EPIDEMIOLOGY
Lymphatic filariasis is a parasitic infection affecting about 120 million people in more than 80 countries (Michael 1996, WHO 2000). It is caused by two main types of filarial worms: Wuchereria bancrofti and Brugia (malayi or timori). Wuchereria bancrofti or "bancroftian filariasis" is widespread, found in tropical regions of Asia, Africa, China, the Pacific islands, and in parts of the Caribbean and South America. "Brugian filariasis" is less common. Brugia malayi is found in parts of Asia stretching from India in the west to Korea in the east while Brugia timori is found in Indonesia (FGN 1996).

Lymphatic filariasis is transmitted by mosquitoes, which become infected when they ingest microfilarial larvae from the blood of a person with lymphatic filariasis. After the larvae develop in the mosquito, they can be transmitted to another person during another blood meal. When they enter the human, the larvae migrate to lymphatic vessels where they develop into macrofilariae (adult worms). When adult female worms become sexually mature, they can mate and produce microfilariae. These migrate to the blood and complete the life cycle. The exact length of time it takes for the parasites to develop from infective larvae to sexually mature adult forms in humans (prepatent period) is uncertain but thought to be about 12 months (Mahoney 1971).

The number of microfilariae worms in a person's blood changes during the day and exactly when depends on the species. Most species show high levels during the night and peak between 10 pm to 4 am (Simonsen 1997); this coincides with the time when mosquito vectors are actively feeding. In the Pacific islands including Fiji, Samoa, and the Philippines, some strains of Wuchereria bancrofti microfilariae peak in numbers during the day (Scott 2000).

CLINICAL FEATURES
People with filariasis may have no symptoms, or a variety of acute and chronic symptoms. People without symptoms may be found with damaged lymphatic elements, including widening of the lymphatic vessels (lymphagiectasia), and thickening of the spermatic cord, if examined very carefully (Addiss 2000, Dreyer 2000).

People with chronic disease commonly have hydrocoele (excess fluid inside the scrotal sac), lymphoedema (swelling and enlargement of affected areas of the body), and elephantiasis (long standing enlargement and swelling of the limbs, scrota, or breasts associated with skin thickening).

Filarial infection is usually diagnosed by testing the blood for microfilariae, but this does not detect all people infected. An antigen assay is more sensitive and is useful for blood collected during the day or night (Weil 1997). This assay indicates the presence of the adult worm and detects people with an infection but without microfilariae. Ultrasound imaging will demonstrate adult worms, and movements will show that they are alive (Dreyer 1995).

How the filarial worm causes disease is not well understood. The following mechanisms have been proposed: adult worms living in and damaging lymph vessels; immunological reactions to the presence and death of filarial worms; or secondary infections of affected areas, which contribute significantly to both acute and chronic disease manifestations (Dreyer 2000). Researchers have also suggested that toxins released by Wolbachia bacteria ‐ endosymbiotic bacteria found within the cells of filarial worms ‐ cause disease (Taylor 2001).

CONTROL
One aim of the global lymphatic filariasis control strategy is to reduce microfilariae in the community to levels that prevent transmission (Ottesen 1997, Ottesen 1999). It is unclear whether drug based control programmes should aim simply for a reduction in microfilarial densities or complete clearance of microfilariae from the blood. This is because the level of microfilaraemia (microfilariae in the blood) below which an individual cannot infect mosquitoes is uncertain. Belding 1952 refers to observations that suggest that 0.5 microfilariae per cubic millimetre will fail to infect a mosquito, 3 produce optimal infections, while 10 kill the mosquito. This raises the question of whether drug induced reduction in microfilaraemia can potentially increase transmission, when microfilaraemia falls to a level that enhances the efficiency of mosquito vectors. Mass drug administration programmes need to aim for a sustainable reduction in microfilarial loads below a critical threshold, or a complete clearance of microfilariae from the blood of infected people in order to have an appreciable impact on transmission. The impact on transmission can be enhanced, if currently available antifilarial drugs demonstrate a killing or sterilizing effect on adult worms, in addition to their effect on microfilariae.

It has been observed that some infected people lose their microfilariae in the absence of treatment (Vanamail 1990). However, microfilaraemia prevalence rates are believed to be stable over time in endemic communities in the absence of community treatment (Meyrowitsch 1995). Stability in microfilaraemia prevalence in endemic communities can be attributed to the fact that while some people are losing their microfilariae, others are acquiring new infections, resulting in a steady state situation (Vanamail 1990, Weil 1999).

DIETHYLCARBAMAZINE AND IVERMECTIN
Diethylcarbamazine has been in use for filariasis for more than 50 years. For many years, the recommended regimen for diethylcarbamazine was daily courses of 6 mg/kg for 12 days (WHO 1984). For reasons related to practicality in community mass treatment, alternative diethylcarbamazine dosage regimens, including spaced weekly, monthly, annual, and biannual single doses have also been tried (Eberhard 1989, Andrade 1995, Simonsen 1995). Ivermectin is used for the treatment of onchocerciasis and has been reported to potentially have a role in the control of lymphatic filariasis (Cartel 1990, Coutinho 1994, Cao 1997).

Adverse effects of antifilarial drugs are an important consideration in lymphatic filariasis control as they can be serious and prevent people from completing treatment. There are two types of adverse effects to antifilarial drugs: those that are related to drug toxicity and can occur in infected and non‐infected people, and include nausea, anorexia, vomiting, or drowsiness; and those related to the inflammatory response mounted by the infected person to dying worms (WHO 1984, Dreyer 1994). Systemic effects are mainly due to dying microfilariae and can include fever, headache, malaise, myalgias (muscle pain), and haematuria (blood in urine). The severity of these effects is thought to relate to the level of pretreatment microfilarial load (Coutinho 1994, Haarbrink 1999, Horton 2000). Local effects are mainly due to dying adult worms and can include localized pain, tender nodules, lymphadenitis (inflammation of the lymph nodes), and lymphangitis (inflammation of lymph vessels). The risk of local effects may be higher with diethylcarbamazine than with ivermectin because of its reported partial action on macrofilariae, but this has not been formally assessed (Dreyer 1994, Dreyer 1995, Figueredo‐Silva 1996).

ALBENDAZOLE
Albendazole is used widely to treat intestinal parasites and has been suggested to have a potential role in lymphatic filariasis control (Ottesen 1999). A report from an informal consultation on albendazole in lymphatic filariasis suggests that albendazole in repeated high doses has a killing or sterilizing effect on adult Wuchereria bancrofti worms (Jayakody 1993, CDS/FIL 1998). However, uncertainty remains as to whether it has an effect on microfilariae or on the adult worm. It is unclear whether adding albendazole to either diethylcarbamazine or ivermectin increases the risk of adverse effects, but Horton 2000, in a narrative review of the safety of albendazole combinations with diethylcarbamazine or ivermectin, suggests that adding albendazole to either drug did not appear to increase the frequency or severity of adverse effects.

In this review, we aim to summarize the evidence for the effects of albendazole alone or in combination with diethylcarbamazine or ivermectin in the individual treatment and community control of lymphatic filariasis.