ONCHOCERCOSIS MANSONELLA CO-INFECTION PRESENTINGAS A SUBCUTANEOUS NODULE IN A CHILD

John Q. Davies and Marta C. Cohen & Department of Histopathology,Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom

Fiona Shackley & Department of Pediatrics, Sheffield Children’s NHS FoundationTrust, Sheffield, United Kingdom

Tim C. Clarke & Department of Microbiology, Royal Hallamshire NHS FoundationTrust, Sheffield, United Kingdom

Richard E. Page & Department of Plastic Surgery, Sheffield Children’s NHSFoundation Trust, Sheffield, United Kingdom

& A 11-year-old girl presented with a subcutaneous lesion on the forehead, thought to be animplantation dermoid cyst. Microscopic examination revealed an onchocercoma. Microfilariae werefound in the blood indicating a co-infection with Mansonella perstans. This case demonstrates thediagnostic difficulties of a parasitic co-infection uncommonly encountered in Europe.

Keywords Mansonella, onchocerciasis, onchocercoma, pathology, pediatric

INTRODUCTION

An infectious disease is generally regarded by most clinicians as a dis-tinct entity caused by a single pathogen. This is often not the case whendealing with tropical diseases such as parasitic co-infections that are com-mon [1]. In this situation each of the pathogens can contribute to the over-all disease by influencing pathogenesis and clinical manifestation(s). Ittherefore seems likely that multiple infections may well give rise to a con-fusing diagnostic picture, particularly in countries that do not commonlyencounter tropical diseases. This case shows the difficulties encounteredby European clinicians and pathologists in correctly identifying and

Address correspondence to Dr. Marta C. Cohen, Department of Histopathology, SheffieldChildren’s NHS Foundation Trust, Western Bank S10 2TH, Sheffield, United Kingdom. E-mail: Marta.Cohen@sch.nhs.uk

Fetal and Pediatric Pathology, 26:47–53, 2007Copyright # Informa HealthcareISSN: 1551-3815 print/1551-3823 onlineDOI: 10.1080/15513810701394793

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diagnosing filarial nematode co-infections that are otherwise common inmany African countries.

CASE REPORT

An 11-year-old girl was seen in the outpatient department with anasymptomatic 1� 1 cm, cystic lesion of the forehead that had been presentfor some years (Figure 1). She had been hit by a stone on the forehead afew months before the swelling appeared. The lesion was removed withthe presumptive diagnosis of an implantation dermoid. She was otherwisewell with no other skin lesions. The eosinophil count at presentation wasslightly elevated at 0.82 (11.2%). Ophthalmic examination demonstratednumular keratitis. Retinal changes were not found.

MATERIALS AND METHODS

The surgical specimen consisted in an ellipse of skin that was fixed in10% buffered formalin. Paraffin-embedded sections were cut in 4mm thick-ness and stained using the haematoxylin and eosin method. Investigationfor Loa loa and mansonellosis were performed on EDTA and citrated bloodsamples, respectively.

RESULTS

Histological examination revealed a subcutaneous nodule showingcoiled adult worms immersed in heavily inflamed fibrous tissue. The

FIGURE 1 1� 1 cm lesion of the forehead.

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inflammatory infiltrate included numerous eosinophils. An adult femalenematode worm (Figure 2) with associated rounded transverse striationson the cuticle and uteri filled with larva was clearly visible in the sections(Figure 3). A diagnosis of ‘‘onchocercoma’’ was suggested.

On further questioning the patient was found to be a recent immigrantfrom Congo. Because of the risk of co-infection with Loa loa and the poten-tial for significant side effects consequent to treatment with Ivermectin inthe presence of Loa loa, an EDTA blood sample was obtained. The EDTAblood sample showed unsheathed microfilaria. The possibility of these

FIGURE 2 Microscopic appearance of the subcutaneous nodule. There are multiple cross-sectionsthrough a gravid female worm with a surrounding chronic inflammatory response (H&E, originalmagnification�20).

FIGURE 3 Transverse section of a female worm with the uteri filled with microfilariae (H&E�40).Inset: Cuticle with protuberances (arrow) (H&E�60).

Onchocercoma and Mansonella Co-Infection 49

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being unsheathed Loa loa was raised but a consequent citrate sample con-firmed them to be Mansonella perstans (Dipetolenema perstans) (Figure 4).She was treated with Ivermectin 50 mg=kg as a single dose. Further ophthal-mologic follow-up and a further dose of Ivermectin was planned for 6months later.

DISCUSSION

Human filariasis is caused by eight main species of nematodes (roundworms) that inhabit the lymphatics and subcutaneous tissues. Major clinicalmorbidity is caused by three of these: Wuchereria bancrofti and Brugia malayicause lymphatic filariasis, whereas Onchocerca volvulus causes onchocerciasis(river blindness). The other five species, which generally cause less signifi-cant disease, are Loa loa, Mansonella perstans, M. streptocerca, M. ozzardi, andBrugia timori.

Onchocerca volvulus is the only member of this genus known to infecthumans [2, 3]. The infection is acquired through bites from the speciesSimulium or black fly that breeds along rivers. The disease is limited toAfrica, Central America, and northern South America. It is estimated thatthere are 18 million cases worldwide with 17.5 million found in Africa and600,000 visually impaired [4, 5]. Nigeria is the most infected region. Theadult worms live in the dermis and connective tissue and produce microfi-lariae. These migrate through the body but mainly in the upper dermis andthe eye. When the Simulium bites an infected individual, it ingests themicrofilaria during a blood meal. The larvae migrate from the gut of the

FIGURE 4 Unsheathed Mansonella perstans microfilaria in a thick blood film. Note that the microfi-laria has terminal nuclei extending to the end of a straight blunt tail. Inset: Low power of the microfi-laria (Giemsa, original magnification�200).

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black fly to the thoracic muscle where they develop into infective larvae in 6to 9 days and are ready to be transmitted into another host [6]. The risk ofprogressive eye involvement may span a number of years. Consequentlychemotherapeutic treatment, and where appropriate, surgical excision isimportant.

Ivermectin is the treatment of choice but if there is associated co-infec-tion with Loa loa, an allergic encephalopathy may occur. In onchocerciasis,microfilariae in the circulation are extremely uncommon [2]. The diag-nosis of an ‘‘onchocercal nodule’’ in this patient therefore was queriedby the additional findings of microfilariae in the blood. External reviewof the histological sections was undertaken to resolve the situation and thiscorroborated the diagnosis of onchocerciasis. At the same time, furtherexamination of a blood citrate sample confirmed the microfilariae to beMansonella perstans.

The diagnosis of O. volvulus can be made by histologic examination of anodule by collecting skin snips from an infected area, immersing them insaline, and observing microscopically for the active microfilaria, or by usingmore sophisticated tests such as enzyme linked immunoabsorbent assay(ELISA) or polymerase chain reaction (PCR) [5]. O. volvulus microfilariaemeasure 220 to 360mm in length and 5 to 9 mm in width. From anterior toposterior they have a cephalic space, anterior nuclei, terminal nuclei, a cau-dal space, and a tail with tapered point [5].

Onchocercosis is the most common helminthic infection found in thesubcutaneous tissue. Although the morphology of the adult O. volvulusworm is similar to that of other round worms, such as W. bancrofti, it canbe confidently identified by careful examination of the worms cuticle,which in onchocerca has deep rounded transverse striations. These, how-ever, show great variation in distance: they are close at the anterior endof the parasite but much further apart (up to 70 mm) throughout most ofthe length of the nematode and appear as rounded protuberances asshown in Figure 3 (inset) [3]. As in our case, the adult O. volvulus presentsin the subcutaneous tissue tightly coiled and encased in fibrotic scar tissue,conforming a nodule [2, 3]. An additional diagnostic consideration in thisanatomical location was that of Mansonella streptocerca, which occasionallycan present clinically as a skin papule but usually only after chemotherapy[7]. The morphological distinction is not difficult, as adult M. streptocercahave a smooth cuticle and are smaller than their onchocercal counterparts(female diameter �100 mm vs. 350 mm) [3, 7].

The finding of small (200� 4.5 mm in dimension) unsheathed microfi-lariae, that contained a single row of nuclei extending up to the blunt tail(Figure 4) was confusing in this case as it prompted an additional diagnosisof Mansonella perstans [7, 8]. Despite multiple microfilariae being present inthe blood, M. perstans is felt not to cause significant pathology in humans

Onchocercoma and Mansonella Co-Infection 51

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[8]. The importance of accurate diagnosis is relevant to exclude the pres-ence of other more pathogenic filariae.

M. perstans can result however in painless conjunctival nodules, second-ary eye lid swelling, and proptosis. Third stage larvae are introduced intothe skin of the human host during a blood meal of an infected midge(genus Culicoides). The larvae develop into adults that reside in body cavi-ties, most commonly the peritoneal cavity or pleural cavity. Because of theirhabits the adults are rarely seen but they have been found to be cylindricalin shape with lengths and diameters of 4–5 cm� 0.06 mm in males and7.8 cm� 0.12 mm in the females. The mated adults produce unsheathedmicrofilariae that circulate in the blood in equal amounts during day ornight (nonperiodic). When a Culicoides has a blood meal, the microfilariaeare transmitted from the blood to the midge’s midgut through the hemo-coel to the thoracic muscles of the arthropod where they develop into first-stage larvae and subsequently into third-stage infective larvae. Thesemigrate to the midge’s proboscis and can infect another human whenthe midge takes a blood meal [8, 9].

Mansonella perstans is widely distributed throughout Africa and SouthAmerica. In certain locations in Zaire, Nigeria, Ghana, Sierra Leone, IvoryCoast, Zambia, and Uganda extremely high proportions of the inhabitantsshow signs of infection. Villages surveyed in Cameroon were found highlyendemic for onchocerciasis and mansonellosis with prevalence rangingfrom 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans[10].

In our case, the demonstration of unsheathed microfilariae excludedthe diagnosis of filarial parasites with sheathed larvae (Wuchereria bancrofti,Brugia malayi, B. timori, and Loa loa). Of the unsheathed varieties, only onch-ocerciasis and streptocerciasis are the major differential diagnostic consid-erations in skin snip specimens and not in blood smears, as in this case.Nevertheless, the microfilariae in onchocerciasis are sharply angulated,whereas in streptocerciasis a ‘‘shepherd’s hook’’ tail is present [7]. Finallythe unsheathed microfilariae of M. ozzardi, not found in Africa, have abutton-hooked, tapered tail to distinguishes it from M. perstans.

SUMMARY

Onchoceriasis may present with minimal symptoms but accurate diag-nosis and treatment are important because of the risk of eye damage. Poss-ible co-infection with Loa loa should be considered prior to treatment.Co-infection with other microfilariae may result in a confusing diagnosticpicture. With the recent increase in immigration from tropical countries,unusual cases such as this one may be expected to become more wide-spread in the future.

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REFERENCES

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2. Studeman K, Fishback JL, Connor DH. Onchocerciasis. In Pathology of Infectious Diseases, 1st ed.,vol. 2. Connor DH, Chandler FW, Manz HJ, et al., eds. Stamford, CT: Appleton & Lange,1505–1526, 1997.

3. Neafie RC. Morphology of Onchocerca volvulus. Am J Clin Pathol 57(5):574–586, 1972.4. Basanez MG, Boussinesq M. Population biology of human onchocerciasis. Philos Trans R Soc Lond

B Biol Sci 354(1384):809–826, 1999.5. Okulicz JF, Stribich AS, Elston DM, Schwartz RA. Cutaneous onchocercoma. Int J Dermatol

43:170–172, Int. J Dermatol.6. Connor DH, Morrison NE, Kerdel-Vegas F, et al. Onchocerciasis. Onchocercal dermatitis. Lymph-

adenitis and elephantiasis in the Ubangi territory. Hum Pathol 1:553–579, 1970.7. Byran J, Connor DH. Mansonella streptocerca infection (Streptocerciasis). In Pathology of Infectious

Diseases, 1st ed., vol 2. Connor DH, Chandler FW, Manz HJ, et al., eds. Stamford, CT: Appleton &Lange, 1997.

8. Baird JK. Mansonella perstans infection (Mansonelliasis). In Pathology of Infectious Diseases, 1st ed.,vol. 2. Connor DH, Chandler FW, Manz HJ, et al., eds. Stamford, CT: Appleton & Lange,1487–1491, 1997.

9. www.dpd.cdc.gov/dpdx10. Wanji S, Tendongfor N, Esum M, et al. Epidemiology of concomitant infections due to Loa loa, Man-

sonella perstans, and Onchocerca volvulus in rain forest villages of Cameroon. Med Microbiol Immu-nol 19:15–21, 2003.

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