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Loa loa—does it deserve to be neglected?

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Summary

More than 10 million people in western and central Africa are estimated to be infected with Loa loa filarial nematodes. Like most other infectious diseases, L loa filariasis (loiasis) covers a wide range of symptoms. Severe complications have been reported; however, most observations are anecdotal, typically in travellers. The widespread use of filaricidal drugs within eradication programmes of Onchocerca volvulus and Wuchereria bancrofti led to the observation that concomitant L loa infection increases the risk of severe treatment-associated, life-threatening complications. Initiatives were therefore launched to map the risk of loiasis. Insight about the epidemiology of L loa has advanced notably; however, its effect on the individual as well as on the community level has not been well studied. In the absence of appropriate studies, L loa is commonly judged a harmless nematode, and loiasis as a separate entity does not belong to the list of neglected tropical diseases to be controlled or eradicated in worldwide campaigns. We advocate reorientation of research efforts towards a patient-centric view of loiasis and, as a first step, to establish the disease burden in disability-adjusted life-years of this chronic infection, and to answer the question of whether loiasis should be included in future control programmes.

Introduction

The startling feature of infection with Loa loa filariae is vividly depicted in an early report:1 “…a single woman, aged 29, attended Dr O'Donovan's clinic at the London Hospital on December 17, 1930. Fifteen months ago she went to the coastal area of Nigeria as a missionary…on the boat returning to this country she noticed in a mirror a white worm about one inch long moving in the skin of the cheek toward the inner canthus of the left eye. …she was advised…to apply pressure to prevent the worm from entering the eye, and when she did so the worm retreated and disappeared.” For many years, reports described the subconjunctival passage of the eye worm through the patient's eye (figure 1). Together with the so-called Calabar swelling, this is the visible and pathognomonic symptom of loiasis. Since its first description by a French surgeon located in Santo Domingo in 1770,2 L loa has been a popular topic for case reports of rare diseases.

14·4 million people live in high-risk regions, which are defined as an area where the estimated prevalence of eye worm is greater than 40%, and 15·2 million people live in intermediate risk areas with an estimated prevalence around 30% (20–40%). From these figures, we estimate that at least 10 million people are infected with L loa. The endemic countries are: Angola, Cameroon, Central African Republic, Chad, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Nigeria, Republic of Congo, and Sudan.3 In some endemic regions loiasis is the second or third most common cause of medical consultations.4, 5

On the basis of our clinical experience in Gabon, we postulated that L loa might not be as harmless as commonly suggested. We searched the literature to identify research needs and propose topics that can be addressed by future research programmes. The earliest reference was from the year 1918.6 Many published articles had been written not because loiasis was the main focus of scientific interest, but the attention was drawn to L loa by other research. For example, when bacteria of the genus Wolbachia were found to have a mutualistic relationship with some filarial nematodes, three research groups were looking independently for the bacteria in L loa worms; none found them.7, 8, 9 In other studies, awareness of L loa increased as a result of serious adverse events to ivermectin—especially encephalopathies—in patients who were treated for Onchocerca volvulus while co-infected with L loa. Then, a series of articles were published on L loa treatment10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 and epidemiology.22, 23, 24, 25, 26 Consequently, the number of publications on L loa increased substantially in the past 20 years.

Section snippets

Epidemiology and diagnosis

The first comprehensive literature review on L loa epidemiology was published in 1997.27 From 2002 to 2010, a large effort was made to assess L loa prevalence using large-scale surveys that implemented a short questionnaire for the history of eye worm (rapid assessment procedures for loiasis, RAPLOA). Of the ten countries with endemic L loa, Gabon and Equatorial Guinea were classified as high risk, with an estimated prevalence of eye worm history greater than 40% and representing a large

Disease treatment

The WHO-recommended first-line treatment of loiasis is diethylcarbamazine,31 which has been clinically studied in patients with onchocerciasis and lymphatic filariasis.32, 33 However, only one randomised controlled trial has investigated a prophylactic regimen in immunologically naive volunteers from the US Peace Corps,34 and we could find no trial on efficacy and adverse events of diethylcarbamazine treatment in patients from an endemic region with ongoing loiasis in our literature search.

Disease symptoms and burden

The range of loiasis symptoms and complications goes from no symptoms at all to various severe complications, such as cerebral (eg, encephalopathy in the absence of treatment), cardiac (eg, endomyocardial fibrosis), pulmonary (eg, pulmonary infiltrates), and renal complications (eg, renal failure), as well as neurological and psychiatric disorders. Many complications are presumably due to immune complex deposition and are frequently accompanied by marked eosinophilia.50, 51 Most publications

Conclusions

The chronic nature of infection, range of symptoms and complications, treatment complications, comorbidity, and economic restrictions mean that large, standardised, and longitudinal studies would be needed to assess fully the effect of L loa on affected populations. Such studies would be complex and might not be cost-efficient. We suspect that the paucity of data is evidence that the disease is viewed as less serious than it really is, and, vice versa—because the disease is thought to be less

Search strategy and selection criteria

We searched PubMed, and included all publications with “Loa loa” or “loiasis” in the title. Non-English publications were included as far as they were indexed in PubMed. Because some non-English, and some earlier literature, used different spelling, the terms “loaiasis” and “Filaria loa” were added to the search. References were subjectively labelled by the two authors in categories: epidemiology, diagnosis, treatment, vector studies, animal models, host parasite interactions, case reports,

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