Vascularized lymph node transfer from thoracodorsal axis for congenital and post filarial lymphedema of the lower limb.

Vascularized lymph node transfer is becoming a popular method to treat lymphedema. We have performed vascularized lymph node transfer for two patients, one with congenital and the other with post filarial lymphedema of the lower limb. Lymph node transfer was performed from the thoracodorsal axis. Both cases exhibited improved results in both limb circumference and quality of life measurements. J. Surg. Oncol. 2017;115:78-83. © 2016 Wiley Periodicals, Inc.

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).

Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial.

BACKGROUND: The aim of this study was to determine whether improvement of filarial lymphedema (LE) by doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity. METHODS: One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) doxycycline (200 mg/d), or (3) placebo matching doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months. RESULTS: Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks. CONCLUSIONS: Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE. Clinical Trials Registration. ISRCTN 90861344.

Lymphatic filariasis and onchocerciasis.

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health.

"Can it be that god does not remember me": a qualitative study on the psychological distress, suffering, and coping of Dominican women with chronic filarial lymphedema and elephantiasis of the leg.

The psychological states of Dominican women with chronic lymphedema and elephantiasis of the leg and the coping strategies they used to ameliorate the negative psychological effects of this condition were explored using modified precepts of grounded theory method. Qualitative data were gathered through in-depth interviewing and focus group discussions held in the Dominican Republic. Thematic results found that compounding their physical disfigurement, functional limitations, and social losses were feelings of depression, embarrassment, social isolation, and despair. Adaptive problem solving and emotion-focused coping strategies that emerged during analysis also are discussed. It is recommended that management of psychological distress should be a significant component of lymphedema management programs in developing countries.

[Disseminated cutaneous leishmaniasis secondary to lymphoedema: two cases]. / Leishmaniose cutanée disséminée sur lymphoedème: deux cas.

BACKGROUND: Dissemination of cutaneous leishmaniasis may take various forms: satellite papules, sporotrichoid nodules and widespread papulonodular lesions (disseminated cutaneous leishmaniasis). We describe a particular clinical form of dissemination in two patients with erysipelas secondary to lymphoedema. PATIENTS AND METHODS: Case 1. A 75-year-old man with diabetes consulted for erysipelas of the leg secondary to lymphoedema. The site of entry was an infected cutaneous leishmaniasis lesion. The initial outcome was favourable under intravenous penicillin G treatment. Twelve days later, some fifty papulonodular lesions appeared and were strictly limited to the erythematous erysipelas plaque. PCR screening of papulonodular lesion smears for Leishman bodies was positive. Histological examination of skin biopsy samples showed lobular panniculitis. Case 2. A 64-year-old woman with diabetes presented erysipelas in the right upper limb secondary to lymphoedema scattered with multiple erythematous, infiltrated, papular lesions in a setting of cutaneous leishmaniasis lesions. PCR analysis of smears taken from the secondary nodular lesions demonstrated the presence of leishmaniasis, while histological analysis of biopsy samples revealed panniculitis. DISCUSSION: Disseminated cutaneous leishmaniasis is characterized by the appearance of multiple (>10) pleomorphic lesions on two or more noncontiguous areas of the body. Our two patients presented certain features of disseminated cutaneous leishmaniasis. However, they were unusual in terms of the strict localisation of nodular lesions to the erysipelas plaque. This particular aspect suggests haemolymphatic dissemination of the protozoan infection from the initial lesion as a result of local factors.

Mapping the geographical distribution of podoconiosis in Cameroon using parasitological, serological, and clinical evidence to exclude other causes of lymphedema.

BACKGROUND: Podoconiosis is a non-filarial elephantiasis, which causes massive swelling of the lower legs. It was identified as a neglected tropical disease by WHO in 2011. Understanding of the geographical distribution of the disease is incomplete. As part of a global mapping of podoconiosis, this study was conducted in Cameroon to map the distribution of the disease. This mapping work will help to generate data on the geographical distribution of podoconiosis in Cameroon and contribute to the global atlas of podoconiosis. METHODS: We used a multi-stage sampling design with stratification of the country by environmental risk of podoconiosis. We sampled 76 villages from 40 health districts from the ten Regions of Cameroon. All individuals of 15-years old or older in the village were surveyed house-to-house and screened for lymphedema. A clinical algorithm was used to reliably diagnose podoconiosis, excluding filarial-associated lymphedema. Individuals with lymphoedema were tested for circulating Wuchereria bancrofti antigen and specific IgG4 using the Alere Filariasis Test Strips (FTS) test and the Standard Diagnostics (SD) BIOLINE lymphatic filariasis IgG4 test (Wb123) respectively, in addition to thick blood films. Presence of DNA specific to W. bancrofti was checked on night blood using a qPCR technique. PRINCIPAL FINDINGS: Overall, 10,178 individuals from 4,603 households participated in the study. In total, 83 individuals with lymphedema were identified. Of the 83 individuals with lymphedema, two were found to be FTS positive and all were negative using the Wb123 test. No microfilaria of W. bancrofti were found in the night blood of any individual with clinical lymphedema. None were found to be positive for W. bancrofti using qPCR. Of the two FTS positive cases, one was positive for Mansonella perstans DNA, while the other harbored Loa loa microfilaria. Overall, 52 people with podoconiosis were identified after applying the clinical algorithm. The overall prevalence of podoconiosis was found to be 0.5% (95% [confidence interval] CI; 0.4-0.7). At least one case of podoconiosis was found in every region of Cameroon except the two surveyed villages in Adamawa. Of the 40 health districts surveyed, 17 districts had no cases of podoconiosis; in 15 districts, mean prevalence was between 0.2% and 1.0%; and in the remaining eight, mean prevalence was between 1.2% and 2.7%. CONCLUSIONS: Our investigation has demonstrated low prevalence but almost nationwide distribution of podoconiosis in Cameroon. Designing a podoconiosis control program is a vital next step. A health system response to the burden of podoconiosis is important, through case surveillance and morbidity management services.

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.

Disrupted social connectedness among Dominican women with chronic filarial lymphedema.

OBJECTIVE: The objectives of this paper were to identify specific factors associated with intact or disrupted social connectedness among Dominican women with chronic filarial lymphedema and better understand the impact of disrupted connectedness on their lives. METHODS: Data were collected through 28 individual interviews and 3 focus group discussions of 28 women from filariasis-endemic areas of the Dominican Republic presenting with lymphedema of one or both legs. RESULTS: The confluence of chronic and acute stressors with severity of lymphedema lead women to rely on others for social support. Women described complications of aging, disability, reduced social networks, and inability to adhere to cultural scripts as contributing to disrupted social connectedness. CONCLUSION: Social disconnectedness appears to exacerbate the negative consequences of living with lymphedema among women. Social connectedness and cultural scripts often define a social role for women that transcend physical deformity and disability, while disrupted social connectedness contributes to social isolation, depressive symptoms, and poor health outcomes. PRACTICE IMPLICATIONS: Further behavioral research into the contribution of intact social connectedness to resiliency and coping is warranted in order to develop effective interventions for women. Identifying women with disrupted social connectedness and engaging them in behavioral interventions to enhance natural social networks and create new or enhanced social support opportunities may mitigate the negative effects of social disconnectedness and improve quality of life.

Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment.

BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

Health workers' agreement in clinical description of filarial lymphedema.

Severity of lymphedema and presence of entry lesions are risk factors for acute bacterial dermatolym-phangioadenitis (ADLA) in those with filarial lymphedema. Recurrent ADLA causes acute morbidity and progression of lymphedema severity; however, there is little work assessing the ability of health workers to reliably stage disease severity and identify risk entry lesions. This knowledge is important in initiation of management and assessing interventions. We evaluated inter-rater reliability with two independent health workers rating both legs of 17 patients using a questionnaire and the Dreyer classification of lymphedema. The health workers could reliably stage lymphedema with high agreement (RMAC weighted kappa of 0.89) and identify nail, interdigital, and other skin lesions. However, there was less consistency in identifying the clinical nature of skin lesions. This indicates that the Dreyer classification can be a replicable way to stage lymphedema and a questionnaire can deliver high observer agreement on the presence of risk lesions.

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).

Lymphoscintigraphy as a diagnostic tool in patients with lymphedema of filarial origin--an Indian study.

Lymphedema is a common clinical problem. Filariasis is the commonest cause of lymphedema in India and is a chronic debilitating disease. The purpose of this study is to highlight the role of lymphoscintigraphy in the evaluation of lymphedema. Our study population consisted of 418 patients diagnosed with filarial lymphedema of different clinical stages referred for lymphoscintigraphy of the limbs by the lymphologist at our institution. An analysis of the various studies was done to determine how lymphoscintigraphy can be useful in documentation of the diagnosis, evaluation, as a screening procedure to prevent progression, and to enhance management of filarial lymphedema.

Evaluating the Burden of Lymphedema Due to Lymphatic Filariasis in 2005 in Khurda District, Odisha State, India.

BACKGROUND: Over 1.1 billion people worldwide are at risk for lymphatic filariasis (LF), and the global burden of LF-associated lymphedema is estimated at 16 million affected people, yet country-specific estimates are poor. METHODOLOGY/PRINCIPAL FINDINGS: A house-to-house morbidity census was conducted to assess the burden and severity of lymphedema in a population of 1,298,576 persons living in the LF-endemic district of Khurda in Odisha State, India. The burden of lymphedema in Khurda is widespread geographically, and 1.3% (17,036) of the total population report lymphedema. 51.3% of the patients reporting lymphedema were female, mean age 49.4 years (1-99). Early lymphedema (Dreyer stages 1 & 2) was reported in two-thirds of the patients. Poisson regression analysis was conducted in order to determine risk factors for advanced lymphedema (Dreyer stages 4-7). Increasing age was significantly associated with advanced lymphedema, and persons 70 years and older had a prevalence three times greater than individuals ages 15-29 (aPR: 3.21, 95% CI 2.45, 4.21). The number of adenolymphangitis (ADL) episodes reported in the previous year was also significantly associated with advanced lymphedema (aPR 4.65, 95% CI 2.97-7.30). This analysis is one of the first to look at potential risk factors for advanced lymphedema using morbidity census data from an entire district in Odisha State, India. SIGNIFICANCE: These data highlight the magnitude of lymphedema in LF-endemic areas and emphasize the need to develop robust estimates of numbers of individuals with lymphedema in order to identify the extent of lymphedema management services needed in these regions.

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.

The pathogenesis of filarial lymphedema: is it the worm or is it the host?

Our understanding of the pathogenesis of filarial lymphedema, although evolving, is still limited. Recurrent bacterial infections play a major role in the progression of lymphedema to elephantiasis, but the host and parasite factors that trigger disease development are not known. Field studies in Haiti show that lymphedema and host responses to parasite antigens cluster in families, consistent with the hypothesis that host genes influence lymphedema susceptibility. The recent recognition that filarial parasites harbor the endosymbiotic bacteria, Wolbachia, also raises questions about the potential contribution of the inflammatory response to Wolbachia antigens to lymphedema development. In this review, we discuss potential risk factors for lymphedema and try to integrate these in a model of pathogenesis.

Episodic adenolymphangitis and lymphoedema in patients with bancroftian filariasis.

In order to explore the relationship between acute and chronic disease, age-specific data on the frequency and duration of episodic adenolymphangitis (ADL) in patients with 3 defined grades of lymphoedema in bancroftian filariasis were examined. The age distribution of grades I and II exhibited a convex age profile, but that of grade III showed a monotonic increase. The mean duration of oedema increased with its grade (grade I, 0.3 years; grade III, 9.9 years). The mean number of ADL episodes in the previous year for all cases was 4.2 and it increased with grade (grade I, 2.4 and grade III, 6.2). The mean duration of each ADL episode for all cases was 4.1 d and it was independent of grade and age. The mean period lost to ADL episodes in the previous year was 17.5 d; it increased from 9.4 d with grade I to 28.5 d with grade III. The results imply that there is a dynamic progression through the grades of lymphoedema and that the frequency of ADL episodes is positively associated with this progression. However, the study design could not separate cause from effect.

Induction of lymphatic lesions by Brugia pahangi in jirds with large and small preexisting homologous intraperitoneal infections.

The effect of intraperitoneal (i.p.) infections induced by inoculations of 30 or 150 Brugia pahangi third-stage larvae (L3) on the development of infections and lymphatic lesions induced by subsequent homologous subcutaneous (s.c.) inoculations were compared in the present study. Lymphatic lesion severity, as judged by the numbers of lymph thrombi present, and lymphatic lesion scores were significantly reduced in both groups of jirds with existing i.p. infections. The numbers of adult worms that developed, locations of these worms, and the subsequent microfilaremias did not differ significantly between groups. All jirds with i.p. infections developed similar antibody titers to crude somatic adult antigen as measured by ELISA. These levels did not change following s.c. infections. Immediate and delayed footpad swelling responses were also similar in all groups. Results of these experiments support and extend previous studies indicating that i.p. infections of B. pahangi induce a hyporesponsive state in jirds to subsequent s.c. infections without significantly affecting the subsequent parasite burden. This effect appears to be independent of the numbers of L3 inoculated i.p. prior to lymphatic-induced infection. Circulating antibody titers and footpad swelling responses to B. pahangi antigen were not reduced in jirds with the hyporesponsive lymphatic inflammatory response and do not correlate with this condition.