Loa Loa Filariasis - Epidemiology

Epidemiology

As of 2009, loiasis is endemic to 11 countries, all in western or central Africa, and an estimated 12-13 million people have the disease. The highest incidence is seen in the following countries:

• Cameroon
• Republic of the Congo
• Democratic Republic of Congo
• Central African Republic
• Nigeria
• Gabon
• Equatorial Guinea

The rates of Loa loa infection are lower but it is still present in and Angola, Benin, Chad and Uganda. The disease was once endemic to the western African countries of Ghana, Guinea, Guinea Bissau, Ivory Coast and Mali but has since disappeared.

Throughout Loa loa-endemic regions, infection rates vary from 9 to 70 percent of the population. Areas at high risk of severe adverse reactions to mass treatment (with Ivermectin) are at present determined by the prevalence in a population of >20% microfilaremia, which has been recently shown in eastern Cameroon (2007 study), for example, among other locales in the region.

Endemicity is closely linked to the habitats of the two known human loiasis veetors, Chrysops dimidiata and C. silicea.

Cases have been reported on occasion in the United States but are restricted to travelers who have returned from endemic regions.

onchocerca co-endemicity map. Source: Gilbert M. Burnham. Ivermectin where loa is endemic

In the 1990s, the only method of determining Loa loa intensity was with microscopic examination of standardized blood smears, which is not practical in endemic regions. Because mass diagnostic methods were not available, complications started to surface once mass ivermectin treatment programs started being carried out for Onchocerciasis, another filariasis. Ivermectin, a microfilaricidal drug, may be contraindicated in patients who are co-infection with loiasis and have associated high microfilarial loads. The theory is that the killing of massive numbers of microfilaria, some of which may be near the ocular and brain region, can lead to encephalopathy. Indeed cases of this have been documented so frequently over the last decade that a term has been given for this set of complication: neurologic serious adverse events (SAEs).

Advanced diagnostic methods have been developed since the appearance the SAEs, but more specific diagnostic tests that have been or are currently being development (see: Diagnostics) must to be supported and distributed if adequate loiasis surveillance is to be achieved.

The righthand image is the result of a geo-mapping study that has overlaid the endemicity of onchocerciasis with loiasis. As one can see, there is much overlap between the endemicity of the two distinct filariases, which complicates mass treatment programs for onchocerciasis and necessitates the development of greater diagnostics for loiasis.

In Central and West Africa, initiatives to control onchocerciasis involve mass treatment with Ivermectin. However, these regions typically have high rates of co-infection with both L. loa and O. volvulus, and mass treatment with Ivermectin can have severe adverse effects (SAE). These include hemorrhage of the conjunctiva and retina, heamaturia, and other encephalopathies that are all attributed to the initial L. loa microfilarial load in the patient prior to treatment. Studies have sought to delineate the sequence of events following Ivermectin treatment that lead to neurologic SAE and sometimes death, while also trying to understand the mechanisms of adverse reactions to develop more appropriate treatments.

In a study looking at mass Ivermectin treatment in Cameroon, one of the greatest endemic regions for both onchocerciasis and loiasis, a sequence of events in the clinical manifestation of adverse effects was outlined.

It was noted that the patients used in this study had a L. loa microfilarial load of greater than 3,000 per ml of blood.

Within 12–24 hours post-Ivermectin treatment (D1), individuals complained of fatigue, anorexia, and headache, joint and lumbar pain—a bent forward walk was characteristic during this initial stage accompanied by fever. Stomach pain and diarrhea were also reported in several individuals.

By day 2 (D2), many patients experienced confusion, agitation, dysarthria, mutism and incontinence. Some cases of coma were reported as early as D2. The severity of adverse effects increased with higher microfilarial loads. Hemorrhaging of the eye, particularly the retinal and conjunctiva regions, is another common sign associated with SAE of Ivermectin treatment in patients with L. loa infections and is observed between D2 and D5 post-treatment. This can be visible for up to 5 weeks following treatment and has increased severity with higher microfilarial loads.

Haematuria and proteinuria have also been observed following Ivermectin treatment, but this is common when using Ivermectin to treat onchocerciasis. The effect is exacerbated when there are high L. loa microfilarial loads however, and microfilaria can be observed in the urine occasionally. Generally, patients recovered from SAE within 6–7 months post-Ivermectin treatment; however, when their complications were unmanaged and patients were left bed-ridden, death resulted due to gastrointestinal bleeding, septic shock, and large abscesses .

Mechanisms for SAE have been proposed. Though microfilarial load is a major risk factor to post-Ivermectin SAE, three main hypotheses have been proposed for the mechanisms.

The first mechanism suggests that Ivermectin causes immobility in microfilariae, which then obstructs microcirculation in cerebral regions. This is supported by the retinal hemorrhaging seen in some patients, and is possibly responsible for the neurologic SAE reported.

The second hypothesis suggests that microfilaria may try to escape drug treatment by migrating to brain capillaries and further into brain tissue; this is supported by pathology reports demonstrating a microfilarial presence in brain tissue post-Ivermectin treatment.

Lastly, the third hypothesis attributes hypersensitivity and inflammation at the cerebral level to post-Ivermectin treatment complications, and perhaps the release of bacteria from L. loa after treatment to SAE. This has been observed with the bacteria Wolbachia that live with O. volvulus.

More research into the mechanisms of post-Ivermectin treatment SAE is needed to develop drugs that are appropriate to individuals suffering from multiple parasitic infections .

One drug that has been proposed for the treatment of onchocerciasis is doxycycline. This drug has been shown to be effective in killing both the adult worm of O. volvulus and Wolbachia, the bacteria believed to play a major role in the onset of onchocerciasis, while having no effect on the microfilaria of L. loa. In a study done at 5 different co-endemic regions for onchocerciasis and loiasis, doxycycline was shown to be effective in treating over 12,000 individuals infected with both parasites with minimal complications. Drawbacks to using Doxycycline include bacterial resistance and patient compliance because of a longer treatment regimen and emergence of doxycycline-resistant Wolbachia. However, in the study over 97% of the patients complied with treatment, so it does pose as a promising treatment for onchocerciasis, while avoiding complications associated with L. loa co-infections .