Malaria Blood Tests Kept Coming Back Negative, but a Bacterial DNA Test Found the Parasite in Fluid Around His Heart

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Within days, he was on a ventilator, and the standard blood tests for malaria kept coming back negative.

The answer finally came from a laboratory test built to identify bacteria, not parasites. Run on heart fluid that had been drained weeks earlier, it picked up DNA from a tiny structure inside the malaria parasite Plasmodium falciparum.

The case was published in ASM Case Reports by clinicians and laboratory scientists from the University of Toronto, McMaster University, Hamilton Health Sciences, and Public Health Ontario. The authors wrote that detecting malaria this way was “not previously reported in the literature.”

The man had no significant medical history, according to the report. He was admitted 25 days into his trip with a racing heart, rapid breathing, anemia, and a pericardial effusion, the medical term for fluid collecting in the sac around the heart. He had no fever at the time.

Doctors drained 240 milliliters of fluid. Bacterial and tuberculosis cultures were negative, and a CT scan showed hazy patches in his right lung, so he was started on antibiotics for possible pneumonia.

The next day, he left the hospital against medical advice because he was uninsured, the authors noted. Two days later, he was back in respiratory distress. He needed a breathing tube and was treated for acute respiratory distress syndrome, a severe form of lung injury.

On day 34 of his trip, he developed a fever. Thick and thin blood smears, the classic microscope test for malaria, and a rapid antigen test were negative on days 36 and 38. Low-level antibody results raised the possibility of a rickettsial infection, a group of bacterial diseases spread by ticks, fleas, and lice, so doctors added the antibiotic doxycycline. He remained unwell. The authors later wrote that those antibody results may have reflected nonspecific reactivity or an unrelated past exposure.

The turning point came from 16S rDNA sequencing, a molecular test that reads a gene found in bacteria. Labs often use it when an infection is suspected but cultures grow nothing.

Malaria parasites are not bacteria. But they carry a plastid-like organelle called the apicoplast, which descends from an ancient bacterium-like ancestor and still has its own 16S gene. On day 54, sequencing of heart fluid collected on day 26 produced a 286-letter stretch of genetic code that matched P. falciparum apicoplast DNA exactly.

Because the test had not been validated for parasites, the team ran malaria-specific checks on the same fluid. A rapid antigen test and two PCR tests for Plasmodium were positive. Under the microscope, the fluid contained dark brown structures resembling hemozoin, a pigment malaria parasites leave behind as they digest hemoglobin. A blood sample taken that day was still negative by microscopy and antigen testing, while blood PCR was indeterminate.

He received a three-day course of atovaquone-proguanil and improved. By day 62, he was off supplemental oxygen, walking with a walker, and discharged home. The report says he remains well on follow-up. The authors acknowledged that atovaquone-proguanil is not the preferred treatment for severe malaria, but they chose it because he was clinically stable and had no detectable parasites in his blood.

Microscopy remains the gold standard for diagnosing malaria, according to the CDC, which advises repeating blood smears every 12 to 24 hours for a total of three sets. The case authors note that microscopy detects about 85% to 93% of cases in clinical studies. False negatives can still happen when parasite levels are low or when parasites hide in small blood vessels.

People who grow up in areas with heavy malaria transmission may also develop partial immunity that keeps parasite counts low. Nigeria has the highest malaria burden in the world, and the authors suggested that partial immunity may explain the man’s unusual presentation. They stressed that this explanation is unconfirmed. The man did not recall ever having malaria, and earlier blood samples were not available for retesting.

Heart involvement is not the textbook picture of malaria, but it is not unheard of. The authors cite reports that pericardial effusion may occur in up to 9.7% of cases. A Brazilian study of 98 adults with uncomplicated malaria, most of them infected with a different species, Plasmodium vivax, found effusions in about 9% of patients at diagnosis. The effusions decreased significantly after treatment.

The authors were clear that 16S testing should not be used as a first-line test when a parasitic infection is suspected. Their broader message was that malaria belongs on the list of possibilities for anyone from or recently in a region where the disease is common, even when routine tests are negative, and that unexpected lab results deserve careful follow-up. More sensitive tests, such as PCR, might have detected the infection sooner, they wrote.

Malaria remains a major global threat. The World Health Organization estimates there were 282 million cases and 610,000 deaths in 2024. In the United States, about 2,000 malaria cases are reported each year, mostly in people who recently returned from travel, often to Africa.

Because this is a single case, it cannot show how often malaria hides this way. Anyone who becomes sick during or after time in a country where malaria is common should tell their clinician about the trip, even weeks later, and seek prompt care for fever or breathing problems.

A man in his 70s from Nigeria, visiting relatives in Canada, developed fluid around his heart and severe lung injury. Malaria blood tests were negative, but DNA testing of the heart fluid revealed Plasmodium falciparum.

The parasite was first detected by a test designed for bacteria. It worked because the parasite’s apicoplast carries a bacteria-like gene. The authors said this approach to detecting malaria had not been reported before.

Can malaria cause fluid around the heart?

Yes, though it is not a typical feature. Reports cited by the authors suggest pericardial effusion may occur in up to about 10% of cases.

Why were the standard malaria tests negative?

Low parasite levels and parasites hiding in small blood vessels can cause false negatives. The authors said partial immunity from past exposure was a possible but unconfirmed explanation in this case.

Should doctors use bacterial DNA tests to diagnose malaria?

No. The authors said 16S testing should not be a first-line test for suspected parasitic infections. More sensitive malaria-specific tests, such as PCR, might have caught this infection sooner.

What should travelers do if they feel sick after a trip?

Seek medical care promptly and tell the clinician where you traveled, even if symptoms start weeks after returning.