Crystal structure of dihydrofolate reductase from the filarial nematode W. bancrofti in complex with NADPH and folate.

Lymphatic filariasis is a debilitating illness with an estimated 50 million cases as of 2018. The majority of cases are caused by the parasitic worm W. bancrofti and additional cases by the worms B. malayi and B. timori. Dihydrofolate reductase (DHFR) is an established target in the treatment of cancer, bacterial, and protozoal infections and may be a potential target for drugs targeting parasitic worm infections, including filariasis. Recent studies have shown that known antifolate compounds, including methotrexate, inhibit the activity of W. bancrofti DHFR (WbDHFR). However, the absence of structural information for filarial DHFRs has limited the study of more in-depth structure-function relationships. We report the structure of WbDHFR complexed with NADPH and folate using X-ray diffraction data measured to 2.47 Å resolution. The structure of WbDHFR reveals the usual DHFR fold and is currently only the second nematode DHFR structure in the Protein Data Bank. The equilibrium dissociation constants for NADPH (90 ± 29 nM) and folate (23 ± 4 nM) were determined by equilibrium titrations. The interactions of known antifolates with WbDHFR were analyzed using molecular docking programs and molecular dynamics simulations. Antifolates with a hydrophobic core and extended linker formed favorable interactions with WbDHFR. These combined data should now facilitate the rational design of filarial DHFR inhibitors, which in turn can be used to determine whether DHFR is a viable drug target for filariasis and whether existing antifolates may be repurposed for its treatment.

Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach.

Proteases are the critical mediators of immunomodulation exerted by the filarial parasites to bypass and divert host immunity. Cystatin is a small (∼15 kDa) immunomodulatory filarial protein and known to contribute in the immunomodulation strategy by inducing anti-inflammatory response through alternative activation of macrophages. Recently, Wuchereria bancrofti cystatin has been discovered as a ligand of human toll-like receptor 4 which is key behind the cystatin-induced anti-inflammatory response in major human antigen-presenting cells. Considering the pivotal role of cystatin in the immunobiology of filariasis, cystatin could be an efficacious target for developing vaccine. Herein, we present the design and in-silico analyses of a multi-epitope-based peptide vaccine to target W. bancrofti cystatin through immune-informatics approaches. The 262 amino acid long antigen construct comprises 9 MHC-I epitopes and MHC-II epitopes linked together by GPGPG peptide alongside an adjuvant (50S ribosomal protein L7/L12) at N terminus and 6 His tags at C terminus. Molecular docking study reveals that the peptide could trigger TLR4-MD2 to induce protective innate immune responses while the induced adaptive responses were found to be mediated by IgG, IgM and Th1 mediated responses. Notably, the designed vaccine exhibits high stability and no allergenicity in-silico. Furthermore, the muti epitope-vaccine was also predicted for its RNA structure and cloned in pET30ax for further experimental validation. Taken together, this study presents a novel multi-epitope peptide vaccine for triggering efficient innate and adaptive immune responses against W. bancrofti to intervene LF through immunotherapy.

Filariasis presenting as pancytopenia in a child.

A female child hailing from South Asia, India presented with pallor, multiple petechiae and ecchymosis. Based on the clinical picture and demography, the differentials considered were pancytopenia of nutritional origin, acute leukaemia, autoimmune and infective aetiologies. After ruling these out by respective tests, a literature review was done which revealed the possibility of filariasis especially in a patient with eosinophilia which was present in our case. A repeat peripheral blood smear study with a nocturnally drawn sample revealed multiple microfilariae and a diagnosis of filariasis was made. The patient was treated with triple drug therapy of diethylcarbamazine (6 mg/kg), ivermectin (6 µg/kg) and albendazole (400 mg) administered as a single dose. Subsequent haemograms showed improved cell counts. This along with a previous handful of case reports emphasises filariasis as one of the differentials of pancytopenia and should be kept in mind while evaluating for the same, especially in the endemic areas.

Community-based trial assessing the impact of annual versus semiannual mass drug administration with ivermectin plus albendazole and praziquantel on helminth infections in northwestern Liberia.

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five rounds of semiannual MDA, respectively. Mixed effects logistic regression models showed decreases in odds of antigenemia positivity were 91 and 74% at that time in the annual and semiannual treatment zones, respectively (p < 0.001). Semiannual MDA was slightly more effective for reducing Onchocerca volvulus microfiladermia prevalence and at follow-up 3 were 74% (from 14.4 to 3.7%) and 83% (from 23.6 to 4.5%) in the annual and semiannual treatment zones, respectively. Both treatment schedules had similar beneficial effects on hookworm prevalence. Thus, annual and semiannual MDA with ivermectin and albendazole had similar beneficial impacts on LF, onchocerciasis, and STH in this setting. In contrast, MDA with praziquantel had little impact on hyperendemic Schistosoma mansoni in the study area. Results from a long-term follow-up survey showed that improvements in infection parameters were sustained by routine annual MDA provided by the Liberian Ministry of Health after our study endpoint.

In-silico evidences on filarial cystatin as a putative ligand of human TLR4.

Cystatin is a small molecular weight immunomodulatory protein of filarial parasite that plays a pivotal role in downregulating the host immune response to prolong the survival of the parasite inside the host body. Hitherto, this protein is familiar as an inhibitor of human proteases. However, growing evidences on the role of cystatin in regulating inflammatory homeostasis prompted us to investigate the molecular reasons behind the explicit anti-inflammatory trait of this protein. We have explored molecular docking and molecular dynamics simulation approaches to explore the interaction of cystatin of Wuchereria bancrofti (causative parasite of human filariasis) with human Toll-like receptors (TLRs). TLRs are the most crucial component of frontline host defence against pathogenic infections including filarial infection. Our in-silico data clearly revealed that cystatin strongly interacts with the extracellular domain of TLR4 (binding energy=-93.5 ± 10 kJ/mol) and this biophysical interaction is mediated by hydrogen bonding and hydrophobic interaction. Molecular dynamics simulation analysis revealed excellent stability of the cystatin-TLR4 complex. Taken together, our data indicated that cystatin appears to be a ligand of TLR4 and we hypothesize that cystatin-TLR4 interaction most likely to play a key role in activating the alternative activation pathways to establish an anti-inflammatory milieu. Thus, the study provokes the development of chemotherapeutics and/or vaccines for targeting the cystatin-TLR4 interaction to disrupt the pathological attributes of human lymphatic filariasis. Our findings are expected to provide a novel dimension to the existing knowledge on filarial immunopathogenesis and it will encourage the scientific communities for experimental validation of the present investigation. Communicated by Ramaswamy H. Sarma.

Investigating immunological interaction between lymphatic filariasis and COVID-19 infection: a preliminary evidence.

The foremost concerns of COVID-19 vaccines are safety and efficacy, which becomes grave in countries with a high burden of Neglected Tropical Diseases. Studies proposed helminthic infections might alleviate the efficacy of COVID-19 vaccines. We share preliminary evidence on the association between filariasis and COVID-19 infection. We collated 2 ml of blood from 174 participants residing in filariasis endemic area. To determine filarial antigen, the Og4C3 test and for COVID-19 antibodies, tests through ELISA was performed. COVID-19 antibodies were present among 74/174 (42.5%), whereas filarial antigens were detected in 24/174 (13.8%) participants. An insignificant association [OR = 0.855 (0.36-2.034)] between two was observed. Hence, people in filarial endemic regions can continue taking vaccines without worrying about their efficacy due to the helminthic load in community.

Recombinant antigens used as diagnostic tools for lymphatic filariasis.

Lymphatic filariasis (LF) is a parasitic disease caused by the worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. It is a tropical and subtropical illness that affects approximately 67 million people worldwide and that still requires better diagnostic tools to prevent its spread and enhance the effectiveness of control procedures. Traditional parasitological tests and diagnostic methods based on whole protein extracts from different worms are known for problems related to sample time collection, sensitivity, and specificity. More recently, new diagnostic tools based on immunological methods using recombinant antigens have been developed. The current review describes the several recombinant antigens used as tools for lymphatic filariasis diagnosis in antigen and antibody capture assays, highlighting their advantages and limitations as well as the main commercial tests developed based on them. The literature chronology is from 1991 to 2021. First, it describes the historical background related to the identification of relevant antigens and the generation of the recombinant polypeptides used for the LF diagnosis, also detailing features specific to each antigen. The subsequent section then discusses the use of those proteins to develop antigen and antibody capture tests to detect LF. So far, studies focusing on antibody capture assays are based on 13 different antigens with at least six commercially available tests, with five proteins further used for the development of antigen capture tests. Five antigens explored in this paper belong to the SXP/RAL-2 family (BmSXP, Bm14, WbSXP-1, Wb14, WbL), and the others are BmShp-1, Bm33, BmR1, BmVAH, WbVAH, BmALT-1, BmALT-2, and Wb123. It is expected that advances in research with these antigens will allow further development of tests combining both sensitivity and specificity with low costs, assisting the Global Program to Eliminate Lymphatic Filariasis (GPELF).

Interruption of lymphatic filariasis transmission in Manaus, a former focus of Wuchereria bancrofti in the Western Brazilian Amazon / Interrupción de la transmisión de la filariasis linfática en Manaos, anteriormente un foco de Wuchereria bancrofti en la Amazonia occidental de Brasil / Interrupção da transmissão da filariose linfática em Manaus, anteriormente um foco de Wuchereria bancrofti na parte leste da Amazônia brasileira

ABSTRACT Objective. To confirm the absence of Wuchereria bancrofti autochthonous cases in Manaus, a former focus of lymphatic filariasis in the Western Brazilian Amazon. Methods. A field survey was carried out in 2016 using immunochromatographic rapid tests (ICT card) for the detection of circulating filarial antigens in blood. The sample included a group of 3 000 schoolchildren aged 6 to 10 years enrolled in schools from different urban areas of Manaus (including the former lymphatic filariasis focus in the city) and a group of 709 adolescents and adults, between the ages of 11 and 85 years, born and raised in different areas of Manaus. Results. All of the individuals tested negative for W. bancrofti antigen. Conclusions. Although Manaus was once considered endemic, this focus no longer seems to be active for lymphatic filariasis transmission. The results of this study could support the certification by the World Health Organization of the lymphatic filariasis transmission elimination exercise in Brazil.

RESUMEN Objetivo. Confirmar la ausencia de casos autóctonos de Wuchereria bancrofti en Manaos, anteriormente un foco de filariasis linfática en la Amazonia occidental de Brasil. Métodos. En el 2016 se llevó a cabo una encuesta en el terreno con pruebas rápidas inmunocromatográficas (tiras inmunocromatográficas) para detectar antígenos filáricos circulantes en sangre. La muestra constó de un grupo de 3 000 escolares de 6 a 10 años matriculados en escuelas de diferentes zonas urbanas de Manaos (incluida la zona que anteriormente era el foco de filariasis linfática en la ciudad) y de un grupo de 709 adolescentes y adultos, de edades comprendidas entre 11 y 85 años, nacidos y criados en diferentes áreas de Manaos. Resultados. Todas las personas dieron negativo en la prueba de antígeno de Wuchereria bancrofti. Conclusiones. Aunque hubo un tiempo en que Manaos se consideraba zona endémica, parece que este foco de transmisión de la filariasis linfática ya no está activo. Los resultados de este estudio podrían brindar apoyo a la certificación de la Organización Mundial de la Salud respecto de los esfuerzos realizados en Brasil para eliminar la transmisión de la filariasis linfática.

RESUMO Objetivo. Confirmar a ausência de casos autóctones de Wuchereria bancrofti em Manaus, anteriormente um foco da filariose linfática na parte leste da Amazônia brasileira. Métodos. Uma pesquisa de campo foi realizada em 2016 com o uso de teste rápido por imunocromatografia (cartão ICT) para detecção de antígenos de microfilárias circulantes no sangue. A amostra estudada consistiu de um grupo de 3 000 crianças escolares entre 6 e 10 anos de idade matriculados em escolas de diferentes áreas da zona urbana de Manaus (englobando a área anteriormente com o foco de filariose linfática) e um grupo de 709 adolescentes e adultos entre 11 e 85 anos de idade nascidos e crescidos em diferentes áreas de Manaus. Resultados. Todos os indivíduos pesquisados tiveram teste negativo para o antígeno da W. bancrofti. Conclusões. Apesar de Manaus ter sido anteriormente uma área endêmica, parece que não existe mais foco ativo de transmissão da filariose linfática na cidade. Os resultados deste estudo podem servir para embasar a certificação pela Organização Mundial da Saúde da eliminação da transmissão da filariose linfática no Brasil.

Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: Reducing 'number needed to test' by targeting older age groups, hotspots, and household members of infected persons.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission.

Pancytopenia: a rare cause for a common presentation.

Filariasis is a major public health hazard in tropical and subtropical countries and is endemic among the Indian population. Asymptomatic microfilariaemia, elephantiasis, acute adenolymphangitis, hydrocoele and chronic lymphatic disease are its common manifestations. We hereby report a case of microfilaria found in the bone marrow presenting as pancytopenia. There was no classical feature of elephantiasis or lymphoedema present.

Space occupying lesion of brain: An unusual site for a common infection.

Filariasis is a public health menace and is a cause for concern due to its endemicity in tropical and subtropical countries of Africa, Asia, and Western Pacific. Even in endemic areas, it is rare to find filariasis in fluid specimens especially cerebrospinal fluid. Herein, we report a case of unsuspected filarial parasitic infection in an adult male admitted as a case of space occupying lesion in brain with suspicion of lymphoma/granulomatous disease on the basis of clinicoradiological details. To the best of our knowledge, such an extensive brain involvement by filariasis has not been reported before.

Microfilariae in bone marrow aspirate of a case of myelofibrosis: A cause or coincidence?

Filariasis is among the common parasitic infestations found in India, with Wuchereria bancrofti being the most common causative organism. Presentation ranges from clinically asymptomatic to profound elephantiasis. It is also detected incidentally in diagnostic samples such as body fluids, fine needle aspirates, peripheral blood smears, and other cytological smears. Its detection in bone marrow aspirates with an associated hematolymphoid neoplasm is rare, with only a few case reports. We report one such case of young male who presented with leukocytosis of 253 × 109/L with basophilia and massive splenomegaly. Bone marrow aspirate smears showed the presence of microfilariae along with other features of a myeloproliferative neoplasm (MPN). The present case is probably the first case of finding a microfilaria in a case of MPN.

Microfilaria in urine cytology: Report of three cases with review of literature.

Lymphatic filariasis is a major public health problem in the developing countries. In India, around 90% of the cases are attributed to Wuchereria bancrofti species morphologically identified as sheathed parasites with tail tip free of nuclei. Microfilariae have been described in urine specimens from patients with chylous and achylous hematuria as well as in a spectrum of other body fluids. Case reports describe their presence in aspirates from numerous neoplasms. However, their association with urothelial carcinoma in urine sediment has been rather rare with only three cases described previously. We report three cases of filariasis in urine cytology, one of which was associated with atypical urothelial cells. Our aim is to stress on the possibility of concomitant filariasis in body fluids and aspirates with other significant findings, especially in endemic areas. Identification of the same renders complete diagnosis and proper treatment to the patient.

Wuchereria bancrofti macrophage migration inhibitory factor-2 (rWbaMIF-2) ameliorates experimental colitis.

Immunomodulatory molecules produced by helminth parasites are receiving much attention recently as novel therapeutic agents for inflammation and autoimmune diseases. In this study, we show that macrophage migration inhibitory factor (MIF) homologue from the filarial parasite, Wuchereria bancrofti (rWbaMIF-2), can suppress inflammation in a dextran sulphate sodium salt (DSS)-induced colitis model. The disease activity index (DAI) in DSS given mice showed loss of body weight and bloody diarrhoea. At autopsy, colon of these mice showed severe inflammation and reduced length. Administration of rWbaMIF-2 significantly reduced the DAI in DSS-induced colitis mice. rWbaMIF-2-treated mice had no blood in the stools, and their colon length was similar to the normal colon with minimal inflammation and histological changes. Pro-inflammatory cytokine genes (TNF-α, IL-6, IFN-γ, IL-1ß, IL-17A and NOS2) were downregulated in the colon tissue and peritoneal macrophages of rWbaMIF-2-treated mice. However, there were significant increases in IL-10-producing Treg and B1 cells in the colon and peritoneal cavity of rWbaMIF-2-treated mice. These findings suggested that rWbaMIF-2 treatment significantly ameliorated the clinical symptoms, inflammation and colon pathology in DSS given mice. This immunomodulatory effect of rWbaMIF-2 appeared to be by promoting the infiltration of Treg cells into the colon.

Isolated Epitrochlear Filarial Lymphadenopathy: Cytomorphological Diagnosis of an Unusual Presentation.

Filariasis is a major public health problem in tropical countries like India. Despite the large number of people at risk, detection of eggs with or without larva (microfilaria) on fine-needle aspiration cytology is very unusual, especially in an uncommon site or incidentally detected in clinically unsuspected cases of filariasis with the absence of microfilariae in the peripheral blood. A 19-year-old male presented with swelling over medial aspect of left arm (just above the elbow), with no other specific signs and symptoms. Fine needle aspiration cytology revealed an adult gravid female filarial worm in a background of reactive lymphoid cells and lymphohistiocytic clusters. We report a case with elaborate fine needle aspiration cytology findings of filarial worm infestation with unusual presentation of isolated epitrochlear lymph node involvement in a clinically unsuspected case and recommend clinicians and pathologists to consider a high index of suspicion for such infections at uncommon sites especially in endemic territories, as early diagnosis and treatment prevent the more severe manifestations of disease.

Rare association of microfilaria with poorly differentiated mucin-secreting metastatic carcinoma in liver aspirate cytology.

Filariasis, a neglected tropical disease (NTD), is mainly caused by nematodes-Wuchereria bancrofti, Brugia malayi and B. timori Apart from profoundly disabling and disfiguring major clinical manifestations-lymphoedema, elephantiasis and hydrocoele-asymptomatic microfilaremia is common in endemic areas. Despite this, it is very rare to detect microfilariae in body fluids or aspirates. As per the literature search, this is the third case documenting incidental detection of microfilariae with metastatic deposits in the liver aspirate. Here, a 35-year-old man underwent image-guided fine-needle aspiration cytology of liver nodule. Liver aspirate cytology revealed poorly differentiated mucin-secreting metastatic carcinoma and coincidental presence of microfilariae of W. bancrofti Recently, microfilaria has frequently been found to be associated with the debilitated, immunocompromised condition and various neoplasm/cancer/malignancy. Hence, meticulous investigation should be undertaken to search for hidden pathology, whenever microfilariae are detected; and to deeply scrutinise aspirates for such parasites always, especially in endemic regions.

Elimination of lymphatic filariasis as a public health problem from the Arab Republic of Egypt.

Lymphatic filariasis (LF) has been known in Egypt since ancient times. By 1930s it was recognized to be a major public health problem in the Nile Delta, and to be caused by Wuchereria bancrofti and transmitted by Culex pipiens. Remarkably, as a result of widespread DEC treatment and intensive vector control by the Ministry of Health and Population (MoHP), the infection rate of LF declined in the 1960s. However, relaxation of these efforts resulted in resurgence of filariasis in the 1980s and 1990s. In 2000, Egypt was among the first countries to join the WHO global efforts to eliminate LF as a public health problem by initiating a national LF elimination programme (NLFEP). This article reviews the history of LF control activities and summarizes the NLFEP extensive interventions to eliminate LF in Egypt. Based on MoHP data, mass drug administration (MDA) with DEC and ALB was started in 2000 in 161 implementation units (IUs). Additional IUs were included in subsequent MDA rounds, with the last IU included in 2007. MDA stopping surveys were conducted based on WHO guidelines (2005; 2011). Information about the presence of those suffering from lymphoedema/elephantiasis and hydrocele patients was collected, and care provided to those needing care in five rural health units (RHU) by primary health care system providers who were given training on LF morbidity management and disability prevention (MMDP). The NLFEP made excellent progress due to strong collaboration between different ministries, through intensive training and supervision, and the use of advocacy for mobilization of endemic communities. The epidemiological coverage for all MDA rounds was effectively ≥80%. Antigenemia levels found in schoolchildren during transmission assessment surveys (TAS) in 166 IUs approximately 10 years after stopping MDA was 0%. In 2017, TAS conducted in additional 29 IUs indicated 0.1% antigenemia and 0% microfilaremia. In 2015, the registration of chronic LF patients was updated to 1472 lymphoedema and 18 hydrocele patients. Lymphoedema patients were trained on self-management, and hydrocele patients were referred to local General Hospitals for surgery. Thus, after over a decade of sustained effort, Egypt met the WHO criteria for successful elimination of LF as a public health problem. In December 2017, WHO validated Egypt as the first country in the Eastern Mediterranean Region to successfully achieve elimination.

Influence of seasonal variation on reported filarial attacks among people living with lymphedema in Ghana.

BACKGROUND: Lymphatic Filariasis (LF) is a vector-borne neglected tropical disease caused by the filarial nematode parasites that can lead to the disfiguring swelling of the limbs (lymphedema or elephantiasis for late stage) and/or genitalia (hydrocele) in men. Growing evidence suggests that not only are filarial lymphedema patients confronted with huge societal stigma and discrimination, but also experience acute filarial attacks accompanied by swelling of the affected part(s), fever, wounds and peeling of the skin of affected limbs(s). However, the extent to which seasonal variation influence filarial attacks among people with lymphedema was highly speculated without empirical evidence and was thus investigated. METHODS: In light of this, a cross-sectional study where 142 (70.4% females and 29.6% males) lymphedema patients were recruited from 8 established Wuchereria bancrofti endemic communities in the Ahanta West District, Ghana was carried out to investigate the prevalence and seasonal variation (rainy/wet and dry seasons) of acute filarial attacks. Chi-square test was used to test for association between frequency of attacks and seasonality. The STROBE guidelines for reporting cross-sectional studies was adopted. RESULTS: The average lymphedema leg stage was 2.37 and 2.33 for left and right legs, respectively, while mossy lesions, sores and ulcers were observed among 33.1% of patients with late stage disease (elephantiasis). It was found that 97 (68.3%) of the study participants experience filarial attacks during the wet season and 36 (25.4%) reported the incidence of filarial attacks during both seasons (wet and dry) while 9 (6.3%) of the study participants did not experience any attack at all. CONCLUSIONS: Findings from the present study show compelling evidence that the frequency and the prevalence of filarial attacks is significantly increased during wet seasons compared to the dry season.