REVIEW Open Access
Loa loa vectors Chrysops spp.: perspectiveson research, distribution, bionomics, andimplications for elimination of lymphaticfilariasis and onchocerciasisLouise Kelly-Hope1* , Rossely Paulo1,2, Brent Thomas1, Miguel Brito2,3, Thomas R. Unnasch4 andDavid Molyneux1
Background: Loiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiatawhich are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individualswith high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drugadministration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significantchallenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. Thecontrol of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the currentknowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research.
Results: We identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata.These were collated into a database summarising the publication, field and laboratory procedures, speciesdistributions, ecology, habitats and methods of vector control. The majority of articles were from the 19501960s.Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudanhighlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams orswampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is morereadily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed toimpact on L. loa transmission included personal repellents, household screening, indoor residual spraying,community-based environmental management, adulticiding and larviciding.
Conclusions: This is the first comprehensive review of the major L. loa vectors for several decades. It highlights keyvector transmission characteristics that may be targeted for vector control providing insights into the potential forintegrated vector management, with multiple diseases being targeted simultaneously, with shared human andfinancial resources and multiple impact. Integrated vector management programmes for filarial infections, especiallyin low transmission areas of onchocerciasis, require innovative approaches and alternative strategies if the eliminationtargets established by the World Health Organization are to be achieved.
Keywords: Loa loa, Loiasis, Tropical eye worm, Chrysops, Vector control, Lymphatic filariasis, Onchocerciasis, Neglectedtropical diseases, NTDs, Africa, Integrated vector management, Bionomics
* Correspondence: Louise.Kelly-Hope@lstmed.ac.ukEqual contributors1Department of Parasitology, Liverpool School of Tropical Medicine,Liverpool, UKFull list of author information is available at the end of the article
The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Kelly-Hope et al. Parasites & Vectors (2017) 10:172 DOI 10.1186/s13071-017-2103-y
BackgroundLoiasis - also known as Tropical eye worm, is a filarialdisease caused by Loa loa, a parasite which mainlyoccurs in Central and West African rainforests [1, 2].Loa loa is transmitted by two main species of tabanidflies (Order Diptera: Family Tabanidae) of the genusChrysops, and include Chrysops silacea (Austen) and C.dimidiata (Wulp), which are forest canopy dwellers.The distribution of loiasis has recently been well docu-mented and mapped from large-scale community fieldsurveys based on the presence of eye worm [2, 3], anddefined earlier by remote sensing maps of forest andforest edges . The risk of loiasis geographically coin-cides with the boundaries of equatorial rainforest, withthe tropical dense and mosaic savanna forests (outsidethe Congo River Basin) shown to be important determi-nants of L. loa as they are natural habitats of the mainChrysops spp. [2, 5].Loiasis symptoms are considered to be relatively mild
but include itching and swelling as the worm movesunder the skin and causes lesions, typically in the ex-tremities, called Calabar swellings and the passage ofthe adult worm in the sub-conjunctiva of the eye .However, the real danger of loiasis occurs when an in-fected person with high levels of L. loa microfilariae(Mf) in their blood (>30,000 Mf/ml) take the drug iver-mectin or diethylcarbamazine (DEC) for the treatmentof lymphatic filariasis (LF) or onchocerciasis. These in-dividuals are at increased risk of a severe adverse event(SAE), which may result in encephalopathy and death[6, 7]. A recent cohort study has also found an in-creased risk in mortality among individuals with a highMf loads of L. loa .Severe adverse events were first documented during
ivermectin distribution projects in Cameroon in theearly stages of the African Programme for Onchocercia-sis Control (APOC) when the community directed treat-ment with ivermectin (CDTi) was the main intervention.Later SAEs were also recorded in the DemocraticRepublic of Congo (DRC), and SAEs have had signifi-cant negative repercussions for the onchocerciasisprogrammes over the past two decades reducing theopportunities to expand ivermectin distribution andreducing adherence to mass drug administration. Thethreat of SAEs have prevented the Global Programmeto Eliminate LF (GPELF) scaling up mass drug ad-ministration (MDA), as ivermectin was consideredunacceptable given the associated risks, and an alter-native strategy of twice a year albendazole was rec-ommended where LF and L. loa were co-endemic. Asboth the LF and onchocerciasis programmes havedefined elimination objectives the problem of L. loaassociated SAE risk must be resolved if elimination isto be achieved.
In L. loa co-endemic areas, the LF Programme has anadvantage as the main vectors are Anopheles spp. andmalaria control measures are known to impact on thetransmission of Wuchereria bancrofti parasite, in par-ticular indoor residual spraying (IRS) and bed nets orlong-lasting insecticidal nets (LLINs) impregnated withpyrethroids . However, the major challenge lieswith onchocerciasis, now targeted for elimination andwhich now includes treating low transmission areas,previously described as hypo-endemic and not in-cluded in the APOC programme as the disease was notconsidered to be a major public health problem. Themethod of determination of the endemicity of oncho-cerciasis to be eligible for MDA with ivermectin wasbased on the prevalence of nodules in small samples ofadults (50), and if found to be less than 20% it was con-sidered no MDA was necessary as the area was definedas hypo-endemic. The extent of the areas of lowtransmission of Onchocerca volvulus have been identi-fied, and mapping the risk of L. loa in these areas deter-mined. This has helped to identify a number of areas ofhighest risk of L. loa-associated SAEs, which have beenreferred to as hypo-endemic hotspots, and will helpcountry programmes and partners to plan locally thedefined interventions necessary .The use of this information for both the LF and on-
chocerciasis programmes is a prerequisite for effectiveprogrammatic success if the ever persistent problem ofloiasis is to be addressed by programmes, and the elim-ination of LF and onchocerciasis is to become a reality. The epidemiological complexity of these problemshas been highlighted by Molyneux et al. , and morerecently by the observations that there is cross-reactivity of the rapid antigen diagnostic BinaxNOWFilariasis immunochromatographic test (ICT), wherepositive ICT positive cases have been shown to be theresult of infection with L. loa, thus complicating thediagnostic and monitoring assessments required of LFprogrammes .To date the control of the Chrysops vector of L. loa
has not been considered as a potential alternative oradditional strategy to address the problem co-endemicloiasis presents to the LF and onchocerciasis eliminationprogrammes. It is possible it could play an important roleif correct strategies are deployed. However, a better under-standing of the major vectors transmitting L. loa is essen-tial and timely given the World Health Organization(WHO) defined Roadmap targets for the elimination ofLF and onchocerciasis, and the challenges identified .The aim of this review, is to collect and synthesise thecurrent knowledge of the distribution of the two mainvectors C. silacea and C. dimidiata, highlighting mainfield and laboratory procedures, species distributions,ecology, habitats, potential methods of vector control and
Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 2 of 15
areas for future research, which may have implications forthe filariasis elimination programmes in a significant partof Africa.
MethodsA systematic search and collation of data in the peer-reviewed published literature on the two main Chrysopsspp. of vectors of L. loa was conducted using PubMed,JSTOR, SCOPUS and Google online sources. Search terms,and combinations thereof, included Loa loa, L. loa, loiasis,Rapid Assessment Procedure for Loiasis (RAPLOA), Chry-sops, C. silacea and C. dimidiata, Tabanid, Africa. All pub-lished literature with information on the two mainChrysops vector species, was reviewed. Information onother secondary vectors were documented where appropri-ate to provide perspective on the different potential vectors;however, they were not the focus of the review. Furtherreferences were obtained from the references listed withinarticles, and from the references within those articles andso on. Articles that were not obtainable through onlinesources were sourced through the Liverpool School ofTropical Medicine Library where possible. Information onthe articles were collated into a database in Excel (Micro-soft) (Additional file 1). The following information wassummarised:
Publication profile including (i) number of articles;(ii) time of publication (year and decade); (iii) typeof article (research, review, thesis, report); (iv)journal/ publisher (name); and (v) institution (nameand location; based on lead authors affiliation);
Study features including (i) country and locality;(ii) type of study (field, laboratory, field/laboratory);and (iii) study period (start and duration);
Field and laboratory procedures including (i)collection methods (adult and immature stages ofChrysops); (ii) species identification; and (iii)infection detection;
Species distribution, ecology and habitatsincluding (i) distribution and ecology; (ii) immaturestage habitats; (iii) adult habitats; (iii) host seekingpatterns; (iv) host preference; and (v) flight range;
Factors influencing spatial-temporal transmis-sion including (i) abundance patterns (daily,monthly seasonal); (ii) spatial environmental factors;and (iii) temporal environmental factors,anthropogenic factors (plantations, wood fire);
Methods of vector control including (i) defensivecontrol measures (screening, repellents, clearingforest and bush); and ii) aggressive control measures(insecticide larvicides, adulticides).
Information on the study locations included in thepublished documents were geo-referenced and imported
into the geographical information system software ArcGIS10.1 (ESRI, Redlands, CA) to produce a new vector distri-bution map based on the knowledge synthesised in thisreview.Based on the information reviewed, key points related
to field and laboratory procedures, species distribution,ecology and habitats, spatial-temporal transmission andmethods of vector control were highlighted in a seriesof excerpts, and areas for potential future research weresummarised.
ResultsPublication profileIn total, 89 published documents with information onthe two main L. loa vectors C. silacea and C dimidiatawere collated into a database (see Additional file 1). The number of articles published per decaderanged from 0 to 37, with the highest number pub-lished in the 1950s (Fig. 1). The majority of articleswere research based (n = 68) with several related re-views or combinations of research/ review (n = 18), onebook chapter, conference abstract, and one PhD thesisby Crewe in 1956 . The three most extensivereviews were published over 50 years ago by Gordon etal. 1950 , as part of the Symposium on Loiasis in1955  and in book chapters by Oldroyd , whiletwo briefer, more general reviews, were published in de-cades thereafter [84, 89], More than half of the researcharticles were part of a series of interlinking studies andinclude the following:
(i) Observations on Chrysops silacea and C. dimidiataat Benin, southern Nigeria by Davey and ORourkepublished in 1951 (three articles) ;
(ii) Studies on the intake of microfilaria by their insectvectors, their survival and their effect on thesurvival of their vectors by Kershaw and Dukebetween 1951 and 1954 (six of ten articles)[38, 40, 41, 44, 59, 60];
(iii) Studies on the epidemiology of filariasis in WestAfrica, with special reference to the BritishCameroons and the Niger Delta by Kershaw andNicholas between 1950 and 1955 (three of sixarticles) [29, 39, 45];
(iv) Studies on the biting habits of Chrysops by Dukebetween 1955 and 1959 (seven articles) ;
(v) Studies on the control of the vectors of loiasis inWest Africa by W. Crewe and P. Williams between1962 and 1964 (eight of nine articles) ;
(vi) Studies of Ethiopian Chrysops as possible vectorsof loiasis by W. Crewe and P. Williams publishedbetween 1954 and 1960 (three articles) [42, 63, 64];
(vii) The bionomics of the tabanid fauna of streams inthe rain-forest of the Southern Cameroons
Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 3 of 15
published by W. Crewe and P. Williams between1961 and 1962 (four articles) .
The majority of articles were published in the Annalsof Tropical Medicine and Parasitology (n = 45): activebetween 1907 and 2012 and now known as Pathogensand Global Health, and the Transactions of the RoyalSociety of Tropical Medicine and Hygiene (n = 13; activesince 1907), two major journals s...