2.3 Filariae with circulating microfilariae

Filariae parasitize the tissue of terrestrial vertebrates and produce the first larval stages, the microfilariae. They are transmitted by blood-sucking arthropods, Diptera, ticks or mites. In the vectors, the first two larval stages are intracellular parasites of polyploid or syncytical tissues. The third larval stage infests the vertebrate host and is called the metacyclic or invasion larva. It moults to the fourth, sexually dimorphic, larval stage, which then becomes the adult worm.

The invasion route of the metacyclic larvae follows the lymph vessels to the right heart chamber and lungs, depending on the final position of the adult worms (fig. 2.21, page 52).

In the definitive host, the development of filariosis occurs in three phases: prepatency (invasion, migration, habitation, maturation and fertilization of the worms), patency (parasitaemia is at first labile, later stable and finally intermittant) and postpatency (parasitaemia extinct). These phases correspond to distinct immunological states: conditioning, balancing or shifting and experienced (fig. 2.22, page 53).

For microscopical diagnosis, evidence of microfilariae is essential, either in the circulating blood or in the tissue lymph of the skin. The microfilariae are investigated in a stained blood smeer or skin biopsy. The presence of a sheet and the arrangement of the cell nuclei in the tail is used (fig. 2.23, page 54). Ultrastructural analysis reveals a well-differentiated larva equipped with organs for penetration and excretion, but without an intestine (fig. 2.24, page 55).

The serious pathological symptoms observed in humans appear after repeated infestations leading to a long-lasting patency and an accumulated worm load; often, parasitosis has entered the phase of postpatency.

Wuchereria bancrofti and Brugia malayi: The adult worms live in the lymphatic vessels and cause inflammations that lead to a local blockage of lymphatic drainage and swelling in the distal areas of the affected part of the body: elephantiasis. The mirofilariae circulate in the peripheral blood and, in the case of W. bancrofti, show pronounced nocturnal periodicity. In B. malayi, this is less common or does not occur. The vectors are nocturnally active mosquitoes. W. bancrofti is distributed throughout the tropics, whereas B. malayi is limited to the pacific region. Both have strain-specific variants and form pathogen-vector complexes.

Loa loa: The adult worms migrate through the subcutaneous tissues and cause temporary local oedemas. Sometimes, they appear in the connective tissue of the eye. The microfilariae are diurnally periodic and are transmitted by tabanids of the genus Chrysops.

Mansonella spec.: The adult worms of M. perstans live in serous body cavities, those of M. streptocerca in subcutaneous tissue and those of M. ozzardi in the fatty tissue of the abdomen and in the mesenteries. They cause little or no pathological reactions. The aperiodic microfilariae are transmitted by Ceratopogonids.

In order to undertake research, the filariae of small mammals are kept in the laboratory: Acanthocheilonema viteae in the gerbil (adult worms live in subcutaneous tissues, microfilariae are aperiodic and circulating, vectors are soft ticks); Litomosoides sigmodontis in the hispid cotton rat (adult worms live in the pleural and peritoneal cavities, mirofilariae are aperiodic and circulating, vector is a mite); Dirofilaria immitis in the dog (adult worms in the right heart chamber, microfilariae nocturnal and circulating, vector is a mosquito); Monanema martini in the striped mouse and the Nile rat (adult worms live in the mucosa of the caecum and colon, microfilariae in lymph of the skin of ears and nose, vectors are hard ticks).

A circadian periodicity of the mirofilariae is based on an endogenic rhythm that is synchronized by the physical activity of the warmblooded host and the linked increased consumption of oxygen. During the day time, nocturnal microfilariae are held back between the arterial and venous capillaries in the lung because of the higher differential oxygen tension. In diurnal microfilariae, the sensitivity to the difference in the O2 tension is lowered by the slightly raised body temperature.

The turnover of the microfilariae is regulated by the fecundity of the adult worms and by the elimination rate of the microfilariae by the host organism (fig. 2.25, page 58). In Litomosoides sigmodontis there is an output-regulation of turnover: a short-living partial population, which is stationary in the lung, and a long-living circulating population has to be assumed. The stationary microfilariae bind circulating antibodies specific to their surface proteins, leaving the rest in circulation and thus ready for transmission (fig. 2.26, page 58). In Acathocheilonema viteae there is an input-regulation: subcutaneously located adults reduce their fecundity according to signals of the circulating microfilariae (fig. 2.27, page 59). The turnover of microfilariae corresponds to the amount of foreign protein metabolized permanently by the host.

The natality in vivo of a female worm may be calculated during constant parasitemia and worm load as the normal embryos per female and the duration of development. It may be confirmed experimentally as natality in vitro by microfilariae delivered per female and day during the phase of constant delivery. The fecundity of a female is the natality of the female multiplied by the mean time span of her fertility; this designates the ability to reproduce and conceive and provides an indication of the production of sperm (Box 2.2, page 62). The total amout of microfilariae circulating in a host individual is calculated from the daily natality of all reproductive females and the geometric mean of the life expectancy of the microfilariae. The quantitative estimation of the body volume of worm load and microfilarial load by turnover reveals the metabolic burden of the parasitosis experienced by the host and thereby the balance that has to be achieved between host and parasite.

Filarioses end spontaneously after the life expectancy of the adult worms has passed. In human filariosis, this can last for five to ten years. Protective immunity remains absent. Filarioses that last longer occur because of reinfestations, as a rule in endemic areas.

The immune response is conditioned by the moults of the invasive stages during prepatency so that the host’s defence components are suppressed during patency. The resulting premunition corresponds to the defense of the host by the parasite; this involves the parasite using the immune system of the host to prevent further invasion by other members of its own parasite species, thereby avoiding overcrowding of the parasite within the host and optimizing the parasite-host balance economically. This is analagous to the territorial behaviour of free-living animals; these animals defend their territory against invasion by other members of their own species but this ceases when they die (natural mortality or death from external sources). In the case of parasitism, the latter occurs when all adult worms have disappeared after death from age or following therapy.

In the definitive host, the worm load increases proportionally only after low doses of inoculated invasive larvae. As experimentally proved a minimum dose of two invasive larvae of different sex is sufficient to create a patent filariasis of ordinary duration in one third of hosts. Even extremely high inoculation doses, singly or repeated, do not lead to lethal overparasitization.

The population dynamics of filariae comprises numerous feed-back mechanisms, in the vertebrate definitive host and in the vector. The negative-binomial distribution of the mean density of circulating microfilariae in a definitive host population and their clumped distribution in the skin guarantees the further development in the vector, even at low mean densities.

In the vector the development of microfilariae to invasive larvae is determined by three independent relationships (see fig. 2.28, page 63):

(1) There is a positive correlation between the mortality, i.e. the rate of killed vectors (mosquitoes, ticks, etc.) and the number of ingested microfilariae (grey columns); the more microfilariae are taken up by a vector individual, the more vectors are killed.

(2) There is a negative correlation between the rate of vectors with no invasive larvae and the numbers of ingested microfilariae (columns in bright pink). The more microfilariae are presented and therefore taken up by a vector, the fewer vector individuals remain with no mirofilariae.

(3) The invasive larvae per vector that develop from ingested microfilariae distribute negatively-binomially in the vector population and this remains independent of the amount of ingested microfilariae (red columns).

Thus, the transmission capacity of the vector population (daily inoculation rate of man measured as annual transmission potential, ATP) is balanced independently of the vector capacity of the definitive vertebrate host population, i.e. the total amount of microfilariae present in the definitive vertebrate hosts.

Periodicity and dermatotropism of the microfilariae indicate a close relationship between the corresponding parasite and the attacking behaviour of its vector. Adult worms and microfilariae normally occur in different body regions of their hosts. Cutifilaria spec. represents a significant exeption: the adult worms live intracutaneously surrounded by their microfilariae in the red deer, horse and reindeer (fig. 2.29, page 65).

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