The filariases

Under this generic title are grouped a variety of diseases which bear little relation to each other pathologically, although they are produced by nematode worms all belonging to the superfamily Filariodea. Man is the definitive host of several filarial nematodes. Their embryos (microfilariae) are taken up by insect vectors when feeding on man. They pass through a developmental cycle lasting about 2 weeks, at the end of which infective larvae are present in the proboscis. When the insect next feeds, the larvae escape and pass through breaches of the skin surface into the tissues.

Filariasis (Bancroftian and Malayan)

Filariasis results from infection with the parasite nematodes Wuchereria bancrofti and Brugia malayi. It is estimated that at least 120 million people throughout the world are infected and 1 billion are 'at risk' of infection in about 90 countries. Indeed, the prevalence is increasing worldwide due to uncontrolled urbanization in many of the endemic countries. The life cycle is shown in Figure 7.14.

The features of the life cycles of these two filariae are practically identical {Brugia malayi alone may also infect animals as well as man). The adult worms live in the lymphatic system where the female worms, which are viviparous, produce sheathed microfilariae which are about 200-300 (xm long. Many species of mosquitoes, belonging to the genera Culex, Aedes, Anopheles and Mansonia, can act as intermediate hosts of W. bancrofti and B. malayi.

The microfilariae of B. malayi can be distinguished from those of W. bancrofti on morphological grounds and by their staining reaction to Giemsa.

Microfilariae of both W. bancrofti and B. malayi appear in the peripheral blood at distinct times of the day - a characteristic referred to as periodicity. The controlling mechanism for this periodicity has never been satisfactorily explained. It does not appear to depend on the parasympathetic system, nor is the microfilarial count influenced by alterations in the corticosteroid level in the blood of man, or by a general anaesthetic.

B. timori is a nocturnal periodic species found in Indonesia and transmitted by A. barbirostris.

Epidemiology

The geographical distribution of the parasites is determined largely by climate and the distribution of their mosquito vectors (see Fig. 7.15).

Whereas W. bancrofti has so far been found only in man, B. malayi is a parasite of both man and animals.

The most consistent sign of infection is the appearance of microfilariae in the peripheral blood but many microfilaria carriers are apparently symptom-free and remain so for many years or for life. Severe disabling symptoms or deformity are usually due to a long period of exposure and reinfection.

Males are usually more frequently affected than females. This higher incidence of microfilaraemia in males is probably due to a greater chance of infection; it is possible, however, that a hormonal influence may be responsible. Most surveys for either form of W. bancrofti have shown low microfilaria rates in children below the age of 5 years, probably because W. bancrofti takes a long time to produce a patent microfilaraemia. In contrast, it has been shown that high microfilarial rates occur in children under 5 years with both forms of B. malayi; thus, a low infection rate among children under 5 years usually implies low transmission for B. malayi in the area surveyed.

Rapid mapping techniques have been developed as well as indirect methods, such as the use of key informants responding to self-administered questionnaires about the prevalence of hydrocele and lymphoedema; and the use of mobile health workers to examine an established number of persons for lymphoedema and hydrocele, have been successfully employed to assess the endemicity of filariasis in Ghana and elsewhere.

WUCHERERIA BANCROFTI

Occurrence:

Organism: Reservoir. Transmission: Control:

Worldwide in the tropics

Wuchereria bancrofti Humans

Culex and Anopheles spp.

Treatment with dietm '. arbamai; ne and Albendazole Ivermectin ana Alb jnda;. Je

(in areas where onchocerciasis coexists) ¡I I ^^^p ^

Vector control

Mosquitoes may also bite animals in 8. malayi transmission

Mosquitoes bite man and inject larvae in both 8. malayi and W. bancrofti

Mosquitoes may also bite animals in 8. malayi transmission

Mosquitoes bite man and inject larvae in both 8. malayi and W. bancrofti

Filariases

Mosquitoes take up larvae from blood

Figure 7.14: Life cycles of Bancroftian and Malayan filariases. Brugia malayi may infect animals.

Mosquitoes take up larvae from blood

Figure 7.14: Life cycles of Bancroftian and Malayan filariases. Brugia malayi may infect animals.

also

Two biologically different forms of W. bancrofti exist:

■ nocturnal periodic;

■ diurnal subperiodic.

Nocturnal periodic

The microfilariae appear in the eripheral mlraci between 10 pm and 2 am. This form is predominant]}' an infection of urban communities, transmitted by

Brugia Malayi
Figure 7.15: Distribution of Wuchereria bancrofti and Brugia malayi.

the domestic night-biting mosquito Culex quinque-fasciatus; as well as by Anopheles species in the African region and elsewhere (Plate 89). It has an almost worldwide distribution, occurring in Central and South America, West, Central and East Africa, Egypt and South East Asia (see Fig. 7.15).

predominantly an infection of rural populations, in contrast to the usual urban distribution of W.

bancrofti. There are two forms of B. malayi:

■ nocturnal periodic;

■ nocturnal subperiodic.

Diurnal subperiodic

In this form, microfilariae are present in appreciable numbers throughout the 24 hours but show a consistent minor peak diurnally (usually sometime in the afternoon). It is restricted to Polynesia and is transmitted mainly by day-biting mosquitoes (Aedes spp.). The growth of the human population, uncontrolled increasing urbanization and migration have all contributed to an increase in the prevalence of W. bancrofti.

Nocturnal periodic

The microfilariae show markedly nocturnal periodicity in the blood (10 pm to 2 am). This form has a tendency to occur in small endemic foci in countries extending from the west coast of India to New Guinea, the Philippines and Japan. It is transmitted by the Mansonia mosquitoes of open swamps (Plate 90), lakes and reservoirs, which bite mainly at night and also Anopheles species. The periodic form is found mainly in man, and animal infections are rare.

BRUGIA MALAYI

Occurrence:

South East and East Asia

Organism:

Brugia malayi

Reservoir:

Humans, animals

Transmission:

Mansonia and Anopheles spp.

Control:

Treatment with

diethylcarbamazine and

Albendazole

Vector control

Human infection with B. malayi has only been recognized in Asia (see Fig. 7.15), where it is

Nocturnal subperiodic

In the subperiodic form the microfilariae tend to be present throughout the 24 hours with a minor nocturnal peak from 10 pm to 6 am. This nocturnally subperiodic form has been found, to "; ite, only in Malaysia, Borneo and Palawan Islkä in the Philippines. It is transmitted by the Shmsonia of swamp forest, mosquitoes which will bite :n diade at any time and also by CoquiUethidia crassipek. i; -contrast to the periodic form, the subperiodic form is found in many animals (p 'matts^i carnivoiet rodents, etc.) as well as man.

LABORATORY DIAGNOSIS OF FILARIASIS

Isolation

The finding of microfilariae in the blood provides the certain diagnosis of filarial infection. It is important to realize that microfilariae may be absent in the very early or late stages of the infection - thus in only 4% of patients with elephantiasis and 30% with hydrocoeles are microfilariae found in the blood.

Thick blood films should be taken at the appropriate times (e.g. at night for microfilaria of W. bancrofti) and fresh cover-slip preparations examined. Simultaneously, dried, stained specimens should be made and the microfilariae identified. Many techniques are available for concentrating blood microfilariae.

Microfilariae may also be found in fluid obtained from hydrocoeles, varices, pleura, joints and in ascitic fluid. Eosinophilia is usually present. Occasionally the adult filarial worms may be found in biopsy of lymph glands, or by X-ray when calcified.

Antigen detection tests on children's blood have shown that 2% are infected by the age of 2 years and 16% by the age of 4 years in endemic areas. They also obviate the use of taking night blood films. A rapid dipstick method for the diagnosis of B. malayi is available.

Serology

Serodiagnostic methods for the diagnosis of filari-asis have been widely used. There is a range of variation in the results obtained and these variations derive partly from differences in technique of antigen preparation. These immunodiagnostic methods are group specific (i.e. positive in any filarial infection) and on the whole still unsatisfactory especially as they are unable to discriminate between past exposure, treated cases and current infection. Circulating filarial antigens can be detected in a drop of blood with the use of monoclonal antibodies using a dot ELISA technique which can be carried out without sophisticated equipment.

In central laboratories DNA-based technology can be used for diagnosis of filarial infection, both in humans and in the mosquito vectors by PCR-based assays, which provide excellent sensitivity and specificity.

CONTROL OF FILARIASIS

The filariases may be controlled by reducing the human reservoir with mass drug administration (MDA) and attacking the vector mosquitoes.

In 1997, the World Health assembly called for the elimination of lymphatic filariasis as a public health problem. The major thrust of the programme is MDA, which has been greatly facilitated by the free donation of Albendazole by Glaxo Smith Kline and Mectizan (Ivermectin) by Merck & Co., for as long as they are needed for the elimination of the disease.

MDA can be achieved either by the distribution of diethylcarbamazine (DEC)-fortified salt as has been successfully used in China and India, or by single annual or semi-annual treatment of DEC plus albendazole as is being envisaged in the global filariasis elimination programme. In areas where filariasis coexists with onchocerciasis and loaiasis, DEC 6mg/kg plus Ivermectin 400g/kg will be coadministered. The aim of the MDA programme is to reach the entire global at-risk population over the next 20 years.

Community involvement could be enhanced by simultaneously providing symptomatic treatment for lymphoedema based on regular washing of skin with soap and water, limb elevation, topical application of antibiotics and antifungal creams (Plate 91). The delivery of drugs could be either through existing health services or community directed. Mathematical models could provide powerful tools for analysis, prediction and control strategies.

The vector

Control measures may be taken against the aquatic stages of the mosquito by eliminating breeding places, using insecticides to kill aquatic forms; or in the case of Mansonia mosquitoes, destroying, by herbicides or hand collection, the water vegetation on which the insect is dependent. The insecticidal control of most adult culicine mosquitoes is important. Where the vectors are anophelines, malaria control methods are effective. Larval control of C. quinquefasciatus is now only possible by using pyrethroids such as pcrmcthri n. siuçe resistance to the organophosphorus insecticides is now widespread.

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