Maryland’s first local malaria case in 40 years initially duped doctors

Catching malaria in the US is extremely rare, but when it happens, the mosquito-borne parasite can masquerade as another parasite that's regularly found in the country, leading to a misdiagnosis that has foiled doctors around the world for years. Such was the case this year in Maryland, when the state saw its first locally acquired malaria case in over 40 years, according to a report this week. The misdiagnosis led the patient to a weeks-long treatment for the wrong infection and held up public health responses to pinpoint and thwart further transmission. To date, the source of the patient's infection remains a mystery. As global travel and climate warming expand malaria's range, awareness of the diagnostic pitfall and better testing will be increasingly needed, the report's authors suggest. The report was published Thursday in the Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report. Malaria rages in large swaths of the world but was considered eliminated from the US in 1951. Still, there are around 2,000 malaria cases in the US each year, all linked to travel to areas with malaria transmission. The state of Maryland sees around 200 such cases in a typical year. Then there are years like this one—when there were nine malaria cases that were locally acquired (not linked to travel) in the US: seven in Florida, one in Texas, and one in Maryland. It was the first year in two decades that any locally acquired malaria was found anywhere in the US. The last local cases occurred in 2003 in Palm Beach, Florida. Yet, the three states' cases were not linked. The seven cases in Florida clustered in a swampy area near an imported malaria case. The unrelated Texas case was also in the vicinity of an imported case. In Florida and Texas, the cases were caused by the malaria parasite Plasmodium vivax, which spreads in many places around the world, including South and East Asia, the Western Pacific, and South America. In Maryland, the case involved P. falciparum, which causes the deadliest form of malaria and spreads heavily in African countries.

Maryland case

On August 6, a previously healthy Maryland resident showed up at a health facility after seven days of fever, muscle pain, and malaise. The person had no recent international travel but noted taking daily walks near home and having recently been bitten by a tick. Lab tests showed anemia, low blood platelets, and a buildup of bilirubin (which occurs when red blood cells break down). The patient also had parasites in their red blood cells. These symptoms and findings match two diseases: malaria and another parasitic infection called babesiosis, which is caused by Babesia parasites and spread in the US by ticks. Given the circumstances, doctors admitted him to a hospital and began treatment for babesiosis. On August 9, a blood smear report indicated P. falciparum, though. The doctors shared the smear images with the CDC, but the images weren't clear enough for CDC experts to distinguish whether Babesia or P. falciparum were in the patient's red blood cells. With special stains and microscopy, both parasites look like little rings inside red blood cells.

One key way to tell them apart is the appearance of a classic "Maltese cross morphology" in babesiosis, which occurs when four Babesia parasite rings arrange themselves within the red blood cell to look like a cross under the microscope. Malaria parasites don't do this, but the Maltese cross may not be immediately apparent in a blood smear and can be easily missed by an untrained examiner. By August 10, the patient was feeling better and was released from the hospital with a plan to complete a seven-day babesiosis treatment. On August 15, Maryland's state public health laboratory confirmed P. falciparum with microscopy, a rapid test, and a genetic test (PCR). On August 18, the CDC confirmed the finding with a positive P. falciparum PCR test and a negative Babesia PCR. After that, public health officials released a public health notice of the malaria case, began active case-finding efforts, and surveilled local mosquitoes. No other cases were found in the vicinity, and of 21 local mosquitoes tested by the CDC, all were negative for P. falciparum.

Multi-national mix-ups

This is far from the first time clinicians have mixed up malaria and babesiosis. In 2015, health officials in Canada reported the vexing case of an Indian man who traveled to Canada and appeared at a health facility with all the signs of malaria. Given his India origin, where malaria spreads, and a positive pan-Plasmodium PCR test, doctors initially believed it to be malaria. However, a rapid malaria test was negative, leading them to do further examinations, upon which they determined it was actually babesiosis. A more careful look at the blood smear revealed Babesia parasites, and a PCR confirmed the tick-borne parasite. They later found out the man had stopped over in Massachusetts before arriving in Canada. While in the US, he visited a family living in a highly wooded area, where he was bitten by a tick. As for the positive pan-Plasmodium PCR test, the researchers realized that the genetic probe they were using "happens to share a high degree of sequence homology" with Babesia, thus it was a false-positive result. In Africa, where malaria is prevalent, researchers have similar problems. In 2018, researchers in Spain and Equatorial Guinea reported the case of a woman who, over an eight-month period, received six diagnoses of malaria but did not get better after repeated treatment. Finally, because of the treatment failures, clinicians at Hospital La Paz in Bata, Equatorial Guinea, took a closer look at her case and noted Maltese crosses in her blood smears. The woman traveled to Spain a week later, where clinicians confirmed the finding of babesiosis. It's unclear where she picked up the Babesia infection, though. Every year, the woman spent a week visiting a rural area of Spain where babesiosis had been detected before. But her symptoms first developed in Equatorial Guinea, many months after her annual visit to Spain. The data on babesiosis in Equatorial Guinea and Africa overall is shaky, partly due to how easy it is to confuse it with malaria. One bright spot in this confusion is that the treatment for babesiosis and malaria has some overlap. The common malaria treatment, Malarone, contains atovaquone, an anti-parasitic drug that is also used in the treatment for babesiosis. The Maryland patient was initially treated for babesiosis with a combination of drugs, including atovaquone, which may explain why there was clinical improvement despite the misdiagnosis. When malaria was diagnosed, the patient was given the malaria treatment of artemether-lumefantrine (Coartem).