The CDC recommends refugees from Loa loa-endemic countries in Africa “should not receive presumptive ivermectin for strongyloidiasis prior to departure. Management of Strongyloides should be deferred until arrival in the United States, unless Loa loa is excluded by reviewing a daytime (10 AM to 2 PM) Giemsa-stained blood smear. Deferral of treatment for strongyloides until after the refugee arrives in the United States is acceptable. Guidance is available for management of Strongyloides following arrival in the United States in the Domestic Intestinal Parasite Screening Domestic Intestinal Parasite Guidelines - CDC.”
These recommendations apply to those coming through the IOM resettlement process or asylum seekers or immigrants who choose to be screened. Unfortunately, this approach misses many immigrants and asylum seekers who do not know about routine screening and many Africans who originate in non-Loa loa infected regions and do not think to tell their clinicians they migrated through Loa loa endemic areas, living there often for months to years. Consider the following example:
A 32 year old Eritrean man granted asylum in the United States was being screened by the county Refugee Screening Program. During the exam, the nurse saw a white fiber coming off the iris of his eye and was concerned she might be seeing a migrating Loa loa filaria. She referred the patient for further evaluation to the Refugee Health Promotion Program at Harborview Medical Center which sees recently-arrived refugee cases. At the time of his presentation, he was a fit, comfortable, relatively healthy Eritrean male who had been a welder and had experienced trauma to his right eye by a hot metal fragment while welding nearly a decade ago. This fragment left him with a semilunar contusion of the sclera, but no other abnormality was seen. The white fiber near his iris was not evident. His refugee screening labs were significant only for a positive QuantiFERON. Everything else was negative or within normal range.
Years ago he escaped Eritrea to neighboring Sudan. He lived there for 7 years and moved around the southern Sudan, eventually locating to Juba, and from there driving a truck throughout the region including Uganda. He could not recall any prolonged illnesses or recurrent fevers or swollen joints. He would not have mentioned Sudan had we not asked explicitly about his migration pathway and work history. One would not normally be concerned about Loa loa in an asymptomatic patient from Eritrea. However, because of his 7 years in Sudan there was a possibility of Loa loa exposure. Because of the potential eye finding witnessed by the nurse we decided to assess the possibility of exposure and sent labs for schistosomiasis, strongyloidiasis, and blood for microfilariae. These tests were negative. We contacted Dr. Thomas Nutman at NIH who heard the case and suggested we send serum to his lab in Bethesda to assess for anti-filarial IgG, and specifically strongyloides, Loa loa, and Wuchereria bancrofti antigens. His IgG to Loa loa was strongly positive at 1:589. In spite of the absence of microfilaria in his blood, Dr. Nutman recommended treatment. The treatment of choice is Diethylcarbamazine (DEC), and a call to the CDC and the appropriate documentation and lab results resulted in a 21-day treatment course for this man. He could not have afforded the cost of Albendazole at nearly $400 dollars for 2 tablets, nor could the hospital easily charity that medication.
Loiasis is caused by the filiarial nematode Loa loa and is transmitted by the bite of the Chrysops fly. It is endemic to west and central Africa and it is estimated that between 3 and 13 million people are infected. The prevalence of infection exceeds 40 percent in high-risk areas of central African countries. After an individual is bitten by an infected fly, adult worms reproduce after 6 to 12 months and produce thousands of larval microfilariae that are released in the bloodstream. Adult worms can live for more than 20 years in the human host. Most infected individuals are asymptomatic, however the most common clinical manifestations of loiasis are transient localized subcutaneous swelling (Calabar swellings) and migration of the adult worm across the subconjunctiva of the eye. Other less frequent complications include cardiomyopathy, due to the inflammatory effects of prolonged eosinophilia, and nephropathy. Encephalitis is another potential complication which is most often seen in the setting of treatment with diethylcarbamazine or ivermectin. Symptoms can include headache, insomnia, or coma and can result in death. Individuals with unknown Loa loa infection are at risk of encephalitis when treated with ivermectin for stronglyoides infection.
This case raises several issues. How many cases of Loa loa are missed because we are unaware of the migration history of patients by focusing on their country of origin and first asylum? How many cases go untreated because they are asymptomatic and their microfilariae burden is nil? How significant is it to miss these cases for their long term health? If we screened all suspicious cases would the NIH laboratories be able to handle that volume of serum sent for antigen testing and would the CDC be able to provide DEC for these cases? These questions are a little unsettling and not readily answered, yet we need to have a reasonable and consistent approach to screening and treatment.
References
Kamgno, J., Pion, S. D., Chesnais, C. B., Bakalar, M. H., D’Ambrosio, M. V., Mackenzie, C. D., … Boussinesq, M. (2017). “Test and not treat” for onchocerciasis control in a Loa loa endemic area. The New England Journal of Medicine, 10.1056/NEJMoa1705026. Advance online publication. http://doi.org/10.1056/NEJMoa1705026
Whittaker, Walker, Pion, Chesnais, Boussinesq, & Basáñez. (2018). The Population Biology and Transmission Dynamics of Loa loa. Trends in Parasitology, 34(4), 335-350.World Health Organization African Programme for Onchocerciasis Control (APOC). (2010). Map of the estimated prevalence of eye worm history in Africa [map]. Retrieved from http://www.who.int/apoc/raploa/en