The Impact of the COVID-19 Pandemic on People With Lymphedema in an Endemic Area for Lymphatic Filariasis in Brazil.

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.

[Physiopathology of vulvar elephantiasis of filarial origin. A case report]. / Fisiopatología de la elefantiasis vulvar de origen filarial. A propósito de un caso.

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.

Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

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 ß-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.

Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor-mediated lymphangiogenesis.

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.

Simulating a Transmission Assessment Survey: An evaluation of current methods used in determining the elimination of the neglected tropical disease, Lymphatic Filariasis.

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 nth 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.

Case Report: Periorbital Filariasis Caused by Brugia malayi.

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.

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells.

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.

Insecticide resistance mapping in the vector of lymphatic filariasis, Culex quinquefasciatus Say from northern region of West Bengal, India.

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.

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis.

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.

The Concept of Chronic Edema-A Neglected Public Health Issue and an International Response: The LIMPRINT Study.

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 Development and Validation of the LIMPRINT Methodology.

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.

The social, physical and economic impact of lymphedema and hydrocele: a matched cross-sectional study in rural Nigeria.

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.

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

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.

OBJECTIFS: Cette étude comparative longitudinale a investigué l'effet de la chimiothérapie préventive (CP) sur les modifications tissulaires cachées associées à la filariose lymphatique (FL) chez les jeunes vivant dans une zone d'endémie pour la FL au Myanmar. MÉTHODES: La compressibilité des tissus et le liquide libre extracellulaire dans les membres inférieurs des personnes âgées de 10 à 21 ans ont été mesurés par indurométrie et spectroscopie de bioimpédance (BIS). Les mesures de base ont été prises en octobre 2014, la distribution en masse de médicament (DMM) annuelle a été administrée en décembre et en mars 2015, et une CP additionnelle a été offerte aux cas positifs pour la FL qui avaient manqué la DMM. Des mesures de suivi ont été prises en février et juin 2015. RÉSULTATS: 50 cas positifs pour l'antigène et 46 témoins négatifs ont été inclus. L'administration de CP auto-déclarée était de 60,1% durant la DMM de 2014 et de 66,2% au total. Au deuxième suivi, 24 des 34 cas et 27 des 43 témoins avaient pris la CP. Des différences significatives et cliniquement pertinentes entre les groupes au départ n'ont pas été trouvées après la CP. Les modèles mixtes linéaires bayésiens ont montré un changement significatif des scores d'indurometrie aux deux mollets pour les cas positifs pour l'antigène qui prenaient une CP (mollet dominant: -0,30 [IC95%: -0,52, -0,07], p <0,05, mollet non dominant: - 0,35 [IC95%: -0,58, -0,12], p <0,01). Les changements chez les participants négatifs pour l'antigène ou ceux qui ne prenaient pas de CP n'étaient pas significatifs. CONCLUSION: Cette étude est la première tentative d'utilisation d'outils simples, conviviaux sur le terrain, pour suivre les modifications du tissu conjonctif après le traitement de personnes asymptomatiques infectées par la FL. Les résultats suggèrent que la CP seule est suffisante pour inverser les modifications lymphatiques cachées. Un suivi plus long de plus grandes cohortes est nécessaire pour confirmer ces améliorations et déterminer si elles persistent ou non. Ces résultats devraient inciter à redoubler d'efforts pour surmonter la faible couverture en CP, qui rate beaucoup de jeunes infectés, en particulier les hommes, qui ne sont pas au courant de leur statut d'infection, qui ne sont pas motivés pour prendre une CP et risquent de développer un lymphœdème. L'indurométrie et la BIS devraient être considérées dans l'évaluation du lymphoedème associé à la filariose lymphatique.

[Current status of chronic filariasis in Huai'an City].

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.

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis.

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 1ß). 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.

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.

Comparison and functional characterisation of peripheral blood mononuclear cells isolated from filarial lymphoedema and endemic normals of a South Indian population.

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.

Setaria digitata in advancing our knowledge of human lymphatic filariasis.

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.

Wuchereria bancrofti infection in rural tropical guinea savannah communities: Rapid epidemiological assessment using immunochromatographic card test and prevalence of hydrocoele.

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.