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Abnormalities of the leg lymphatics are not specific for bancroftian filariasis
TRANSACTIONS OFTHE ROYAL SOCIETY OFTROPICALMEDICINE AND HYGIENE (1998)92,650-652
Abnormalities
of the leg lymphatics
are not specific for bancroftian
filariasis
Marchettil, Willy F. Piessens 2, Zulma Medeiross and Gerusa Dreyer3 IHospital das Clinicas, Universidade Federal de Pernambuco, Recif, Brazil; 2Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA; JDepartamento de Parasitologia, Centro de PesquisasAggeu MagalhrieslFIOCRUZ, Recife, Brazil Fernanda
Abstract Studies using conventional angiography or non-invasive scintigraphy have revealed widespread abnormalities in the lymphatics of the legs of patients with bancroftian filariasis, regardless of whether clinical lymphoedema is present. To determine if the observed changes were specific for filarial infections, we imaged the lymphatics of both legs in native residents of an area in Brazil where filariasis is not endemic. Study participants were matched by age, socioeconomic status and physical activities to patients with filariasis in Recife, evaluated in parallel. Based on textbook criteria, only one of 15 study participants had a completely normal lymphoscintigram. Modest to severe pathology of the leg lymphatics was observed in the remaining 14 residents of the non-endemic area and in 49 of 50 patients with bancroftian filariasis. These results indicated that factors other than filarial worms are a common cause of subclinical pathology of the leg lymphatics in north-eastern Brazil, and that the latter is not specific for bancroftian filariasis. Keywords: filariasis, bancroftian filariasis, Wuchereriubancrofti, leg lymphatics, lymphoscintigraphy Introduction Since the 196Os, several studies using radiographic lymphangiography have detailed extensive damage to the lymphatics of the legs of patients with clinical lymnhoedema due to filarial infection. Abnormalities inlymphatic obstruction with clude lymphangiectasis, formation of collateral vessels. dermal backflow of lymph, and tilling defects in draining lymph nodes (COHEN et al., 1961; CAHILL & KAISER, 1964; KAEANJAV1970). Lymphangioscintigraphy studies =& performed during the past few years reveal that similar abnormalities in the superficial lvmphatics of the legs are also present in patients with bancroftian filariasis without clinical lvmnhoedema (WITTE et al.. 1993; FREEDMAN et al.; 1994, 1995; ‘DISSANAYAKE et al.; 1995). These findings suggest that subclinical lymphatic damage is an early phase of disease caused by Wuchereria bancrofti. This hypothesis is consistent with radiological and pathological findings in experimental filarial infections in several animal models (GOONERATNE, 1973; SCHACHER et al., 1973; HINES et al., 1985). It is further supported by the finding that some degree of dilatation can be detected by ultrasonography in virtually all scrotal lymphatics that contain live adult worms (AMARAL et al., 1994; NOROES et al., 1996a, 1996b). We have observed the same range of lymphoscintigraphic abnormalities described by others in our own population of asymptomatic patients with W bancrofti microfilaraemia: one or more segments of the leg lymphatics that were scanned were abnormal in 49 of the first 50 microfilaraemic patients we evaluated with this technique. However, the apparent discrepancy in many patients between the site of the most severe lymphatic damage (distal lymphatics in the legs and thighs) and the preferential location of adult worms in men (lymphatics in the scrotum) raised doubts in our minds about the filarial aetiology of the lymphatic lesions in the lower extremities. To determine if the observed subclinical lymphatic pathology was uniquely associated with bancroftian filariasis, we imaged the superficial lymphatics of both legs in 15 uninfected volunteers. Materials
and Methods
Study population
All uninfected volunteers were native male residents of an area in Brazil where filariasis is not endemic. The absence of infection was confirmed by failure to detect Address for correspondence: Dr Gerusa Dreyer, Centro de Pesquisas Aggeu MagalhaesiFIocRuz, Av. Moraes Rego s/n, Cidade Universitaria, Recife, PE 50670-420, Brazil; phone +55 81 2714000, fax +55 81 453 1911.
adult worms or lymphangiectasis by ultrasonography of the scrotal area with a 7-5 MHz probe (AMARAL et al., 1994), microfilariae by Nuclepore@ filtration of 10 mL of venous blood obtained at night (DENNIS & I(EAN, 1971), and Og4C3 tilarial antigenaemia by enzymelinked immunosorbent assay (MORE & COPEMAN, 1990; ROCHA et al., 1996). All uninfected men were soldiers who were matched by age, socioeconomic status and physical activity to soldiers in Recife, who constituted the majority of filariasis patients we had examined by lymphoscintigraphy before- the present study. None of the control subiects had clinical lvmphoedema of the lower extremities. Microtilaraemic patients with bancroftian filariasis were volunteers horn among those attending: the filariasis clinic at the Centro de Pesauisas Aggeu”Magalhaes in Recife, Brazil. The filarial dance sign (AMARAL et al., 1994) was present in intrascrotal lymphatics of all microfilaraemic patients participating in the study. Lymphangioscintigraphy
Lymphangioscintigraphy was done in the Hospital das Clinicas (Federal Universitv of Pernambuco, Recife, Brazil) with a STARCAM~~ 3200 (General Electric, Schenectadv. NY. USA) in line with a high resolution collimator. The superficial lymphatics w&re visualized with 99mTc-labelled dextran 500 and scanned as described by FREEDMAN et al. (1994), except that serial static images were collected starting 30 min after subcutaneous injection of 725 mBq of tracer in 0.1 mL in the first interdigital space of each foot. After bilateral injection of the tracer, volunteers were asked to walk barefoot for about 400 m to stimulate lymphatic flow in a physiological manner. Results Based on published criteria (NAWAZ et al., 1985; WEISLEDER & WEISLEDER. 1988). onlv one volunteer had a completely normal scan of ;he lymphatics from the injection site between the toes to the para-aortic area. Scintigrams from the other 14 study participants were abnormal in at least one lymphatic segment. The pattern and extent of subclinical lymphatic pathology in the legs of these young men (all were either 20 or 21 years old) were remarkably similar to those observed in patients with bancroftian filariasis. This is illustrated in the Figure, which represents the range of lymphatic abnormalities seen in our non-endemic controls. In most uninfected volunteers, the lymphatic vessels were only moderately abnormal by traditional criteria. However, extensive collateral vessel formation, dermal backflow (as seen in the 2 panels on the far right in parts A and B of the Figure) and filling defects of draining lymph
ABNORMALITIES
OF LEG LYMI’HATICS
IN BANCROFTIAN
FILARIASIS
651
tions. Such causal relationship may exist, but our results indicated that subclinical uathologv in the sunerficial lymphatics of the legs is not specific for bancroftian filariasis
because
it can be present
in uninfected
per-
sons. Filarial worms per se are therefore not likely to be the only common cause of subclinical damage to the leg lymphatics
in residents
of endemic
areas.
Acknowledgements We thank all participants in this study, especially the non-infected volunteers who travelled great distances to be examined in Recife. This study was supported by the UNDPWorld Bank/WHO Special Programme for Research and Training in Tropical Diseases, FIOCRUZ (PAPES no. 02) and FACEPE (project 0157.2.13/94). Written informed consent was obtained from all volunteers who participated in the study, which was reviewed and approved by the Ethical Committee of the Hospital das Clinicas, Universidade Federal de Pernambuco. Figure. Lymphoscintigraphs of 5 representative non-endemic controls (panel A) and 5 asymptomatic patients with Wuchereriu bancrofti microfilaraemia (panel B). Scans of the upper (u) and lower (1) parts of both legs are arranged by increasing degree of abnormality. The scans for the 2 subjects shown on the far left side of panels A and B are considered to be normal variants.
nodes (not shown) were present in 5 uninfected volunteers and in 21 of 50 microtilaraemic patients (42%) with bancroftian lilariasis. Discussion
These findings strongly support the concept that conditions other than bancroftian filariasis are a common cause of abnormal superficial lymphatics in the legs. Whether this is unique to north-eastern Brazil or occurs in other (sub)tropical areas remains to be determined. However, the cause(s) of this pathology is (are) unclear. Three filariasis-free subjects had possible bacterial entry lesions on a foot but denied ever having an episode of acute adenolymphangitis or cellulitis and their scans are not included in the Figure. It is unknown whether
chronic low grade infection of the skin leads to subclinical lymphatic damage detectable by scintigraphy, but acute streptococcal skin infections are a common cause of elephantiasis in the tropics (ACTON & -0, 1929; GRACE et al.. , 1932: , PONS. 1936: SUAREZ, 1936). Alternatively, the strenuous daily physical activities of our volunteer soldiers may have contributed to subclinical lymphatic pathology in these young men. The absence of adult worms and parasite-induced intrascrotal lymphangiectasis, microfilaraemia and Maria1 antigenaemia, negative tilarial serology (data not shown), and lifelong residence in a non-endemic area all render it extremely unlikely that the lymphatic pathology in our study subjects
was due to occult
filariasis.
While
it is ev-
ident that live adult worms can cause nearby lymphatics in the scrotal area in men to dilate (NOROES et al., 1996b), lymphangiectasis in these patients is a localized, not a systemic condition because it does not affect contralateral lymphatics in the left hemiscrotum, for example, when adult worms are present only on the right side. Our findings thus highlight the potential pitfalls of clinical research that fails to include appropriate control subjects. Studies on the use of scintigraphy in lymphatic filariasis published to date have included very few control subjects from the countries in which the studies were done (India, Brazil and Sri Lanka), and no attempt
has been made to match such uninfected controls from non-endemic areas in these countries to filariasis patients
with
respect
to socioeconomic
status, living
con-
ditions and physical activity. It has also been assumed that norms established in highlv developed countries apply to residents of filariasis-endemic areas. It is therefore not surprising that bancroftian filariasis is believed to cause the lymphatic changes observed in such popul-
References Acton. H. W. & Rae, S. S. (19291. . , The imnortance of secondarv infections in the causation of filarial lvmohanaitis. Indian 21 Y M;dical Gazette, 64421-423. Amaral, F., Dreyer, G., Figueredo-Silva, J., Noroes, J., Cavalcanti, A., Samico, S. C., Santos, A. & Coutinho, A. (1994). Live adult worms detected bv ultrasonoaraohv in human bancroftian filariasis. American Journal of-TTipkal Medicine and Hygiene, 50,753-757. Cahill, K. M. & Kaiser, R. L. (1964). Lymphangiography in bancroftian filariasis. Transactions of the Royal Society of Tmpical Medicine and Hwiene. 58. 356-362. Cohen, L. B., Nelson,“G., Wood, A. M., Manson-Bahr, I? E. C. & Bowen, R. (1961). Lymphangiography in filarial lymphedema and elephantiasis. American Journal of Tropical Medicine and Hygiene, 10, 843-848. Dennis, D. T. & Kean, B. H. (197 1). Isolation of microfilariae: report of a new method. Journal of Parasitology, 57, 1146-l 147. Dissanayake, S., Watawana, L. & Piessens, W. F. (1995). Lymphatic pathology in Wuchereria bancrofti microfilaraemic infections. Transactions of the Royal Society of Topical Medicine and Hygiene, 89, 5 17752 1. Freedman, D. O., de Almeida Filho, I’. J., Besh, S., Maia e Silva, M. C., Braga, C. & Maciel, A. (1994). Lymphoscintigraphic analysis of lymphatic abnormalities in symptomatic and asymptomatic human filariasis. .yournal of Infectious Diseases, i70; 927-933. Freedman, D. O., de Almeida Filho, I? J., Besh, S., Maia e Silva, M. C., Braga, C., Maciel, A. & Furtado, A. F. (1995). Abnormal lymphatic function in presymptomatic bancroftian filariasis. Journal of Infectious Diseases, 171, 99771001. Gooneratne, B. W. M. (1973). A chronological lymphographic study of cats experimentally infected with Brugia filariasis from 5 days to 5 years. Lymphology, 6, 127-149. Grace,A.W., Grace, F. B. &Warren, S. (1932).The parallel incidence of Filaria bancrofti and the beta-hemolytic streptococcus in certain tropical countries. American Journal of Tropical Medicine, 12, 493-508. Hines, S. A.,Williams, J. L., Doyle,T. J., Crandall, R. B., Crandall, C. A. & Nayar, J. K. (1985). Lymphangiography in ferrets infected with Brugia malayi. Lymphology, 18, 173-174. Karanjavala, D. K. (1970). Lymphangiography in the management of filarial chyluria. Annals of the Royal College of Surgeons of England, 46, 267-276. More, S. J. & Copeman, D. B. (1990). A highly specific and sensitive monoclonal antibody-based ELISA for the detection of circulating antigen in bancroftian filariasis. Tropical Medicine and Parasitology, 41,403-406. Nawaz. K.. Hamad. M.. Sadek. S.. Awdeh. M.. Hieazi, E.. Eklof, B. &Abdel-Dayem, H. M. (1985). Lympho&intigraphy in peripheral lymphedema using technetium-labelled human serum albumin. Normal and abnormal patterns. Lymphology, 18, 181-186. Noraes, J., Addiss, D., Amaral, F., Coutinho, A., Medeiros, Z. & Dreyer, G. (1996a). Occurrence of living adult Wuchereria bancrofti in the scrotal area of men with microfilaraemia. Transactions of the Royal SocietyI" of Tropical Medicine and Hv_ giene, 90, 55-56. I Noroes, J., Addiss, D., Santos, A., Medeiros, Z, Coutinho, A. & Drever. G. (1996b‘l. Ultrasonoaraohic evidence of abnorma1 lymphatic vessels in young men with adult Wuchereria bancrqfii infection in the scrotal area. Journal of Urology, 156, 409-412.
TRANSACTIONS
OFTHE
ROYAL SOCIETY
OFTROPICAL
MEDICINE
Pons, J. A. (1936). The treatment of recurrent tropical lymphangitis with special reference to the therapeutic value of streptococcus vaccines and filtrates. Puerto Rico Journal of Public Health and Tropical Medicine, 12, 114-139. Rocha, A., Addiss, D., Ribeiro, M. E., Noraes, J., Baliza, M., Medeiros, Z. & Dreyer, G. (1996). Evaluation of the Og4C3 ELISA in Wuchereriu bancrofti infection: infected persons with undetectable or ultra-low microfilarial densities. Tropical Medicine and International Health, 1, 859-863. Schacher, J. F., Edeson, J. F. B., Sulahian, A. & Rizk, G. (1973). An 18-month longitudinal lymphographic study of filarial disease in dogs infected with Brugiupahangi (Buckley and Edeson, 195 6). Annals of Tropical Medicine and Pamitology, 67, 81-94.
1 Short Report 1 Vulva1 mycetoma: a rare cause of bladder outlet obstruction A. H. Fahal* and A. R. A. Sharfy Department of Surgery, Faculty of Medicine, University of Khartoum, P.O. Box 102, Khartoum, Sudan Keywords:
mycetoma, Actinomadura pelletierii, vulva, Sudan
We report a patient with vulva1 mycetoma due to Actinomadura pelletierii infection, who presented with acute urine retention. We believe that such presentation has not been previously reported. Case report The patient, a 20 years old female from central Sudan, presented to the surgical accident and emergency department at Khartoum Teaching Hospital, Sudan with acute urine retention. After failed urethral catheterization, due to a massive vulva1 mycetoma and tight vulva1 circumcision, a suprapubic catheter was inserted under general anaesthesia. The patient was then referred to the mycetoma clinic at Soba University Hospital, Khartoum, Sudan.
Fig. 1. Massive mycetoma involving the vulva, perineum the upper part of the medial aspect of the right thigh.
and
Her condition had started 10 years before admission with a small painless mass in the upper part of the medial aspect of the right thigh, which gradually progressed. Eighteen months before admission, during pregnancy, the mass rapidly increased in size and even*Author for correspondence.
AND
HYGIENE
(1998) 92,652-653
Suarez, J. (1936). Clinical findings in 139 cases of recurrent tropical lymphangitis. Puerto Rico Journal of Public Health and Tropical Medicine, 12, 81-99.
Weisleder, H. & Weisleder, R. (1988). Lymphedema: evaluation of qualitative lymphoscintigraphy in 238 patients. Radiology, 167, 729-735.
Witte, M. H., Jamal, S., Williams, W. H., Wine, C. L., Kumaraswami, V., McNeil, G. C., Case, T. C. & Panicker, T. M. R. (1993). Lymphatic
abnormalities
in lymphatic
filariasis
as
depicted by lymphangioscintigraphy. Archives of Internal Medicine, 153,737-744.
Received 27 July 1998; revised 27 August 1998; accepted for publication 27 August 1998
tually multiple sinuses discharging red grains developed. Local surgical excision was attempted one year ago in another hospital but the mass soon recurred. Recently, sexual intercourse had become impossible due to the mycetoma. She had no past history of local trauma or surgery at the mycetoma site. Her family, social and drug histories were not contributory. On examination the patient was in pain and depressed. Head and neck, cardiovascular and respiratory systems were normal. A suprapubic catheter was noted on abdominal examination. Local examination revealed a massive mycetoma involving the upper aspect of the medial side of the right thigh, perineum and vulva with purulent discharge and tight circumcision. The inguinal lymph nodes were enlarged (Fig. 1). Antibodies against A. pelletieriz’ were detected by counter-immunoelectrophoresis. Intravenous urography revealed bilateral gross hydronephrosis and hydroureters with bladder neck obstruction (Fig. 2). Cystoscopy, performed under general anaesthksia aft& dilation of a tight urethral stricture, revealed an oedematous mucosa and multiple submucosal gritty swellings. A biopsy showed hypertrophic transitional epithelium with heavy acute and chronic inflammatory cell infiltration with eosinophilia. No fungal grain or parasite ovum was seen. After the urethral dilation, a urethral catheter was inserted and the suprapubic one was removed. Histopathological examination of the vulva1 specimen showed grains and inflammatory reaction characteristic of A. pelletierii infection. The patient was started on streptomycin sulphate, one gram per day for one month, and then on alternate davs with rifamoicin 300 mg: dailv. At follow-uu 3 m&ths later, he; general con&ion had improved with a reasonable local response to the treatment, but she needs regular urethral dilation. Comment Mycetoma is a slowly progressive subcutaneous chronic granulomatous infection caused by true fungi (Eumycetoma) or higher bacteria (Actinomycetoma). Mycetoma is characterized by the triad of a subcutaneous painless mass, sinuses, and discharge containing grains. The foot is the commonest site, but lesions on the hands, back and perineum are also seen. In endemic areas, rarer sites such as the testes, mandible, paranasal sinuses and eyelid have been reported; however, the vulva is not a frequent site (FAHAL & HASSAN, 1992; FAHAL et al., 1994, 1996). The mode of infection in perineal mycetoma is believed to be local inoculation of the causative organism in soil after trauma (%WGOUB, 1985). However, in this patient, there was no antecedent history
of trauma
or surgery
apart from
ritual
cir-
cumcision at the age of 7 years. It is probable that inoculation of A. pelletierii occurred by contamination during the procedure or subsequently from the soil. The early presentation of a lump on the thigh is probably an extension of a vulva1 lesion, which was very small and unnoticed by the patient.
Abnormalities
of the leg lymphatics
are not specific for bancroftian
filariasis
Marchettil, Willy F. Piessens 2, Zulma Medeiross and Gerusa Dreyer3 IHospital das Clinicas, Universidade Federal de Pernambuco, Recif, Brazil; 2Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA; JDepartamento de Parasitologia, Centro de PesquisasAggeu MagalhrieslFIOCRUZ, Recife, Brazil Fernanda
Abstract Studies using conventional angiography or non-invasive scintigraphy have revealed widespread abnormalities in the lymphatics of the legs of patients with bancroftian filariasis, regardless of whether clinical lymphoedema is present. To determine if the observed changes were specific for filarial infections, we imaged the lymphatics of both legs in native residents of an area in Brazil where filariasis is not endemic. Study participants were matched by age, socioeconomic status and physical activities to patients with filariasis in Recife, evaluated in parallel. Based on textbook criteria, only one of 15 study participants had a completely normal lymphoscintigram. Modest to severe pathology of the leg lymphatics was observed in the remaining 14 residents of the non-endemic area and in 49 of 50 patients with bancroftian filariasis. These results indicated that factors other than filarial worms are a common cause of subclinical pathology of the leg lymphatics in north-eastern Brazil, and that the latter is not specific for bancroftian filariasis. Keywords: filariasis, bancroftian filariasis, Wuchereriubancrofti, leg lymphatics, lymphoscintigraphy Introduction Since the 196Os, several studies using radiographic lymphangiography have detailed extensive damage to the lymphatics of the legs of patients with clinical lymnhoedema due to filarial infection. Abnormalities inlymphatic obstruction with clude lymphangiectasis, formation of collateral vessels. dermal backflow of lymph, and tilling defects in draining lymph nodes (COHEN et al., 1961; CAHILL & KAISER, 1964; KAEANJAV1970). Lymphangioscintigraphy studies =& performed during the past few years reveal that similar abnormalities in the superficial lvmphatics of the legs are also present in patients with bancroftian filariasis without clinical lvmnhoedema (WITTE et al.. 1993; FREEDMAN et al.; 1994, 1995; ‘DISSANAYAKE et al.; 1995). These findings suggest that subclinical lymphatic damage is an early phase of disease caused by Wuchereria bancrofti. This hypothesis is consistent with radiological and pathological findings in experimental filarial infections in several animal models (GOONERATNE, 1973; SCHACHER et al., 1973; HINES et al., 1985). It is further supported by the finding that some degree of dilatation can be detected by ultrasonography in virtually all scrotal lymphatics that contain live adult worms (AMARAL et al., 1994; NOROES et al., 1996a, 1996b). We have observed the same range of lymphoscintigraphic abnormalities described by others in our own population of asymptomatic patients with W bancrofti microfilaraemia: one or more segments of the leg lymphatics that were scanned were abnormal in 49 of the first 50 microfilaraemic patients we evaluated with this technique. However, the apparent discrepancy in many patients between the site of the most severe lymphatic damage (distal lymphatics in the legs and thighs) and the preferential location of adult worms in men (lymphatics in the scrotum) raised doubts in our minds about the filarial aetiology of the lymphatic lesions in the lower extremities. To determine if the observed subclinical lymphatic pathology was uniquely associated with bancroftian filariasis, we imaged the superficial lymphatics of both legs in 15 uninfected volunteers. Materials
and Methods
Study population
All uninfected volunteers were native male residents of an area in Brazil where filariasis is not endemic. The absence of infection was confirmed by failure to detect Address for correspondence: Dr Gerusa Dreyer, Centro de Pesquisas Aggeu MagalhaesiFIocRuz, Av. Moraes Rego s/n, Cidade Universitaria, Recife, PE 50670-420, Brazil; phone +55 81 2714000, fax +55 81 453 1911.
adult worms or lymphangiectasis by ultrasonography of the scrotal area with a 7-5 MHz probe (AMARAL et al., 1994), microfilariae by Nuclepore@ filtration of 10 mL of venous blood obtained at night (DENNIS & I(EAN, 1971), and Og4C3 tilarial antigenaemia by enzymelinked immunosorbent assay (MORE & COPEMAN, 1990; ROCHA et al., 1996). All uninfected men were soldiers who were matched by age, socioeconomic status and physical activity to soldiers in Recife, who constituted the majority of filariasis patients we had examined by lymphoscintigraphy before- the present study. None of the control subiects had clinical lvmphoedema of the lower extremities. Microtilaraemic patients with bancroftian filariasis were volunteers horn among those attending: the filariasis clinic at the Centro de Pesauisas Aggeu”Magalhaes in Recife, Brazil. The filarial dance sign (AMARAL et al., 1994) was present in intrascrotal lymphatics of all microfilaraemic patients participating in the study. Lymphangioscintigraphy
Lymphangioscintigraphy was done in the Hospital das Clinicas (Federal Universitv of Pernambuco, Recife, Brazil) with a STARCAM~~ 3200 (General Electric, Schenectadv. NY. USA) in line with a high resolution collimator. The superficial lymphatics w&re visualized with 99mTc-labelled dextran 500 and scanned as described by FREEDMAN et al. (1994), except that serial static images were collected starting 30 min after subcutaneous injection of 725 mBq of tracer in 0.1 mL in the first interdigital space of each foot. After bilateral injection of the tracer, volunteers were asked to walk barefoot for about 400 m to stimulate lymphatic flow in a physiological manner. Results Based on published criteria (NAWAZ et al., 1985; WEISLEDER & WEISLEDER. 1988). onlv one volunteer had a completely normal scan of ;he lymphatics from the injection site between the toes to the para-aortic area. Scintigrams from the other 14 study participants were abnormal in at least one lymphatic segment. The pattern and extent of subclinical lymphatic pathology in the legs of these young men (all were either 20 or 21 years old) were remarkably similar to those observed in patients with bancroftian filariasis. This is illustrated in the Figure, which represents the range of lymphatic abnormalities seen in our non-endemic controls. In most uninfected volunteers, the lymphatic vessels were only moderately abnormal by traditional criteria. However, extensive collateral vessel formation, dermal backflow (as seen in the 2 panels on the far right in parts A and B of the Figure) and filling defects of draining lymph
ABNORMALITIES
OF LEG LYMI’HATICS
IN BANCROFTIAN
FILARIASIS
651
tions. Such causal relationship may exist, but our results indicated that subclinical uathologv in the sunerficial lymphatics of the legs is not specific for bancroftian filariasis
because
it can be present
in uninfected
per-
sons. Filarial worms per se are therefore not likely to be the only common cause of subclinical damage to the leg lymphatics
in residents
of endemic
areas.
Acknowledgements We thank all participants in this study, especially the non-infected volunteers who travelled great distances to be examined in Recife. This study was supported by the UNDPWorld Bank/WHO Special Programme for Research and Training in Tropical Diseases, FIOCRUZ (PAPES no. 02) and FACEPE (project 0157.2.13/94). Written informed consent was obtained from all volunteers who participated in the study, which was reviewed and approved by the Ethical Committee of the Hospital das Clinicas, Universidade Federal de Pernambuco. Figure. Lymphoscintigraphs of 5 representative non-endemic controls (panel A) and 5 asymptomatic patients with Wuchereriu bancrofti microfilaraemia (panel B). Scans of the upper (u) and lower (1) parts of both legs are arranged by increasing degree of abnormality. The scans for the 2 subjects shown on the far left side of panels A and B are considered to be normal variants.
nodes (not shown) were present in 5 uninfected volunteers and in 21 of 50 microtilaraemic patients (42%) with bancroftian lilariasis. Discussion
These findings strongly support the concept that conditions other than bancroftian filariasis are a common cause of abnormal superficial lymphatics in the legs. Whether this is unique to north-eastern Brazil or occurs in other (sub)tropical areas remains to be determined. However, the cause(s) of this pathology is (are) unclear. Three filariasis-free subjects had possible bacterial entry lesions on a foot but denied ever having an episode of acute adenolymphangitis or cellulitis and their scans are not included in the Figure. It is unknown whether
chronic low grade infection of the skin leads to subclinical lymphatic damage detectable by scintigraphy, but acute streptococcal skin infections are a common cause of elephantiasis in the tropics (ACTON & -0, 1929; GRACE et al.. , 1932: , PONS. 1936: SUAREZ, 1936). Alternatively, the strenuous daily physical activities of our volunteer soldiers may have contributed to subclinical lymphatic pathology in these young men. The absence of adult worms and parasite-induced intrascrotal lymphangiectasis, microfilaraemia and Maria1 antigenaemia, negative tilarial serology (data not shown), and lifelong residence in a non-endemic area all render it extremely unlikely that the lymphatic pathology in our study subjects
was due to occult
filariasis.
While
it is ev-
ident that live adult worms can cause nearby lymphatics in the scrotal area in men to dilate (NOROES et al., 1996b), lymphangiectasis in these patients is a localized, not a systemic condition because it does not affect contralateral lymphatics in the left hemiscrotum, for example, when adult worms are present only on the right side. Our findings thus highlight the potential pitfalls of clinical research that fails to include appropriate control subjects. Studies on the use of scintigraphy in lymphatic filariasis published to date have included very few control subjects from the countries in which the studies were done (India, Brazil and Sri Lanka), and no attempt
has been made to match such uninfected controls from non-endemic areas in these countries to filariasis patients
with
respect
to socioeconomic
status, living
con-
ditions and physical activity. It has also been assumed that norms established in highlv developed countries apply to residents of filariasis-endemic areas. It is therefore not surprising that bancroftian filariasis is believed to cause the lymphatic changes observed in such popul-
References Acton. H. W. & Rae, S. S. (19291. . , The imnortance of secondarv infections in the causation of filarial lvmohanaitis. Indian 21 Y M;dical Gazette, 64421-423. Amaral, F., Dreyer, G., Figueredo-Silva, J., Noroes, J., Cavalcanti, A., Samico, S. C., Santos, A. & Coutinho, A. (1994). Live adult worms detected bv ultrasonoaraohv in human bancroftian filariasis. American Journal of-TTipkal Medicine and Hygiene, 50,753-757. Cahill, K. M. & Kaiser, R. L. (1964). Lymphangiography in bancroftian filariasis. Transactions of the Royal Society of Tmpical Medicine and Hwiene. 58. 356-362. Cohen, L. B., Nelson,“G., Wood, A. M., Manson-Bahr, I? E. C. & Bowen, R. (1961). Lymphangiography in filarial lymphedema and elephantiasis. American Journal of Tropical Medicine and Hygiene, 10, 843-848. Dennis, D. T. & Kean, B. H. (197 1). Isolation of microfilariae: report of a new method. Journal of Parasitology, 57, 1146-l 147. Dissanayake, S., Watawana, L. & Piessens, W. F. (1995). Lymphatic pathology in Wuchereria bancrofti microfilaraemic infections. Transactions of the Royal Society of Topical Medicine and Hygiene, 89, 5 17752 1. Freedman, D. O., de Almeida Filho, I’. J., Besh, S., Maia e Silva, M. C., Braga, C. & Maciel, A. (1994). Lymphoscintigraphic analysis of lymphatic abnormalities in symptomatic and asymptomatic human filariasis. .yournal of Infectious Diseases, i70; 927-933. Freedman, D. O., de Almeida Filho, I? J., Besh, S., Maia e Silva, M. C., Braga, C., Maciel, A. & Furtado, A. F. (1995). Abnormal lymphatic function in presymptomatic bancroftian filariasis. Journal of Infectious Diseases, 171, 99771001. Gooneratne, B. W. M. (1973). A chronological lymphographic study of cats experimentally infected with Brugia filariasis from 5 days to 5 years. Lymphology, 6, 127-149. Grace,A.W., Grace, F. B. &Warren, S. (1932).The parallel incidence of Filaria bancrofti and the beta-hemolytic streptococcus in certain tropical countries. American Journal of Tropical Medicine, 12, 493-508. Hines, S. A.,Williams, J. L., Doyle,T. J., Crandall, R. B., Crandall, C. A. & Nayar, J. K. (1985). Lymphangiography in ferrets infected with Brugia malayi. Lymphology, 18, 173-174. Karanjavala, D. K. (1970). Lymphangiography in the management of filarial chyluria. Annals of the Royal College of Surgeons of England, 46, 267-276. More, S. J. & Copeman, D. B. (1990). A highly specific and sensitive monoclonal antibody-based ELISA for the detection of circulating antigen in bancroftian filariasis. Tropical Medicine and Parasitology, 41,403-406. Nawaz. K.. Hamad. M.. Sadek. S.. Awdeh. M.. Hieazi, E.. Eklof, B. &Abdel-Dayem, H. M. (1985). Lympho&intigraphy in peripheral lymphedema using technetium-labelled human serum albumin. Normal and abnormal patterns. Lymphology, 18, 181-186. Noraes, J., Addiss, D., Amaral, F., Coutinho, A., Medeiros, Z. & Dreyer, G. (1996a). Occurrence of living adult Wuchereria bancrofti in the scrotal area of men with microfilaraemia. Transactions of the Royal SocietyI" of Tropical Medicine and Hv_ giene, 90, 55-56. I Noroes, J., Addiss, D., Santos, A., Medeiros, Z, Coutinho, A. & Drever. G. (1996b‘l. Ultrasonoaraohic evidence of abnorma1 lymphatic vessels in young men with adult Wuchereria bancrqfii infection in the scrotal area. Journal of Urology, 156, 409-412.
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Pons, J. A. (1936). The treatment of recurrent tropical lymphangitis with special reference to the therapeutic value of streptococcus vaccines and filtrates. Puerto Rico Journal of Public Health and Tropical Medicine, 12, 114-139. Rocha, A., Addiss, D., Ribeiro, M. E., Noraes, J., Baliza, M., Medeiros, Z. & Dreyer, G. (1996). Evaluation of the Og4C3 ELISA in Wuchereriu bancrofti infection: infected persons with undetectable or ultra-low microfilarial densities. Tropical Medicine and International Health, 1, 859-863. Schacher, J. F., Edeson, J. F. B., Sulahian, A. & Rizk, G. (1973). An 18-month longitudinal lymphographic study of filarial disease in dogs infected with Brugiupahangi (Buckley and Edeson, 195 6). Annals of Tropical Medicine and Pamitology, 67, 81-94.
1 Short Report 1 Vulva1 mycetoma: a rare cause of bladder outlet obstruction A. H. Fahal* and A. R. A. Sharfy Department of Surgery, Faculty of Medicine, University of Khartoum, P.O. Box 102, Khartoum, Sudan Keywords:
mycetoma, Actinomadura pelletierii, vulva, Sudan
We report a patient with vulva1 mycetoma due to Actinomadura pelletierii infection, who presented with acute urine retention. We believe that such presentation has not been previously reported. Case report The patient, a 20 years old female from central Sudan, presented to the surgical accident and emergency department at Khartoum Teaching Hospital, Sudan with acute urine retention. After failed urethral catheterization, due to a massive vulva1 mycetoma and tight vulva1 circumcision, a suprapubic catheter was inserted under general anaesthesia. The patient was then referred to the mycetoma clinic at Soba University Hospital, Khartoum, Sudan.
Fig. 1. Massive mycetoma involving the vulva, perineum the upper part of the medial aspect of the right thigh.
and
Her condition had started 10 years before admission with a small painless mass in the upper part of the medial aspect of the right thigh, which gradually progressed. Eighteen months before admission, during pregnancy, the mass rapidly increased in size and even*Author for correspondence.
AND
HYGIENE
(1998) 92,652-653
Suarez, J. (1936). Clinical findings in 139 cases of recurrent tropical lymphangitis. Puerto Rico Journal of Public Health and Tropical Medicine, 12, 81-99.
Weisleder, H. & Weisleder, R. (1988). Lymphedema: evaluation of qualitative lymphoscintigraphy in 238 patients. Radiology, 167, 729-735.
Witte, M. H., Jamal, S., Williams, W. H., Wine, C. L., Kumaraswami, V., McNeil, G. C., Case, T. C. & Panicker, T. M. R. (1993). Lymphatic
abnormalities
in lymphatic
filariasis
as
depicted by lymphangioscintigraphy. Archives of Internal Medicine, 153,737-744.
Received 27 July 1998; revised 27 August 1998; accepted for publication 27 August 1998
tually multiple sinuses discharging red grains developed. Local surgical excision was attempted one year ago in another hospital but the mass soon recurred. Recently, sexual intercourse had become impossible due to the mycetoma. She had no past history of local trauma or surgery at the mycetoma site. Her family, social and drug histories were not contributory. On examination the patient was in pain and depressed. Head and neck, cardiovascular and respiratory systems were normal. A suprapubic catheter was noted on abdominal examination. Local examination revealed a massive mycetoma involving the upper aspect of the medial side of the right thigh, perineum and vulva with purulent discharge and tight circumcision. The inguinal lymph nodes were enlarged (Fig. 1). Antibodies against A. pelletieriz’ were detected by counter-immunoelectrophoresis. Intravenous urography revealed bilateral gross hydronephrosis and hydroureters with bladder neck obstruction (Fig. 2). Cystoscopy, performed under general anaesthksia aft& dilation of a tight urethral stricture, revealed an oedematous mucosa and multiple submucosal gritty swellings. A biopsy showed hypertrophic transitional epithelium with heavy acute and chronic inflammatory cell infiltration with eosinophilia. No fungal grain or parasite ovum was seen. After the urethral dilation, a urethral catheter was inserted and the suprapubic one was removed. Histopathological examination of the vulva1 specimen showed grains and inflammatory reaction characteristic of A. pelletierii infection. The patient was started on streptomycin sulphate, one gram per day for one month, and then on alternate davs with rifamoicin 300 mg: dailv. At follow-uu 3 m&ths later, he; general con&ion had improved with a reasonable local response to the treatment, but she needs regular urethral dilation. Comment Mycetoma is a slowly progressive subcutaneous chronic granulomatous infection caused by true fungi (Eumycetoma) or higher bacteria (Actinomycetoma). Mycetoma is characterized by the triad of a subcutaneous painless mass, sinuses, and discharge containing grains. The foot is the commonest site, but lesions on the hands, back and perineum are also seen. In endemic areas, rarer sites such as the testes, mandible, paranasal sinuses and eyelid have been reported; however, the vulva is not a frequent site (FAHAL & HASSAN, 1992; FAHAL et al., 1994, 1996). The mode of infection in perineal mycetoma is believed to be local inoculation of the causative organism in soil after trauma (%WGOUB, 1985). However, in this patient, there was no antecedent history
of trauma
or surgery
apart from
ritual
cir-
cumcision at the age of 7 years. It is probable that inoculation of A. pelletierii occurred by contamination during the procedure or subsequently from the soil. The early presentation of a lump on the thigh is probably an extension of a vulva1 lesion, which was very small and unnoticed by the patient.