Occult Filariasis Research Articles

Occult Filariasis in a Case of Lymphocytic Thyroiditis Diagnosed on Fine Needle Aspiration Cytology: An Unusual Finding of Dual Pathology

Filariasis is a common public health problem in Southeast Asia. The two species of worms most commonly associated with this disease are Wuchereria bancrofti and Brugia malayi. Cases of microfilaraemia have also been reported from atypical sites in the past. None of the previously reported cases of microfilaria in the thyroid gland have described occult filariasis against a background of lymphocytic thyroiditis. The authors present a case of incidental microfilaria in a case of lymphocytic thyroiditis, diagnosed on fine needle aspiration cytology of thyroid swelling in a female, a coexistence of dual pathology. There has been no case in literature where filariasis was reported against a background of lymphocytic thyroiditis. Peripheral blood examination also did not show any evidence of filariasis.

Tropical Pulmonary Eosinophilia Masquerading as Interstitial Lung Disease: An Interesting Case Report with Review of Literature

Tropical Pulmonary Eosinophilia (TPE) is a form of occult filariasis characterised clinically by paroxysms of nocturnal cough, wheezing and dyspnoea . It is due to hyper-responsive pulmonary reaction to trapped microfilaria inside the lung tissue. Though it is common in endemic areas, it is frequently misdiagnosed mostly as bronchial asthma or tuberculosis and the patient continues to suffer without being treated appropriately. A 36-year-old male, who presented with fever, cough and shortness of breath for a period of 6 months was misdiagnosed as Interstitial Lung Disease (ILD) and was put on antifibrotic agents without any relief of symptoms. He was thoroughly investigated with routine haematological tests, Absolute Eosinophil Count (AEC), X-ray of chest, High Resolution Computed Tomography (HRCT) thorax including bronchoalveolar lavage and was diagnosed as Tropical Pulmonary Eosinophilia (TPE). Diethyl Carbamazine citrate (DEC) was initiated and patient had satisfactory recovery. So in endemic areas the possibility of TPE should always be kept in mind while evaluating cases presenting with chronic cough, dyspnea and wheezing even if the radiological imaging may mimic ILD.

Cytological diagnosis of microfilariae in clinically unsuspected cases: A retrospective review of 12 cases.

Filariasis is a major health problem in India. Despite the high prevalence, microfilariae are rarely found in cytology smears. Most of the cases are incidentally found, solely or in association with other pathologies. This study was undertaken to analyse the prevalence and cytological findings of cases of incidentally found microfilariae in cytology smears (fine needle aspiration cytology [FNAC]/exfoliative cytology) from different parts of the body. This was a retrospective study over 3years, in which cases of microfilariae in aspirates from swelling of different locations, body fluids, and pap smears were reviewed, and the clinicopathological data analysed. Out of 11 530 cases of FNAC, 8700 cases of fluid cytology, and 9000 of conventional cervicovaginal smears, 12 cases (0.04%) of incidental findings of microfilariae were documented in cytology smears. The cases were diagnosed from lymph node (one case), hand (one case), scrotal area (one case), axilla (one case), breast (one case), subcutaneous tissue (three cases), urine (three cases), and Pap smear (one case). We found eosinophilia in one case (8.3%) of filarial lesions. We found two cases of incidental findings of microfilariae in association with malignant lesions. Cytology smear examination can play an important role in diagnosing occult filariasis in clinically unsuspected cases in association with other pathologies.

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Background: Bancroftian Filariasisisatropical and sub tropical disease caused by Wuchereriabancrofti and transmitted by the Culexmosquitoes. The diagnosis of it is conventionally made by demonstrating microfilaria eintheperipheral blood smear. Microfilariae and adult filarial worm have been incidentally detected in fine needle aspirate of swelling at various sites in amicrofilaremic patients. Currently 1.4 billion people worldwide are at risk of being infected. In India 600 million people are at risk of filariasis.Cytology has important role in the diagnosis of occult Filariasis. Objectives: To discuss the role of FNAC in diagnosing occult Filariasis. Material and Methods: This is a retrospective study carried out in the Department of Pathology at SRMS IMS, Bareilly, Uttar Pradesh. Aspiration was made by 22-23 gauze needle, smears were stained by Papanicolaou and May-GrünwaldGiemsa stain. Result:16 cases of cytological specimensincidentallyshowed microfilaria without any clinical suspicion which included breast lumps (three cases), thyroid swelling (three cases), lymph nodes (two cases), subcutaneous swelling (two cases), ascitic fluid (one case), pleural fluid (one case), lung mass (one case), scrotal swelling (one case), cervical smear (one case) and space occupying lesion in liver (one case). Fragments of adult worm were reported in four cases. Only one patient with scrotal swelling had microfilaremia. Conclusion:FNAC can play an important role in diagnosing occult Filariasis in clinically unsuspected cases.

The spectrum of disease in lymphatic filariasis.

Lymphatic filariasis affects predominantly the poorer sector of a community, who can least afford to have the disease. According to an estimate by the World Health Organization in 1984, more than 90 million people are currently infected. It is postulated that the different disease manifestations of filariasis are caused by different host immune responses. An understanding of the clinical spectrum of lymphatic filariasis is essential for the effective treatment and control of the disease, and for correctly correlating clinical status with host immune responses. The disease should be divided into lymphatic filariasis caused by adult worms and occult filariasis due to hyper-responsiveness of the host against microfilariae. The acute stage of filariasis is characterized by episodic adenolymphangitis, followed by obstructive lesions one or more decades later. In brugian filariasis, adenolymphangitis is most commonly observed at the inguinal region, and elephantiasis predominantly involves the leg below the knee. In bancroftian filariasis, the lymphatics of the male genitalia are frequently affected, leading to epididymo-orchitis and hydrocele. Lymphatic filariasis runs an accelerated clinical course in previously unexposed adult migrants. Occult filariasis is not a disease of public health importance. It is characterized by lymphadenopathy, asthmatic bronchitis, hypereosinophilia, and an increase in the production of antibodies, especially immunoglobulin, against microfilarial antigens.

Lymphatic filariasis: possible pathophysiological nexus with oxidative stress

Wuchereria bancrofti-mediated lymphatic filariasis is widely prevalent. Diversity in immune response presumably may lead to myriad clinical presentations, such as overt chronic filariasis, occult filariasis with atypical systemic manifestation and asymptomatic microfilariae carrier state. Anticipated oxidative stress during inflammatory response to infective conditions might complicate the immune response and thus might alter the disease outcome. The present study was carried out to assess the status of oxidative stress in different clinical presentations of bancroftian filariasis. Twenty-five microfilariae carriers and 30 cases each of chronic filariasis and occult filariasis were compared to 30 endemic normal individuals. Serum malondialdehyde level and superoxide dismutase enzyme activity were measured by spectrophotometric methods and levels of filarial antigen were measured by ELISA. In the filarial cases, the levels of these parameters were assayed again after treatment with diethylcarbamazine citrate (DEC). Results showed significant (P<0.05) association of oxidative stress with chronic and occult filariasis but not with microfilarial carriers. DEC therapy in both clinical cases and carriers resulted in a significant reduction of oxidative stress associated with decreased antigen level (P<0.01). These findings suggest the possible involvement of oxidative stress in filarial disease pathology.

Periocular filarial lymphoedema

Nine filarial species infect man but the lymphatic dwellers Wuchereria bancrofti, Brugia malayi and the subcutaneous Onchocerca volvulus are responsible for most infections worldwide. The species most commonly involved in lymphatic filariasis are W bancrofti, B malayi and B timori of which bancroftian filariasis is the most frequent. B malayi is mostly confined to South-East Asia [1]. B timori is restricted to Indonesian islands [2]. The common manifestations of lymphatic filariasis include asymptomatic microfilaraemia, early filariasis (filarial fever, lymphadenitis, lymphangitis, funiculitis, epididymitis, filarial orchitis and filarial abscess), chronic obstructive filariasis (lymph node enlargement, thickened lymphatic channels, hydrocele, chyluria, chylocele, chylous ascitis, chylous diarrhoea, elephantiasis and lymphoedema) and occult filariasis (tropical pulmonary eosinophilia, filarial arthritis, diffuse mesangial proliferative glomerulonephritis, pericardial and endomyocardial fibrosis, raised intracranial pressure with nerve palsies and allergic response to helminths leading to vesiculobullous lesions and urticaria). Though involvement of the eye in lymphatic filariasis has been reported, it is rare. We report a rare case of filarial lymphoedema involving the periocular tissues.

Diagnosis of Wuchereria bancrofti infection by the polymerase chain reaction employing patients' sputum.

A preliminary evaluation of the diagnostic potential of a polymerase chain reaction (PCR) assay using diurnally collected sputum from bancroftian filariasis patients is described. A new set of PCR primers amplifying a 254-bp-long sequence termed AccI, derived from a long dispersed repeated sequence and SspI primers previously employed for PCR-based diagnosis were employed in this study with similar results. Of the 34 sputum samples from patients, 32 (94%) were PCR positive. Of the 18 patients with low to high microfilaremia (21-1560 microfilariae/ml), 16 (88.8%) were PCR positive. Of the remaining 16 patients, 6 with very low microfilaremia (2-6 microfilariae/ml) and 10 without microfilaremia, all (100%) were PCR positive. Two PCR-positive cases among the 13 endemic normal individuals tested (15.4%) may represent cases of occult filariasis. PCR amplification was also demonstrated with one PCR-positive sputum aliquot when mixed with 14 sputum aliquots from uninfected (PCR-negative) individuals. The potential diagnostic merits of the sputum-PCR assay are discussed.

Filarial Antibody Detection in Suspected Occult Filariasis in Children in an Endemic Area

A study was conducted in filarial endemic area for diagnosis of occult filariasis in various clinical conditions in children. Thirty-five age- and sex-matched controls (endemic-15, non-endemic-10, disease control-10), 16 classical lymphatic filariasis, and 92 occult filariasis (clinical conditions which fall in the spectrum of occult filariasis and suspected to be filarial), were subjected to peripheral night blood smear examination for microfilaria (mf) and stick ELISA test using mf ES antigen for filarial antibodies. In the control group none showed mf and only 3 per cent (1/35) among endemic control were positive for filarial antibodies. In classical filariasis 1 per cent (2/16) showed mf and 94 per cent (15/16) had filarial antibodies. In suspected occult filariasis 1 per cent (one case of arthritis) showed mf and 62 per cent (57/92) showed filarial antibodies. These consisted of tropical pulmonary eosinophilia 63 per cent (15/24), arthritis where no cause could be ascertained on investigation 64 per cent (27/42), nephrotic syndrome 69 per cent (11/16), acute glomerulonephritis with ASO < 200 units 38 per cent (3/8), and cardiomyopathy 50 per cent (1/2). Correlation with age showed that 80 per cent (4/5) of cases of arthritis seen in 0-4 years of age group and 82 per cent (11/9) of nephrotic syndrome in the 10-14 years of age group were positive for filarial antibody. Arthritis due to other causes and minimal change nephrotic syndrome are uncommon in these respective age groups. It is concluded that the role of filariasis in endemic areas in these disease states cannot be denied and needs to be studied further.

Filarial antibody and antigen detection in different clinical conditions in an endemic area

The study was conducted in filarial endemic area for various clinical presentations and diagnosis of occult filariasis. A total of 157 cases of various clinical presentations namely tropical pulmonary eosinophilia, monoarthritis, polyarthritis, glomerulonephropathy, tenosynovitis, inguinal lymphadenopathy, generalised lymphadenopathy, retroperitonial lymphadenopathy, endomyocardial fibrosis and acute conjunctivitis were screened for filarial antigen and antibody by enzyme linked immunosorbent assay (ELISA). Out of 157 cases, 107 cases were positive for antigen or antibody, suggesting the role of filarial infection in these clinical presentations. All the 107 cases were treated with diethylcarbamazine citrate (DEC) and some of the patients who were followed showed relief in signs and symptoms. Hence assay of filarial antigen and/or antibody may be useful for diagnosing occult filarial syndromes for better management and further appropriate treatment.

Parasite Antigenemia in Untreated and Treated Lymphatic Filarial Infections

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.

Tropical Pulmonary Eosinophilia

Tropical pulmonary eosinophilia is an unusual pulmonary disorder caused by occult filariasis. Presentation can be varied and can mimic asthma, pulmonary tuberculosis, or atypical pneumonia. We have reported a case of tropical pulmonary eosinophilia mimicking lymphangitic carcinomatosis.

Enhanced Inflammation to Brugia malayi Microfilariae in Ferrets Infected with Trichinella spiralis

Intravenous (i.v.) injection ofmicrofilariae (mf) ofB. malayi in the ferret (Mustella putoriusfuro) has proven to be a convenient experimental method for study of the pathogenesis of occult filariasis. Following i.v. injection of mf, ferrets develop eosinophilia, immune clearance of circulating mf, and inflammatory responses to mf characteristic of tropical filarial eosinophilia or the Meyers-Kouwenaar (MK) syndrome of occult filariasis in man (Thompson et al., 1985, Experimental Parasitology 60: 181-194). Lesions visible on the surface of the liver, principally abscesses ofeosinophils measuring 1-2 mm in diameter, have been used to evaluate the inflammatory reactivity to mf. The number of lesions that develop following i.v. injection of mf is positively correlated with the level of peripheral blood eosinophils, but the relationship of lesion development to immune responses or hypersensitivity remains unclear (Thompson et al., 1985, loc. cit.). A preliminary observation indicated that Trichinella infection in ferrets induced eosinophilia and an enhanced inflammatory reaction to injected mf without evidence of cutaneous hypersensitivity to antigens ofmf. The objectives of the present study were to confirm the enhanced inflammatory reactivity to mf induced by Trichinella infection and to characterize the cellular and immune responses to mf in these ferrets which, it was considered, could help clarify mechanisms active in the pathogenesis of occult filariasis. The experimental procedures and immunologic assays have been described previously (Thompson et al., 1985, loc. cit.; Thompson et al., 1986, Zeitschrift fur Parasitenkunde 72: 525-535). To confirm that Trichinella infection altered

Brugia malayi: Intravenous injection of microfilariae in ferrets as an experimental method for occult filariasis

Microfilaremia, immune responses, and pathology were compared in ferrets infected with 100 third-stage larvae of Brugia malayi (subperiodic strain) or injected intravenously with 10 6 microfilariae. Ferrets ( Mustela putorius furo) inoculated with third-stage larvae typically became patent during the third month after infection, with a mean patency of 123 ± 25 (SE) days. Ferrets injected intravenously with microfilariae exhibited a relatively constant microfilaremia for 3–4 weeks and usually cleared microfilariae before the fourth month. Ferrets that cleared microfilariae after intravenous injection of microfilariae or after infection with third-stage larvae failed to become patent or became amicrofilaremic within 3 weeks after a challenge intravenous injection of 10 6 microfilariae. Clearance of circulating microfilariae was associated with eosinophilia and serum antibody specific for the microfilarial sheath in ferrets injected with microfilariae and in most ferrets infected with third-stage larvae. Ferrets infected with third-stage larvae and necropsied after clearance of microfilariae had tissue inflammatory reactions to microfilariae characteristic of occult filariasis (tropical eosinophilia) in man; these ferrets exhibited immediate cutaneous hypersensitivity and circulating reaginic antibody to antigens of microfilariae. In ferrets necropsied following two intravenous injections of microfilariae, the majority of ferrets examined within 10 days after clearance of microfilariae had visible liver lesions to microfilariae identical to those of the ferrets infected with third-stage larvae; immediate cutaneous hypersensitivity and reaginic antibody were not consistently detected in ferrets injected with microfilariae. Sera from ferrets that had cleared circulating microfilariae were transferred passively into ferrets made microfilaremic by intravenous injection of microfilariae. Sera with microfilarial sheath-reactive IgG antibody titers (⩾1:200) and microfilarial agglutination titers (⩾1:40) rapidly cleared injected microfilariae (<24 hr); this serum also cleared or greatly reduced circulating microfilariae established by an infection with third-stage larvae; only the IgG-containing fraction of the sera was active in immune clearance. Sera that cleared microfilariae of B. malayi did not clear circulating microfilariae of Dirofilaria immitis or prevent recurrence of circulating microfilariae of B. malayi in ferrets infected with adult filariae. Ferrets were examined at 1 and 3 weeks after transfer of sera and injection of microfilariae for lesions on the surface of the liver typical of occult infection. Ferrets that received sera inducing a rapid clearance of microfilariae did not develop liver lesions or eosinophilia. Only certain sera containing reaginic antibody to microfilarial antigens were associated with an accelerated development of liver lesions and eosinophilia. By the third week after injection, ferrets receiving normal sera had liver pathology and eosinophilia comparable to those receiving sera that induced the early development of lesions. There was a significant linear correlation between the numbers of surface liver lesions and the absolute numbers of blood eosinophils in all the ferrets injected with microfilariae.

A monoclonal antibody-based immunoradiometric assay for detection of circulating antigen in Bancroftian filariasis.

A monoclonal antibody designated Gib 13 has been used in an immunoradiometric assay (IRMA) to detect circulating antigen in the sera of Wuchereria bancrofti-infected subjects from an endemic area of Papua New Guinea. A clear association between the presence of patent infection and the Gib 13 target epitope in serum was established because 93% of microfilaremic individuals were antigen-positive. Moreover, there was a significant correlation between levels of serum antigen and blood microfilarial counts. Detection of circulating antigen in amicrofilaremic subjects with acute symptoms of lymphatic filariasis, and 53% of asymptomatic amicrofilaremic subjects, but not in nonendemic controls, suggests that the Gib 13 IRMA will also be of value in the diagnosis of occult filariasis. However, as in all IRMA based on detection of potentially immunogenic molecules in man, antibodies can be expected to be the major contributor to reduced sensitivity of the assay.

Drug trials with levamisole hydrochloride and diethylcarbamazine citrate in Bancroftian and Malayan filariasis

Seventy-eight microfilaraemic patients with Wuchereria bancrofti and Brugia malayi infections were treated with various oral levamisole hydrochloride total dosage regimes of 150 to 3,150 mg and total diethylcarbamazine citrate (DEC) of 36 and 126 mg per kg body-weight. Significant microfilaricidal and probable macrofilaricidal effects were seen at total levamisole hydrochloride dosages of 300 to 3,150 mg and the DEC dosages. The optimum dosage regime with levamisole hydrochloride recommended for treatment of microfilaraemic patients is 100 mg initially followed by 100 mg twice daily for 10 days. This dosage regime was as effective as a total oral dosage of DEC at 126 mg per kg body-weight. Side reactions were dose-dependent, mild and transient, with fever being the most common. One patient developed fits after 150 mg levemisole hydrochloride. The pathophysiology of these side reactions is discussed and it is recommended that levamisole hydrochloride, as a probable alternative for the treatment of patent and occult filariasis, should be used only under close medical supervision.

SPECIFIC ALLERGIC SENSITISATION TO FILARIAL ANTIGENS IN TROPICAL EOSINOPHILIA SYNDROME

Reaginic antibodies to antigens from thehuman filarial parasites Wuchereria bancrofti and Brugia malayi and the animal parasite Dirofilaria immitis were studied by histamine release from basophils in 7 patients with tropical eosinophilia (T.E.) and 18 patients with other manifestations of filarial infection (lymphatic changes or symptomless microfilaræmia). All the patients had antibodies to all three filariæ but T.E. patients were more highly sensitised. T.E. patients responded more to antigens from microfilariæ than did patients with non-T.E. filariasis and responded more to microfilarial antigens from the human parasites than to those from the animal parasite. These findings support the view that T.E. is a form of occult filariasis which results from host hypersensitivity to the microfilarial stage of parasites which, in other individuals, cause the more common lymphatic manifestations of filarial disease.

Aspects of the life-history of Dirofilaria roemeri in naturally and experimentally infected kangaroos, wallaroos and wallabies

Spratt D. M., 1972. Aspects of the life history of Dirofilaria roemeri in naturally and experimentally infected kangaroos, wallaroos and wallabies. International Journal for Parasitology, 2: 139–156. The incidence, distribution, number and size of Dirofilaria roemeri in wild kangaroos, wallaroos and wallabies is reported. Pathological reactions in naturally and experimentally infected hosts are discussed. The wallaroo is a normal host; the prepatent period is 9 months and microfilariae exhibit diurnal sub-periodicity in the peripheral blood. The grey kangaroo and red-necked wallaby are abnormal hosts; microfilariae are absent from the blood due to their destruction in eosinophilic granulomas in capsules surrounding adult worms. D. roemeri infections in wallaroos and kangaroos resemble the human disease conditions of classical and occult filariasis. The evolution of D. roemeri in macropodids is discussed.

Filarial antibodies and eosinophilia in human subjects in an endemic area

Blood samples from 96 subjects from 5 villages in an area endemic for Malayan filariasis in Malaysia were examined for the presence of microfilariae, level of eosinophilia, and presence of antibodies to microfilariae and to infective larvae of Brugia malayi. Subjects were grouped according to clinical signs or symptoms attributable either to readily discernible filarial infections or to a form of occult filariasis generally known as “eosinophilic lung”. Certain patterns of antibody production were discernible in that humoral antimicrofilarial antibodies were found in all persons with elephantiasis and in smaller proportions of subjects in other groups, but not in subjects with microfilaraemia or chronic asthma. Antibodies against the infective larva were commonly found in all groups, most often in subjects with microfilaraemia, elephantiasis, and eosinophilia. The interrelationships between sensitization to filarial antigens in subjects with microfilaraemia, eosinophilia, and occult filariasis were discussed.

Dirofilaria tenius containing microfilariae in man.

SummaryAn adult female D. tenuis containing microfilariae was found in the subcutaneous tissues of the abdominal region of a man from Florida. Structures resembling dead microfilariae were seen within nearby granulomata. The eosinophilia, antibody titers, and apparent response to diethylcarbamazine suggest occult filariasis similar to that seen in Southeast Asia.