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Objectives: To investigate the repercussions of the COVID-19 pandemic on lymphedema patients from an endemic area of lymphatic filariasis. Methods: The study descriptive compared sociodemographic and clinical aspects, risk of falling and quality of life, prior and during the COVID-19 pandemic in 28 lymphedema patients, older than 18 years old and under investigation of filarial infection. For the evaluation of functional mobility, the Time Up and Go test and The Medical Outcome Study Short Form-36 Health for quality of life, was used. Results: An increase in interdigital and dermal lesions, a higher frequency of acute dermatolymphangioadenitis crises and risk of falling, worsening of quality of life in the domains of physical functioning, general health, vitality, and mental health during the pandemic was observed. Conclusion: Our findings of clinical worsening and quality of life of patients during the COVID-19 pandemic indicate the need to reinforce the goal of the Lymphatic Filariasis Program regarding the follow-up of these patients in the actions of the Global Program for the Elimination of Lymphatic Filariasis, due to the discontinuity in the care during the pandemic., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Aquino, Aguiar-Santos, Rocha, Coutinho, Nascimento, Moretti, Silva, Lima, Bonfim and Medeiros.)

Genital filariasis is an uncommon infectious entity in the western world. It has characteristic clinical features and a well-recognized endemic area that causes typical histological alterations. We report a case of a 32-year-old woman, a native of Mozambique, who presented with vulvar elephantiasis as a pendulous tumor with a maximum diameter of 15cm. A large part of the genital mass was resected. Microscopically, hyperkeratosis with irregular acanthosis, a notable thickening of dermis with dense fibrosis and inflammatory clusters of patchy distribution, mostly made up of plasma cells, was seen. Since the parasite was not observed, an exclusion diagnosis was made, as frequently happens with this lesion., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2-positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.

Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and β-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Introduction: The World Health Organization (WHO) recommends Transmission Assessment Surveys (TAS) to determine when an evaluation unit (EU) (a designated population survey area) has achieved elimination of transmission of the vector-borne macroparasitic disease Lymphatic Filariasis (LF). These determinations are based on combining data from multiple survey units within an EU; it is unclear how underlying cluster-level variation influences the outcome of the TAS at EU level. We simulate LF infection distribution in an EU and compare three methods for assessing whether LF elimination has occurred based on currently recommended decision thresholds and sampling methods., Methods: We simulate an EU divided into clusters of varying size and disease prevalence. We produce 1000 samples according to LF TAS examples and WHO guidelines and compare three decision-making approaches: lot quality assurance sampling (LQAS) (recommended by WHO), one-sided interval estimate (CI), and n th order statistic (MAX). Summary statistics demonstrating the "pass" rate for the EU under different disease transmission conditions are generated using a versatile SAS® macro., Results: As the prevalence of LF decreases, the LQAS and CI approaches produce increased likelihood of a pass outcome for an EU while some cluster units may still have a high likelihood of transmission. The MAX provides an alternative that increases the likelihood of determining a pass only once the whole area has a low likelihood of transmission. LQAS and CI approaches designed to estimate the LF prevalence in the EU miss hotspots that will continue to transmit infection while the MAX approach focuses on identifying clusters with high risk of transmission., Conclusions: The current TAS methodology has a flaw that may result in false predictions of LF transmission interruption throughout an EU. Modifying the TAS methodology to address results from extreme clusters rather than being based on mean prevalence over an EU will result in greater success for global elimination of LF., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Brugia malayi is a lymphatic nematode that accounts for approximately 10% of lymphatic filariasis cases worldwide. It is endemic in several countries in South and Southeast Asia. In Thailand, B . malayi is endemic in the southern region. The extralymphatic presentation of B . malayi is rare. Here, we report the case of a woman residing in the central region of Thailand who presented with an erythematous periorbital nodule at the left medial canthal area caused by lymphatic filaria. A viable sexually mature filarial adult was removed from the lesion. The nematode species was identified as B. malayi by histology staining and DNA sequencing of the partial mitochondrial 12S ribosomal RNA (rRNA) gene. As far as we know, this is the first case report of B . malayi presenting with a periorbital nodule that has occurred in a disease non-endemic area of Thailand with possibly a zoonotic origin.

Objective: To understand the current status of chronic filariasis patients in Huai'an City, so as to provide insights into the future care of chronic filariasis patients., Methods: According to the data pertaining to the historically registered chronic filariasis patients in Huai 'an City, each case was followed up and the baseline data of chronic filariasis patients were captured using questionnaire survey. The demographic and clinical features of the patients, and the distribution and coverage of the care sites were analyzed., Results: There were still 616 chronic filariasis patients in Huai'an City, including 229 men (37.2%) and 387 women (62.8%), and 93.2% were aged 60 years and older. The chronic filariasis patients were found across the 8 counties (districts) across the city, and the cases were predominantly detected in Lianshui (40.3%), Huaiyin (30.8%) and Yuyi (8.0%). There were 49.0% of the patients with lymphedema or elephantiasis alone, 10.2% with chyluria alone, 1.0% with hydrocele of tunica vaginalis alone, 2.4% with lymphatic inflammation or lymphadenitis alone, and 37.3% with two or more types of symptoms, respectively, and all cases with lymphedema or elephantiasis alone had the sites of edema in the lower limbs, with over 90% at stages I to III. Currently, there are 81 care sites in the city covering 567 patients. The mean number of care activities was 3.2 times in 2018, and the mean cumulative duration of caring activities was 18.4 years in the care sites., Conclusions: Although the number of chronic filariasis patients has remarkably decreased, the number remains high in Jiangsu Province, and the cases are characterized by high age and long course of disease. Further caring activities are required to improve the quality of life in chronic filariasis patients.

Background: Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation., Methodology/principal Findings: Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DRposCD38pos CD4 T cells and effector memory cells CD4 T cells (CD45ROposCD27neg) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections., Conclusions/significance: W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection., Competing Interests: The authors have declared that no competing interests exist.

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Culex quinquefasciatus is a vector of lymphatic filariasis and vector control strategies normally involve the use of synthetic insecticides targeted against them. Extensive and uncontrolled use of these synthetic insecticides has led to the development of insecticide resistance in the mosquito vectors. In this context, to study the resistance status of Cx. quinquefasciatus, field populations were collected from three districts of Northern part of West Bengal and tested against insecticides (5% malathion, 0.05% deltamethrin, 0.05% lambdacyhalothrin,0.75% permethrin, 0.1% propoxur, 4% DDT and Temephos). Qualitative and quantitative enzyme assay was also conducted in order to find the role of detoxifying enzymes behind the development of insecticide resistance. This study revealed the presence of widespread resistance amongst the field populations of Cx. quinquefasciatus throughout the studied regions. Moreover, the result of native PAGE and biochemical enzyme assay may be linked to some extent in the involvement of the detoxifying enzymes in conferring resistance against insecticides in most of the tested Cx. quinquefasciatus populations. The present study involving the survey of resistance status may be of immense help during the implementation of vector control strategies throughout this region., Competing Interests: The authors have declared that no competing interests exist.

Background: Lymphatic filariasis (LF) is a mosquito-borne parasitic disease and a major cause of disability worldwide. To effectively plan morbidity management programmes, it is important to estimate disease burden and evaluate the needs of patients. This study aimed to estimate patient numbers and characterise the physical, social and economic impact of LF in in rural Nigeria., Methods: This is a matched cross-sectional study which identified lymphedema and hydrocele patients with the help of district health officers and community-directed distributors of mass drug administration programmes. A total of 52 cases were identified and matched to 52 apparently disease-free controls, selected from the same communities and matched by age and sex. Questionnaires and narrative interviews were used to characterise the physical, social and economic impact of lymphedema and hydrocele., Results: Forty-eight cases with various stages of lower limb lymphedema, and 4 with hydrocele were identified. 40% of all cases reported feeling stigma and were 36 times (95% CI: 5.18-1564.69) more likely to avoid forms of social participation. Although most cases engaged in some form of income-generating activity, these were low paid employment, and on average cases spent significantly less time than controls working. The economic effects of lower income were exacerbated by increased healthcare spending, as cases were 86 times (95% CI: 17.48-874.90) more likely to spend over US $125 on their last healthcare payment., Conclusion: This study highlights the importance of patient-search as a means of estimating the burden of LF morbidity in rural settings. Findings from this work also confirm that LF causes considerable psychosocial and economic suffering, all of which adversely affect the mental health of patients. It is therefore important to incorporate mental health care as a major component of morbidity management programmes.

Lymphedema has always been a neglected global health care problem. A central requirement for the development of any chronic disease is the clear use of public health definitions that can be used internationally to define populations. The term "lymphedema" has historically been defined as either primary, resulting from failure of lymphatic development, or secondary, following damage to the lymphatics (e.g., cancer treatment, injury, or filariasis). Attempts to integrate causes of edema arising from damage to the venous system or the effects of gravity, immobility, and systemic disease have rarely been integrated. More recently, the prominent role of the lymphatics in tissue fluid homeostasis in all forms of chronic edema has been recognized. These advances led to the development of the term: "Chronic edema: a broad term used to describe edema, which has been present for more than three months." It can be considered an umbrella term that includes not only conventional "lymphedema" but also chronic swelling, which may have a more complex cause. This definition has been adapted in the international epidemiology study (LIMPRINT) that identified people throughout the health and social care systems in participating countries. Clearer definitions will allow for examination of this important public health problem that is likely to escalate given the projections of an aging population with multiple comorbidities. It will be possible to define both the hidden mortality and morbidity associated with complications, such as cellulitis and the impact on health-related quality of life. This evidence is urgently required to lobby for increased resource and effective health care in an increasingly competitive health care arena in which more established conditions have greater priority and funding.

The acronym Limprint stands for Lymphedema IMpact and PRevalence INTernational and was run under the auspices of the International Lymphedema Framework (ILF), a charity dedicated to improving provision of care globally. The primary aim was to identify the number of people with chronic edema (chronic edema present for >3 months and due to a range of underlying etiologies and associated risk factors) within diverse health services in nine participating countries and to determine its impact using validated methods. An international protocol and sampling framework, online data capture system, and standard operating procedures were adopted. An international consensus was used to create a core data tool that covered 13 domains. Specialist data on demographics and disability, details of swelling, wounds, cancer, and health-related quality of life were also available for sites. The study protocol was designed to allow flexibility in the types of studies undertaken within complex health care systems. All cases were confirmed using the modified pitting test. Sensitivity and specificity for this method were determined in Japanese and European populations. Following confirmation of a chronic edema case, Lymphologists defined whether it was a primary of a secondary form. The study was designed to provide robust evidence that chronic edema is an important and unrecognized public health problem in health services with significant morbidity. Without evidence of the size and complexity, it will remain considered a rare phenomenon and people affected will be denied access to appropriate treatment that would allow them to have fulfilled and productive lives.

Objectives: This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar., Methods: Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015., Results: A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant., Conclusion: This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema., (© 2019 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Mild to moderate adverse events (AEs) are common after treatment of lymphatic filariasis (LF) and pose a major challenge for the global LF elimination program. We studied changes in cytokine levels and filarial worm components in plasma of subjects with and without AEs following treatment of LF., Methods: Participants (n = 24) were hospitalized and monitored for AEs following treatment. Cytokines (27), filarial DNA, circulating filarial antigen (CFA), and immune complexes were measured in plasma samples collected before and after treatment., Results: Levels for 16 cytokines increased after treatment in individuals with moderate AEs compared to individuals with no and/or mild AEs. These included 3 major proinflammatory cytokines (interleukin 6, tumor necrosis factor α, and interleukin 1β). Eotaxin-1 levels were elevated at baseline in individuals who developed moderate AEs after treatment; thus, eotaxin-1 is a potential biomarker for AE risk. CFA and filarial DNA levels increased more in individuals with moderate AEs after treatment than in people with no/mild AEs., Conclusions: Increases in cytokine, filarial DNA, and CFA levels were associated with development of AEs following treatment of LF. Improved understanding of the pathogenesis of AEs may lead to improved methods for their prevention or management that could increase compliance in elimination programs., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: The underlying problem in lymphatic filariasis is irreversible swelling of the limbs (lymphoedema), which is a unique feature of lymphatic insufficiency. It is still unclear whether the natural ability of lymphatics to form functional lymphatic vasculature is achieved or attenuated in the lymphoedemal pathology. Clinical studies have clearly shown that circulating lymphatic progenitors (CLPs), a subset of bone marrow-derived mononuclear cells (PBMCs), contribute to post-natal lymph vasculogenesis. CLP-based revascularisation could be a promising strategy to bypass the endothelial disruption and damage incurred by the filarial parasites. Thus our aim was to compare and characterise the functional prowess of PBMCs in physiological and lymphoedemal pathology., Methods: PBMCs were isolated from venous blood sample from drug-naive endemic normals (EN) and drug-deprived filarial lymphoedema (FL) individuals using density gradient centrifugation. Adhesion, transwell migration and in vitro matrigel assays were employed to characterise the lymphvasculogenic potential of PBMCs. CLPs were phenotypically characterised using flow cytometry; expression levels of lymphatic markers and inflammatory cytokines were quantified using qRT-PCR and ELISA, respectively., Results: PBMCs from FL group display poor adherence to fibronectin (P = 0.040), reduced migration towards SDF-1α (P = 0.035), impaired tubular network (P = 0.004) and branching point (P = 0.048) formation. The PBMC mRNA expression of VEGFR3 (P = 0.039) and podoplanin (P = 0.050) was elevated, whereas integrin α9 (P = 0.046) was inhibited in FL individuals; additionally, the surface expression of CD34 (P = 0.048) was significantly reduced in the FL group compared to the EN group., Conclusion: PBMCs from filarial lymphoedema show defective and dysregulated lymphvasculogenic function compared to endemic normals., (© 2017 John Wiley & Sons Ltd.)

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.

Setaria digitata is a filarial parasite that causes fatal cerebrospinal nematodiasis in goats, sheep and horses, resulting in substantial economic losses in animal husbandry in the tropics. Due to its close resemblance to Wuchereria bancrofti, this nematode is also frequently used as a model organism to study human lymphatic filariasis. This review highlights numerous insights into the morphological, histological, biochemical, immunological and genetic aspects of S. digitata that have broadened our understanding towards the control and eradication of filarial diseases.

Lymphatic filariasis (LF) caused by the nematode Wuchereria bancrofti is a major public health concern in endemic communities worldwide. Among tropical diseases it is second to malaria in terms of disability adjusted life years. The Nigerian LF elimination programme has been slated for 2015. Currently, there is paucity of published data on the problem in rural Ebonyi State. This survey was conducted in six rural communities of southwestern Ebonyi State to assess its prevalence among the population and provide baseline data for incorporation into the national LF elimination programme. Immunochromatographic card test (ICT) for detecting circulating filarial antigen (CFA) using whole blood and overt clinical manifestations (lymphoedema and hydrocoele) were used as epidemiological tools. All the studied communities were endemic for active bancroftian filariasis. Of the 600 randomly selected subjects aged ≥10 years, an overall prevalence of 23.50% was established (range, 17.00 - 30.00%). Overall, the antigenaemic prevalence was similar; there was a trend of slightly higher prevalence in males (24.34%) than females (22.39%). The between-gender prevalence difference was not statistically significant (χ² = 8.16, df = 1, p = 0.05) based on CFA positivity. Antigenaemia prevalence was age-dependent, increased exponentially and peaked at 20.57% in subjects in the 40-49 years age category. Lymphoedema and hydrocoele attributable to W. bancrofti were observed in 4.05% of subjects examined. Generally, hydrocoele was observed in 1.69% males, whereas lymphoedema was presented by 2.36% (1.35% females; 1.01% males) of studied population. None of the male subjects had both the two clinical features. Results of this study showed that W. bancrofti infection is widespread in southwestern Ebonyi State, Nigeria, and is a major health issue. There is a need for mass mobilization, mass education and community involvement in sustained intervention programme toward lymphatic filariasis elimination.

Background: Lymphoedema and hydrocoele are the two most common clinical manifestations of lymphatic filariasis (LF). In order to effectively target morbidity management strategies, more information is rapidly needed on morbidity burden across all endemic countries. The purpose of this study was to develop and test an SMS tool (MeasureSMS) which enables trained community-based health workers to report basic information on all cases they identified., Methods: The tool was trialled in Chikwawa district, Malawi and Ahanta West district, Ghana in 2014. Salaried health surveillance assistants (HSAs) identified and reported cases in Malawi whereas volunteer community health workers (CHWs) were used in Ghana. Health workers were trained in recognising lymphoedema and hydrocoeles and submitting individual case data using MeasureSMS, after which they undertook a LF morbidity survey. After the reporting period, a random sample of reported cases was visited by a physician to verify the health workers' diagnoses. The proportion of correctly diagnosed cases i.e. the positive predictive value (PPV) was then calculated., Results: HSAs in Malawi successfully reported 256 unique cases by SMS from 107 communities (166 hydrocoele, 88 lymphoedema, 2 with both), resulting in an estimated adult prevalence of 17.7 per 10,000 and 33.0 per 10,000 for lymphoedema and hydrocoele respectively. In Ghana, despite being less experienced in using SMS, CHWs successfully reported 360 unique cases by SMS from 33 communities (169 hydrocoele, 185 lymphoedema, 6 with both), resulting in an estimated adult prevalence of 76.9 per 10,000 and 70.5 per 10,000 adults for lymphoedema and hydrocoele respectively. The verification exercise resulted in a PPV for lymphoedema and hydrocoele diagnosis of 90 % (n = 42, 95 % CI 76.5 - 96.9) and 92 % (n = 49, 95 % CI 79.5 - 97.4) in Malawi and 94 % (n = 34, 95 % CI 78.9 %-99.0 %) and 47 % (n = 59, 35.1 %-61.7 %) in Ghana, indicating that non-invasive methods for diagnosing hydrocoeles needed to be further emphasised., Conclusions: The study concludes that given the appropriate education and tools, community-based health workers are exceptionally well-placed to participate in quantifying LF morbidity burden, and other NTDs with observable symptoms. This concept has the potential to enable national programmes to more effectively monitor their community impact in an efficient, timely and cost-effective way.

Helminths induce strong regulatory and T helper 2-type responses, whereby antibody-derived host protection and regulation are essential components. Lymphatic filariasis is an immune-mediated spectral disease that manifests as two main clinical outcomes: chronic pathology or asymptomatic infection. These outcomes depend on a multitude of factors, including parasite-induced immunoregulation and host genetic background; antibody responses contribute to this outcome. N-glycosylation of the Fc region of antibodies is a post-translational modification required for the structure and molecular function, influencing host inflammatory and regulatory responses. Altered IgG glycosylation correlates with disease, whereby decreased galactosylation is associated with inflammation while increased sialylation is associated with anti-inflammatory responses. We purified N-linked glycans from the Fc region of total IgG from Wuchereria bancrofti-infected patients characterizing the two clinical manifestations (chronic pathology and asymptomatic infection) and compared them to infection-free endemic normals. Using capillary electrophoresis, we found that there was no difference in galactosylation of total IgG between the three groups; however, asymptomatically infected patients had significantly lower levels of disialylated IgG compared to endemic normals and patients with pathology. These data suggest that while galactosylation does not contribute to disease outcome, sialylation may be involved in asymptomatic infection., (© 2014 John Wiley & Sons Ltd.)

Lymphatic filarial disease is known to be associated with elevated Th1 responses and normal or diminished Th2 responses to parasite-specific antigens. The roles of Th17 cells and the recently described Th22 cells have not been examined in detail in either filarial infection itself or in filarial disease (e.g., lymphedema and elephantiasis). To explore the roles of Th17 and Th22 cells and their subsets, we examined the frequencies of these cells in individuals with filarial lymphedema (chronic pathology [CP]), in clinically asymptomatic infected (INF) individuals, and in uninfected (UN) individuals ex vivo and in response to parasite and nonparasite antigens. Those with disease (CP) had significantly expanded frequencies of Th17 and Th22 cells, compared with either INF or UN individuals, at baseline (ex vivo) and in response to parasite antigens. This antigen-driven expansion of Th17 and Th22 cells was dependent on interleukin 1 (IL-1), IL-23, and, to lesser extent, transforming growth factor β (TGF-β), as blockade of any of these cytokines resulted in significantly diminished frequencies of Th17 and Th22 cells. Our findings, therefore, suggest that filarial parasite-driven expansion of Th17 and Th22 cells is associated with the pathogenesis of filarial infections and disease., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

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

We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone with active filarial infection and penile edema. The genital edema with onset at 6 months of age may have been due to a congenital abnormality in lymphatic drainage. Other possible causes of childhood lymphedema, including Milroy's disease, are discussed., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Lymphatic filariasis caused by Wuchereria bancrofti is a serious public health problem in rural communities of Nigeria. The study assessed the prevalence of lymphatic filariasis and associated clinical morbidities in Ado-Odo Ota Local Government Area of Ogun State. Microscopic examination of thick blood smears of 500 participants of both sexes and age ranging from 1 to 79 years was conducted. Visual observations of clinical manifestations of chronic infection were also conducted. The overall prevalence and intensity of infection were 21% and 21.4 mf/mL of blood respectively. Microfilaraemic prevalence was significantly higher in males (27.1%) than in females (16%) (P < 0.001). However, intensity of infection was not gender and age dependent (P > 0.05). The overall prevalence of all clinical manifestations of infection due to W. bancrofti is 15% with hydrocele, limb and breast elephantiasis constituting 16.9%, 4.6% and 5.1% of the total population respectively. Prevalence of hydrocele and limb elephantiasis was significantly higher in the older age groups (P < 0.05). Occurrence of elephantiasis of the breast in women however was not associated with age (P > 0.05). Integrated approach through chemotherapy and vector control is therefore advocated to reduce morbidity due to infection in this study area., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during 1995-2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P ≤ 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P ≤ 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.

Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas - where most LF occurs - do not easily comply with human organization and behaviour in urban areas, and partly because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites with varying distance from the city centre were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Although there was evidence of considerable reduction in infection and transmission, there was still LF in the city, with mf and CFA prevalences well above the cut-off levels for stopping MDA. In this respect, the LF situation resembled that seen in nearby rural areas outside the city. The study emphasizes the importance of motivating the urban individuals to engage and comply with the full range of LF intervention measures (MDAs, use of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources for morbidity management, to ensure true elimination of LF as a public health problem., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Past case reports and recent data from LF mapping surveys indicate that LF occurs in Zambia, but no studies have been carried out to document its epidemiology and health implications. The present study assessed infection, disease, transmission and human perception aspects of LF in an endemic area of Luangwa District, South-East Zambia, as a background for planning and implementation of control., Methods: Two neighbouring rural communities were registered and a questionnaire survey undertaken. Clinical examination, and sampling of blood for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 antigen (marker of exposure to transmission), were carried out during the daytime. Blood from CFA positive individuals was examined for microfilariae (mf) at night. Vector surveys were carried out in selected households, using light traps., Results: 985 individuals aged ≥ 1 year were registered. The CFA prevalence increased with age from 1.2% in age group 1-14 years to 20.6% in age group 50+ years (overall 8.6%). Wuchereria bancrofti mf were identified in 10.9% of CFA positive individuals (corresponding to a community prevalence of 0.9%). Prevalence and intensity of Bm14 antibodies were much higher in individuals ≥ 30 years than in younger individuals (57.2 vs. 19.3%; 0.594 vs. 0.241 OD-values). Elephantiasis and hydrocele were well known clinical manifestations in the area, but only one case of hydrocele was detected in the study population. Identified potential vectors were Anopheles funestus and An. gambiae., Conclusion: The study confirmed that LF was endemic in the study communities, but infection and disease prevalence was low. Several indications, including a marked recent decline in CFA prevalence, suggest that transmission in the area is on the decrease, perhaps because of intensive application of malaria control measures targeting the Anopheles vectors. It is recommended that mass drug administration is initiated to accelerate this positive trend of decline in LF transmission in the area.

Lymphatic filariasis, one of the most debilitating diseases associated with the lymphatic system, affects over a hundred million people worldwide and manifests itself in a variety of severe clinical pathologies. The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system in maintenance of body fluid balance and physiological interstitial fluid transport. The resultant contractile dysfunction of the lymphatics causes fluid accumulation and lymphedema, one of the major pathologies associated with filarial infection. In this review, we take a closer look at the contractile mechanisms of the lymphatics, its altered functions, and remodeling during an inflammatory state and how it relates to the severe pathogenesis underlying a filarial infection. We further elaborate on the complex host-parasite interactions, and molecular mechanisms contributing to the disease pathogenesis. The overall emphasis is on elucidating some of the emerging concepts and new directions that aim to harness the process of lymphangiogenesis or enhance contractility in a dysfunctional lymphatics, thereby restoring the fluid imbalance and mitigating the pathological conditions of lymphatic filariasis., (© 2012 John Wiley & Sons Ltd.)

Filariasis is prevalent in tropical and subtropical areas and is endemic in regions of India. Lymphatic filariasis in India is caused mainly by two species of nematodes: Wuchereria bancrofti and Brugia malayi, which invade the human lymphatic system. We report two cases of superficial cystic lesions of the upper limb revealed on fine needle aspiration (FNA) to be clinically unsuspected filariasis. Despite similar aetiologies, both cases revealed variations in aspirate nature, smear morphology and peripheral blood findings. FNA provides definitive diagnosis and is an important tool for diagnosing soft tissue swellings owing to filariasis.

Filariasis is a common public health problem in Asian countries. In this report, the authors have described detection of microfilaria in the cytological specimen of adrenal lymphoma. To the best of our knowledge, this is the first reported case in the literature where microfilaria was seen in an adrenal gland involved by lymphoma. The literature is briefly reviewed.

Background: In order to initiate a disease elimination programme for lymphatic filariasis based on mass drug administration, a proper understanding of the geographical distribution and degree of risk is essential., Methods: An investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out among 785 people in four communities of Yakurr Local Government Area of Cross River State, Nigeria between March and August, 2009. Finger prick blood smear samples collected from the subjects were examined for W. bancrofti using standard parasitological protocol. The subjects were also screened for clinical manifestations of lymphatic filariasis., Results: Of the 785 persons examined, 48 (6.1%) were positive for microfilariae in their thick blood smear. There was a significant difference in the prevalence of lymphatic filariasis among the various age groups (P < 0.01) although peak prevalence occurred between 41-60 years. There was no significant difference in prevalence and density with respect to sex (P > 0.05). The overall mean microfilarial density of the infected individuals was 5.6 mf/50 μl. There was a significant variation (P < 0.01) in mean microfilarial density within the communities, ranging from 4.7 to 6.4 mf/50 μl. The only clinical sign found in the study area was lymphoedema of the leg recording 2 (0.3%) prevalence., Conclusions: The National Lymphatic Filariasis Elimination Programme should intervene by expanding the distribution of albendazole and ivermectin to all endemic areas including Yakurr Local Government Area of Cross River State, Nigeria.

Filarial lymphatic pathology is of multifactorial origin, with inflammation, lymphangiogenesis, and innate immune responses all playing important roles. The role of Toll-like receptors (TLRs) in the development of filarial pathology is well characterized. Similarly, the association of pathology with elevated levels of plasma angiogenic factors has also been documented. To examine the association between TLR function and the development of lymphangiogenesis in filarial infections, we examined TLR- and filarial antigen-induced expression and production of various angiogenic growth factors. We demonstrate that TLR ligands (specifically TLR2, -3, and -5 ligands) induce significantly increased expression/production of vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (Ang-1) in the peripheral blood mononuclear cells of individuals with lymphatic pathology (CP individuals) compared to that in cells of asymptomatic infected (INF) individuals. Similarly, filarial antigens induce significantly enhanced production of VEGF-C in CP compared with INF individuals. TLR2-mediated enhancement of angiogenic growth factor production in CP individuals was shown to be dependent on mitogen-activated protein kinase (MAPK) and NF-κB signaling, as pharmacologic inhibition of either extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, or NF-κB signaling resulted in significantly diminished production of VEGF-A and Ang-1. Our data therefore strongly suggest an important association between TLR signaling and lymphangiogenesis in the development of pathology in human lymphatic filariasis.

The objective of this work is to evaluate the usefulness of a standardized clinical classification of hydroceles in lymphatic filariasis endemic countries to guide their surgical management. 64 patients with hydroceles were operated in 2009-2010, in Level II hospitals (WHO classification), during two visits to Fiji, by the same mobile surgical team. The number of hydroceles treated was 83. We developed and evaluated a much needed clinical classification of hydroceles based on four criteria: Type (uni/bilateral); Side (left/right); Stage of enlargement of the scrotum rated from I to VI; Grade of burial of the penis rated from 0 to 4. It lead to the conclusion that 1) A Stage I or II hydrocele, associated with Grade 0 or 1 penis burial could be considered a "Simple Hydrocele". The surgical treatment is simple with no anticipated early complication. WHO Level II of health care structure seems adapted. 2) A Stage III or IV hydrocele associated with Grade 2, 3 or 4 penis burial could be considered a "Complicated Hydrocele". The operation is longer, more complicated and the possibility of occurrence of complications seems greater. A level III health care facility would be more adapted under the normal functioning of the health system. We conclude that a standardized clinical classification of hydroceles based on the Stage of enlargement of the scrotum and the Grade of burial of the penis appears to be a useful tool to guide the decision about the level of care and the surgical technique required. We use the same classification for penoscrotal lymphoedema. A decision tree is presented for the management of hydroceles in lymphatic filariasis endemic countries which could usefully complement the "Algorithm for management of scrotal swelling" proposed by WHO in 2002. An international classification system of hydroceles would also allow standardization and facilitate study design and comparisons of their results.

Background: Infection with Wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. Matrix metalloproteinases (MMPs) are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of metalloproteinases (TIMPs) are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance between MMPs and TIMPs is considered critical in mediating tissue pathology., Methods: To elucidate the role of MMPs and TIMPs in filarial pathology, we compared the plasma levels of a panel of MMPs, TIMPs, other pro-fibrotic factors, and cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection to those with clinically asymptomatic infections (INF) and in those without infection (endemic normal [EN]). Markers of pathogenesis were delineated based on comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN)., Results and Conclusion: Our data reveal that an increase in circulating levels of MMPs and TIMPs is characteristic of the filarial disease process per se and not of active infection; however, filarial disease with active infection is specifically associated with increased ratios of MMP1/TIMP4 and MMP8/TIMP4 as well as with pro-fibrotic cytokines (IL-5, IL-13 and TGF-β). Our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma MMPs and TIMPs, the balance between MMPs and TIMPs is an important factor in regulating tissue pathology during active infection.

Lymphatic filariasis (LF)-related disability affects 40 million people globally, making LF the leading cause of physical disability in the world. Despite this, there is limited research into how the impacts of LF-related disability are best measured. This article identifies the tools currently being used to measure LF-related disability and reviews their applicability against the known impacts of LF. The findings from the review show that the generic disability tools currently used by LF programs fail to measure the majority of known impacts of LF-related disability. The findings from the review support the development of an LF-specific disability measurement tool and raise doubt about the suitability of generic disability tools to assess disability related to neglected tropical diseases (NTDs) globally.

In order to guarantee the fulfillment of their complex lifecycle, adult filarial nematodes release millions of microfilariae (MF), which are taken up by mosquito vectors. The current strategy to eliminate lymphatic filariasis as a public health problem focuses upon interrupting this transmission through annual mass drug administration (MDA). It remains unclear however, how many rounds of MDA are required to achieve low enough levels of MF to cease transmission. Interestingly, with the development of further diagnostic tools a relatively neglected cohort of asymptomatic (non-lymphedema) amicrofilaremic (latent) individuals has become apparent. Indeed, epidemiological studies have suggested that there are equal numbers of patent (MF(+)) and latent individuals. Since the latter represent a roadblock for transmission, we studied differences in immune responses of infected asymptomatic male individuals (n = 159) presenting either patent (n = 92 MF(+)) or latent (n = 67 MF(-)) manifestations of Wuchereria bancrofti. These individuals were selected on the basis of MF, circulating filarial antigen in plasma and detectable worm nests. Immunological profiles of either Th1/Th17, Th2, regulatory or innate responses were determined after stimulation of freshly isolated PBMCs with either filarial-specific extract or bystander stimuli. In addition, levels of total and filarial-specific antibodies, both IgG subclasses and IgE, were ascertained from plasma. Results from these individuals were compared with those from 22 healthy volunteers from the same endemic area. Interestingly, we observed that in contrast to MF(+) patients, latent infected individuals had lower numbers of worm nests and increased adaptive immune responses including antigen-specific IL-5. These data highlight the immunosuppressive status of MF(+) individuals, regardless of age or clinical hydrocele and reveal immunological profiles associated with latency and immune-mediated suppression of parasite transmission.

Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF), making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.

Lymphatic filariasis can be associated with the development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Toll-like receptors (TLRs) are thought to play a major role in the development of filarial pathology. To elucidate the role of TLRs in the development of lymphatic pathology, we examined cytokine responses to different Toll ligands in patients with chronic lymphatic pathology (CP), infected patients with subclinical pathology (INF), and uninfected, endemic-normal (EN) individuals. TLR2, -7, and -9 ligands induced significantly elevated production of Th1 and other proinflammatory cytokines in CP patients in comparison to both INF and EN patients. TLR adaptor expression was not significantly different among the groups; however, both TLR2 and TLR9 ligands induced significantly higher levels of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinases (MAPK) as well as increased activation of NF-κB in CP individuals. Pharmacologic inhibition of both ERK1/2 and p38 MAP kinase pathways resulted in significantly diminished production of proinflammatory cytokines in CP individuals. Our data, therefore, strongly suggest an important role for TLR2- and TLR9-mediated proinflammatory cytokine induction and activation of both the MAPK and NF-κB pathways in the development of pathology in human lymphatic filariasis.

Lymphatic filariasis (LF), a common parasitic infection in tropical countries, causes lymphoedema of limbs, hydrocele and acute attacks of dermato-lymphangio-adenitis. Recent advances in diagnosis have helped to recognize that LF infection is often acquired in childhood. Newly available diagnostic techniques like sensitive antigen and antibody assays, Doppler ultrasonography and lymphoscintigraphy have helped to understand the subclinical pathology caused by this infection, which was hitherto generally believed to be irreversible. Recent studies indicate that drugs used in the mass drug administration (MDA) programme under GPELF are capable of reversing the sub-clinical lymphatic damage in children and provide benefits other than interruption of transmission. Albendazole and ivermectin used in MDA are effective against soil-transmitted helminthic infections common in children in LF endemic areas. Thus MDA had other 'beyond LF' benefits in treated children including increased appetite, weight gain, greater learning ability and concentration, better school attendance and prevention of anaemia. MDA should no longer be viewed as a measure for interrupting transmission alone. Recent findings of reversibility of early lymphatic pathology in treated children indicate that both MDA and 'foot-hygiene' measures are effective strategies in preventing and managing morbidity. Programme managers should effectively utilize this information to strengthen their advocacy efforts to achieve high and sustainable coverage in MDA.

Lymphedema related to lymphatic filariasis (LF) is a disabling condition that commonly manifests in adolescence. Fifty-three adolescents, 25 LF infected and 28 LF non-infected, in age and sex-matched groups, using the Binax ICT rapid card test for filarial antigen were recruited to the study. None of the participants had overt signs of lymphedema. Lymphedema assessment measures were used to assess lower limb tissue compressibility (tonometry), limb circumference (tape measure), intra- and extra-cellular fluid distribution (bioimpedance) and joint range of motion (goniometry). The mean tonometric measurements from the left, right, and dominant posterior thighs were significantly larger in participants with LF compared to participants who had tested negative for LF (p = 0.005, p = 0.004, and p = 0.003, respectively) indicating increased tissue compressibility in those adolescents with LF. ROC curve analysis to define optimal cut-off of the tonometry measurements indicated that at 3.5, sensitivity of this potential screening test is 100% (95%-CI = 86.3%, 100%) and specificity is 21.4% (95%-CI = 8.3%, 41.0%). It is proposed that this cut-off can be used to indicate tissue change characteristic of LF in an at-risk population of PNG adolescents. Further longitudinal research is required to establish if all those with tissue change subsequently develop lymphedema. However, thigh tonometry to identify early tissue change in LF positive adolescents may enable early intervention to minimize progression of lymphedema and prioritization of limited resources to those at greatest risk of developing lifetime morbidity.

This study was conducted on patients attending Al-Hussein University Hospital and Mansura University Hospitals. Sheets were filled out on each patient (age, residence, occupation, family similar condition, travelling, disease duration, symptoms suggesting acute dermatolymphangitis attacks, frequency and duration. They were 25 lymphoedema patients and 8 controls (17 males & 16 females) and subjected to clinical and parasitological examinations. According to residence, five patients were from Giza Govemorate (18.18%), four from Dakahlia G. (12.12%), four from Gharbia G. (12.12%), five from Menoufia G. (15.15%), four from Sharkia G. (12.12%), two cases from Kafr Elsheikh G. (6.06%) and one patient from Assiut G. (3.03%). In controls, 6 were from Al-Hussein Cairo G. (15.15%), and two cases (6.06) from Al-Abbassia. They were 48% farmers (10 male & 2 female); 4% grocers (1 male); 8% carpenters (2 male); and 40% house wife (10 female). According to lymphedema site: 3 cases (12%) were bilateral lower limbs lymphedema (2 female & 1 male), 13 cases (52%) had right lower limb lymphedema (6 female & 7 male), and 9 cases (36%) had left lower limb lymphedema (4 female & 5 male). They were 18 (72%) with below knee extension of lymphedema (10 male & 8 female) and 7 (28%) above knee extension of lymphedema (3 male & 4 female). Grade of lymphedema was one case (male) with grade II lymphedema (4%), 13 cases (52%) with grade III (7 male & 6 female) and 11 cases (44%) with grade IV (5 male & 6 female). Duration of lymphedema was one case with grade II lymphedema in a period of 3 years, 13 cases with grade III lymphedema and the durations of lymphedema for these cases were (one case with 5 years duration, 3 cases were > 6-9 years,6 cases were > 9-12 years and 3 cases were > 12 years) and 11 cases with grade IV lymphedema and duration of lymphedema for these cases were (one case with 6 years duration, 2 cases were > 6-9 years,3 cases were > 9-12 years and 5 cases were > 12 years).

Background: Chronic hydrocele is the most common manifestation of bancroftian filariasis, an endemic disease in 80 countries. In a prospective study, we evaluated the occurrence of intrascrotal lymphangiectasia, gross appearance/consistency of the testis, and the efficacy of complete excision of hydrocele sac in patients living in a bancroftian filariasis endemic area who underwent hydrocelectomy at the Center for Teaching, Research and Tertiary Referral for Bancroftian Filariasis (NEPAF)., Methodology/principal Findings: A total of 968 patients with uni- or bilateral filarial hydrocele (Group-1) and a Comparison Group (CG) of 218 patients from the same area who already had undergone hydrocele-sac-sparing hydrocelectomy elsewhere were enrolled at NEPAF. Twenty-eight patients from the Comparison Group with hydrocele recurrence were re-operated on at NEPAF and constitute Group-2. In Group-1 a total of 1,128 hydrocelectomies were performed (mean patient age of 30.3 yr and mean follow-up of 8.6 yr [range 5.3-12]). The hydrocele recurrence rates in Group-1 and in the Comparison Group (mean age of 31.5 yr) were 0.3%, and 19.3%, respectively (p<0,001). There was no hydrocele recurrence in Group-2 (mean patient age of 25.1 yr and mean follow-up of 6 yr [range 5-6.9]). Per surgically leaking or leak-prone dilated lymphatic vessels were seen in the inner or outer surface of the hydrocele sac wall or in surrounding tissue, particularly in the retrotesticular area, in 30.9% and in 46.3% of patients in Group-1 and Group-2, respectively (p = 0.081). The testicles were abnormal in shape, volume, and consistency in 203/1,128 (18%) and 10/28 (35.7%) of patients from Group-1 and Group-2, respectively (p = 0,025)., Conclusions/significance: Lymph fluid from ruptured dilated lymphatic vessels is an important component of chronic filarial hydrocele fluid that threatens the integrity of the testis in an adult population living in bancroftian filariasis endemic areas. To avoid hydrocele recurrence the authors advise complete excision of hydrocele sac and when identified, leaking or leak-prone dilated lymphatic vessels should be sutured or excised.

Background: Approximately 14 million persons living in areas endemic for lymphatic filariasis have lymphedema of the leg. Clinical studies indicate that repeated episodes of bacterial acute dermatolymphangioadenitis (ADLA) lead to progression of lymphedema and that basic lymphedema management, which emphasizes hygiene, skin care, exercise, and leg elevation, can reduce ADLA frequency. However, few studies have prospectively evaluated the effectiveness of basic lymphedema management or assessed the role of compressive bandaging for lymphedema in resource-poor settings., Methodology/principal Findings: Between 1995 and 1998, we prospectively monitored ADLA incidence and leg volume in 175 persons with lymphedema of the leg who enrolled in a lymphedema clinic in Leogane, Haiti, an area endemic for Wuchereria bancrofti. During the first phase of the study, when a major focus of the program was to reduce leg volume using compression bandages, ADLA incidence was 1.56 episodes per person-year. After March 1997, when hygiene and skin care were systematically emphasized and bandaging discouraged, ADLA incidence decreased to 0.48 episodes per person-year (P<0.0001). ADLA incidence was significantly associated with leg volume, stage of lymphedema, illiteracy, and use of compression bandages. Leg volume decreased in 78% of patients; over the entire study period, this reduction was statistically significant only for legs with stage 2 lymphedema (P = 0.01)., Conclusions/significance: Basic lymphedema management, which emphasized hygiene and self-care, was associated with a 69% reduction in ADLA incidence. Use of compression bandages in this setting was associated with an increased risk of ADLA. Basic lymphedema management is feasible and effective in resource-limited areas that are endemic for lymphatic filariasis.

Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.