Antibiotics help combat elephantiasis

The disease is triggered off by the bite of an infected mosquito: together with its anticoagulant the mosquito pumps threadworm larvae into its host's body. These gravitate towards the lymph nodes, where they grow into threadworms which may be up to ten centimetres long. The body reacts by producing inflammation which halts the flow of lymphatic fluid. The consequence of this is that arms, legs and genitals swell to monstrous proportions – hence the name elephantiasis. More than 120 million people worldwide are infected with the pathogen wuchereria bancrofti.

Adult wuchereria worms have a lifespan of up to five years. During this time they produce millions of offspring, what are known as micro-filariae, each of them smaller than the full stop at the end of this sentence. If the host is bitten again by a mosquito, the micro-filariae are ingested together with the blood. Inside the insect they mature into infectious worm larvae, thereby completing the circle.

'Although the drugs currently in use kill the micro-filariae, they largely leave the adult worms unscathed,' Bonn parasitologist Professor Achim Hörauf explains. 'Due to the long lifespan of the wuchereria worms, therapy lasts several years, during which time the symptoms continue to persist.' What is more, the drugs may cause severe side-effects.

De-worming the roundabout way

Yet the threadworm, too, has a sub-tenant, and this may be its Achilles heel, since in each wuchereria worm there are specific bacteria which are absolutely indispensable to the parasite's survival. If these bacteria die, the parasite will also die sooner or later. 'This is why wuchereria is susceptible to antibiotics which are normally used against bacterial infections,' Professor Hörauf emphasises. One example is doxycyclin, which has been used for decades for infections of the respiratory tract and the gastro-intestinal tract.

In their study the medical experts in Tanzania treated 72 male patients for eight weeks with doxycyclin or a placebo. Initially the patients' blood was swarming with micro-filariae: the researchers counted up to 1,300 of them per millilitre of blood. Eight months later they had almost completely disappeared; only in one patient were sporadic micro-filariae still detected. However, the proportion of micro-filariae also dropped in the placebo group – an effect which was probably due to the improved care given the test persons.

Unlike the drugs in use up to now the antibiotic also killed off the adult worms. Fourteen months after being treated with doxycyclin the doctors were only able to detect the typical movements of the worms ('the dance of the filariae') on ultrasound in one in five patients. In the placebo group the rate was 89%. In the doxycyclin group the concentration of specific worm proteins in the blood fell by over half.

Effective, cheap, few side-effects

'The importance of these findings for therapy should not be underestimated,' Professor Hörauf emphasises. 'The mature worms are after all responsible for such symptoms of the disease as the extreme swelling of the limbs. In the past there was no effective and reliable method of combating them.' The effectiveness of the antibiotic might be even greater than what was measured: 'We cannot exclude the possibility that several patients became re-infected in the months following treatment with doxycyclin. It is therefore quite possible that all the worms were killed and the remaining 20% are the result of re-infection which would no longer occur if infection was effectively prevented.

Doxycyclin has been used for many years and has only minor side-effects. However, in young children it may cause irreparable damage to the teeth and slow down growth of the bones. For this reason the antibiotic should not be used during pregnancy, either. For adolescents and adults, however, the drug is harmless. Moreover, it is comparatively cheap. 'Its biggest advantage is that it is already licensed for medical use,' Professor Hörauf points out. 'Elephantiasis hits the poor most of all. It is therefore not likely that the pharmaceuticals industry will develop completely new drugs.'

From University of Bonn

Permalink

June 24, 2005