Clinical Pearls & Morning Reports
Published June 7, 2023
Eosinophilia affects 8 to 9% of returning travelers and is a common reason for patients to be referred to an infectious disease clinic. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: How is Mansonella perstans transmitted to humans?
A:M. perstans is one of eight filarial parasites that infect humans. The pathogen is transmitted through a bite from one of several species of culicoides midges. Infective third-stage larvae migrate from the bite site in the skin and mature over a period of several months, becoming adult worms that are typically found in the peritoneal, pleural, and pericardial cavities. The adult worms can live for at least 10 years.
Q: What symptoms are associated with M. perstans infection?
A: Nonspecific symptoms — such as pruritus (with or without accompanying rash), urticaria, arthralgias, and myalgias, as well as marked fatigue and abdominal symptoms— occur frequently with M. perstans infection. Eosinophilia is also common. When specific symptoms occur, they are predominantly related to migration of adult worms and include transient subcutaneous swellings that are similar to Calabar swellings (transient localized angioedema typical of Loa loa infection), as well as serositis and ocular symptoms.
A: The definitive diagnosis of M. perstans infection is made through the detection of the parasite microscopically. Most often, this is accomplished through the identification of microfilariae in a blood smear. In rare cases, adult worms can be identified in tissue specimens. Several quantitative PCR assays specific for M. perstans have been developed and used successfully in the context of clinical trials and field-based studies. The use of these assays for the diagnosis of individual patients or for molecular identification in tissue samples remains an approach that is limited to the research setting. Antifilarial IgG and IgG4 serologic assays that are based on crude filarial antigens can be positive in patients with M. perstans infection, but these assays cannot be used to distinguish between active and previous infection. Moreover, there is extensive cross-reactivity among the various filarial species, so a definitive species-specific diagnosis cannot be made with serologic testing alone.
A: It was discovered that the intracellular endosymbiont wolbachia is present in many filariae that cause infection in humans, including O. volvulus, W. bancrofti, B. malayi, and B. timori, with L. loa being the most notable exception. Wolbachia has been definitively shown to be present in M. perstans parasites from Mali, Cameroon, Ghana, and Gabon. These findings paved the way for the use of doxycycline in patients with M. perstans infection. Randomized trials have shown that doxycycline has activity against wolbachia in M. perstans infection and is nearly 100% effective in clearing M. perstans microfilariae from the blood for at least 24 months. In addition, several case reports have shown that doxycycline can drive sustained clearance of M. perstans microfilariae. Because wolbachia is present at much greater numbers in adult worms (macrofilariae) than in microfilariae, the effect of doxycycline is thought to be primarily macrofilaricidal. Therefore, on the basis of limited data regarding M. perstans infection, the administration of a dose of a microfilaricidal agent (e.g., ivermectin) before and soon after a 6-week course of doxycycline has been advocated for accelerating and sustaining microfilarial clearance.