-borne illness or toxin
Hodgkin disease
Relapsing fever
Poliomyelitis
Schistosomiasis (acute Katayama fever)
Seizure disorder
HIV infection

Workup

Laboratory Studies

  • Helpful studies include a CBC, electrolyte panel, renal function tests, pregnancy test, urinalysis, free serum haptoglobin, urine and blood cultures, and thick and thin blood smears. For those patients who may receive quinine or primaquine, a G-6-PD test should be ordered. Lumbar puncture may be indicated in patients who have encephalopathy in which the diagnosis is not clear. Rapid HIV testing may also be indicated in select cases. 
  • Laboratory diagnosis in the ED may be limited in hospitals that do not have personnel who are well acquainted with malaria or special tests for rapid detection of the disease.
  • The British Committee for Standards in Haematology has guidelines on the laboratory diagnosis of malaria.3

Imaging Studies

  • A chest radiography may be helpful if respiratory symptoms are present.
  • If CNS symptoms are present, a CT scan of the head may be obtained once the patient is stable to evaluate evidence of cerebral edema or hemorrhage.

Other Tests

  • Microhematocrit centrifugation
    • Using this method with the CBC tube is a more sensitive method of detection of malaria infection.
    • However, microhematocrit centrifugation does not allow the identification of the species of Plasmodium. To determine that species, a peripheral blood smear must be examined.
  • Giemsa-stained thick and thin peripheral blood smears
    • These smears are the criterion standard for malaria detection and should be sent to the laboratory immediately, since malaria is a potentially life-threatening infection.
    • When reading the smear, 200-300 oil-immersion fields should be examined (more if the patient recently has taken prophylactic medication, because this temporarily may decrease parasitemia).
    • One negative smear does not exclude malaria as a diagnosis; several more smears should be examined over a 36-hour period.
  • Fluorescent dyes/ultraviolet indicator tests: Several different dyes allow laboratory results to be obtained more quickly. These methods require the use of a fluorescent microscope (QBC II System, Becton-Dickinson's Quantitative Buffy Coat [QBC] method). Fluorescent /ultraviolet tests may not yield speciation information. 
  • Polymerase chain reaction
    • Polymerase chain reaction (PCR) is a very specific and sensitive test for determining if the species of Plasmodium are present in the blood of an infected individual. PCR is not usually available in most clinical situations. 
    • PCR is also very effective at detecting the Plasmodium species present in patients with parasitemias as low as 10 parasites/mL of blood.
  • Rapid diagnostic tests (RDTs) examples include Para Sight-F test (Becton Dickinson Advanced Diagnostics), ICT Malaria P.f/P.v (Binax Inc), OptiMAL pLDH (DiaMed USA, LLC), Kat-Quick (Katmedical CC), and Rapimal MT Pf Dipstick (Cellabs Pty Ltd) (dipstick tests). Note: This list is not all-inclusive; research individual tests for comparative efficacy and cost.
    • These tests are useful in detecting P falciparum infections, while some also may detect other plasmodia antigens. RDTs are based on antibody recognition of the histidine rich protein 2 (HRP-2) antigen of P falciparum and, in most cases, it has been found to be as specific as microscopy studies.4 A false-positive result may occur up to 2 weeks or more after treatment due to persistence of circulating antigens.
    • Some RDTs may be able to detect P falciparum in parasitemias that are below the threshold of reliable microscopic species identification.
    • RDTs are not as effective when parasite levels are below 100 parasites/mL of blood, and the test rarely is negative in those with high parasitemias. For these reasons, always confirm RDT test results with a second type of screening test when possible.
    • RDTs may not be available in the United States due to lack of FDA approval. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs, at Malaria Rapid Diagnostic Tests.
    • In one study, RDTs were found to perform better than microscopy under routine conditions. RDTs performed by the health facility staff were 91.7% (95% confidence interval [CI], 80.8-100%) sensitive and 96.7% (95% CI, 92.8-100%) specific. Microscopy was 52.5% (95% CI, 33.2-71.9%) sensitive and 77% (95% CI, 67.9-86.2%) specific.5

More on Malaria

Overview: Malaria
Differential Diagnoses & Workup: Malaria
Treatment & Medication: Malaria
Follow-up: Malaria
Multimedia: Malaria
References

References

  1. Centers for Disease Control and Prevention. Malaria. Topic Home. Last updated May 21, 2009. Available at http://www.cdc.gov/malaria/index.htm.

  2. Cox-Singh J, Davis TM, Lee KS, et al. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis. Jan 15 2008;46(2):165-71. [Medline].

  3. [Guideline] Bailey JW, Williams J, Bain BJ, Parker-Williams J, Chiodini P. General Haematology Task Force. Guideline for laboratory diagnosis of malaria. London (UK): British Committee for Standards in Haematology. 2007;19. [Full Text].

  4. Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. Dec 2007;77(6 Suppl):119-27. [Medline].

  5. de Oliveira AM, Skarbinski J, Ouma PO, et al. Performance of malaria rapid diagnostic tests as part of routine malaria case management in Kenya. Am J Trop Med Hyg. Mar 2009;80(3):470-4. [Medline].

  6. Hanson J, Hossain A, Charunwatthana P, et al. Hyponatremia in severe malaria: evidence for an appropriate anti-diuretic hormone response to hypovolemia. Am J Trop Med Hyg. Jan 2009;80(1):141-5. [Medline].

  7. [Guideline] World Health Organization. Guidelines for the Treatment of Malaria. 2006;[Full Text].

  8. [Guideline] Filler SJ, MacArthur JR, Parise M, Wirtz R, Eliades MJ, Dasilva A, et al. Locally acquired mosquito-transmitted malaria: a guide for investigations in the United States. MMWR Recomm Rep. Sep 8 2006;55:1-9. [Medline][Full Text].

  9. [Guideline] Centers for Disease Control and Prevention. Treatment of Malaria (Guidelines for Clinicians). Last updated May 18, 2009. [Full Text].

  10. Carmona-Fonseca J, Alvarez G, Maestre A. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. Am J Trop Med Hyg. Feb 2009;80(2):188-93. [Medline].

  11. US Food and Drug Administration. FDA News. FDA Approves Coartem Tablets to Treat Malaria. April 8, 2009. Available at http://www.fda.gov/bbs/topics/NEWS/2009/NEW01989.html.

  12. Centers for Disease Control and Prevention. Atlanta, GA: DHHS; 2009. Malaria and Travelers. Available at http://www.cdc.gov/malaria/travel/index.htm.

  13. Ballou WR, Arevalo-Herrera M, Carucci D, et al. Update on the clinical development of candidate malaria vaccines. Am J Trop Med Hyg. Aug 2004;71(2 Suppl):239-47. [Medline].

  14. Barat LM, Bloland PB. Drug resistance among malaria and other parasites. Infect Dis Clin North Am. Dec 1997;11(4):969-87. [Medline].

  15. Bledsoe GH. Malaria primer for clinicians in the United States. South Med J. Dec 2005;98(12):1197-204; quiz 1205, 1230. [Medline].

  16. Busch MP, Kleinman SH, Nemo GJ. Current and emerging infectious risks of blood transfusions. JAMA. Feb 26 2003;289(8):959-62. [Medline].

  17. Carter R, Mendis KN. Evolutionary and historical aspects of the burden of malaria. Clin Microbiol Rev. Oct 2002;15(4):564-94. [Medline].

  18. Centers for Disease Control and Prevention. The Impact of Malaria, a Leading Cause of Death Worldwide. Available at http://www.cdc.gov/malaria/impact/index.htm.

  19. Day N, Dondorp AM. The management of patients with severe malaria. Am J Trop Med Hyg. Dec 2007;77(6 Suppl):29-35. [Medline].

  20. Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA. May 23 2007;297(20):2264-77. [Medline].

  21. Humar A, Ohrt C, Harrington MA, Pillai D, Kain KC. Parasight F test compared with the polymerase chain reaction and microscopy for the diagnosis of Plasmodium falciparum malaria in travelers. Am J Trop Med Hyg. Jan 1997;56(1):44-8. [Medline].

  22. Jong EC, McMullen R. Travel medicine problems encountered in emergency departments. Emerg Med Clin North Am. Feb 1997;15(1):261-81. [Medline].

  23. Malaria in an immigrant and travelers -- Georgia, Vermont, and Tennessee, 1996. MMWR Morb Mortal Wkly Rep. Jun 13 1997;46(23):536-9. [Medline].

  24. Maude RJ, Plewes K, Faiz MA, et al. Does artesunate prolong the electrocardiograph QT interval in patients with severe malaria?. Am J Trop Med Hyg. Jan 2009;80(1):126-32. [Medline].

  25. Murphy GS, Oldfield EC 3rd. Falciparum malaria. Infect Dis Clin North Am. Dec 1996;10(4):747-75. [Medline].

  26. Silver HM. Malarial infection during pregnancy. Infect Dis Clin North Am. Mar 1997;11(1):99-107. [Medline].

  27. World Health Organization. Global Malaria Programme (GMP). Available at http://www.who.int/malaria..

  28. World Health Organization. Malaria Rapid Diagnostic Tests. Available at http://www.wpro.who.int/sites/rdt/home.htm.

Further Reading

Keywords

malaria, paludism, paludismo, black water fever, blackwater fever, mosquito vector, plasmodia, species, mosquito, mosquito bite

Contributor Information and Disclosures

Author

Miguel C Fernández, MD, FAAEM, FACEP, FACMT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernández, MD, FAAEM, FACEP, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Eric M Kardon, MD, FACEP, Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center
Eric M Kardon, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Eric L Weiss, MD, DTM&H, Director of Stanford Travel Medicine, Medical Director of Stanford Lifeflight, Assistant Professor, Departments of Emergency Medicine and Infectious Diseases, Stanford University School of Medicine
Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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