Giant Scrotal Hydrocele and Bilateral Leg Lymphedema as Clinical Manifestation of Chronic Lymphatic Filariasis.

A 51-year-old male came with the complaint of recurrent swelling in the scrotum and legs. Swelling of the scrotum first appeared 17 years ago in the left scrotum approximately the same size as an apple and underwent surgery. However, 2 years after surgery, the swelling reemerged and gradually increase in size in both scrotums. Left leg swelling began to emerge 5 years ago followed by right leg 3 years after. The patient lives in Sarmi regency Papua province (endemic).

Role of persistent processus vaginalis in hydroceles found in a tropical population.

BACKGROUND: Lymphatic obstruction by Wuchereria bancrofti is thought to be the mechanism for development of tropical hydrocele in men and for elephantiasis, mostly in women. Hydrocele prevalence is used to determine the effectiveness of para site eradication programs. METHODS: We maintained a prospective log of operations performed at 1 Canadian Field Hospital during its relief mission to Léogâne, Haiti. Information regarding duration of symptoms, type of previous surgery (if any), surgical approach, associated inguinal hernia and volume and appearance of hydrocele fluid in patients with tropical hydroceles were recorded. RESULTS: From January to March 2010, 4922 patients were seen, none of whom had elephantiasis. Of the 64 patients who collectively underwent 69 inguino-scrotal procedures, 5 patients had inguinal hernia repair several years after hydrocele excision via the scrotum, 19 patients with bilateral hydroceles underwent a scrotum-only approach, and 45 patients had an inguinal approach (33 unilateral and 12 bilateral) to repair 57 hydroceles. A patent processus vaginalis was present in 50 of 57 (88%) hydroceles where the groin was explored. CONCLUSION: Hydroceles remain common in Léogâne despite successful eradication of filariasis with mass drug administration using diethylcarbamazine-fortified cooking salt. Persistent patent processus vaginalis is a more likely cause than persistent filariasis. There is probably little difference between hydrocele in developed countries and tropical hydrocele other than neglect. Hydrocele prevalence is not a measure of the effectiveness of parasite eradication programs.

Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of lymphedema in the doxycycline-treated patients being significantly lower compared to placebo patients 12 mo after treatment. The reduction in the stages manifested as better skin texture, a reduction of deep folds, and fewer deep skin folds. In conclusion, a 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.

Chronic clinical manifestations related to Wuchereria bancrofti infection in a highly endemic area in Kenya.

Clinical examinations were conducted in an effort to provide baseline data for a pilot filariasis elimination programme implemented in a Wuchereria bancrofti-endemic focus in Malindi district, Kenya. Of 186 males aged 15 years and above examined, 64 individuals (34.4%) had hydrocele, and the prevalence of the manifestation in those above 40 years old was 55.3%. The prevalence of leg lymphoedema in persons aged 15 years and above was 8.5%, with a higher rate in males (12.6%) than in females (5.7%). The overall prevalence of inguinal adenopathy was 8.6%, and males had a significantly higher (12.9%) prevalence of adenopathy than females (5.1%) (P<0.001). The data in the present study provided support for consideration of filarial infection as a possible cause of inguinal lymphadenopathy in bancroftian filariasis-endemic areas. The results of this study also indicate that lymphatic filariasis is a serious public health problem in the northern coastal areas and morbidity control programmes should be implemented to alleviate the suffering of those affected.

Health status of lymphatic filariasis assessed from patients using seven domains five levels (7D5L) instrument.

Health status is the standardized description of health condition of individuals either normal or ill due to diseases and is presented as multidimentional profiles. In an effort to develop an indicator to assess the impact of morbidity intervention against lymphatic filariasis (LF), we assessed the health status of seven different clinical manifestations (health states) of LF from the patient's perspective. One hundred and seventy-four filarial patients either with hydrocele or lymphoedema were involved in the study. Acute episode of adenolymphangitis (ADL) among chronic patients was considered as co-morbidity. Severity levels, focusing on physical, mental and social dimensions of health were defined and quantified, using seven domains and five levels (7D5L) instrument, an extended form of EuroQol (5D3L). All the seven domains of health are affected by filarial disease, with the levels of severity varying with health states. The mean severity score of ADL (25.8) was significantly higher compared to lymphoedema (10.7) and hydrocele (6.9) (P<0.05). In males, the mean score of lymphoedema (11.6) was significantly higher in comparison to hydrocele (P<0.05). The severity scores increase with the progression of filarial disease but independent of gender. The health states of LF were further classified based on the percentage of severity according to International Classification of Functioning, Disability and Health (ICF) on impairments. Lymphoedema grade 4 (oedema with skin changes) and ADL were ranked as severe. The importance of these findings is discussed in view of priority setting and evaluating the morbidity management under Global Programme for Elimination of Lymphatic Filariasis (GPELF).

Clinical case estimates of lymphatic filariasis in an endemic district of Bangladesh after a decade of mass drug administration.

BACKGROUND: Bangladesh has a high burden of lymphatic filariasis (LF) disease. This survey estimated the current number of clinical cases in a historically endemic district after a decade of mass drug administration (MDA). METHODS: A cluster survey was conducted in 30 villages of Nilphamari District. Ten households per village were randomly selected, and individuals with LF clinical conditions identified. Hydrocoele and lymphoedema (leg, arm, breast) cases were quantified and mapped, and differences by sex, age, severity of disease and episodes of acute dermatolymphangioadenitis attacks (ADLA) examined. RESULTS: From 1242 surveyed >10 years old 55 individuals (4.4%) with LF clinical conditions were identified. Males were mostly affected by hydrocoeles, and females by leg lymphoedema. Higher prevalence and more advanced stages of disease were found in older age groups. CONCLUSIONS: Overall low prevalence of severe clinical disease was found, which has positive implications for the elimination goal. Future planning of MMDP strategies will need to address the varying clinical conditions, severity of disease and impact of ADLAs affecting different sub-groups of the population. It will also be important to monitor for new cases, and examine the shift in age distribution of cases over time.

The association between microfilaraemia and disease in lymphatic filariasis.

A standard tenet in the epidemiology of lymphatic filariasis is that patent infection is negatively related to chronic disease. We examine the empirical evidence for this relation by using published data from field studies carried out in a variety of bancroftian filariasis endemic areas. Meta-analysis of the individual study results for each disease category of hydrocele in males only, lymphoedema only, and both conditions combined (total chronic disease) indicate, contrary to expectation, no evidence for a negative association between infection and disease. Indeed, the trend of the empirical evidence is towards the opposite direction, with the majority of studies showing equal propensity of disease in microfilaraemics (mf+ves) and amicrofilaraemics (mf-ves), and more studies indicating a positive rather than a negative relation. There was also a trend for more positive studies for hydrocele compared to lymphoedema. Theoretical analysis suggests that between-study differences in blood sample volumes are unlikely to confound this finding. Analysis of between-study heterogeneity suggests that variations in the local incidence or prevalence of infection rather than unique geographical, including vector, differences might underlie the observed between-study variability in the microfilaraemia-disease association. These results are discussed in terms of dynamic explanations for infection-disease relations in lymphatic filariasis.

Polymerase chain reaction-based technique for the detection of Wuchereria bancrofti in human blood samples, hydrocele fluid, and mosquito vectors.

Oligonucleotide primers were designed to amplify a 490-basepair DNA fragment in the 5' end of the pWb 12 repeated DNA sequence in Wuchereria bancrofti for specific amplification of W. bancrofti DNA by the polymerase chain reaction (PCR). A single microfilaria in 100 microliter of blood or added to 1 ml of blood, a single third-stage larva in a pool of 20 uninfected mosquitoes, or 0.4 pg of W. bancrofti genomic DNA added to 100 microliter of human blood or serum can be detected by this PCR method. The parasite DNA in human blood and hydrocele samples and in mosquitoes was isolated free of any PCR inhibitors using simple purification techniques. Detection of PCR products was carried out by agarose gel electrophoresis, followed by staining with ethidium bromide and visualization under ultraviolet illumination. The results indicate that the PCR method is species-specific, rapid, and more sensitive than that of DNA probes and routine microscopy.

Loiasis: "Calabar" swellings and involvement of deep organs.

The authors report clinical and histopathologic changes in six patients with symptomatic loiasis. One patient had cutaneous swellings, three patients presented with hydrocele, one patient developed bowel obstruction, and one had generalized fatal loiasis. The first five patients had localized lesions provoked by adult worms; all were surgically removed. The sixth patient died of disseminated loiasis that included a severe loal encephalitis. The authors discuss the mechanism of "Calabar" swellings, the reaction to adult Loa loa worms and loal encephalitis.

Sensitivity and specificity of ultrasound detection and risk factors for filarial-associated hydroceles.

To better understand risk factors for hydrocele as a consequence of Wuchereria bancrofti infection, 342 men more than 15 years of age in an endemic area in Papua New Guinea were evaluated. Thirty-four subjects (9.9%) had hydrocele by physical examination. Ultrasound examination detected hydroceles in 57 men (16.7%). Compared with ultrasonography, the sensitivity of physical examination was 44.3%, the specificity was 98.2%, and the positive predictive value was 73.5%. Hydrocele was independently associated with age (odds ratio [OR] = 3.3, P < 0.01) and intensity of infection as determined by filarial antigenemia (OR = 2.3, P = 0.07). Dilation of spermatic cord lymphatics detectable by ultrasound did not correlate with hydrocele, but was associated with the presence of infection. These observations suggest that filarial pathology of the male genitalia is under-reported when evaluated by physical examination alone and that duration and intensity of infection are risk factors for hydrocele.

Rapid assessment for lymphatic filariasis in central Nigeria: a comparison of the immunochromatographic card test and hydrocele rates in an area of high endemicity.

The rapid immunochromatographic card test (ICT) for Wuchereria bancrofti circulating filarial antigen is being used to map areas endemic for lymphatic filariasis. However, the ICT is expensive; thus, surveys based on this test must be relatively limited. Our study was conducted to determine if village-based hydrocele surveys could be used to supplement the ICT surveys in the mapping activities. We compared in 144 Nigerian villages the two assessment methods, ICT and examination for clinical hydrocele, in random samples of 30 adults selected using a procedure that obtained 15 younger males (reported age = 16-39 years old) and 15 older males (> or = 40 years), based on the assumption that hydrocele rates may be more prevalent in older age groups. The men were asked if they had scrotal swelling, then examined and tested by the ICT. We found a weakly positive correlation between village prevalence determined by the ICT and hydrocele (r = 0.041, P < 0.001). Only villages with hydrocele rates of 20% or greater were also consistently classified as having endemic filariasis by the ICT. There was no correlation between an individual's ICT positivity and clinical presence of hydrocele, and questioning about scrotal swelling was not predictive for presence of hydrocele. More research is needed to determine if community level hydrocele prevalence surveys can offer an economical and broadly applicable supplement to the ICT for determining the endemicity of filariasis.

The use of grid sampling methodology for rapid assessment of the distribution of bancroftian filariasis.

The recent World Health Assembly Resolution to eliminate lymphatic filariasis as a public health problem once more brings to the fore the need for reliable data for the effective planning of disease control programmes. Most countries do not have data on the distribution of lymphatic filariasis and are therefore not in the position to initiate control programmes based on sound baseline data. We tested in Ghana in 1998-99 a method for the Rapid Assessment of the Geographical Distribution of Bancroftian Filariasis (RAGFIL) that uses a spatial sampling grid with 50 km between sampled villages, rapid assessment surveys for filariasis prevalence in the sampled villages and spatial analysis to estimate the geographical distribution of filariasis throughout the study area. The prevalence contours obtained with the 50 x 50-km sampling grid were operationally similar to those obtained with a 25 x 25-km grid. The predicted prevalence was not statistically different from the sample survey prevalence in 57 independent villages and the 50 x 50-km grid appears adequate for rapid mapping of filariasis. For the purpose of filariasis mapping, the antigen test would seem a better diagnostic test than clinical examination for hydrocoele. We recommend that a regional approach to mapping be used because of the importance of cross-border foci as demonstrated by our findings from the north of Ghana. Application of the method will provide the minimal information required for effective planning of treatment programmes, and will facilitate estimation of the number of people to be treated. It will also help improve estimates of the number of people at risk and affected, and of the burden of disease due to lymphatic filariasis in Africa.

Prevalence of hydrocele as a rapid diagnostic index for lymphatic filariasis.

The real burden of lymphatic filariasis in most endemic areas remains unknown even thought it is a major public health problem in many tropical countries, particularly in sub-saharan African. The nocturnal periodicity of the parasite requires parasitological examinations to be done at night. The aim of this study was to develop and validate rapid epidemiological assessment tools for the community diagnosis of lymphatic filariasis, that may be used in the future to determine the distribution of the disease and identify high risk communities in Ghana. Twenty communities with varying endemicity of filariasis were sampled from 3 endemic districts. Community members were selected for the study using a modified Expanded Programme for Immunization (EPI) cluster sampling technique. The prevalence of hydrocele was high (range 4.5-40.75%, mean = 17.78%) and the community prevalence of microfilaraemia correlated well with that of hydrocele (r = 0.84). The findings suggest that it is possible to obtain reliable and valid estimates of the community burden of lymphatic filariasis using the prevalence of hydrocele as a diagnostic index.

A randomized, double-blind, placebo-controlled study with diethylcarbamazine for the treatment of hydrocoele in an area of Tanzania endemic for lymphatic filariasis.

Hydrocoele is common in men in Wuchereria bancrofti-endemic areas, the treatment for which is currently surgical intervention. Two community studies have recently suggested that the antifilarial drug diethylcarbamazine (DEC) may have a beneficial effect of reducing the size of hydrocoeles of filarial origin. To test this hypothesis, a double-blind, placebo-controlled study was carried out in 1998 and 1999 in an area of north-eastern Tanzania where microfilaria (mf) carrier rates and hydrocoele prevalence rates were known to be high. Ninety-eight adult male volunteers (aged > or = 15 years) with chronic hydrocoele received DEC 300 mg per day for 12 days (49 patients), or placebo (49 patients). Circumferential and ultrasonographic measurements of the scrotum, and a serum sample for measuring W. bancrofti antigen, were obtained at the onset and after 3, 6 and 12 months. Scrotal size and hydrocoele fluid volume indices were calculated. No statistically significant differences in volumetric measurements between the DEC and placebo groups were found at any of the follow-ups. Separate analyses dividing patients by antigen status, hydrocoele size or presence of thickening of the scrotal skins gave similar results. Geometric mean intensity of W. bancrofti antigen was significantly lower in the DEC group than in the placebo group (P = 0.008), indicating that lack of compliance was not a significant factor. Two months into the treatment trial, mass treatment with monthly low-dose DEC was given to the rest of the community. We conclude that DEC is not effective in reducing the size of hydrocoele of filarial origin. Interventions to replace or supplement hydrocoelectomy should be investigated.

Pathogenesis of filarial hydrocele: risk associated with intrascrotal nodules caused by death of adult Wuchereria bancrofti.

Although testicular hydrocele is the most common clinical manifestation of bancroftian filariasis, its pathogenesis is poorly understood, as is its relationship to inflammatory scrotal nodules following death of adult Wuchereria bancrofti. Between 1994 and 1998, we prospectively determined the incidence and clinical evolution of nodule-associated acute hydrocele in men attending 2 outpatient clinics in Recife, Brazil who were infected with W. bancrofti, had living adult worms detectable by ultrasound in the intrascrotal lymphatic vessels, and were scheduled for treatment with 6 mg/kg diethylcarbamazine (DEC). A total of 132 men developed 173 scrotal nodules 1-7 (mean 4.2) d after DEC treatment and another 47 developed 58 spontaneous nodules before they received DEC treatment. These 179 men with a single 'nodule event' (simultaneous development of > or =1 scrotal nodules) were followed-up by serial physical and ultrasound examinations for 18 months. Overall, 40 (22.3%) men developed acute hydrocele, 3 of whom underwent biopsy and hydrocele repair. Of the remaining 37 men, 9 (24.3%) developed chronic hydrocele and 28 had acute hydrocele resolution within 14-210 (mean 60.9) d. Rate of chronic hydrocele was similar for men who received DEC and those with spontaneous nodules. Seventeen (42.5%) men with hydrocele had multiple scrotal nodules, compared with 28 (20.1%) men who did not develop hydrocele (P= 0.007). Of 134 men with single nodules, superior paratesticular nodules were found in 56.5% and 29.7% of those with and without hydrocele, respectively (P = 0.02). Acute hydrocele occurs frequently following death of adult W. bancrofti and single episodes of scrotal nodule formation. Chronic hydrocele may develop following 5.1% of these episodes.

Filaria dance sign and subclinical hydrocoele in two east African communities with bancroftian filariasis.

During population-wide cross-sectional surveys for Wuchereria bancrofti microfilaremia, circulating antigenaemia, and clinical disease in a high and a low endemicity community in East Africa in 1998, a portable ultrasound scanner was used simultaneously to examine the scrotal tissue of the male populations (n = 422 and 328, respectively) for signs of adult worms. The overall microfilaria (mf) and circulating filarial antigen (CFA) prevalences in the scanned males were 30.8% and 53.6% in the high and 4.3% and 19.8% in the low endemicity community, respectively. During ultrasound examination, the filaria dance sign (FDS)--indicating the presence of live adult W. bancrofti worms--was observed in 16.1% and 6.7% of the males in these communities, respectively. This examination also revealed that subclinical hydrocoele (fluid accumulation in the scrotal sac, not detected during physical examination for clinical hydrocoele) was very common, affecting 25.3% and 15.5% of the examined males in the high and low endemicity community, respectively. Both of these ultrasonographic signs started to appear around the age of puberty and were most common in adults. In the high endemicity community, the prevalence and mean intensity of mf and CFA were considerably higher in FDS-positive than in FDS-negative adult males, whereas no obvious difference in these parameters was noted between adult males with and without subclinical or the combination of clinical and subclinical hydrocoele. Associations were less clear in the low endemicity community, probably because of the low number of infected individuals. The application of ultrasonography as a tool in bancroftian filariasis epidemiological field studies thus indicated that scrotal pathology may be much more common in endemic areas than hitherto reported.

Tanzania filariasis project. Survey methodology and clinical manifestations of bancroftian filariasis.

In a Bancroftian filariasis survey on the coast of Tanzania microfilaria rates rose with age reaching 53% in the 60-69 year group followed by a slight fall above this age. The most important clinical manifestations were hydrocoele, funiculitis and elephantiasis, with hydrocoele presenting the most serious public health problem. Hydrocoele rates increased with age reaching 90% above the age of 70. The highest proportion of large hydrocoeles were also in the older age groups. A satisfactory methodology was established for the planning of future surveys leading to control.

Tanzania filariasis project: studies on microfilaraemia and selected clinical manifestations of Bancroftian filariasis.

In a total of 1977 males aged 5 years and over examined in 21 cluster samples on the coast of Tanzania, the overall rate for microfilariae of Wuchereria bancrofti was 32%. Hydrocoele and elephantiasis rates were 39% and 3%, respectively. The rates and severity of these 2 clinical manifestations increased in the older age groups. Both the microfilarial density and prevalence increased rapidly in the early age groups, followed by a levelling off and then a slight fall in old age. There was no association between microfilarial densities or rates and the overall prevalence of hydrocoele, but a negative association was demonstrated between microfilaraemia and hydrocoeles and elephantiasis. A comparison between the length of residence in an endemic area and the microfilarial and clinical sign rates showed evidence for the long incubation period for W. bancrofti and for the slow development of hydrocoeles and elephantiasis.

[A case of human dirofilariasis (D. repens) of the spermatic cord]. / Un caso di dirofilariasi umana (D. répens) del funicolo spermatico.

A 52 year old man, living in the province of Trapani (Sicily), presented with right hydrocele and slight orchialgia. The patient underwent epididymectomy and resection of T. vaginalis. The "tunica" was involved by a granulomatous process, containing a parasite of genus Dirofilaria (D. repens). Dirofilaria repens is a filarial nematode. Dogs, foxes and cats are the definitive hosts and principal reservoirs of the parasite. In humans the parasite dies before reaching sexual maturity and the result is an inconspicuous granulomatous reaction in the subcutaneous tissue. S. Pampiglione et al. (Cattedra di Parassitologia Veterinaria dell'Università di Bologna-Italy) reported from 1971 more than 30 cases of human Dirofilariasis in Italy, suggesting that the parasite is able to migrate from the inoculation site to other districts (lung, eye etc.). The case is exceptional for the localization of the parasite (never reported) and can contribute to a better knowledge of the disease.