Clinical Filariasis Research Articles

Studi Epidemiologi dan Gambaran Program Eliminasi Filariasis Limfatik di Kabupaten Bogor

Abstract. Filariasis is still a health problem in Bogor Regency. The discovery of filariasis sufferers hasgrowing during the year since 2004 until now with a total of 117 people. The mass prevention drugadministration program (POPM) has been implemented since 2015. This study aims to identify theepidemiological distribution of clinical filariasis sufferers and an overview of the achievement of filariasiselimination program in Bogor district. The research using descriptive design with a quantitative approach.The data in this study used secondary data from Bogor District Health Office and Bogor Central Bureau ofStatistics. Data were analyzed descriptively and identify differences and relationships between variablesused the chi-square test. The results of the study showed the epidemiological distribution of filariasis inBogor Regency with predominantly female patients (59.8%) and productive age (36-45 years). The resultsfrom chi-square test showed that there was a significant difference between the age groups and theincidence of filariasis from year to year with a P value (0.000) <0.05, while the relationship between sex andthe incidence of filariasis from year to year did not show a significant difference with the P value ( 0.07)>0.05. The spread of filariasis tends to fluctuate and continues to increase (75%). The results of therelationship test showed that there was no significant relationship between the number of cases and the levelof family welfare with a P value (0.279)> 0.05. The implementation of POPM, both treatment outcomes andtreatment success rates, has exceeded the national target.Keywords: Epidemiology, Filariasis, POPM, Bogor, Indonesia

Caring for patients in the global programme to eliminate lymphatic filariasis.

Clinical lymphatic filariasis (LF) is a debilitating, disfiguring medical condition with severe psychosocial consequences for patients and their families. Addressing these patients’ medical needs is a major component of the global programme to eliminate lymphatic filariasis (GPELF). In the 20 y of providing a minimal package of care many thousands of surgical operations to correct LF hydrocoeles been performed and national programmes in >90% of LF endemic countries have received the training needed to care for their patients. The creation of educational materials detailing appropriate patient care, together with increased funding, have been key catalysts in increasing awareness of clinical LF in recent years. Nevertheless, the implementation of care for these patients has often faced challenges that have led to delays in fully implementing the patient care component of GPELF; these include locating these often stigmatised individuals, maintaining provision of the necessary consumables (e.g. soaps and creams) and maintaining programme support within already overstretched national LF teams. As the LF global programme moves to achieve success by 2030 it will be vital to continue to focus efforts on the care and rehabilitation of those suffering from lymphoedema and hydrocoeles, learning from the experiences of the past 20 y.

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.

Anti-filarial immunity blocks parasite development and plays a protective role.

Lymphatic filariasis is a complex parasitic disease having a spectrum of clinical parameters which are critical in deciding the severity of the pathogenesis. Individuals residing in the endemic areas are categorized into different clinical groups such as: EC (endemic controls-free of disease and infection), AS (asymptomatic carriers- free of disease but carries both antigens and microfilaria (Mf) in circulation), CR (cryptic-free of disease and Mf but having circulatory antigen) and CH (chronic-having manifestations of elephantiasis and hydrocele). The immune response to the parasitic infection is well studied, whereas the protective mechanism explaining the fate of antigenemia and filaremia between AS and CR group remains unexplained. Increased anti-Mf antibodies have been implicated for Mf clearance in experimental infection models whereas its role in clinical filariasis is not known. Here, we followed up two groups of 24 and 33 CR cases for 18 and 36 months respectively and analyzed both the clinical parameters and the anti-filarial antibody response. The humoral response to both whole filarial antigen and Mf antigens as well as recombinant active parasitic antigens was significantly higher in CR cases than AS individuals, whereas the clinical parameters remain unchanged. This study made insights into the protective immune mechanism responsible for the clearance of Mf from circulation in CR individuals.

Increased Fas ligand expression of peripheral B-1 cells correlated with CD4+ T-cell apoptosis in filarial-infected patients.

Cellular hyporesponsiveness observed during helminth infections is attributed to factors such as antigen-presenting cells (APC) dysfunction, increased interleukin-10(IL-10), regulatory T cells and induction of CD4+ T (Th)-cell apoptosis. Increased Fas ligand (FasL) expression on the surface of B-1 cells and induction of apoptosis of Th cells by FasL-expressing B-1 cells due to helminth infection were demonstrated in murine model of helminth infection where as profile of FasL expression, Th-cell apoptosis and correlation between these two populations of cells in clinical filariasis remain unknown. In this study, we have scored the profile of apoptotic Th-cell population and FasL-expressing B-1 cells in different clinical categories of filariasis. The peripheral apoptotic T-helper cells were significantly increased in filarial patients compared to endemic controls. Expression of FasL on the surface of peripheral B-1 cells increased in filarial patients and positively correlated with peripheral apoptotic T-helper cells indicating FasL-expressing B-1 cells may be one of the important mediators of Th-cell apoptosis and immune anergy during filarial pathology.

English

English

Filariasis in Japan some 25 years after its eradication.

Japan is said to have eradicated filariasis some 25 years ago, but the exact time (and even the definition of eradication) is not clear. However, the results of successful control programs clearly indicate that the number of microfilaria carriers had been reduced to a very low level long before the “eradication”. As filariasis disappeared, the once stigmatized disease quickly lost clinical significance. At the same time, the number of parasitologists and researchers interested in filariasis dwindled quickly to only a handful in the whole country 10-15 years after the disappearance. Filariasis problems in Japan still remain as sequelae of the old infection. However, young clinicians have little knowledge of filariasis, and the rare, localized and non-lethal disease is disappearing also from the memory of doctors. On the other hand, some doctors continue to encounter cases of lymphedema, hydrocele and chyluria. Some of these are diagnosed as filarial in origin, and in most cases the diagnosis is based on the fact that the patients were born and brought up in the past endemic areas. Practically, there is no reliable way of diagnosing the old clinical filariasis. Some immunodiagnostic methods are available but they are not very specific. The purpose of this review is to describe what is happening with filariasis in Japan about 25 years after its eradication. The review will highlight the situation of chyluria, the most common sequela, and its treatment, recent filarial infections in Japan including imported cases and zoonotic filariasis, and immunodiagnostic methods used for suspected clinical filariasis.

Bancroftian filariasis in the lower Imo River Basin, Nigeria

Wuchereria bancrofti is present in the Lower Imo River Basin with a prevalence of 6.7%. Microfilaraemia was higher among older than younger individuals and there was no significant difference in prevalence between sexes. Microfilarial intensities varied significantly between sexes and also between age groups. On the overall, prevalence of clinical filariasis was higher than prevalence of microfilaraemia. Clinical manifestations related to W. bancrofti were hydrocele, limb and scrotal elephantiasis in that order of importance. Limb elephantiasis was higher among females than among males. Chyluria was not found in the Lower Imo River Basin study population. AJAZEB Vol. 6 2004: pp. 61-65

Assessment of disease and infection of lymphatic filariasis in Northeastern Cambodia.

We assessed the filariasis disease burden in four northeastern provinces of Cambodia by using and validating a key-informant questionnaire, consisting of four questions, with pictures of patients with leg elephantiasis and hydrocoele. The questionnaire was distributed and collected through the school, health and administrative systems. Validation surveys included clinical examination, a card test for W. bancrofti (ICT Filariasis card test, AMRAD) and night blood finger prick examination of patients reported with clinical elephantiasis. Only 48.0% of questionnaires were returned. A total of 220 patients were reported, mostly from Stung Treng (36.8%) and Rattanakiri provinces (35.0%). Key-informants reported patients with lymphatic filariasis with a sensitivity of 85.7% for leg and 97.0% for scrotum morbidity, and with a specificity of 95.6%. However, substantial over-reporting resulted in very low positive predictive values for elephantiasis of 19.4% for legs and of 23.7% for the scrotum. As 97.4% of patients with clinical lymphatic filariasis were older than 40 years, the diagnostic performance of the questionnaire would be improved by restricting its use to that age group. About 0.7% of 3490 W. bancrofti card tests were positive; the prevalence was 1.94% (12/618) in Rattanakiri, 0.38% (4/1055) in Stung Treng and 0.22% (2/919) in Preah Vihear. W. bancrofti microfilaria were identified in blood from two patients in Rattanakiri (0.32%) and from one patient in Stung Treng (0.09%). Brugia malayi microfilaria were identified in blood from five patients in Rattanakiri (0.81%) only. No patients with microfilariaemia were identified in Preah Vehear. In Mondulkiri province all investigations (card test, night blood examination, clinical examination) for lymphatic filariasis were negative. Our findings confirm the usefulness of key-informant questionnaire for the identification of filariasis patients provided that high adherence can be achieved. Lymphatic filariasis infection and disease is present in northern Cambodian provinces but the burdens of disease and infection are relatively low. These results are being used in the implementation of the national control programme for lymphatic filariasis.

Epidemiological Mapping Of Lymphatic Filariasis In Southern Nigeria Preliminary Survey Of Akinyele Local Government Area

Lymphatic filariasis caused by Wuchereria bancrofti is major public health problem in tropical and subtropical countries including Nigeria. The real burden of the disease in most endemic regions remains unknown. The nocturnal periodicity of the parasites requires parasitological examination to be done at night and this is quite cumbersome. The World Health Organization recently recommended two rapid methods for the assessment of lymphatic filariasis (RAGFIL). These RAGFILS methods i.e. using community health workers and key informants were used to rapidly map lymphatic filariasis in Akinyele Local Government area of Oyo State Nigeria. The prevalence of hydrocele and elephantiasis was highly sensitive in identifying this community as endemic for filariasis. The degree of association between finding by health workers and information obtained form the community key informants was high for the two major clinical manifestation of the disease used. Community key informants and health workers did provide useful information on the prevalence of clinical filariasis. These observations suggest that the mean number of cases obtained in the village through key informants and the examination of health workers for the clinical signs of the disease may be considered at an initial level to identify endemic areas. The need to extend this method to rapidly map lymphatic filariasis in Nigeria is discussed. Key words: Lymphatic, Filariasis, Rapid, Mapping, Assessment and Health workers. Afr. J. Clin. Exper. Microbiol. 2004; 5 (3): 231-234

Relationship between Onchocerciasis and <i>Plasmodium falciparum</i> malaria in Communities Endemic for Filariasis in South East Nigeria

Objective: To determine if there is a causal relationship between Plasmodium falciparum and clinical filariasis in individuals exposed to both infections. Methods: An onchocerciasis endemic community in Imo State, South East Nigeria was screened and persons showing overt clinical signs of onchocerciasis were selected for further study. Blood samples of selected persons were examined for presence of different forms of Plasmodium falciparum. Results: Of the 264 individuals [94 males (35%) and 170 females (65%)] 90 individuals (34.1%) had positive blood smears for Plasmodium falciparum. The association between the two parasitic infections although statistically significant does not seem to be causal. Conclusion: Persons who are infected with onchocerciasis seem to also be at the risk of infection with Plasmodium falciparum malaria. Key Words: Onchocerciasis, Endemicity, Malaria Orient Journal of Medicine Vol.16(1) 2004: 23-25

Prevalence Of Onchocerciasis In Umuowaibu Community Of Imo State, South East Nigeria

Objectives:To determine the prevalence of onchocerciasis in individuals residing in the Umuowaibu community of Imo state in South East Nigeria and that of mixed filarial infections among persons with clinical signs of onchocerciasis. Method:An onchocerciasis endemic community in Imo State, South East Nigeria was screened and persons showing overt clinical signs were selected for further study. Blood samples of selected persons were examined for microfilaria. Results:Out of a total population of 750, 264 (35.2%) individuals had signs of clinical filariasis. The exhibited signs include pruritus in 46 persons (16.7%), skin nodules in 71 (27%), leopard skin in 30 (11.23%), skin tumour in 16 (6%), loss of vision in 72 (27.1%) and worms in the eye in 13 (4.5%). No individual exhibited microfilaria in the peripheral blood. Conclusion:The occurrence of clinical signs and the presence of known insect vectors in the area were considered indicators of continuing active disease transmission despite community control measures. Absence of microfilaraemia in patients with overt onchocerciasis suggests the absence of mixed infections probably as a result of immunological, genetic, pathological, nutritional and other mechanisms. Key Words: Onchocerciasis, Endemicity, Microfilaraemia Orient Journal of Medicine Vol.15(3&4) 2003: 39-41

Molecular characterization of a Brugia malayi transglutaminase.

Prior studies have demonstrated that transglutaminase (TGase) from the human filarial parasite Brugia malayi is critical for the growth and development of the larval stages. In this report, we describe the cloning and partial characterization of a cDNA encoding the B. malayi TGase (BmTGase). Using RT-PCR and RACE-PCR, the cDNA was amplified from adult worm mRNA. BmTGase is 1,881 bp long and codes for a protein with a predicted molecular mass of 54 kDa. Amino acid sequence analysis of BmTGase revealed significant homology to the protein disulfide isomerase (PDI), particularly, to the PDI-related protein ERp60, a PDI isoform found in the lumen of endoplasmic reticulum. The activity of recombinant B. malayi TGase enzyme (rBmTG) was found to be calcium-dependent and could be inhibited by EDTA. ELISA studies showed that approximately 88% of 48 sera from healthy Indian patients living in a bancroftian filariasis endemic area were reactive with rBmTG. In contrast, only 33% of sera from patients with clinical filariasis were reactive to rBmTG. Non-endemic sera were uniformly non-reactive. Additional studies are needed to elucidate the role, if any, of B. malayi TGase in protective immunity to filariasis.

Immunocytochemical localization of antigens recognized by human antisera in infective larvae of Wuchereria bancrofti.

Ultrathin sections of L3 of Wuchereria bancrofti embedded in hydrophilic resin were incubated with antisera pools from individuals (1) asymptomatic microfilaremic with different microfilaria (mf) densities (1-100, 101-500, and >1,000 mf/ml); (2) chronic with hydrocele or lymphedema; and (3) with no evidence of microfilaremia or clinical filariasis but residing in an endemic area. The groups of microfilaremic subjects studied presented differences relative to the intensity of labeling, with the density of gold particles per square micrometer proportional to microfilaremia. Incubation of ultrathin sections of W. bancrofti L3 larvae in the presence of antisera from patients exhibiting chronic obstructive lymphatic pathology of hydrocele and from individuals with clear clinical evidence of lymphedema exhibited a strong reaction in the same tissues. Except for the endemic normal group, all groups studied showed reactivity against epitopes in all tissues of infective larvae of W. bancrofti. The cuticle presented an intense labeling, suggesting a possible target structure for immune response.

PORT SITE METASTASES ARE FREQUENT AFTER OPEN LAPAROSCOPY IN PATIENTS WITH ADVANCED OVARIAN CARCINOMA, BUT DO NOT INFLUENCE THE SURVIVAL: AN ANALYSIS OF 173 CASES

The four subclasses of IgG are distinct in structure, function, and degree of participation in the antibody response to complex antigens. Looking for differential responsiveness of potential pathogenetic significance, we have analyzed both quantitatively and qualitatively the filaria-specific IgG subclass responses of 20 patients with lymphatic filariasis presenting either with chronic lymphatic obstructive pathology and elephantiasis (CP) or with asymptomatic microfilaremia (MF). Subclass-specific monoclonal antibodies were used in an enzyme-linked immunosorbent assay to study IgG filarial antibodies quantitatively and in immunoblot analyses to determine qualitatively the subclass antibody specificities. Quantitatively, the most significant differences among patient groups were in levels of IgG4, which were more than 17 times higher in MF patients (geometric mean, 64.7 micrograms/ml) than in those with CP (mean, 3.7 micrograms/ml). When qualitative analyses were done on the same sera, major differences were noted, particularly in the recognition profiles of the IgG1, IgG3, and IgG4 responses. IgG1 and IgG3 responses to antigens were seen especially to antigens with m.w. greater than 68,000 in all patients with elephantiasis, whereas MF patients showed most of their reactivity to antigens less than 68,000. For IgG4, the MF patients showed prominent recognition of antigens throughout the entire range of m.w., whereas those with CP had very little IgG4 recognition of antigens of any m.w. Interestingly, this relationship was essentially reversed in the IgG3 antibody responses (especially to antigens greater than 68,000) and, to a lesser extent, the IgG1 responses. These findings demonstrate correlations of potential cause/effect significance between IgG4 antibody responsiveness and the immunomodulated asymptomatic MF form of clinical filariasis and between IgG3/IgG1 antibody responsiveness and the clinical presentation of CP.

New insights into the natural history and pathology of bancroftian filariasis: implications for clinical management and filariasis control programmes

Journal Article Elimination of lymphatic filariasis as a public health problem. New insights into the natural history and pathology of bancroftian filariasis: implications for clinical management and filariasis control programmes Get access Gerusa Dreyer, Gerusa Dreyer ∗ 1Núcleo de Ensino, Pesquisa e Assistência em Filariose (NEPAF), Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Brazil3Centra de Pesquisas Aggeu Magalhães (CPqAM), Fundação Oswaldo Cruz, Recife, Brazil ∗Address for correspondence: Gerusa Dreyer, Núcleo de Ensino Pesquisa e Assisência em Filariose (NEPAF), Hospital das Clínicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego s/n, 5º andar, Cidade Universitária, Recife, PE 50740-900, Brazil; phone +55 81 241 8807, fax +55 81 242 7307. gd@nlink.com.br Search for other works by this author on: Oxford Academic PubMed Google Scholar Joaquim Norões, Joaquim Norões 1Núcleo de Ensino, Pesquisa e Assistência em Filariose (NEPAF), Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar José Figueredo-Silva José Figueredo-Silva 2Laboratório de Imunopatologia Keiso Asami (LIKA), Departamento de Patologia, Universidade Federal de Pernambuco, Recife, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 94, Issue 6, November-December 2000, Pages 594–596, https://doi.org/10.1016/S0035-9203(00)90200-1 Published: 01 November 2000 Article history Received: 16 March 2000 Accepted: 21 June 2000 Published: 01 November 2000

Immunomonitoring followed by optimal dec therapy for successful management of clinical filariasis in an endemic area

Lymphatic filariasis continues to be the major cause of clinical morbidity in India and other developing tropical countries. One of the major lacunae in the effective management of clinical filarial cases is the non-availability of a suitable diagnostic test for confirming filaria aetiology in acute, chronic and occult clinical cases where microfilariae (mf) are not usually seen in peripheral circulation. Studies in our laboratory have shown the usefulness of filarial antibody and antigen assays using microfilarial excretory-secretory (mf ES) antigen in detecting microfilaraemic, acute and chronic filarial cases and in confirming filarial aetiology in occult infections. Diethylcarbamazine citrate (DEC) is the drug of choice for lymphatic filariasis. Different regimens of DEC have been explored in the treatment of microfilaraemic cases. Immunomonitoring has shown that the seroconversion of antigen and antibody positivity was found to be very helpful in determining appropriate period of DEC treatment for clinical relief and cure in clinical filarial patients and further they did not have recurrence in most of the cases. Optimal DEC (6mg/kg body wt/day for 21 days each month for 3-12 months) therapy was found to be very effective in acute and atypical clinical manifestations such as asthmatic bronchitis, pulmonary eosinophilia, monoarthritis, recurrent upper respiratory tract infections (URI), pneumonia (super imposed infections) in children and minimal hydrocele, epididymoorchitis, lymphangitis, lymphadenitis, acute abdomen, central serous retinopathy, tenosynovitis, pain and swelling in limbs and joints in adults living in filaria endemic areas.

Human antibody responses to Brugia malayi antigens in brugian filariasis

Human antibody responses to Brugia malayi antigens were studied with sera from a Brugia endemic area in South India. Patients with clinical filariasis had significantly higher IgE and lower IgG4 levels to adult worm antigens than people with asymptomatic microfilaraemia. Intermediate antibody levels were observed in endemic normals. A majority of sera from each clinical group contained IgG antibodies to surface antigens of infective larvae (L3) by IFAT. IgG immunoblot studies did not reveal group differences in L3 antigen recognition. IgE antibodies bound to a subset of antigens bound by IgG. IgE antibodies in sera from clinical filariasis patients preferentially bound to L3 antigens at 200, 97, 68 and 58 kDa compared with sera from microfilaria carriers. These results are consistent with prior studies of antibody responses in filariasis and add new information on the targets of IgG and IgE antibodies to L3 antigens in brugian filariasis.

Biased TCR Repertoire in Infiltrating Lesional T Cells in Human Bancroftian Filariasis

To investigate the hypothesis that T cells recognizing specific Ags localize to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR Vbeta gene segments in lesions vs blood in individual patients by RT-PCR ELISA. Vbeta14 and Vbeta24 were overrepresented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PBMC ratios for all Vbetas for all subjects) in 50% and 40% of study subjects, respectively. Overrepresentation of these two Vbetas did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criterion for Vbeta14 overrepresentation was shown to increase in tandem with our current concepts of disease progression (asymptomatic filariasis = 25%; clinical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with Vbeta14 overrepresentation, Vbeta14 represented >20% of the entire lesional Vbeta repertoire. All but one of the 20 study subjects had at least one Vbeta gene segment that was overrepresented in tissue compared with PBMCs. Only a small number of Vbetas, usually three or less, were overrepresented in any single filariasis patient. However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or with clinical filariasis, distinct and limited T cell populations are concentrated in affected tissue.

Bancroftian filariasis in Egypt: visualization of adult worms and subclinical lymphatic pathology by scrotal ultrasound.

The purpose of this study was to explore the value of scrotal ultrasound as a means of evaluating Bancroftian filariasis. Color Doppler ultrasound examinations were performed to look for subclinical hydroceles and motile adult filarial worms (dancing worms) in dilated lymphatics. Sixty-one male subjects from a filariasis-endemic area in Egypt were studied including 19 clinically normal microfilaria (MF) carriers (seven with dancing worms and eight with subclinical hydroceles), 13 MF-negative subjects with positive filarial antigen test results (three with dancing worms and seven with subclinical hydroceles), 22 exposed subjects with no MF and negative antigen test results (no dancing worms, four subclinical hydroceles), and seven subjects with clinical filariasis (no dancing worms, seven hydroceles). Thus, all men tested with clinical filariasis and most clinically normal subjects with either microfilaremia or filarial antigenemia had abnormal ultrasound examination results. Ultrasound findings often changed after therapy with diethylcarbamazine, with disappearance of dancing worms and development of new scrotal calcifications or hydroceles. This study confirms the value of scrotal ultrasound as a means of noninvasively visualizing adult filarial worms and assessing subclinical lymphatic damage in Bancroftian filariasis.