Jean Paul Akue

*International Center For Medical Research Franceville (CIRMF), Gabon* 

#### **1. Introduction**

*Loa loa* encephalitis is becoming an important public health problem, as it impedes the use of some important drugs (ivermectin and DEC) for mass control of filarial disease in parts of West Africa where onchocerciasis is endemic. Loa encephalitis may occur either spontaneously or following chemotherapy targeting *Loa loa*. Although *Loa loa* is restricted to the West African rain forest block, imported cases are described throughout the world, due to intense economic, cultural and touristic population exchanges. The most common clinical features of loiaisis are swelling angioedema (calabar oedema) and ocular passage of the adult worm under the conjunctiva (eye worm). *Loa loa* disease may be particularly severe in expatriates (Nutman et al., 1986). *Loa loa* may cause a localized or systemic disease with involvement of deep organs including the kidney and heart. Only one-third of infected individuals have microfilariae in peripheral blood, leading to an underestimation of the prevalence of this infection. Most expatriates with loiasis have the adult worm but are amicrofilaremic (Churchill et al., 1996). The heterogeneous clinical expression of loisais encephalopathy calls for greater awareness among scientist and medical practitioners worldwide.

#### **2. The pathogen:** *Loa loa*

*Loa loa* is a filarial worm restricted to West Africa (Figure 1), from Guinea in the north through Benin to Uganda in the East, Gabon, Cameroun and Nigeria in the west, and Angola in the South. Parts of Cameroun, Gabon, Nigeria, Congo Brazzaville and Congo Kinshasa (DRC) are hyperendemic. Common clinical signs include eye worm and calabar swelling. *Loa loa* adults produce microfilariae that are released into the peripheral blood. They reach their maximal concentration in peripheral blood during daytime (diurnal periodicity). This larval stage of *Loa loa* is the likely etiologic agent of encephalitis during loiasis. The parasite was first described in 1770 (Mongin, 1770) in the eye of a servant in the island of St Domingue. Only few autochtonous case of loaisis has been reported outside of Africa, in India (Barua et al., 2005; Kethan, 2007), although *Loa loa* can develop successfully in *Chrysops atlanticus*, which is widespread in Louisiana and Mississippi (Orihel & Lowrie, 1975). *Loa loa* is thought to infect 13 million individuals living in endemic zones (Fain, 1978), as well as individuals visiting these areas (Varhaug,2005; Carbonez et al.,2002; Hee-Yoon et

Encephalitis Due to *Loa loa* 343

Second blood meal in new human hostrelease of the infective larvae (L3)

> Larvae develop in subcutaneous tissue of the human into adult worm

*Chrysops dimidiata* and *C. silacea (*Figure 3) (family *Tabanidae*) live in the canopy, and are particularly attracted by smoke and blue tissue. They lay eggs on mud or leaves overhanging water, and the larvae develop in detritus, taking a year before they pupate, with probably seven moults. The pupa is partially buried and the adult emerges after 1-3 weeks. Chrysops is a good intermediate host or vector for *Loa loa*, and it is not unusual to find more than one hundred infective larvae in one fly. For vector control, William (1963) used water emulsions containing various concentrations of DDT, dieldrin, aldrin or gamma-BHC, and found that *Tabanus* larvae were more susceptible than *Chrysops* larvae to all the insecticides tested. Dieldrin emulsion can keep breeding sites free of tabanid larvae for at least eight months (Crewe & Williams, 1964), and has been proposed for the control of chrysops larvae. However, vector control is difficult due to the scale and remote location of

day time microfilariae in peripheral blood

Fig. 2. Life cycle of *Loa loa*

first blood meal: ingestion of microfilariae by chrysop

infective larvae(L3) develop in thorax of chrysop

**3. The vectors** 

breeding sites.

al., 2008). However, this prevalence is based on the detection of microfilariae in blood and may therefore be an under-estimation, as about one-third of subjects are amicrofilaremic (Dupont et al., 1988). The adult worm can survive for up to 15 years in its human host.

Fig. 1. Distribution of *Loa loa*

The life cycle of *Loa loa* (Figure 2) starts when a female fly of the genus *Chrysops* (*C*. *silacea*, *dimidiata* or *distinctipennis*) bites an individual harboring *L. loa* microfilariae. The microfilariae reach the stomach of the fly and migrate to the fat body after several mutations to stage L3 (infective larvae). These migrate to the proboscis and are deposited in the host's skin during the next blood meal. Once in the skin, the infective stages moult and reach the adult stage about a year later. The adult remains under the skin but can migrate to different parts of the body, including the ocular conjunctiva (hence the name 'eye worm'). Microfilariae have a diurnal periodicity, being found in peripheral blood from about 5 am to 7 pm, with peak from 9 am to 5 pm (Kershaw, 1950). The existence of an animal reservoir is a possibility (Fain., 1981), as about 10% of blood meals of *C. silacea* and *C. dimidiate* (Gouteux et al., 1989) from hippopotami, rodents, wild ruminants and monitor lizards contain *L. loa* microfilaria, and human L. loa isolates have been successfully maintained in drills (Duke, 1957), baboons, and patas (Orihel & Moore., 1975), rhesus (Grieve et al., 1985), and mandrill monkeys (Pinder et al., 1994).

al., 2008). However, this prevalence is based on the detection of microfilariae in blood and may therefore be an under-estimation, as about one-third of subjects are amicrofilaremic (Dupont et al., 1988). The adult worm can survive for up to 15 years in its human host.

The life cycle of *Loa loa* (Figure 2) starts when a female fly of the genus *Chrysops* (*C*. *silacea*, *dimidiata* or *distinctipennis*) bites an individual harboring *L. loa* microfilariae. The microfilariae reach the stomach of the fly and migrate to the fat body after several mutations to stage L3 (infective larvae). These migrate to the proboscis and are deposited in the host's skin during the next blood meal. Once in the skin, the infective stages moult and reach the adult stage about a year later. The adult remains under the skin but can migrate to different parts of the body, including the ocular conjunctiva (hence the name 'eye worm'). Microfilariae have a diurnal periodicity, being found in peripheral blood from about 5 am to 7 pm, with peak from 9 am to 5 pm (Kershaw, 1950). The existence of an animal reservoir is a possibility (Fain., 1981), as about 10% of blood meals of *C. silacea* and *C. dimidiate* (Gouteux et al., 1989) from hippopotami, rodents, wild ruminants and monitor lizards contain *L. loa* microfilaria, and human L. loa isolates have been successfully maintained in drills (Duke, 1957), baboons, and patas (Orihel & Moore., 1975), rhesus (Grieve et al., 1985), and mandrill

Fig. 1. Distribution of *Loa loa*

monkeys (Pinder et al., 1994).

Fig. 2. Life cycle of *Loa loa*
