In April 2020, a 38-year-old man visited the outpatient clinic for tropical medicine at the Bernhard Nocht Institute for Tropical Medicine (Hamburg, Germany) 1 week after undergoing endonasal surgery for chronic sinusitis, reporting recurrent facial swelling. Nasal congestion and putrid discharge had started during a 5-week stay in Mysore, South India, his eighth trip in 5 years to the region to attend yoga classes. Two months after returning to Germany, he underwent therapeutic endoscopic septoplasty. Postoperatively, a soft tissue swelling in the right infraorbital and temporal region and general apathy developed, unresponsive to antibacterial therapy. Over 5 weeks, a low-grade eosinophilia of 0.72 × 10⁹/L (10% of total leukocytes) increased to 0.94 × 10⁹/L (14%). The result of an in-house panfilarial IgG-detecting ELISA that used a D. immitis extract as antigen was positive. Liver and kidney function test and serologic test results for Strongyloides, Toxocara, Fasciola, Paragonimus, Cysticerca, and Gnathostoma were unremarkable.

Figure 1

Figure 1. Dirofilaria repensinfection in man in Germany after travel to India. A) Painless temporal subcutaneous swelling (image taken by the patient at the time of maximal protrusion). B) Contrast-enhanced magnetic...

Video 1

Video 1. Surgical removal of subcutaneous adult worm in man in Germany with Dirofilaria repens infection after travel to India.

Video 2

Video 2. Microscopy of vivid Dirofilaria repens microfilariae in man in Germany after travel to India.

Five weeks after his initial visit to our clinic, the patient noticed a painless temporal mass (Figure 1, panel A). Magnetic resonance imaging demonstrated a 10-mm encapsulated lenticular formation in the deep subcutaneous tissue (Figure 1, panel B). The lesion was surgically removed, and histologic examination showed an adult nematode (Figure 1, panel C). Filtration of 5 mL peripheral blood after hypotonic lysis of blood cells and subsequent Giemsa staining of the filter revealed microfilariae with the morphologic characteristics of D. repens (7) (Figure 1, panel D; Appendix; Video 1; Video 2). Sequencing and BLAST analysis (https://blast.ncbi.nlm.nih.gov/Blast.cgi) of a 463-bp fragment of the mitochondrial 12S rDNA (8) amplified from the adult worm and the microfilariae revealed 97.9%–99.2% homology with the Asian genotype of D. repens isolates from India (GenBank accession nos. GQ292761, KX265050, MT808309), followed by 95.6% homology with D. repens isolates from Europe (Greece, accession no. MK192091; Italy accession no., KX265072; Hungary, accession no. KX265070).

Figure 2

Figure 2. Circulating microfilariae/1 mL blood tested 4 times/day for 3 consecutive days in man in Germany with Dirofilaria repens infection after travel to India.

To assess possible periodicity of the microfilaremia, we sampled 5 mL of venous blood 4 times daily for 3 consecutive days and counted microfilariae after blood filtration. Blood was collected at fixed times during the day (6:30 am, 12:00 am, 6:00 pm, and 10:30 pm). Microfilariae were detectable in varying densities in all blood samples; counts fluctuated between 13 and 35 microfilariae/mL. On 2 days, the microfilaremia was highest in the evening and lowest in the morning samples, whereas on 1 day, the inverse pattern was observed. Thus, although it seems that microfilaremia substantially fluctuates during the day, this short assessment found no clear circadian rhythm of D. repens microfilaremia (Figure 2). To test for the presence of endosymbionts, we performed a recently published PCR that detects the FtsZ clade of Wolbachia (9). PCRs on microfilariae and adult worm samples were positive. With a goal of curative treatment, we administered doxycycline at 200 mg daily for 4 weeks, followed by a 15-mg dose of ivermectin. The patient fully recovered; eosinophil counts returned to reference ranges and microfilaremia disappeared.

The areas where human subcutaneous dirofilariasis is endemic are increasing, probably because of climate change, host mobility, and global travel (10). Thus, cases are increasing in areas where this disease is not endemic.

We report a case of microfilaremic D. repens infection, which was initially noted as recurrent swelling, in a human. Molecular analysis indicated an Asian genotype of D. repens nematodes, which has also been referred to as Candidatus Dirofilaria hongkongensis. Recurrent swellings are often misdiagnosed, not taken seriously, and therefore diagnosed late. Most cases of human dirofilariasis are diagnosed after surgical removal of the adult nematode and subsequent histologic workup (3). D. repens microfilaremia in humans has been only rarely described (4,5). Several filarial species result in periodic microfilaremia (11), and these fluctuations can be substantial and relevant for diagnosis. Previous studies of dogs have shown that D. immitis and D. repens microfilaremia fluctuates throughout the day and peaks at night (12). Our results showed no clear circadian rhythm, but microfilaremia tended to be higher in the evening, similar to that of canine hosts. However, at time of blood collection, the patient had received the first doses of doxycycline, which might have affected our results.

In our investigation, the adult worm as well as the microfilariae were positive for Wolbachia. Doxycycline targeting this bacterial endosymbiont might thus be a treatment option similar to that for infection with other species of filariae (13). Molecular analysis of adult worms or microfilariae can reveal new genotypes, thereby increasing our knowledge of parasite biology and ecology (9). According to previous reports, D. repens of the Asian genotype is distributed on the Indian subcontinent (14,15). It remains unclear whether some genetic variants differ in their ability to mature and produce microfilaremia in the human host.

Localized subcutaneous swellings, particularly in the periorbital region, are a typical clinical presentation of D. repens infection; however, diagnosis might be difficult because of the absence of microfilaremia, eosinophilia, or positive serologic results. However, if microfilariae are detectable, they display specific features that enable microscopic differentiation. In conclusion, paramount for establishing the diagnosis of D. repens infection of individual patients are in-depth history taking, a high clinical suspicion, and targeted laboratory evaluation.