With newer definitions of clinical syndromes in lymphatic filariasis and new tools to assess clinical status (e.g. ultrasound, lymphoscintigraphy, circulating filarial antigen assays), approaches to treatment based on infection status and pathogenesis have been proposed (Addiss and Dreyer, 1999). These changing perspectives of lymphatic filariasis have important implications for treatment.
In areas where lymphatic filariasis is endemic, most infected persons are clinically asymptomatic despite the presence of circulating microfilariae. A growing body of evidence indicates that although they may be asymptomatic, virtually all persons with W. bancrofti or B. malayi microfilaremia have some degree of subclinical disease (hematuria, proteinuria, abnormalities on lymphoscintigraphy). Thus, early treatment of asymptomatic persons is recommended to prevent further lymphatic damage. DEC, which has both macrofilaricidal and microfilaricidal properties, is the drug of choice (Ottesen, 1985). The macrofilaricidal action of DEC is not intended to reverse existing lymphatic damage but rather to prevent further adult worm-associated lymphatic damage and dysfunction. The micro-filaricidal activity of DEC clears the blood of microfilariae, reduces the opportunity for mosquito-borne transmission of the parasite, and reverses filaria-associated hematuria and protein-uria.
Regimens that emphasize single-dose diethyl-carbamazine, ivermectin or combinations of single doses of albendazole and diethylcarbama-zine, or albendazole and ivermectin, have each been demonstrated to have a sustained micro-filaricidal effect.
Because lymphatic disease is associated with the adult worm, treatment with DEC is recommended for microfilaria-negative adult worm carriers, i.e. persons who are microfilaria-negative but filaria antigen- or ultrasoundpositive.
Acute Manifestations of Lymphatic Filariasis: Filarial Adenolymphangitis (FADL)
Supportive treatment is recommended, including rest, postural drainage (particularly if the lower limb is affected), cold compresses at the site of inflammation, and antipyretics and analgesics for symptomatic relief. During the acute episode, treatment with antifilarial drugs is not recommended, because it may provoke additional adult worm death and exacerbate the inflammatory response. After the acute attack has resolved, if the patient remains microfilaria- or antigen-positive, DEC can be given to kill the remaining adult worms.
Acute Dermatolymphangioadenitis (ADLA)
Dilatation of the lymphatic vessels induced by the presence of the adult worm eventually leads to lymphatic dysfunction and accumulation of protein-rich fluid in the tissues. The lower limbs, in particular, become predisposed to recurrent bacterial infections. Trauma, interdigital fungal infections, and onychomycosis provide entry sites for these bacteria, which multiply rapidly and cause a reticular lymphangitis of the small collecting vessels (ADLA) (Dreyer and Noroes, 1997; Dreyer and Piessesns, 1999). Treatment with DEC appears to have no effect on the outcome of ADLA (Shenoy et al., 1995). Instead, cold compresses, antipyretics and analgesics are recommended. The patient should remain at rest with the affected limb elevated. Antibiotic therapy must be initiated while awaiting results of cultures of blood or tissue aspirates. The bacteria isolated during these attacks are sensitive to most systemic antibiotics, including penicillin.
Chronic manifestations of lymphatic filariasis include lymphedema, urogenital disease and adenopathy. Although antifilarial drug therapy is rarely, if ever, the 'definitive' treatment for these conditions, such treatment is indicated if the patient has evidence of active infection, e.g. detection of microfilaria or filarial antigen in the blood, or of the 'filaria dance sign' on ultrasound examination. Not infrequently, the inflammatory response secondary to treatment-induced death of the adult worm exacerbates manifestations of chronic disease.
Data indicate that filarial elephantiasis and lymphedema of the leg may be partially reversible with a treatment regimen that emphasizes hygiene, prevention of secondary bacterial infections and physiotherapy. This regimen is similar to that now recommended for treatment of lymphedema in Europe, Australia, and the USA (Foldi et al, 1989; Kobayashi and Miller, 1987; Mortimer, 1990; Campisi, 1991; Casley-Smith and Casley-Smith, 1992; Pappas and O'Donnell, 1992; Boris et al., 1994), where it is known by a variety of names, including 'complex deconges-tive physiotherapy' and 'complex lymphedema therapy'.
A variety of surgical procedures for lymph-edema have been attempted since early in the century (Matas, 1913), but results have generally been unsatisfactory (Watson, 1953; Miller, 1977; Jamal, 1981). These procedures include lymph-angioplasty, lympho-venous anastomosis, and excision ('de-bulking') of fibrotic subcutaneous tissue (Kobayashi and Miller, 1987; Mortimer, 1990; Jamal, 1981).
The chronic urogenital manifestations of lymphatic filariasis include lymphedema and elephantiasis, lymph scrotum, hydrocele, chylocele and chyluria. The principles of treatment of scrotal and penile lymphedema are similar to those described above for lymphedema of the leg, although the prognosis is more guarded. Attention to hygiene and skin care are essential to prevent secondary bacterial infections. Additional treatment for fungi, especially candidiasis, is particularly important. The results of surgical intervention are less than ideal.
Treatment of elephantiasis of the penis is particularly difficult. Surgical procedures have been recommended, but only after secondary bacterial infections have been adequately treated (Bejanga and Husain, 1984).
Hydrocele is the most frequent chronic manifestation of bancroftian filariasis. The prevalence of hydrocele in men increases with age and tends to parallel that of microfilaremia in the general population. The definitive treatment for hydro-cele is surgical; a variety of techniques have been recommended (Lord, 1964; Rodriguez et al.,
1981; Wannas, 1983; Dandapat et al., 1984; Albrecht et al., 1991).
Treatment for chyluria includes rest and a diet rich in protein but low in fat (Yu, 1984). Improvement has been reported when medium-chain triglyceride was the only source of dietary fat (Hashim, 1964). Adequate hydration is recommended to increase the frequency of micturition and decrease the risk of clot formation within the bladder. Surgical treatment for chyluria is controversial, but it is sometimes recommended for severe or intractable cases (Kanetkar et al., 1966; Wickham, 1976). Lymphangiography-directed surgical 'lymphatic disconnection' for intractable cases has been reported to have good results (Karanjavala, 1979).
Tropical Pulmonary Eosinophilia (TPE)
DEC is the drug of choice for treatment of TPE. Characteristically, respiratory symptoms rapidly resolve following treatment with DEC. Because DEC does not appear to kill all the adult worms in most infected persons, the short-term resolution of TPE symptoms following treatment is most likely the result of rapid killing of the microfilariae. A 12 or 21 day course of DEC results in more rapid clearance of microfilaremia than a single 6 mg/kg dose. Therefore, the longer course of treatment is recommended in order to kill microfilariae as rapidly as possible. Despite dramatic initial improvement following conventional treatment with DEC, symptoms recur in approximately 20% of patients 12-24 months after treatment (Udwadia, 1975), and a majority of patients continue to have subtle clinical, radiographic and functional abnormalities 5-40 months after treatment (Dreyer and Noroes, 1997). If the adult worms are visible by ultrasound, ultrasonographic monitoring may be used to assess efficacy of treatment against the adult worm (Dreyer et al., 1996). Repeat treatment may be necessary.
In summary, the currently recommended 12 day, 72 mg/kg course of DEC treatment, or variations thereof (Anonymous, 1998), have remained the standard for many years; however, recent data indicate that single-dose treatment with 6 mg/kg DEC has comparable macrofilaricidal and long-term microfilaricidal efficacy. The 12 day course provides more rapid short-term microfilarial suppression but when other factors are considered, including cost, convenience and patient compliance, it now seems reasonable to recommend single-dose treatment for individual patients with W. bancrofti or B. malayi infection. Single-dose treatment can be repeated every 6-12 months for persons who remain infected. Because it reduces microfilarial density more rapidly, the 12 day course of treatment is recommended for patients with TPE or hematuria, both of which are associated with microfilariae rather than the adult worm (Addiss and Dreyer, 2000).
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