The 24-hour periodicity of microfilariae: biological mechanisms responsible for its production and control

Abstract

An explanation is presented which covers most of the experimental data about the mechanisms by which the periodicity of microfilariae is maintained: During the night-time (with Wuchereria bancrofti and similar filariae) the microfilariae are evenly distributed throughout the blood and they are thus available for ingestion and transmission by mosquitoes. During the day-time they accumulate in the small vessels of the lungs, and hence they are few in the peripheral blood; this phase is probably adapted to allow the microfilariae to enjoy favourable physiological conditions in the lungs. The accumulation is due to an active reflex by the microfilariae themselves; and it probably depends on a sideways migration through the precapillary network of arterioles. The factor in the lungs which holds up the passage of the microfilariae so that they accumulate there (in preference to the capillaries of other organs), is the great increase in oxygen tension, which may be termed the ‘oxygen barrier’. The 24 h cycle of the microfilariae is orientated to the 24 h cycle of the host; and some rhythmic change in the host acts as a cue to the microfilariae. Each microfilaria has a weak endogenous circadian rhythm of its own, but the rhythms of the individual microfilariae are dominated by that of the host, so that all the different individuals do approximately the same thing at the same time, and they do it at the right time (i.e. right for transmission). Different species of microfilariae respond differently to the same stimuli, and they depend on different arrangements for the maintenance of their rhythms. Three main groups of periodic microfilariae may be recognized. ( а ) W. bancrofti, Brugia malayi , etc. These depend upon the absolute size of the venousarterial ( VA ) difference in oxygen tension (‘oxygen barrier’) which is lower by night (e.g. 40 mmHg) than it is by day (e.g. 55 mmHg) and so the microfilariae pass through the lungs by night but accumulate there by day. If at night the patient is caused to breathe oxygen, the arterial oxygen rises; or if he is caused to take vigorous muscular exercise, the venous oxygen tension falls; in both cases the VA difference becomes greater and the microfilariae accumulate in the lungs. ( b ) Loa loa of man, Edesonfilaria malayensis of monkeys in Thailand and Monnigofilaria setariosa of East African mongooses. In this group the sensitivity of the microfilariae to the oxygen barrier is greatly increased or decreased by the 24 h changes in the body temperature of the host. Accordingly, the cycle of microfilariae of this group indirectly depends upon the temperature cycle of the host. ( c ) Dirofilaria immitis , D. repens of dogs, D. aethiops ( corynodes ) of monkeys, etc. These microfilariae are probably sensitive only to the lower range of oxygen tensions, e.g. 30 to 60 mmHg. On the whole their cycle depends on day-night changes in the oxygen barrier as with W. bancrofti , but under special circumstances (as explained in the text) administration of oxygen may cause liberation of microfilariae from the lung instead of accumulation. The mechanism controlling the Pacific type of W. bancrofti cannot yet be identified, since the experimental evidence is insufficient. The behaviour of microfilariae is adapted to promote transmission by arranging the maximum number of microfilariae in the peripheral blood at times when the arthropod vector is likely to bite. The most sophisticated arrangement to achieve this is by a 24 h rhythm—the classical ‘periodicity’. A less sophisticated arrangement is illustrated by various filariae of rodents, e.g. Litomosoides carinii and Dipetalonema witei , in which the parasites are transmitted by mites or ticks which suck blood in the nest or burrow, and the microfilariae are stimulated to swarm in the peripheral blood by a fall in body temperature when the animal sits quietly in its nest. Filariae which are still less sophisticated, e.g. Acanthocheilonema perstans and Dipetalonema gracile , do not possess any arrangements for adjusting the supply of microfilariae in the peripheral blood to the feeding habits of the vectors. Furthermore, some microfilariae, e.g. those of D. immitis and D. repens , are adjusted to their vectors on an annual variation as well as on a 24 h one and they are most numerous in the blood during July and August (when mosquitoes are most numerous in temperate zones). Some hosts (e.g. dogs) have a less marked 24 h rhythm than other hosts (e.g. man and monkey) and the cycles of their microfilariae are similarly less marked.