Lymphatic Filariasis

Organism Wuchereria bancrofti, Brugia malayi and B. timori, nematode worms. Microfilariae, the larval form present in the peripheral blood, are taken into the mosquito's stomach when it feeds on humans (or animal reservoir in B. malayi). The larva loses its sheath inside the mosquito, migrates through the stomach wall and burrows into the muscles of the thorax. It becomes shorter and fatter, commonly described as sausage-shaped. Developmental changes take place and it elongates to a third stage - infective larva. Leaving the thoracic muscles, it migrates to the proboscis where it waits for the mosquito to feed. Forcing its way out of the proboscis, it falls on to the skin, finding a way into the tissues, generally through the wound made by the mosquito (Fig. 15.8). (It is important to realize that the infective larvae are not injected like the malaria parasite.) This developmental stage in the mosquito - from the time of the blood meal until re-infection - takes 11-21 days (average 15 days) at an optimum temperature of 26-27°C (extremes are 17-32°C), a very similar length of time to the development of Plasmodium.

When the larva breaks out of the mosquito to enter the skin, it is a very precarious time for the parasite and only 20-40% are successful. No multiplication takes place in the mosquito, so the single larva that was taken up in the blood meal becomes a single adult in the human. However, many larvae are lost with only about one in 700 succeeding. Since there are male and female worms, it is necessary for the two sexes to meet if the female is to be fertilized. Many are unsuccessful as a result of competition between males, so the intensity of infection will determine the outcome. Once fertilized, microfilariae are liberated into the lymphatic stream, reaching blood vessels via the thoracic duct.

The parasite times its production of microfilariae to coincide with the biting time of the vector mosquito, a phenomenon called periodicity. Mostly this is a nocturnal cycle, with a peak at around midnight, but can also be diurnal, or in the Central and Eastern Pacific Islands, it is aperiodic with similar levels of microfilariae being found throughout the 24 h period.

Microfilariae live for about 6 months and adult worms for 7-12 years although they probably only produce microfilariae for 2-3 years.

Clinical features In the body, the larva reaches the lymphatics and settles down in a lymphatic node to develop into an adult. It is the obstruction of the lymphatic drainage system by the adult worms, especially the fibrotic reaction when they die, that causes the series of disease manifestations. A range of conditions result, including fever, lymphangitis, lymphoedema, hydrocele, elephantiasis and chyluria. Night sweats are a common early indication of infection, with high eosinophilia count found in the blood. An allergic reaction, tropical pulmonary eosinophilia syndrome can also result. Although the signs and symptoms are diverse and variable, in an endemic area, they are often known and a blood sample will soon confirm the diagnosis.

Diagnosis used to be by finding microfilar-iae in a measured sample of blood using a thick blood smear, counting chamber or filtration technique, taken during the peak microfilarial output, which generally means collecting samples at night time. These laborious methods have now largely been replaced by circulating filarial antigen (CFA) detection, either based on ELISA or an immunochromatographic card. However, the card test only diagnoses positive or negative, while the ELISA is semi-quantitative, so where full quantitative measures are required, measured blood sample methods will still need to be used. This will be the case in assessing control programmes, as a

Distribution Filariasis Indonesia

Fig. 15.8. Life cycle and clinical features of lymphatic filariasis.

decrease in the number of microfilariae occurs before conversion to negativity. CFA detection is also not available for B. malayi or B. timori. Different microfilariae need to be differentiated as seen in Fig. 15.9, as several filarial infections may be present in the same locality.

Transmission is by both culicine and ano-pheline mosquitoes producing different pat terns of infection and as a result, different strategies for control (Table 15.3). If Anopheles mosquitoes are the vectors, they are nearly always the same vectors as those that transmit malaria, so the mosquito might well have a double infection or its expectation of life affected by being parasitized by filariasis and/or malaria.

As the microfilaria is quite large and causes damage to the mosquito when it

Microfilaria found in peripheral blood

Microfilaria found in skin

Sheathed

Non-sheathed

Nocturnal periodicity

Diurnal periodicity

No perodicity

Wuchereria bancrofti

Brugia malayi

Loa loa

Onchocerca volvulus

Sheath stained pink by Giemsa stain

Sheath stained red by Giemsa stain

Sheath not stained by Giemsa stain

Graceful curves

Small, round discrete nuclei

No nuclei at tip of tail

Graceful curves

Small, round discrete nuclei

No nuclei at tip of tail

Kinked curves

Large, oval overlapping nuclei

Kinked curves

' Large, oval overlapping nuclei

2 separate nuclei at tip of tail

Nuclei to tip of tail

Microfilaria Loa Loa Giemsa Stain

Spatulate head

No nuclei at tip of tail

Spatulate head

No nuclei at tip of tail

Size 210-320 x 7.5-10 |m Size 170-260 x 5 - 6 |m Size 230-300 x 7.5-10 |im Size 280-330 x 6-9 |m

Fig. 15.9. Differential features of microfilariae of medical importance. (Courtesy: Department of Medical Parasitology, London School of Hygiene and Tropical Medicine.)

bores into the thoracic muscles, the more microfilariae it ingests the more likely it is to be killed by a heavy infection. (In Culex and Aedes mosquitoes, this occurs when the microfilarial density exceeds 50 per 20 mm3 of blood.) This is seen in Fig. 15.10 at point E for both culicine mosquitoes (upper figure) and anopheline mosquitoes (lower figure). The line P represents the equilibrium level (basic reproductive level of 1), whereby above the line, transmissions will increase and below it, infection will die out; so when infection is excessively heavy, mosquito mortality occurs and the infection dies out. In reality, the number of microfilar-iae will decrease below E, mosquitoes will survive sufficiently to transmit again and the level will approach E, or the level of equilibrium, again. This is always the case with culicine transmission, but in the bottom figure, it will be observed that there is also a lower point I below which transmission is not sustained for anopheline mosquitoes. In other words, at low levels of microfilariae, the anopheline mosquito seems to be able to prevent itself from becoming infected. This is probably due to the pharyngeal armature in anopheline mosqui

Table 15.3. The vectors of lymphatic filariasis. (A., Anopheles; Ae., Aedes; C., Culex; M., Mansonia; O, Ochlerotatus.)

Geographical area

Species transmitting W. bancrofti

Species transmitting B. malayi

West Africa, rural

A. gambiae, A. funestus,

East Africa,

A. arabiensis, A. melas,

Madagascar

A. merus

Urban East Africa

C. quinquefasciatus

Egypt

C. pipiens molestus

India, Sri Lanka and

C. quinquefasciatus, A. minimus,

M. amulifsra, M. indiana, M. uniformis,

Maldive Islands

Ae. niveus, O. harinasutai

M. annulata, M. bonnsas, M. divss

China

Ae. togoi, A. sinensis,

As. togoi, A. lsstsri, A. sinsnsis,

A. anthrapophagus

A. anthrapophagus

Vietnam

A. jeyporiensis

Rural Thailand

O. hariniasutai

M. annulata, M. bonnsas, M. uniformis, M. indiana

Malaysia

A. letifer, A. whartoni,

M. annulata, M. annulifsra,

A. maculatus, A. dirus,

M. bonnsas, M. divss, M. uniformis,

A. donaldi, A. letifer,

A. campsstris, A. donaldi

A. maculatus

Indonesia

A. balabacensis, A. leucosphyrus,

M. annulata, M. bonnsas, M. divss,

A. maculatus

A. barbirostris (B. timori)

Philippines

M. divss

New Guinea (PNG

A. farauti, A. punctulatus,

and Irian Jaya)

A. koliensis, C. annulinostris, C. bitaneniorhynchus, M. uniformis

New Caledonia

Ae. vigilax

Fiji

Ae. polynesiensis, Ae. fijiensis, Ae. pseudoscutellaris, Ae. oceanicus

Polynesian Islands

Ae. polynesiensis, Ae. samoanus, Ae. upolensis, Ae. kesseli, Ae. tutuilae, Ae. tabu, Ae. cooki

Northeast Brazil

C. quinquefasciatus

Punctulatus MosquitoMicrofilaria Filaria
Fig. 15.10. The dynamics of culicine-and anopheline-transmitted filariasis. (Reproduced, by permission, from Pichon, G., Perrault, G. and Laigret, J. (1975) Rendement parasitaire chez les vecteurs de filarioses. (WHO/FIL/75.132), World Health Organization, Geneva.)

toes which damages microfilariae. When there are many microfilariae ingested by the mosquito, a sufficient quantity will remain undamaged to produce infection, but at low microfilariae levels, every microfilaria will be damaged. This applies to both W. bancrofti and B. malayi, so for control, the type of mosquito is more important than the species of parasite.

Filarial infection is determined by the number of infected bites, which can either be the result of a high intensity over a short period of time or constant bites over a long period of time. Mosquito mortality occurs when density of microfilariae is excessive, so the chronic, long-term pattern is more common.

Incubation period From infection to the development of adult worms is about 1 year, but the first symptoms may not occur until microfilariae are produced (fever) or worms die (lymphatic obstruction).

Period of communicability Since many infective bites are required to produce infection in humans, there will need to be a continuous supply of infected mosquitoes.

The development cycle in the mosquito is 11-21 days (mean 15 days). The infected person can continue to produce microfilar-iae for more than 10 years, although the maximum output is in the first 3 years.

Occurrence and distribution Only humans are infected with W. bancrofti, but an animal reservoir exists for B. malayi in monkeys, cats and several other animals. All races, both sexes and all ages of persons are equally susceptible to infection. (There are marked differences between individuals developing elephantiasis, but these are immunological rather than ethnic.)

Three types of filariasis are seen - rural filariasis transmitted by nocturnal Anopheles mosquitoes with a generalized distribution similar to that of malaria, urban filariasis transmitted by Culex, with a tendency to invade new areas, and the Polynesian Island variety, which has a homogenous (rural) distribution, but is transmitted by day-and-night biting Aedes mosquitoes.

W. bancrofti is found in the tropical regions of the world, but with only a few foci in South America and the Caribbean. B. malayi is restricted to East and Southeast Asia, overlapping with W. bancrofti in part of its range. B. timori is only found in the islands of Timor, Flores, Alor and Roti (Fig. 15.11). There are more than a billion people at risk in 80 countries.

Control and prevention A similar process to that used for malaria for identifying the best strategies for control can also be applied to filariasis. The various places at which control can be implemented are:

• reduction of the number of infective bites by mosquitoes;

• decreasing the number of microfilariae in the human host;

• reduction of the mosquito's expectation of life;

• decrease the mosquito density;

• alteration of the mosquito biting time;

• reduction of the number of adult worms.

reducing the number of infective bites Multiplication does not take place when the larva enters the host, so the disease process and its severity depends upon repeated entry of parasites into the body, many of which will be unsuccessful. The transmission process is surprisingly inefficient, requiring some 15,500 infected bites to produce a reproducing adult. This means that for Anopheles mosquitoes, approximately eight bites per person per day can take place without the disease being transmitted.

The number of bites can be reduced by taking simple precautions of personal protection - mosquito nets, repellents, protective clothing, etc. ITMN or LLIN should be effective in nocturnally periodic filariasis, transmitted by anopheline mosquitoes. This would be an additional benefit of a malaria control programme.

decreasing the number of microfilariae (mass chemotherapy) Mass drug treatment is the main method used in the filariasis elimination programme, given as an annual single dose treatment to all the population for at least 5 years, preferably 7 years. Two regimes are used:

• albendazole 400 mg + ivermectin 150-200 mcg/kg.

An alternative is to use diethylcarbamazine (DEC)-fortified salt (or fortified soy sauce in China) for 6-12 months, if total compliance can be assured. DEC cannot be used in an area that also has onchocerciasis.

This strategy is likely to work in areas in which filariasis is transmitted by Anopheles mosquitoes, if the number of microfilar-iae can be maintained below the critical threshold (I in Fig. 15.10). One estimate suggests that this level is about 12 microfilariae/ 60 mm3. However, as the Anopheles is also a vector for malaria, reducing the number of parasitizing microfilariae, which cause damage to the mosquito, will increase the mosquito's expectation of life and improve its chance of transmitting malaria. Precautions should, therefore, be taken at the same time to prevent this from happening by the use of ITMN or LLIN.

In areas in which culicine mosquitoes are the vectors, it is unlikely that MDA alone will succeed in eliminating filariasis, as can be seen in Fig. 15.10 and from past experience in control programmes in Samoa and Tahiti. Control of the mosquito also needs to take place, a simple strategy being the use of expanded polystyrene beads, as was used in latrines in Zanzibar and soakage pits in South India (see also below).

Before mounting a mass drug treatment control programme, a complete survey is needed. Follow-up surveys of samples of the population are made at annual intervals. Thirty percent of the treated population should be sampled. Children less than 1 year of age, pregnant and nursing mothers, the sick and the very old should be excluded from mass treatment. Side-effects, especially itching, can be most unpleasant and a pilot control study should precede the main campaign. Considerable care should be taken in areas where both filariasis and onchocerciasis co-exist.

reduction of the mosquito's expectation of life

(vector control) By reducing the lifespan of the mosquito to below that of the developmental period of the parasite within the mosquito (range 10-15 days), transmission of infective larvae will be halted. This can be done by spraying residual insecticides inside houses or by treating mosquito nets.

Where the same vectors transmit both malaria and filariasis, then a joint control programme is cost-effective. ITMN or LLIN are particularly suitable for filariasis control, where there is an anopheline vector and could be used as the only strategy or combined with MDA (see above). The degree of mosquito reduction required is much less for filariasis than it is for malaria; however, mosquito control needs to be for a prolonged period, at least for 7 years and preferably for 10 years.

decrease mosquito density (larviciding) The number of mosquitoes able to bite man is dependent upon the number of larvae that develop into adults, so by reducing the number of larvae, mosquito density is also diminished. This is a supplementary method of malaria control and has also been covered in the section on vector control (Section 3.4.1). Various methods can be used, such as larvicides, genetic modification, environmental or biological control. These methods are particularly appropriate to culicine-transmitted urban filariasis, although the degree of larval reduction required is often difficult to achieve. In enclosed areas of water, such as latrines and septic tanks, expandedpolystyrene beads are very effective.

B. malayi is transmitted mainly by Man-sonia and Anopheles mosquitoes, the Mansonia being particularly difficult to control because the larvae attach themselves to the underside of water plants (especially Pistia), where they are immune to surface oils and larvicides. Removal of these water plants by hand or with herbicides has had some effect.

alteration of mosquito biting pattern The parasite has developed a periodicity of its microfilariae which coincides with the biting pattern of the vector mosquitoes. If it is possible to alter the time mosquitoes bite, then the chance of them taking up microfilaria will also be reduced. This has happened in some places due to the prolonged use of residual insecticides and although it is probably not possible to utilize this as a main control method, it could be of subsidiary value.

reduction of the number of adult worms Unfortunately, there is no specific drug which kills adult worms, although DEC causes substantial mortality, a valuable secondary action to killing microfilariae. The worms lie embedded in the lymphatics so cannot be removed surgically, as practiced in onchocerciasis control.

Adult worms live for approximately 10 years (range 7-12 years), so if re-infection can be prevented for this period, they will die off and there will be no reservoir of infection. It is maintaining control methods for this period of time that is crucial with filariasis.

Treatment for established elephantiasis is unsatisfactory with mutilating surgical

Distribution Philippines Filariasis

WHO 92353

Distribution OnchocerciasisLymphatic Filariasis Pictures
Fig. 15.11. Distribution of the lymphatic filariases. (Reproduced by permission, from WHO (1992) Lymphatic Filariasis: Fifth Report of the WHO Expert Committee on Filariasis. World Health Organization, Geneva, pp. 3-4.)

procedures. If discovered in its early stages of intermittent swelling, before tissue damage has occurred, then pressure bandages can prevent gross elephantiasis from developing. In B. timori, repeat doses of DEC reduce lymphoedema and to a certain extent elephantiasis.

Surveillance Hydrocele or lymph node surveys can be of value in rapidly defining the area of filariasis. Detailed blood surveys are then made.

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Responses

  • bill
    How to differentiate brugia timori and brugia malayi?
    8 years ago
  • Ernesta
    Is lymphatic filariasis decreasing?
    7 years ago
  • Alix
    What is the impact of climate change on lymphatic filariesis?
    3 years ago

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