Peer Reviewed

Case In Point

Pediatric Coinfection With Malaria and Epstein-Barr Virus

Hannah Wilkerson, BS • Ganesh Maniam, BA, MBA • Ryan E. Dean, BS, MBA • Tosin Bewaji, MD, MPH • Efe Okotcha, MD • Raphael Mattamal, MD

Texas Tech University Health Sciences Center at Amarillo, Texas

Wilkerson H, Maniam G, Dean RE, Bewaji T, Okotcha E, Mattamal R. Pediatric coinfection with malaria and Epstein-Barr virus. Consultant. 2021;61(7):e6-e7. doi:10.25270/con.2020.07.00007

Received April 29, 2020. Accepted June 24, 2020. Published online July 30, 2020.

The authors report no relevant financial relationships.

Hannah Wilkerson, BS, Texas Tech Internal Medicine at Amarillo, 1400 S Coulter St, Amarillo, TX 79106 (


An 11-year-old boy presented to his primary care provider (PCP) with a fever of 2 days’ duration. The fever was described as intermittent, particularly occurring in the evenings, and being partially relieved with acetaminophen. The boy’s temperature had not been taken at home. Associated symptoms included intermittent myalgia and reduced appetite, but there had been no vomiting, diarrhea, rash, abdominal pain, night sweats, cough, nasal congestion, sore throat, or fatigue.

The boy had no history of sick contacts, but his travel history was notable for a 1-month visit to Sierra Leone (his native country and an endemic area for chloroquine-resistant malaria). He had returned to the United States approximately 3 weeks prior to presentation. He had been on malaria prophylaxis with mefloquine while in Sierra Leone. He had had a febrile illness a few days after having returned from the trip; he had been taken to see the PCP, who diagnosed a viral illness. The fever had abated after approximately 3 days, until the current episode.

The boy’s current symptoms prompted his mother take him back to his PCP, where the results of a complete blood cell count (CBC) showed pancytopenia with neutropenia. The PCP promptly referred the boy to the hospital for further evaluation.

The patient had no significant medical or surgical history. His family history is significant for sickle-cell disease in his brother, and sickle-cell trait in his mother and his sister. The boy’s hemoglobin electrophoresis test results were unremarkable.

At presentation to the hospital, significant physical examination findings included conjunctival pallor and lymphadenopathy in the left axillary and bilateral anterior cervical nodes. A peripheral blood smear revealed many red blood cells (RBCs) with ring-shaped inclusion bodies, suggestive of malaria. Results of a comprehensive metabolic panel were within normal limits, while a complete blood count revealed anemia (hemoglobin 8.4 gm/dL) and thrombocytopenia (141,000/mcL), with an elevated reticulocyte count at 5% and an absolute neutrophil count of 1359/µL. The C-reactive protein level and erythrocyte sedimentation rate were both elevated at 12 mg/L and 67 mm/hr, respectively, along with the lactate dehydrogenase level at 540 units/L. Serologic test results were positive for Epstein-Barr virus (EBV) IgG and IgM antibodies, consistent with a concurrent EBV infection. Otherwise, urinalysis results were normal, serologic test results for cytomegalovirus were negative, and blood culture and urine culture results were pending.

The patient was started on combination atovaquone/proguanil, 750 mg/300 mg, for 3 consecutive days as per Centers for Disease Control and Prevention guidelines. Due to elevated risk of splenic rupture associated with EBV infection, the patient was discharged with instructions to avoid participation in contact sports for 6 to 8 weeks, with an outpatient follow-up visit to reassess CBC and reticulocyte count.

The final diagnosis was pancytopenia secondary to combined chloroquine-resistant malaria and infectious mononucleosis with EBV.


Malaria is an infection with protozoan parasites of the Plasmodium genus that causes a flulike illness characterized by cyclical fever, headache, and chills, with potential to cause coma and death.1 Transferred to humans by the female Anopheles mosquito, the parasite initially infects the liver, then replicates in RBCs, resulting in severe anemia.1 There are more than 228 million annual malaria cases worldwide, with most occurring in sub-Saharan Africa or South Asia.2 Approximately 2000 cases of malaria are diagnosed in the United States each year, generally in patients with a recent history of travel from an endemic country.3

On the other hand, EBV is a human herpesvirus that infects B lymphocytes to cause a variety of conditions, especially in persons who are immunosuppressed or otherwise immunodeficient.4 In pediatric patients, acquisition of EBV typically presents as infectious mononucleosis.4 However, as a widely disseminated virus, EBV has a wide range of presentations and complications, such as splenic rupture or hematologic abnormalities.4

Coinfection with malaria and EBV, as in our patient’s case, is exceedingly rare in the United States. However, a 2015 study found that infection with γ-herpesviruses, including EBV, suppresses the necessary humoral immunity to combat parasitic infections.5 This increases the susceptibility of children infected with EBV to acquire malaria, and thus coinfection with both EBV and Plasmodium species is more common in endemic regions.5 It is unclear as to which pathogen our patient acquired first—the lack of infectious mononucleosis symptoms and positive serologic test results for EBV IgM and IgG antibodies, in the context of malarial acquisition despite appropriate prophylaxis, suggests that this is a case of EBV infection predisposing the patient to malarial coinfection. A 2004 study determined that the likelihood of malaria coinfection with EBV depends on the stage of viral infection at the time of parasite acquisition,6 which further confounds the ability to determine the sequence of infections in our patient’s case.

Regardless of the coinfection timeline, simultaneous infection with EBV and malaria has additional ramifications for the development of oncologic pathologies. Endemic Burkitt lymphoma is the most prevalent pediatric malignancy in Africa, and a 2011 review suggests that one such underlying mechanism includes coinfection with Plasmodium falciparum malaria and EBV.7 This may be due to malarial induction of polyclonal B-cell expansion, which may act in combination with lytic EBV reactivation to increase the risk of B cell oncologic transformation through MYC translocation.7 A study of 43 children being treated for malaria in Uganda revealed a significant decrease in EBV viral DNA levels after 2 weeks, and this antimalarial-induced reduction of quantitative EBV genome loads suggests a relationship between active malaria infection and EBV reactivation.8 Furthermore, the chronic stimulation of a malarial infection may result in repeated EBV reactivation that eventually blunts the T-cell response against EBV; this would enhance its replication as an oncogenic virus and subsequently result in MYC translocation.7 A study of 57 EBV-seropositive children in Gambia found that malarial infections caused a significant increase in quantitative viral DNA of EBV, suggesting yet another theory—that malarial infections increase the viremia set point for EBV.9 Regardless of the exact mechanism, physicians should be aware of the link between malaria and EBV coinfection with B-cell lymphomas.

Rare coinfections, such as malaria and EBV, present a diagnostic and treatment challenge for clinicians. In this patient’s case, the pancytopenia identified on CBC alarmed the outpatient physician and resulted in hospital admission. The peripheral blood smear was used to diagnose malaria, while serological titers were used to diagnose EBV infection. While the timeline of coinfection remains unclear in this patient’s case, physicians should be aware of the possibility of such presentations despite their relative rarity.


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