Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Malaria Workup

  • Author: Thomas E Herchline, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Oct 27, 2015
 

Approach Considerations

In returning travelers from endemic areas, malaria is suggested by the triad of thrombocytopenia, elevated lactate dehydrogenase (LDH) levels, and atypical lymphocytes. These findings should prompt obtaining malarial smears.

In general, blood cultures should be drawn in a febrile patient. Patients from tropical areas may have more than 1 infection; maintaining a high suspicion for additional infections should be considered when patients do not respond to antimalarials.

Assess hemoglobin (decreased in 25% of patients, often profoundly in young children), platelet counts (thrombocytopenia in 50-68% of patients), and liver function (results abnormal in 50% of patients). Also monitor renal function, electrolytes (especially sodium), and parameters suggestive of hemolysis (haptoglobin, LDH, reticulocyte count). Rapid HIV testing may also be indicated in select cases. Importantly, fewer than 5% of patients with malaria have an elevated white blood cell (WBC) count. If leukocytosis is present, the examiner should entertain a broader list of differential diagnoses. The British Committee for Standards in Haematology has guidelines on the laboratory diagnosis of malaria.[9]

If the patient is to be treated with primaquine, a G-6-PD level should be obtained because primaquine can result in severe hemolysis in these patients.

If the patient has cerebral malaria, obtain a blood glucose level to rule out hypoglycemia as a cause of mental-status changes. Note that intravenous (IV) quinine can induce hypoglycemia; therefore, blood glucose should be monitored when IV quinine is used.

The British Committee for Standards in Haematology revised its Guidelines for the Laboratory Diagnosis of Malaria, intended for use in the United Kingdom but also potentially applicable to other nonendemic areas.[10] Recommendations include the following:

  • Thick and thin films should be routinely used for malaria diagnosis; thick films should be stained with Giemsa or Field stain, thin films with Giemsa or Leishman stain
  • Two observers should examine thick films, with each viewing a minimum of 200 high-power fields; if the films are positive, the species should be determined through examination of a thin film
  • In cases of P falciparum or Plasmodium knowlesi infection, the percentage of parasitized cells or the number of parasites per microliter should be estimated
  • Rapid diagnostic tests for malarial antigen can be used on a supplementary basis when diagnosis is performed by inexperienced staff

Imaging studies

Chest radiography may be helpful if respiratory symptoms are present. If CNS symptoms are present, a computed tomography (CT) scan of the head may be obtained to evaluate evidence of cerebral edema or hemorrhage.

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 species, a peripheral blood smear must be examined.

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. Fluorescent /ultraviolet tests may not yield speciation information.

Polymerase chain reaction assay

PCR assay testing is a very specific and sensitive means of determining if species of Plasmodium are present in the blood of an infected individual. PCR assay tests are not available in most clinical situations. However, they are very effective at detecting the Plasmodium species in patients with parasitemias as low as 10 parasites/mL of blood.

Lumbar puncture

If the patient exhibits mental-status changes, and even if the peripheral smear demonstrates P falciparum, a lumbar puncture should be performed to rule out bacterial meningitis.

Next

Blood Smears

A diagnosis of malaria should be supported by the identification of the parasites on a thin or thick blood smear. In rare occasions, P falciparum infection can present without detectable parasitemia. If no alternative diagnosis is found in an at-risk patient with possible cerebral malaria (ie, unrevealing lumbar puncture findings), initiate therapy for presumptive malaria and continue to obtain additional blood smears to confirm the diagnosis.

When reading a 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.

Thick smears

Three thick and thin smears 12-24 hours apart should be obtained. The highest yield of peripheral parasites occurs during or soon after a fever spike; however, smears should not be delayed while awaiting fever spikes.

Thick smears are 20 times more sensitive than thin smears, but speciation may be more difficult. The parasitemia can be calculated based on the number of infected RBCs. This is a quantitative test.

Thin smears

Thin smears are less sensitive than thick smears, but they allow identification of the different species. This should be considered a qualitative test.

Previous
Next

Alternatives to Blood Smear Testing

Alternative diagnostic methods typically are used if the laboratory does not have sufficient expertise in detecting parasites in blood smears.

Rapid diagnostic tests (RDT)

Immunochromatographic tests based on antibody to histidine-rich protein-2 (PfHRP2), parasite LDH (pLDH), or Plasmodium aldolase appear to be very sensitive and specific.[11, 12] Some RDTs may be able to detect P falciparum in parasitemias that are below the threshold of reliable microscopic species identification. Only one RDT (BinaxNOW) has been approved to date for the diagnosis of malaria in the United State.[13]

In one study, RDTs were found to perform better than microscopy under routine conditions. RDTs performed by the health facility staff were 91.7% sensitive and 96.7% specific. Microscopy was 52.5% sensitive and 77% specific.[14] A recent sudy using loop-mediated amplification technique (LAMP)also suggests that RDTs have accuracy similar to that of nested PCR, with a greatly reduced time to result, and was superior to expert microscopy.[15]

In a study from Tanzania, d'Acremont et al reported that antimalarials could be safely withheld from febrile children (< 5 y) who had negative results from an RDT based on PfHRP2.[16]

RDTs are less effective when parasite levels are below 100 parasites/mL of blood, and, in rare instances, an RDT test is negative in patients with high parasitemias. For these reasons, confirm RDT test results with a second type of screening test when possible. A false-positive result from an RDT may occur up to 2 weeks or more after treatment due to persistence of circulating antigens.

Other tests

In addition to the RDT listed above, new molecular techniques, such as PCR assay testing and nucleic acid sequence-based amplification (NASBA), are also available for diagnosis. They are more sensitive than thick smears but are expensive and unavailable in most developing countries.[17]

The quantitative buffy coat (QBC) is a technique that is as sensitive as thick smears. Because results cannot be used to speciate Plasmodium, a thin smear must be examined.

Malaria is a reportable disease. Identification of parasites by any of the above techniques should prompt notification to the local or state health department.

Previous
Next

Histologic Findings

The table below compares histologic findings for P falciparum, P vivax, P ovale, and P malariae.

Table 1. Histologic Variations Among Plasmodium Species (Open Table in a new window)

Findings P falciparum P vivax P ovale P malariae
Only early forms present in peripheral blood Yes No No No
Multiply-infected RBCs Often Occasionally Rare Rare
Age of infected RBCs RBCs of all ages Young RBCs Young RBCs Old RBCs
Schüffner dots No Yes Yes No
Other features Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. Late trophozoites develop pleomorphic cytoplasm. Infected RBCs become oval, with tufted edges. Bandlike trophozoites are distinctive.
Previous
 
 
Contributor Information and Disclosures
Author

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Director, Public Health, Dayton and Montgomery County, Ohio

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of Ohio, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Emilio V Perez-Jorge, MD, FACP Staff Physician, Division of Infectious Diseases, Lexington Medical Center

Emilio V Perez-Jorge, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, South Carolina Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Michael Stuart Bronze, MD Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Piola P, Nabasumba C, Turyakira E, et al. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010 Nov. 10(11):762-9. [Medline].

  2. McGready R, Lee SJ, Wiladphaingern J, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012 May. 12 (5):388-96. [Medline].

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

  4. Marchand RP, Culleton R, Maeno Y, Quang NT, Nakazawa S. Co-infections of Plasmodium knowlesi, P. falciparum, and P. vivax among Humans and Anopheles dirus Mosquitoes, Southern Vietnam. Emerg Infect Dis. 2011 Jul. 17(7):1232-9. [Medline].

  5. William T, Menon J, Rajahram G, et al. Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia. Emerg Infect Dis. 2011 Jul. 17(7):1248-55. [Medline].

  6. Malaria Surveillance — United States, 2010. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6102a1.htm?s_cid=ss6102a1_e. Accessed: March 1, 2012.

  7. Centers for Disease Control and Prevention. Malaria. Available at http://www.cdc.gov/malaria. Accessed: Sep 15, 2011.

  8. Taylor SM, Parobek CM, Fairhurst RM. Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis. 2012 Jun. 12 (6):457-68. [Medline].

  9. [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].

  10. Bailey JW, Williams J, Bain BJ, et al. Guideline: the laboratory diagnosis of malaria. General Haematology Task Force of the British Committee for Standards in Haematology. Br J Haematol. 2013 Dec. 163 (5):573-80. [Medline].

  11. Rapid diagnostic tests for malaria ---Haiti, 2010. MMWR Morb Mortal Wkly Rep. 2010 Oct 29. 59(42):1372-3. [Medline].

  12. 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. 2007 Dec. 77(6 Suppl):119-27. [Medline].

  13. Centers for Disease Control and Prevention. Notice to Readers: Malaria Rapid Diagnostic Test. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5627a4.htm. Accessed: September 30, 2011.

  14. 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. 2009 Mar. 80(3):470-4. [Medline].

  15. Polley SD, Gonzalez IJ, Mohamed D, et al. Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria. J Infect Dis. 2013 Aug. 208(4):637-44. [Medline]. [Full Text].

  16. d'Acremont V, Malila A, Swai N, et al. Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Infect Dis. 2010 Sep 1. 51(5):506-11. [Medline].

  17. Mens P, Spieker N, Omar S, Heijnen M, Schallig H, Kager PA. Is molecular biology the best alternative for diagnosis of malaria to microscopy? A comparison between microscopy, antigen detection and molecular tests in rural Kenya and urban Tanzania. Trop Med Int Health. 2007 Feb. 12(2):238-44. [Medline].

  18. Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 13. 376(9753):1647-57. [Medline]. [Full Text].

  19. Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2012 Jun 13. 6:CD005967. [Medline].

  20. US Food and Drug Administration FDA Approves Coartem Tablets to Treat Malaria. FDA. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149559.htm. Accessed: April 8, 2009.

  21. Teuscher F, Gatton ML, Chen N, Peters J, Kyle DE, Cheng Q. Artemisinin-induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure. J Infect Dis. 2010 Nov 1. 202(9):1362-8. [Medline]. [Full Text].

  22. Tozan Y, Klein EY, Darley S, Panicker R, Laxminarayan R, Breman JG. Prereferral rectal artesunate for treatment of severe childhood malaria: a cost-effectiveness analysis. Lancet. 2010 Dec 4. 376(9756):1910-5. [Medline].

  23. Amaratunga C, Sreng S, Suon S, et al. Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012 Nov. 12(11):851-8. [Medline].

  24. Othoro C, Johnston D, Lee R, Soverow J, Bystryn JC, Nardin E. Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun. 2009 Feb. 77(2):739-48. [Medline]. [Full Text].

  25. Richards JS, Stanisic DI, Fowkes FJ, et al. Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clin Infect Dis. 2010 Oct 15. 51(8):e50-60. [Medline].

  26. Olotu A, Lusingu J, Leach A, et al. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 2011 Feb. 11(2):102-9. [Medline].

  27. First Malaria Vaccine Approved by EU Regulators. Medscape Medical News. Available at http://www.medscape.com/viewarticle/848608. July 24, 2015;

  28. Janeczko LL. Primaquine protects against P. vivax malaria relapse. Medscape Medical News. Jan 3, 2013. Available at http://www.medscape.com/viewarticle/777109. Accessed: Jan 16, 2013.

  29. Sutanto I, Tjahjono B, Basri H, et al. Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia. Antimicrob Agents Chemother. 2013 Mar. 57 (3):1128-35. [Medline].

  30. Lowes R. FDA Strengthens Warning on Mefloquine Risks. Medscape Medical News. Jul 29 2013. [Full Text].

  31. US Food and Drug Administration. FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects. FDA. Available at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM362232.pdf. Accessed: Aug 6 2013.

  32. Briand V, Bottero J, Noel H, et al. Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine. J Infect Dis. 2009 Sep 15. 200(6):991-1001. [Medline].

  33. Briand V, Cottrell G, Massougbodji A, Cot M. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas. Malar J. 2007 Dec 4. 6:160. [Medline]. [Full Text].

  34. Trape JF, Tall A, Diagne N, et al. Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study. Lancet Infect Dis. 2011 Dec. 11(12):925-32. [Medline].

  35. Centers for Disease Control and Prevention. Atlanta, GA: DHHS; 2009. Malaria and Travelers. Available at http://www.cdc.gov/malaria/travelers/index.html. Accessed: Sep 15, 2011.

  36. The RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011/Oct. 365:[Full Text].

  37. White NJ. A vaccine for malaria (editorial). N Engl J Med. 2011/Oct. 365:[Full Text].

  38. [Guideline] Centers for Disease Control and Prevention. Malaria Diagnosis and Treatment in the United States. Available at http://www.cdc.gov/malaria/diagnosis_treatment/index.html. Accessed: Sep 15, 2011.

  39. Poespoprodjo JR, Fobia W, Kenangalem E, et al. Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic. Clin Infect Dis. 2008 May 1. 46(9):1374-81. [Medline]. [Full Text].

 
Previous
Next
 
Malarial merozoites in the peripheral blood. Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell.
This micrograph illustrates the trophozoite form, or immature-ring form, of the malarial parasite within peripheral erythrocytes. Red blood cells infected with trophozoites do not produce sequestrins and, therefore, are able to pass through the spleen.
An erythrocyte filled with merozoites, which soon will rupture the cell and attempt to infect other red blood cells. Notice the darkened central portion of the cell; this is hemozoin, or malaria pigment, which is a paracrystalline precipitate formed when heme polymerase reacts with the potentially toxic heme stored within the erythrocyte. When treated with chloroquine, the enzyme heme polymerase is inhibited, leading to the heme-induced demise of non–chloroquine-resistant merozoites.
A mature schizont within an erythrocyte. These red blood cells (RBCs) are sequestered in the spleen when malaria proteins, called sequestrins, on the RBC surface bind to endothelial cells within that organ. Sequestrins are only on the surfaces of erythrocytes that contain the schizont form of the parasite.
Schema of the life cycle of malaria. Image courtesy of the Centers for Disease Control and Prevention.
Table 1. Histologic Variations Among Plasmodium Species
Findings P falciparum P vivax P ovale P malariae
Only early forms present in peripheral blood Yes No No No
Multiply-infected RBCs Often Occasionally Rare Rare
Age of infected RBCs RBCs of all ages Young RBCs Young RBCs Old RBCs
Schüffner dots No Yes Yes No
Other features Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. Late trophozoites develop pleomorphic cytoplasm. Infected RBCs become oval, with tufted edges. Bandlike trophozoites are distinctive.
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.