• View in gallery

    Photomicrograph section of excisional biopsy of testis showing intense tissue reaction around a dead female filarial worm. Two uterine reproductive tubes (asterisks) containing infertile eggs and gut (arrow) are present. Scale bar = 50 μm.

  • View in gallery

    Natural course of the infection in relation to symptoms and serological tests in this patient.

  • 1.

    Ramzy RM, Helmy H, Faris R, Gad AM, Chandrashekar R, Weil GJ, 1995. Evaluation of a recombinant antigen-based antibody assay for diagnosis of bancroftian filariasis in Egypt. Ann Trop Med Parasitol 89: 443446.

    • Search Google Scholar
    • Export Citation
  • 2.

    Rao RU, Atkinson LJ, Ramzy RM, Helmy H, Farid HA, Bockarie MJ, Susapu M, Laney SJ, Williams SA, Weil GJ, 2006. A real-time PCR-based assay for detection of Wuchereria bancrofti DNA in blood and mosquitoes. Am J Trop Med Hyg 74: 826832.

    • Search Google Scholar
    • Export Citation
  • 3.

    Keiser PB, Coulibaly Y, Kubofcik J, Diallo AA, Klion AD, Traoré SF, Nutman TB, 2008. Molecular identification of Wolbachia from the filarial nematode Mansonella perstans. Mol Biochem Parasitol 160: 123128.

    • Search Google Scholar
    • Export Citation
  • 4.

    Lal RB, Ottesen EA, 1988. Enhanced diagnostic specificity in human filariasis by IgG4 antibody assessment. J Infect Dis 158: 10341037.

  • 5.

    World Health Organization, 2013. Global programme to eliminate lymphatic filariasis: progress report for 2012. Wkly Epidemiol Rec 37: 389400.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lipner EM, Law MA, Barnett E, Keystone JS, von Sonnenburg F, Loutan L, Prevots DR, Klion AD, Nutman TB; GeoSentinel Surveillance Network. Filariasis in travelers presenting to the GeoSentinel Surveillance Network. 2007. PLoS Negl Trop Dis 1: e88.

    • Search Google Scholar
    • Export Citation
  • 7.

    Nutman TB, Kazura J, 2011. Lymphatic filariasis. Guerrant R, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. Second edition. Philadelphia, PA: Churchill Livingstone, 729.

    • Search Google Scholar
    • Export Citation
  • 8.

    Boyd A, Won KY, McClintock SK, Donovan CV, Laney SJ, Williams SA, Pilotte N, Streit TG, Beau de Rochars MV, Lammie PJ, 2010. A community-based study of factors associated with continuing transmission of lymphatic filariasis in Leogane, Haiti. PLoS Negl Trop Dis 4: e640.

    • Search Google Scholar
    • Export Citation
  • 9.

    Galindo L, Von Lichtenberg F, Baldizon C, 1962. Bancroftian filariasis in Puerto Rico: infection pattern and tissue lesions. Am J Trop Med Hyg 11: 739748.

    • Search Google Scholar
    • Export Citation
  • 10.

    Wartman WB, 1947. Filariasis in American armed forces in World War II. Medicine (Baltimore) 26: 333394.

  • 11.

    Figueredo-Silva J, Norões J, Cedenho A, Dreyer G, 2002. The histopathology of bancroftian filariasis revisited: the role of the adult worm in the lymphatic-vessel disease. Ann Trop Med Parasitol 96: 531541.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Testicular Swelling Due to Lymphatic Filariasis After Brief Travel to Haiti

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  • Infectious Diseases, Hattiesburg Clinic, Hattiesburg, Mississippi; Urology Clinic, Wesley Medical Center, Hattiesburg, Mississippi; Division of Parasitic Diseases and Malaria, CDC, Atlanta, Georgia; Pathology Department, Johns Hopkins University, Baltimore, Maryland; Malaria, Global Health Program, Bill and Melinda Gates Foundation, Seattle, Washington; Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland

After 6 months of a trip to Haiti, a 25-year-old healthy man presented with a 6-week history of a very slow progressive intermittent bilateral testicular pain and swelling. The biopsies in both testicles revealed the presence of a dead filarial parasite. Polymerase chain reaction products of the DNA from the biopsy were shown to have a 100% identity to Wuchereria bancrofti. Despite being uncommon in travelers, this presentation of W. bancrofti highlights the possibility of acquiring W. bancrofti during short-term trips to highly endemic regions of the world (i.e., Haiti).

Case Presentation

A 25-year-old healthy man presented with a 6-week history of a very slow progressive intermittent bilateral testicular pain and swelling. Symptoms started with moderate diffuse pain in the suprapubic area, radiating to both inguinal areas. Two weeks later, a persistent bilateral scrotal swelling along with severe intermittent pain (more in the right than left) continued for the next 4 weeks. Although there were no leukocytes present in the urinalysis, a presumptive clinical diagnosis of epididymo-orchitis was made and a 7-day course of fluoroquinolones was prescribed empirically by the primary care provider, without improvement. At the end of the 6 weeks, the testicular swelling started to decrease and finally resolved but a painless nodule in each testicle was noticed by the patient. He denied any fevers, sweats, or chills. An ultrasound revealed a small hypoechoic nodule about 11 mm in diameter in each testicle with some internal calcifications. An outpatient follow-up visit in 4 weeks was scheduled to assess the growth of these nodules but repeated ultrasound did not reveal any changes. Because of the poor response to antibiotics along with the progression of symptoms, bilateral testicular biopsy to remove both nodules was scheduled. He denied any prior medical condition. He drank only pasteurized milk, denied tuberculosis contacts, or unprotected sexual activity. He was born and raised in rural Mississippi where he has lived all his life. His only travel overseas was about 6 months ago when he went to Léogane, Haiti for 7 days for a missionary/volunteer trip, had several mosquito bites, and did not use personal protective measures. He did not receive pre-traveling counseling. On physical examination, both testicles had a single nodule with very mild swelling and tenderness on palpation around the epididymis. Some small inguinal lymphadenopathies were palpable bilaterally. Eosinophilia was absent. The histopathology examination showed acute inflammation with focal necrosis and structures of a parasite (Figure 1).

Figure 1.
Figure 1.

Photomicrograph section of excisional biopsy of testis showing intense tissue reaction around a dead female filarial worm. Two uterine reproductive tubes (asterisks) containing infertile eggs and gut (arrow) are present. Scale bar = 50 μm.

Citation: The American Society of Tropical Medicine and Hygiene 91, 1; 10.4269/ajtmh.14-0030

Diagnosis

The biopsies in both testicles revealed the presence of a dead filarial parasite that was thought to be either a zoonotic Brugia spp. or Wuchereria bancrofti (Wb). Both parasites have been found in testicular tissues. The size of the worm was ~120 μm in diameter. The worm was a non-gravid female in which two reproductive tubes and the intestine were visible (Figure 1); in some sections the cuticle appeared thicker over the lateral chords, a finding that suggests a Brugia spp. rather than W. bancrofti (Figure 1). Although W. bancrofti more commonly infects the genital tract, because of the unusual nature of the case, we entertained the possibility of this being a zoonotic Brugia infection acquired in Mississippi.

However, about 3 months after the onset of symptoms a Bm14-based IgG4 immunoassay (ELISA) performed at the Centers for Disease Control and Prevention (CDC) was negative.1 To clarify the species of the filarial worm found on biopsy, DNA was extracted from an unstained paraffin-embedded tissue section and real-time polymerase chain reaction (PCR) was performed at the Laboratory of Parasitic Diseases, NIAID, NIH; using two separate Wb-specific primer/probe sets targeting the Wb LDR repeat and the Wb intergenic transcribed spacer (ITS), as described previously.2,3 Both assays were positive for W. bancrofti DNA at threshold cycle (Ct) values between 27 and 29. In addition, using PCR to amplify the ITS in the 5S rRNA gene,3 the product was sequenced and shown to have a 100% identity to W. bancrofti (GenBank accession no. U31644). One year after the onset of symptoms, when antifilarial IgG and IgG4 was performed at the National Institutes of Health, both were positive (IgG = 63.6 μg/mL; normal range 0–14 μg/mL; IgG4 = 509 ng/mL; normal 0 ng/mL).4 The patient received 12 days of diethylcarbamazine at a dose of 6 mg/kg/day per CDC recommendations and tolerated the medicine well. Evolution of clinical presentation and serological tests are illustrated in Figure 2.

Figure 2.
Figure 2.

Natural course of the infection in relation to symptoms and serological tests in this patient.

Citation: The American Society of Tropical Medicine and Hygiene 91, 1; 10.4269/ajtmh.14-0030

Final Diagnosis: Bilateral Testicular Nodules Caused by W. bancrofti in a Traveler

Discussion

Lymphatic filariasis (LF), a chronic devastating parasitic disease, affects an estimated 120 million people in 73 countries worldwide.5 The acquisition of LF by a traveler to an endemic area is uncommon. According to the GeoSentinel Surveillance Network, a global network of specialized travel/tropical medicine clinics on six continents, filarial infections represent only 0.6% of the total individual patient encounters. Of reported filarial infections, those caused by Onchocerca volvulus (37%) are the most common, followed by Loa loa (25%) and W. bancrofti (25%).6 In these analyses, the majority of those infected with W. bancrofti had durations of exposure > 6 months.6,7 In contrast, the patient described had only a one week stay in Haiti. Interestingly, his entire stay was in Léogane, an area formerly known to be hyperendemic for W. bancrofti despite seven rounds of mass drug administration, which had been carried out. It is known, however, that transmission of W. bancrofti has not been interrupted there yet.8 Furthermore, this patient helps elucidate the natural history of W. bancrofti infection (Figure 2). Indeed, the time of exposure to the time of development of a juvenile adult worm was ~6 months with his symptoms occurring for the subsequent 6 weeks. Later, the testicular swelling resolved, but testicular nodules harboring the adult parasites as shown by pathological examination were noted.

Classic histopathologic findings in W. bancrofti infection can include a range of conditions, from viable adult worms with minimal host response (a few inflammatory cells), and secondary dilatation of lymphatics, to granulomatous reactions with variable degrees of worm disintegration. Ultimately, scarring (and fibrosis) occurs with an absence of identifiable adult worms. This last stage, scarring with absence of worms may not resolve over time.9

Clinically, this case reminds us of the natural history of LF that was well documented in U.S. military troops in the South Pacific Islands during World War II.10 The incubation period (between landing in an endemic area and the onset of symptoms) was reported to be as early as 1 month in U.S. soldiers. The clinical manifestations of the infection can be variable (from asymptomatic to severe local reactions)7 with the majority of infected individuals in endemic areas being clinically asymptomatic. Nevertheless, a high prevalence of disease (23%) has been reported in autopsy studies several decades ago.9,11

In travelers, military personnel, and other expatriates who acquire W. bancrofti infection, the presence of microfilaremia in the blood is rare. We did not screen for microfilaria in the blood before surgery because the diagnosis was not clear at the time. However, based on the size and reproductive status of the worm, and length of incubation, it is likely that the worms had not fully matured (and the female was not gravid) making microfilaremia unlikely. Eosinophilia may be present in only half of the patients with W. bancrofti and its absence does not exclude the infection10; we note that the Bm14-based IgG4 immunoassay (ELISA) was negative 3 months after onset of symptoms, whereas 1 year after the onset of symptoms both antifilarial IgG and IgG4 were positive. These serologic differences reflect the prolonged time from infection to the development of an antifilarial IgG4 response and the lower sensitivity of a single recombinant antigen than crude worm extract in diagnostic screening1; the lack of personal protective measures such as insect repellent and bed net use may have increased the likelihood of exposure to infected mosquitoes in this individual.

Based on the morphology of the adult parasite in histopathological tissues, it would have been difficult to differentiate with certainty between zoonotic Brugia and Wuchereria. The molecular identification of W. bancrofti was crucial in arriving at a final diagnosis.

In conclusion, despite being uncommon in travelers, this presentation of W. bancrofti highlights the possibility of acquiring W. bancrofti during short-term trips to highly endemic regions of the world (i.e., Haiti). Given the rarity of this infection in short-term travelers, this case should encourage clinicians to be aggressive in their pursuit of biopsy material even in a returned traveler from a filarial-endemic region of the world.

ACKNOWLEDGMENTS

We thank the ASTMH clinic group for the vivid discussion by e-mail before making the final diagnosis.

  • 1.

    Ramzy RM, Helmy H, Faris R, Gad AM, Chandrashekar R, Weil GJ, 1995. Evaluation of a recombinant antigen-based antibody assay for diagnosis of bancroftian filariasis in Egypt. Ann Trop Med Parasitol 89: 443446.

    • Search Google Scholar
    • Export Citation
  • 2.

    Rao RU, Atkinson LJ, Ramzy RM, Helmy H, Farid HA, Bockarie MJ, Susapu M, Laney SJ, Williams SA, Weil GJ, 2006. A real-time PCR-based assay for detection of Wuchereria bancrofti DNA in blood and mosquitoes. Am J Trop Med Hyg 74: 826832.

    • Search Google Scholar
    • Export Citation
  • 3.

    Keiser PB, Coulibaly Y, Kubofcik J, Diallo AA, Klion AD, Traoré SF, Nutman TB, 2008. Molecular identification of Wolbachia from the filarial nematode Mansonella perstans. Mol Biochem Parasitol 160: 123128.

    • Search Google Scholar
    • Export Citation
  • 4.

    Lal RB, Ottesen EA, 1988. Enhanced diagnostic specificity in human filariasis by IgG4 antibody assessment. J Infect Dis 158: 10341037.

  • 5.

    World Health Organization, 2013. Global programme to eliminate lymphatic filariasis: progress report for 2012. Wkly Epidemiol Rec 37: 389400.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lipner EM, Law MA, Barnett E, Keystone JS, von Sonnenburg F, Loutan L, Prevots DR, Klion AD, Nutman TB; GeoSentinel Surveillance Network. Filariasis in travelers presenting to the GeoSentinel Surveillance Network. 2007. PLoS Negl Trop Dis 1: e88.

    • Search Google Scholar
    • Export Citation
  • 7.

    Nutman TB, Kazura J, 2011. Lymphatic filariasis. Guerrant R, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. Second edition. Philadelphia, PA: Churchill Livingstone, 729.

    • Search Google Scholar
    • Export Citation
  • 8.

    Boyd A, Won KY, McClintock SK, Donovan CV, Laney SJ, Williams SA, Pilotte N, Streit TG, Beau de Rochars MV, Lammie PJ, 2010. A community-based study of factors associated with continuing transmission of lymphatic filariasis in Leogane, Haiti. PLoS Negl Trop Dis 4: e640.

    • Search Google Scholar
    • Export Citation
  • 9.

    Galindo L, Von Lichtenberg F, Baldizon C, 1962. Bancroftian filariasis in Puerto Rico: infection pattern and tissue lesions. Am J Trop Med Hyg 11: 739748.

    • Search Google Scholar
    • Export Citation
  • 10.

    Wartman WB, 1947. Filariasis in American armed forces in World War II. Medicine (Baltimore) 26: 333394.

  • 11.

    Figueredo-Silva J, Norões J, Cedenho A, Dreyer G, 2002. The histopathology of bancroftian filariasis revisited: the role of the adult worm in the lymphatic-vessel disease. Ann Trop Med Parasitol 96: 531541.

    • Search Google Scholar
    • Export Citation

Author Notes

* Address correspondence to Luis A. Marcos, Hattiesburg Clinic. #4 Medical Boulevard, Hattiesburg, MS 39402. E-mail: marcoslrz@yahoo.com

Authors' addresses: Luis A. Marcos, Infectious Diseases, Hattiesburg Clinic, Hattiesburg, MS, E-mail: marcoslrz@yahoo.com. Nathan P. Shapley, Urology Clinic, Wesley Medical Center, Hattiesburg, MS, E-mail: nps@megagate.com. Mark Eberhard and LeAnne M. Fox, Division of Parasitic Diseases and Malaria, CDC, Atlanta, GA, E-mails: mle1@cdc.gov, meberhard@cdc.gov, and lff4@cdc.gov. Jonathan I. Epstein, Pathology Department, Johns Hopkins University, Baltimore, MD, E-mail: jepstein@jhmi.edu. Alan Magill, Malaria, Global Health Program, Bill and Melinda Gates Foundation, Seattle, WA, E-mail: Alan.Magill@gatesfoundation.org. Thomas B. Nutman, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD, E-mail: tnutman@niaid.nih.gov.

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