Spleens That Stayed Enlarged: Congolese Refugees in Nine States, 2015–2018

In 2014, the physicians who examine U.S.-bound refugees before departure at resettlement sites in Uganda — panel physicians from the International Organization for Migration (IOM), doing the Department of State's required checks — noticed an unusual number of Congolese refugees with enlarged spleens, splenomegaly. The expectation, from the medical literature on malaria, was that the condition would fade within months of leaving a malaria area. For many of these refugees it did not.

Why an enlarged spleen matters

Many conditions can enlarge the spleen, among them various infections, liver disease and cancer. An enlarged spleen can disturb the blood counts and cause abdominal pain, and it raises the risk that a blunt blow ruptures the spleen, causing life-threatening internal bleeding.

How the investigation came about

Before departure, every patient had been treated with praziquantel for schistosomiasis and at least one dose of artemether-lumefantrine for malaria.

Who was studied

CDC approached the 10 states with the most patients, plus Georgia, which is close to CDC. Nine took part: Arizona, California, Idaho, New York, Pennsylvania, South Carolina, Utah and Washington, and Georgia. Investigators went through every available clinical record from after arrival, asked the treating clinicians about any other cases among Congolese refugees, and collected laboratory results that might point to a cause.

• 135 Congolese refugees with splenomegaly settled in the nine states between April 2015 and May 2017.
• 90 (66.6%) of them belonged to just 22 families. In New York, clinicians found six cases by checking the relatives of known patients.
• Records after arrival existed for 117: 96 diagnosed overseas (86 from IOM's original cohort, 10 more found later in U.S. records) and 21 diagnosed only in the United States.
• At the first U.S. screening examination — always within 90 days of arrival, as CDC recommends — the spleen was enlarged in 64 of the 96 diagnosed overseas and in all 21 found domestically: 85 patients in all.

Idaho's figures were incomplete: records had been submitted for 14 of the state's 32 known cases, with 18 more pending.

Congolese refugees with unresolved splenomegaly, by stage of resettlement. CDC

How long it lasted

Of the 85, 64 (75.3%) came back to a clinic, for anything, more than six months after arriving. Among them:

• the median time from arrival to the last visit at which the spleen was still enlarged was 9.0 months (range 0.3 to 27.9 months);
• 35 (54.7%) had persistent splenomegaly — a spleen that could still be felt six months after leaving a malaria area — in some cases beyond two years.

What the tests showed

Laboratory results existed for 84 of the 85 with an enlarged spleen, and for 24 of the 32 without one at their first U.S. exam.

Of 46 patients checked for malaria by blood smear after arrival, six were positive: two showed Plasmodium falciparum, four P. vivax or P. ovale, and two a coinfection of P. malariae with P. vivax or P. ovale. P. vivax and P. ovale can cause relapsing malaria, which is one reason the authors think malaria may still be the main underlying cause.

The missing primaquine

CDC's recommendation that every Congolese refugee with splenomegaly receive primaquine after arrival had not changed — yet only 31 of 117 (26.5%) had it documented in their charts, and none had documentation of finishing the 14-day course. Three patients received praziquantel after arrival. Possible reasons for the gap, in the authors' view:

• U.S. physicians did not know about the recommendation.
• G6PD testing meant repeat visits.
• The course is long.
• There were safety concerns.
• Primaquine was not always available.

What clinicians should do

Limits of the study

1. Clinic visits came at irregular intervals, so the findings likely understate how long the spleens stayed enlarged.
2. Many patients were lost to follow-up, so the study cannot say what share recovered after their first screening.
3. Data quality varied widely between clinics, and U.S. diagnostic results — especially the more sensitive molecular tests — were mostly unavailable.
4. The 21 cases first found after arrival suggest the condition was underdiagnosed overseas; more careful spleen examination before departure might catch more.

Sources

Based on Zambrano LD, Samson O, Phares C, et al., "Unresolved Splenomegaly in Recently Resettled Congolese Refugees — Multiple States, 2015–2018," MMWR Morbidity and Mortality Weekly Report volume 67, number 49, Centers for Disease Control and Prevention; a work of the United States government in the public domain. The report's discussion gives 47% for past Schistosoma infection, 22% for eosinophilia and "two thirds" for patients without primaquine, which do not match its own results (50.0%, 27.3% and 31 of 117 treated); this page gives only the results.