Treatment of loiasis
Treatment of loiasis is complex and needs to be tailored to the parasitological features of the individual patient and to the overall risk-benefit balance. Treatment of loiasis is not without risk and severe to life threatening complications of treatment may occur particularly if antifilarial drugs are chosen inappropriately.
Three drugs with different pharmaceutical mechanisms are commonly used to treat loiasis. These drugs are diethylcarbamazine (DEC), ivermectin (IVM) and albendazole (ALB).
Diethylcarbamazin (DEC):
DEC is active against the adult worm (macrofilaricidal) and the microfilariae (microfilaricidal). It is, therefore, considered the gold standard for curative treatment of loiasis. DEC acts against the macro- and microfilariae by inducing paralysis. DEC leads to complete cure in around 40-80% of patients per treatment cycle when used in a three to four-week regimen. Due to its rapid onset of action, a significant proportion of patients experience moderate to severe adverse drug reactions, particularly at the beginning of treatment. Severe and life-threatening reactions such as encephalopathy appearing commonly within 24 hours after treatment initiation occur mostly in individuals with a microfilaraemia above 2,000 mf/mL and are often associated with retinal haemorrhages.
Ivermectin (IVM):
IVM has been used on a large scale in single dose mass-drug administration to fight onchocerciasis and lymphatic filariasis. IVM can dramatically reduce the microfilarial load of L. loa by around 90% with a single dose. Repeated monthly administration leads to complete and prolonged clearance of microfilaraemia in loiasis. IVM may lead to acute anaphylactic reactions and the occurrence of ivermectin-associated encephalitis. To reduce the risk for the occurence of serious adverse events, IVM should be administered in individuals with a microfilaraemia between 2,000 mf/ml and 8,000 mf/ml. The use of IVM may be considered to reduce the microfilarial load to enable subsequent curative therapy with DEC.
Albendazole (ALB):
ALB is a broad-spectrum benzimidazole anthelmintic drug that acts on parasite microtubules. The required duration of treatment with ALB is 400 – 800 mg/day for at least 3-4 weeks. ALB has a delayed, probably mainly indirect effect on microfilarial counts (reduction begins after about two weeks) and appears effective against adult stages of L. loa in treatment regimens lasting several weeks. Therefore, albendazole has been used in individuals with hypermicrofilaraemia > 8,000 mf/ml to reduce microfilaraemia before administering IVM or DEC. The administration of prolonged albendazole therapy in combination with single-dose IVM may be considered even if the efficacy of this regimen remains unclear.
To date, data are available from only a few hundred patients treated with albendazole regimens, so no definitive conclusions can be drawn about the safety and efficacy of albendazole in treating loiasis. However, there is growing evidence that ALB may, at least in some individual cases, cause loiasis-encephalitis following treatment.
- Diethylcarbamazine (first-line treatment)9 mg/kg in three divided doses daily for 21 days; more than one treatment cycle of 21 days may be necessary as cure rate is between 40% and 80% per cycle; contraindication in patients co-infected with onchocerciasis
- Albendazole (alternative treatment option)400 mg* twice daily for 4-week treatment cycle; cure rate is unclear
- Albendazole–ivermectin (alternative treatment option)Albendazole (as described above) followed sequentially by single-dose 150–200 μg/kg ivermectin; conflicting reports on overall cure rate
- Diethylcarbamazine (first-line treatment)Slow titration starting with 50 mg single dose on day 1, 50 mg three times on day 2, 100 mg three times on day 3, and subsequent 9 mg/kg divided in three daily doses until day 21; each 21-day treatment cycle leads to a 40–80% cure rate; more than one cycle may be needed; contraindication in patients co-infected with onchocerciasis
- Albendazole (alternative treatment option)400 mg* twice daily for 4-week treatment cycle leads to relatively safe reduction of microfilaraemia; cure rate is unclear
- Albendazole–ivermectin† (alternative treatment option)Albendazole (as described above) followed sequentially by single-dose 150–200 μg/kg ivermectin leads to relatively safe reduction of microfilaraemia; conflicting reports on overall cure rate
- Albendazole (first-line treatment)400 mg* twice daily for 4-week treatment cycle as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
- Ivermectin (first-line treatment)150–200 μg/kg single dose as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
- Albendazole–ivermectin† (alternative treatment option)Albendazole (as described above) followed sequentially by single dose 150–200 μg/kg ivermectin as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
- Albendazole (first-line treatment)400 mg* twice daily for 4-week treatment cycle as stand-alone treatment or as preparatory treatment to lower microfilaria load to less than 8000 microfilariae per mL for sequential treatment with ivermectin† as stand-alone treatment or as preparatory treatment to lower microfilaria to less than 2000 microfilariae per mL for sequential treatment with diethylcarbamazine (see above)
- Apheresis (first-line treatment)Mechanical reduction of microfilaria load by several cycles of apheresis safely reduces microfilaria load before treatments as indicated above
- Albendazole (alternative treatment option)Rare reports on encephalopathy associated with albendazole therapy indicates that this treatment approach is not without risk; gradual reduction of microfilariae is the treatment objective before treatment as indicated above for loiasis with microfilaria less than 30 000 microfilariae per mL
- Antihistamines and corticosteroidsAntihistamines and corticosteroids may be used for the first few days of treatment to reduce the severity of adverse drug reactions; however, adjunct treatments have no influence on the occurrence or severity of potentially life-threatening serious adverse events including encephalopathy
*200 mg administered twice daily has also been shown to exert a substantial effect on microfilarial load. Given albendazole’s overall limited bioavailability with important interindividual and intraindividual variability and the good safety profile of albendazole at a daily dose of 800 mg, a dose regimen of 400 mg twice daily is suggested in this proposed treatment algorithm. †Ivermectin is administered after 28 days of albendazole therapy and confirmation of microfilaraemia below 8000 microfilariae per mL.
Other therapeutic drugs
Clinical trials have been performed with mixed results to improve the treatment of loiasis. The efficacy of imatinib against loiasis has been evaluated and has not met the expections. Currently, moxidectin, a macro-lactone related to ivermectin, is undergoing phase II clinical trials in Gabon (ICTRP ID: PACTR202303704849277) and Cameroon (ClinicalTrials.gov ID: NCT04049851). Levamisole is currently evaluated in phase II and III Clinical Trials (ClinicalTrials.gov ID: NCT06252961) in Congo. Further drugs, such as flubendazole and oxfendazole, are investigated for their therapeutic potential.
Treatment considerations in pregnancy and lactation
To date, loiasis is not known to cause adverse birth outcome. Vertical transmission pre-, intra-, or postpartum have not been reported. Thus, it is currently not recommended to treat pregnant or lactating women. Treatment should be initiated after pregnancy and lactation.
Non-medical treatment
The adult worm may be machanically extracted carefully during eye worm or transient intradermal passage. Apheresis is another non-medical intervention, which has successfully been employed in patients with hyper-microfilaraemic loiasis . Here, the mechanical reduction of microfilaraemia in several cycles safely reduces microfilarial loads and thus prepares the patient for safe follow-on treatment with curative antifilarial drugs.
