Introduction:

Figure 1. The parasitology examination of a peripheral blood sample revealed the presence of Loa loa with a parasitemia of 100 parasites per microliter.

CSF : Cerebrospinal fluid

The CSF protein and sugar were normal. Direct bacteriological examination of the CSF was negative, and numerous live microfilariae were seen on CSF microscopy with estimated count of 20 microfilariaes/50 microliter. Giemsa and Haematoxylin stain demonstrated sheathed microfilariae with nuclei extending to the tip of the larva worm. The CSF and blood cultures for bacterial or fungal infections were persistently negative and china ink stain to detect Cryptococcus neoformans capsules was also negative.

With our clinical examination and investigations excluding other possible causes of meningitis, the Loa loa microfilariae presence in the CSF of this patient was the primary mechanism responsible of the meningitis rather than a secondary event. Due to his low parasitemia (low Loa loa filaria count of 100 parasites per microliter), our patient received a single oral dose of 9 mg of ivermectin (1.5 tablets of 6 mg), and there were no neurological complications related to this therapy. The patient's neurologic condition improved with resolution of his headaches and eosinophilia. A follow-up lumbar puncture revealed a white blood cell count of 1/mm³ and the repeated blood film and CSF fluid analysis 2 weeks later showed the absence of Loa loa microfilariae in both body fluids.

Discussion

The classical signs of the chronic Loa Loa infection are  itching, unpleasant sensation of migratory movements of the adult worms under the conjunctiva and Calabar swellings [1,2]. The neurological complications associated with Loa loa infection are usually the consequence of treatment with diethylcarbamizine (DEC) or ivermectin (Mectizan), although it may be rarely caused spontaneously by adult worm or of microfilaria (mf) [3,4,5,6]. Indeed, even in the absence of previous antifilarial treatment, Loa Loa microfilariae can cause the blood-brain barrier (BBB) disruption and penetrate into the CNS, CSF and meningeal space where they may induce a cellular immunological reaction [7,8,9].  This immune response could play a crucial role  through proinflammatory cytokines and vasoactive amines release, complement activation and influx of inflammatory cells causing vessel destruction, meningitis or meningoencephalitis [3,4,7]. Addionally, the chronic circulation of mf may also lead to cerebral microcirculation obstruction or hemorrhages [8]. Therefore, the neurological manifestations may include asthenia, somnolence, headaches, motor and/or sensory deficits, troubles of sensation, brainstem syndrome, cognitive impairment and altered consciousness [2,7]. Nevertheless, these neurological complications depend upon many factors such as the levels of circulating Loa loa microfilariae in the bloodstream (typically exceeding ≥ 30,000 microfilariae/mL), duration and level of exposure, number of secondary bacterial and fungal infections, the degree of host immune response and other cofactors such as drugs and coinfection [1]. To our knowledge, the only cases of meningoencephalitis unrelated to antifilarial drug in patients infected with Loa loa are those reported by Vitris M et al (1989)., and Taiwo SS et al (2007) and in these 2 cases, the disease course was unfavorable with fatal outcome [5,6]. Thus we have described in this article an original case  of meningtis associated with Loa Loa infection in a patient harboring low parasitemia, who was successfully treated with a single oral dose of 9 mg of ivermectin.

The first cases of threatening neurological serious adverse event (SAEs) following the use of antifilarial treatment for loiasis began to be described in regions that were co-endemic for Loa Loa and Onchocerca volvulus (river blindness) with significantly higher risk when the Loa loa microfilaremia exceed 8000 microfilariae per mL of blood [4,8,9]. Thus, it is probable that the drug provokes the passage of Loa Loa  microfilariae into the CSF and brain tissue with a massive mf death, and that the latter, floating passively in the blood circulation, may finally provoke embolisms in the capillaries and induce inflammation, especially in the brain (encephalopathies) [5,6]. This passage may be faciltaed by some conditions including concomitant infections (trypanosomiasis, syphilis, onchocerciasis, acute encephalitis, or Plasmodium infection);  comorbidities (chronic vascular disease) and genetic predisposition [1,2,5,6,8]. Therefore, in order to reduce the incidence of DEC-related neurologic SAEs in subjects with high pre-treatment level of microfilaremia (≥8000 mf/mL), authors have recommended a 3-week regimen of albendazole (ALB), apheresis sessions, or ivermectin treatment [9].

According to 2003 Scientific Working Group on SAEs, the principles to follow for the management of Loa Loa ivermectin-related encephalopathy would appear to be early hospitalization, good nursing care, maintenance of fluid, electrolyte/nutritional support, antihistamines for putative inflammatory lesions in the CNS, and antibiotics to prevent or control possible secondary infections [3,4,8]. Corticosteroids should be avoided because evidence of efficacy is lacking, and potential of harmful effects [9].

Although regarded as a benign condition, significant excess mortality has been recently ascribed to the chronic infection by Loa Loa. Higher mortality and fatal outcome are essentially reported when CNS is directly involved and in cases with late diagnosis and delayed management [1,3]. Unfortunately, the majority of patients who have survived after spontaneous or antifilarial-induced Loa Loa encephalopathy showed sequellae including motor defects, extrapyramidal disorders, ataxia, disturbances of balance, aphasia, psychomotor slowing, psychiatric sequelae or dementia [6,9].

Conclusion

The spontaneous neurological complications of Loa Loa infection are fairly rare and various. The risk of meningitis and encephalopathy in a previously healthy person occur essentially when the Loa loa microfilaremia exceed 8000 microfilariae per mL with the presence of Loa Loa mf in the CSF. We have described an original case of a patient presenting Loa Loa infection with low parasitemia and who developed meningitis unrelated to antifilarial drug, successfully treated with a single oral dose of 9 mg of ivermectin. Thus, such neurological manifestations in endemic countries should raise the question of filarial infection and prompt early diagnosis and adequate treatment, to avoid severe sequellae.

Funding declaration

No funding sources to declare

Conflict of interest

The authors have no conflict of interest.