REVIEW Open Access Loa loa vectors ? REVIEW Open Access Loa loa vectors Chrysops ... implications

  • Published on
    21-Jun-2018

  • View
    212

  • Download
    0

Transcript

  • 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

    Abstract

    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

    http://crossmark.crossref.org/dialog/?doi=10.1186/s13071-017-2103-y&domain=pdfhttp://orcid.org/0000-0002-3330-7629mailto:Louise.Kelly-Hope@lstmed.ac.ukhttp://creativecommons.org/licenses/by/4.0/http://creativecommons.org/publicdomain/zero/1.0/

  • 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 [4]. 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 [1].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 [8].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 [911]. 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 [12].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[13]. The epidemiological complexity of these problemshas been highlighted by Molyneux et al. [13], 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 [1417].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 [18].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)[19103]. 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 [57]. The three most extensivereviews were published over 50 years ago by Gordon etal. 1950 [28], as part of the Symposium on Loiasis in1955 [47] and in book chapters by Oldroyd [61], 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) [3032];

    (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) [5056];

    (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) [7583];

    (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) [6871].

    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 still publishing today.There were other journals that published papers onChrysops spp. from Belgium, Egypt, France, Germany,Pakistan, UK and Zimbabwe, the details are found in theAdditional file 1. Based on the lead authors affiliation,the majority of the research was undertaken by univer-sities or research centres.The majority of articles were from researchers based at

    the Helminthiasis Research Scheme, Kumba, British Cam-eroons (now in Cameroon), which was set up specificallyon the recommendation of the Colonial Medical ResearchCommittee to study loiasis with collaborating partnersfrom the University of Liverpool and/or the LiverpoolSchool of Tropical Medicine, UK, and collectively accountfor more than half the studies published. It was recognisedthat in order to control loiasis, a better understandingof the Chrysops spp. vectors driving transmission wasrequired [66].

    Study features: location, type and periodThe majority of research studies were conducted inCameroon in the surrounds of Kumba and Bombe vil-lages in an area formerly known as British Cameroonsin the south western region of the country (n = 48), andclose to where the Helminthiasis Research Scheme wasbased. Other research studies were conducted in Nigeria(southern States: Cross River, Oyo, Ogun, Ondo), Congo(Chaillu Mountains), DRC (nationwide), EquatorialGuinea (Bioko Island), Gabon (Reserve Ipassa-IRETMakokou) and Sudan (southern region). The most

    common type of study was field-based (n = 30) or a com-bination of field/ laboratory-based (n = 28) with only a fewlaboratory-based studies (n = 6). Overall, information onthe study period was irregular with the year the studystarted most regularly documented. More specific infor-mation on the exact month, season and duration of stud-ies were less well documented.

    Field and laboratory proceduresCollection methodsAll field-based studies involved outdoor collections eitherof adult or immature-stage/ larval stages and were mainlyrelated to measuring transmission patterns includingspecies abundance and infection rates (Additional file 1).The main method of collecting adult Chrysops spp. wasthe use of local men (historically known as fly-boys),with hand nets to capture the host-seeking fly, which oncecaught were secured in containers or test tubes for quanti-fication or further analysis in the laboratory.

    Adult collection method Each fly-boy was armed witha small hand-net made of mosquito-netting, about 6inches in diameter and a short handle about 12 incheslong, and with a test-tube. or each team of boys hadone Barraud cage in which to keep the catch sat downand caught flies that came to feed on him transferringto them to the cage. (Kumba, Cameroon)

    The immature stages of Chrysops were collected usinga simple apparatus built to sieve mud from shallowstreams or swampy areas to identify larvae and pupae.Historical photographs of the field apparatus are shownin Additional file 2 [47, 57].

    Immature-stage/larvae and pupae collectionmethod it consisted of a wooded-framed sieve 16inches square and 2 inches deep mounted on four legsto form a table 30 inches high; ordinary mosquito-

    Fig. 1 Number of articles per decade 19002010

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 4 of 15

  • screening wire is used for the active sieve. On top ofthe table rests a similar sieve without legs and a inch square mesh. The table is fixed in a suitable pos-ition, usually standing in the stream and mud fromthe breeding site is placed on the upper coarse sieveand washed through with water. Large pieces of debris,sticks and stones are retained by the coarse sieve,which is then removed. The mud is then slowly washedthrough the fine sieve and the larvae and pupae col-lected as they become visible. (Kumba, Cameroon)

    Species identificationInformation on species identification were not commonlydocumented, however, from the articles published, both C.silacea and C. dimidiata have only been identified anddistinguished from each other by morphological features[54, 61]. Overall, the two species are similar with a charac-teristic colour, longitudinal black stripes on abdomen,mottled wings and large head and eye (Fig. 2). In someparts of West Africa, C. silacea is known as the Red Fly[61, 66, 102] due to its bright orange abdomen with shortblack stripes, which was considered distinct from C. dimi-diata with its paler colour and broader longer stripes.Field workers were found to have no problem distinguish-ing them apart with noted typical silacea and dimidiatacharacteristics [21, 23, 66].

    Infection detectionLoa loa were documented to be found in the fat-body ofabdomen and to a lesser extent the fat-body of thethorax and head of Chrysops spp. Loa loa larvae wereclassified into different stages including sausage (L1),larval stage 2 (L2) and larval stage 3 or infective stage(L3), with the development of microfilariae to the infect-ive stage estimated to take between 10 and 12 daysbased on laboratory experiments [22, 23]. Dissecting

    Chrysops spp. under a microscope was the only methodused for detecting infection, which involved separatingthe head, thorax and abdomen manually, and identifyingthe presence (parous) or absence (nulliparous) of L. loalarva [56, 99]. Transmission was related to the frequencyof L3 found in the head of the flies and the bitingdensity of vectors with the main measures including (i)parous rates (PR) estimated as the proportion of parousflies to the total number dissected; (ii) potential infectionrates (PIR) estimated as proportion of flies with L3s; (iii)infective rates (IR) determined as the proportion of flieswith L3s in the head [90, 99, 103].

    Species distribution, ecology and habitatsDistribution and ecologyThe broad distributions of the main vectors, C. silaceaand C. dimidiata are shown in maps (Fig. 3), which werebased on available georeferenced data of study locationsand four historical maps (see Additional file 3). OverallC. silacea and C. dimidiata have been found throughoutthe greater part of the tropical equatorial rainforest.They are considered to become less dominant on thefringes where other species may replace them as vectors,as seen in southern Sudan and Central Nigeria where C.distinctipennis is the dominant savanna species, and wellknown to local inhabitants [24, 46]. Additional forestspecies include C. langi and C. centurionis, while C.zahrai is a forest-fringe species and C. longicornis both aforest and savanna species [61]. However, these add-itional species were not considered to be primary vectorsof human L. loa, and more associated with maintainingthe monkey strain of L. loa through crepuscular bitingand nocturnal periodicity. They were reported to be reluc-tant to feed on humans; however, C. zahrai was reportedto feed on humans if they are out in the forest after darkduring peak biting time of this species. Table 1 summa-rises key characteristics of the different species in relationto habitat, host, and periodicity [46, 47, 73].Overall, C. silacea and C. dimidiata were considered

    to have similar habitats, and in addition to rainforests,have been found in rubber plantations, palm oil grovesand fringes of mangrove swamps [32]. Both speciesfrequently occur together; however, in some areas onespecies was found to dominate the other, and acrossdifferent ecological settings with C. silacea more likelyto adapt to human influenced environments. For ex-ample, C. silacea was reported to be more abundant inKumba, Cameroon (rainforest), Sapele, Nigeria (rubberplantation) and Congo (rainforest) [91]; however, thelatter author noted that C. dimidiata was more abun-dant in the palm groves within the forested study area.Chrysops dimidiata was reported to be more abundantin Benin, Nigeria (palm grove) [30]; Eseka in centralCameroon (rainforest) [61], Bioko island, Equatorial

    Fig. 2 Picture of Chrysops silacea. Source: https://www.cdc.gov/parasites/loiasis/

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 5 of 15

    https://www.cdc.gov/parasites/loiasis/https://www.cdc.gov/parasites/loiasis/

  • Guinea (rainforest) [100], and in Akamkpa Community,Cross Rivers State, Nigeria (rainforest); however, for thelatter it was noted that C. silacea was more abundantin the adjacent mangrove forest [102].

    Immature stage habitatsThe Chrysops larvae and pupae were found to have welldefined microhabitats, which were characterised bydensely shaded streams and swamps, shallow slow flow-ing or standing water, with fine soft mud covered bylayers of decaying leaves [28, 32, 57]. These habitatswere noted be markedly acidic probably due to the decay-ing organic matter. Chrysops larvae were also reported inthe streams draining the borders of a rubber plantationsinto the surrounding mangrove swamps. Photographs oftypical breeding sites are shown in Crewe [57], and

    Gordon et al. [26] available in Additional file 2. In Benin(Nigeria), extensive larval habitat studies where C. dimi-diata was the dominant vector, showed larvae were pre-dominately found in less than three inches of mud, and inareas of saturated or damp mud but not where water wasone foot, or mud more than three inches in depth [26, 32].

    Chrysops silacea forested larval breeding siteChrysops at Kumba considered very restricted, andconfined to certain habitats in densely shaded, whereslowly moving water passes over a layer of mud coveredin decaying vegetation. Generally, the thickly overgrownvalleys flanking the residential areas have denselyshaded streams at the bottom, and in parts the streamsare impeded by vegetation, making the water slow, andthe bottom is covered by fine sand overlaid with soft

    Fig. 3 Map showing reported species distribution

    Table 1 Summary of primary and secondary Chrysops spp. main characteristics

    Species Ecological distribution Peak biting time Putative host Main biting location

    C. silacea Forest Day Human Ground

    C. dimidiata Forest Day Human Ground

    C. langi Forest Crepuscular/Nocturnal Monkey Canopy

    C. centurionis Forest Crepuscular/Nocturnal Monkey Canopy

    C. zahrai Forest-fringe Crepuscular Monkey/Human Canopy/Ground

    C. longicornis Forest/Savanna/Wooded areas Crepuscular Monkey Canopy

    C. distinctipennis Savanna Crepuscular Monkey/Human Canopy/Ground

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 6 of 15

  • mud which is covered in decaying leaves and consideredChrysops breeding places (Kumba, Cameroon).

    Chrysops dimidiata plantation larval breeding sitebreeding was confined to certain reaches of the river:where banks were swampy and where there was athick mass of decaying vegetable matter over mulch,larvae were common, but where the edges of the riverwere clear-cut and sandy, and thus devoid of organicmatter, no specimens were ever taken. (Benin, Nigeria)

    Adult habitatsChrysops silacea and C. dimidiata were considered to beforest canopy dwellers descending to bite the humanpopulation in the forested or plantation areas. Chrysopssilacea in particular has been reported to avoid the dee-pest shade and the brightest sunlight, and found to bemost abundant in the patchy light-shade of intermediateareas [47]. This vector has been found to bite at all levelsof the forested areas, and throughout plantations, andwill leave shelter to cross small clearings to enter housesor attack local workers. In Sapele, Nigeria, the rubberplantations bounded by swamps were considered to pro-vide exclusive contact sites between human and flies,with no competing hosts. This appeared to lead to adifferent transmission pattern with many labourers in-fected, a high abundance of Chrysops and high levels ofinfection in local Chrysops populations [21, 32, 61].

    Rubber plantation (predominately Chrysops silacea)The rubber trees are mature about 50 feet high. Thebranches are interlaced, and form a continuous thickcanopy, which casts a deep shade through which littledirect sunlight penetrates There is no monkeypopulation in the canopy, and the attention of the fliesare concentrated upon the African rubber-tappers. Mov-ing about their duties, and clearly visible from above.(Sapele, Nigeria)

    Adult host-seekingChrysops silacea and C. dimidiata were considered tobe practically noiseless, persistent daylight feedersattacking the ankles and the lower limbs most com-monly [31, 57]. They were considered to hunt mainlyby sight and noted to be attracted to colour and move-ment; however, specific studies on host seeking behav-iour also found an olfactory stimulus related to forestleaves burning in wood fires [51] this attraction to firesperhaps due to the CO2 derived from them. It was alsonoted that both species were more attracted to a groupof people rather than to an individual, and biting ratesof C. silacea increased up to six times as they movedthrough the forest [31, 52, 55]. Chrysops silacea wasreported to be more attracted to darker colours or the

    colour blue/ light blue [72]. In the laboratory, Connal &Connal [22] noted during feeding experiments thatguinea pigs with dark patches were bitten more thanwhite ones, and suggested Chrysops was able to distin-guish colour.Both Chrysops vectors peak biting times were closely

    associated with the diurnal periodicity of microfilariaeof L. loa in humans [21, 33]. Several studies inCameroon, Congo and Nigeria found that these twovectors were almost exclusively active between dawnand dusk [47, 61]. Peak biting times were reported inthe morning (c.911 am), with a decrease aroundmidday and a smaller peak in the afternoon (c.34 pm)[21, 28, 33, 57, 99, 102]. In Benin, Nigeria labourerswere noted to be frequently bitten until midday, whenthe temperature reaches a maximum and the fliesretreated to shaded areas [31]. Detailed studies on C. sila-cea in Kumba indicated that bi-phasic diurnal biting cyclewas associated with changes in light intensity, temperatureand relative humidity throughout the day. Specifically, thebiting activity of C. silacea appeared to increase with a risein temperature to 6685 F and decrease with a rise inrelative humidity of 56100% [33, 35].

    Chrysops silacea in forested area Seldom attacks inbright sunlight, preferring shade of trees or shelter ofverandas, and stops when temperatures reachmaximum values in the afternoon. The fly referred toas the softly-softly fly as it makes no sound as ithovers. Bites parts not in full view such as back ofankles, legs, outer hands. Bite not painful, butwithdrawal is painful, and can cause considerableirritation, extensive swelling for a few minutes to hoursafter the bites

    Host preference and patternsWhile C. silacea and C dimidata were associated withthe transmission of human L. loa, it was noted that theymay attempt to feed on monkeys and other animals dur-ing the day; however, with monkeys there was minimalopportunity to take microfilaria from the nocturnallyperiodic L. loa found in monkeys. Host preference stud-ies by Gouteux & Noireau [87] found that both Chrysopsspecies had similar feeding patterns and that humans(8990%) were the main hosts; however, blood mealswere also identified from hippopotamus, which wereonly present in rivers not in close proximity, leading theauthors to suggest that Chrysops were able to fly overlarge distances. Gordon et al. [26] raised importance ofunderstanding the relationship between Chrysops infectivedensity and human infection rates for control and curativemeasures, and aimed to defined the different levels of risk,and explain why there may be disparities within and

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 7 of 15

  • between populations and subgroups such as adults, chil-dren, Africans and Europeans.

    Chrysops density, infection and human risk figures of fly-density, fly-infection and an eight-hourbiting-period as indicative of conditions at Kumbaduring the months of June and July, i.e. at the height ofthe Chrysops season, then, on average, each Europeanwould be exposed to the risk of infection with Loa loaonce in every five days. (Kumba, Cameroon)

    Flight rangeMark-release-recapture studies in Kumba, Cameroonfound Chrysops could readily travel 1 mile (~1.6 km) ina day, and up to two miles (~3.2 km) through the forestsix days after release. In Benin, Nigeria, Chrysops werefound to fly up to at least 1200 yards (1 km), but thiswas considered not to be the maximum distance inwhich the fly could cover [31]. This is in agreement withdetailed studies on C. dimidiata in Cameroon [94], andanother study conducted in secondary forest habitats inCameroon [97] found the maximum flight range for C.dimidata was 4.5 km and for C. silacea 2.2 km; however,it was noted that 50% of Chrysops were found within800 m, and 80% within 1500 m from release point.

    Factors influencing spatial-temporal transmissionAbundance pattern measuresAdult Chrysops abundance was based on biting ratesmeasured as boy-hours in historical studies, and by thenumber of flies caught per man per hour (fly/man/hours) or tabanid per man per day (T/MD) in more re-cently published articles [91, 99]. Several factors wereidentified as influencing the biting cycles and infectionrates, which were primarily related to spatial and tem-poral environmental and anthropogenic factors.

    Spatial environmental factorsSpatial environmental factors were related to thechanges in forest density and light intensity both verti-cally and horizontally. For example, Kettle [35] revealedan association between the diurnal cycle of light inten-sity measured and the biting cycle of C. silacea inKumba, Cameroon. Further detailed studies of bitingand infection rates were conducted at different canopyheights with platforms constructed in the forest for fly-boys to collect species and information on light inten-sity, temperature and saturation-deficiency [50]. Thehighest biting and infection rates were found mid- can-opy between 28 and 92 ft (~8.528 m), which includeshaded areas with intermediate light, temperature andsaturation measures, compared with the hotter lightercanopy top at 130 ft (~40 m) and the darker coolerground level sites.

    Several studies examined the relationship between for-ested and cleared areas, and found decreasing bitingrates with deforestation related to anthropogenic planta-tion and human habitation development [90]. However,the rate of reduction varied between sites dependingupon the amount and distance from forested vegetation,as well as by species with C. dimidiata noted to be moreconfined to forested areas, e.g. in Makokou, Gabon[101], and in the Chaillu Mountains, Congo [91]. Chry-sops silacea was more dominant in villages whereas C.dimidiata was rarely found in open the environment,favouring primary and secondary forested areas. Duke[53] also examined C. silacea differences between a for-ested site, a total cleared site and a cleared site with rub-ber saplings. Biting and infection rates measured atregular intervals up to 400 yards (~366 m) in both thecleared sites, showed significant reductions in abundanceand infection rates at an increasing distance from theforest site. However, the rates of reduction were moregradual in the cleared site with rubber saplings, com-pared with the total cleared site).

    Forest clearing and reduction in biting rates In acleared area planted with rubber saplings 1012 feethigh, the biting density fell to one-tenth of the forest valueat 530 yards from the forest In an area of total clear-ance planted with rubber saplings 1.52 feet high, thebiting density fell to one-tenth of the forest at 100 years.

    Kershaw [47] also discusses the effect of widespreadclearing associated with village, town and commercial de-velopment and suggests that strip of half a mile of clearedmay be sufficient to significantly reduce human risk.

    Temporal environmental factorsTemporal environmental factors were related to climateand seasonality. For example, in Kumba, Crewe [57]found that C. silacea biting rates increased with rainfallbut dropped with the onset of very heavy rain, suggest-ing that pupae could not survive excessive ground wateror flooding. Another study on C. silacea in a differentpart of Cameroon [97], and in the Chaillu Mountains,Congo [91], also found significantly higher biting ratesduring the rainy season compared with the dry season.Similarly, in areas where C. dimidiata was the main vec-tor such as the Cross River State, Nigeria, the highestbiting rates were observed during the rainy season, butpredominantly late in the season [102]. This late rainyseason peak was also noted in Bombe, Cameroon byDuke [54].

    Wood firesWood fires were identified as an additional anthropogenicfactor influencing transmission. Duke [43, 51] initially

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 8 of 15

  • observed that the smoke of wood fires appeared to attractC. silacea and detailed studies found a six-fold increase inbiting densities of C. silacea, but not C. dimidiata, in therainforest in Kumba, Cameroon, with increases mostmarked during the morning when flies were more com-mon at ground level.

    Wood fire as an attractant It is shown that bitingdensity of Chrysops silacea at ground level in the rain-forest at Kumba is increased more than six times whencatches are made in the presence of a wood fire. Evi-dence is produced to show that flies released for bitingat canopy level are attracted down to ground level bythe smell of wood smoke, thereby accounting for an in-creased biting density.

    In the Chaillu Mountains, Congo, similar increases inbiting densities with the presence of wood fires werefound, with a 8.5-fold increase at ground level and 5-fold increase in the canopy for C. silacea, but with littleor no effect on C. dimidiata [93]. More recently Wanjiet al. [99] used wood fires as part of the collection toolfor a study in Kendonge, Cameroon, recognising it as afield method to increase Chrysops numbers for quantifi-cation and analysis.

    Methods of vector controlIn relation to the control of the Chrysops vector, overallfew practical measures have been suggested; however, sev-eral historical articles referred to studies and potentialmethods [26, 32, 7583] of control, which Gordon [28]divided into two main categories and sub-categories in-cluding the following: (i) Defensive Methods of Control:screening and repellents; clearing of forest and of bush;and (ii) Aggressive Methods of Control: measures di-rected against adult Chrysops; measures directed againstimmature stages of Chrysops.

    Defensive control measuresDefensive control measures included screening andrepellents, which noted several examples, including thatin Benin (Nigeria) one house was screened for a periodof eight months with no Chrysops entering the room,and that 60% or undiluted DMP (dimethyl phthalate) ap-peared to be a satisfactory personal repellent againstChrysops, with protection provided to local workers fora minimum of 2 to 3 h [32]. It also included the possibleclearing of dense bush in close proximity to housing butconcerns were expressed over the practicality of this,and also if it may as a result increase other vectors, suchas Anopheles and the transmission of malaria [28]. Duke[53] also noted that selective clearing measures may beapplicable on organized plantations, where flies are

    numerous and human populations are at risk in rela-tively compact areas.

    Screening and repellents for control 60 per centDMP, when applied to the skin gave completeprotection, netting soaked in this solution failed torepel the flies which passed just as readily through theimpregnated as through the unimpregnated netting 30 per cent DMP gives little or no protection againstChrysops.

    Clearing for control the highest incidence ofChrysops was observed in bungalows lying close to thedense bush. We suggest, therefore, that the annual grantshould be increased to allow more generous clearing ofbush since flies appear to approach dwellings alongeven narrow strips of bush.

    Aggressive control methodsAggressive control methods included those against boththe adult and immature stages of Chrysops with insecti-cides. For adults, it was suggested that indoor residualspraying (IRS) may help to reduce density as they poten-tially rest on walls and ceilings waiting to obtain theirblood meals, or spraying the undergrowth in the vicinityof the oviposition sites may be of value [28].For the immature stages, spraying foliage where eggs

    are laid was suggested, and also the possibility of clear-ing bush and trees to remove shade or the canalising ofstreams to remove stagnant vegetation may help toreduce fly density [28, 32]. Detailed studies on theapplication of DDT (dichlorodiphenyltrichloroethane)dieldrin, aldrin and gamma-BHC (gamma-hexachloro-cyclohexane) found that all insecticides were able topenetrate breeding site mud to a depth of 2 to 6 in.(~515 cm), with dieldrin most persistent and highlyeffective as shown in the series of articles on vectorcontrol [78, 83]. Williams & Crewe [83] highlighted thesuccess of a 14-square-mile application which reducedC. silacea and C. dimidiata by 70% and the number ofinfective larvae of L. loa in Chrysops by 62%. However,they also noted the difficulties in treating large areas ofmud and raised significant concerns about the possibleseepage of insecticides into streams, which could createpublic health problem by adversely affecting other non-target animals and humans. Table 2 further summarisesthe findings of the studies and discussions highlightedin the article [81].

    Insecticidal larval spray for control Dieldrinemulsion containing one part in 640 of the activeagent, applied at the rate of four pints to 100 squarefeet, kept breeding site free of tabanid larvae for atleast eight months. This concentration of dieldrin

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 9 of 15

  • should be sufficient to control the vectors of loiasis inthe rain-forest.

    Areas of potential future researchBased on the extensive research summarised in thisreview, the following are considered to be areas of po-tential future research, which will build on the currentknowledge:

    (i) Determine alternative trapping methods forcollecting adult Chrysops spp. that do not involvehuman-landing catches (i.e. fly-boys);

    (ii) Review and assess the potential range of attractants,including wood-fires and trap colour, that mayincrease adult catch numbers;

    (iii)Determine the optimal time and labour efficientmethods for identifying breeding sites andcollecting larvae for analysis within high riskcommunities;

    (iv)Determine the relationship between Chrysopsinfection rates and human loiasis risk, and ifxenomonitoring could play a role in determiningthe level of risk within a community;

    (v) Determine the capacity of local entomologists,community members and field workers to identifymain Chrysops spp. high risk breeding and bitingareas within communities and workplaces to helptarget control measures;

    (vi)Determine if the ecological and climatic aspects ofvector habitats and behaviour, including the extentof deforestation and the potential role in reducingrisk, can be predicted over larger geographical areasusing remote sensing satellite imagery and modelledenvironmental data;

    (vii) Determine the geographical extent of overlappingvector-borne disease infections to better determinehow IVM could be effectively implemented.

    DiscussionThis paper presents the first extensive review on thetwo main L. loa vectors C. silacea and C. dimidiata inmore than 50 years. This is important as these areneglected vectors of the neglected disease, loiasis,which although not formally listed as an NTD by theWHO has a significant impact on the elimination pro-grammes of LF and onchocerciasis [18]. Studies on theepidemiology of loiasis, and the Chrysops vectors thatdrive transmission should have more prominence asstudies highlight the potential clinical impact of loiasison individuals [8]. Efforts to scale up elimination activ-ities for other co-endemic filarial diseases such as LFand onchocerciasis have been prioritised, and all pos-sible methods of control need to be considered [104].This review recommends that the control of L. loa vec-tors is considered as an additional strategy to reducethe transmission of L. loa where the elimination of LFand onchocerciasis is compromised by the risk of L. loainduced encephalopathies; this may be particularly per-tinent in hypo-endemic onchocerciasis areas wherethere are currently no safe chemotherapy options rec-ommended [12], and where currently only doxycyclineis a viable alternative chemotherapy [105, 106].The review highlighted that the majority of studies

    were conducted in the 1950s and 1960s, when there wasa surge of interest in the control of loiasis as an import-ant disease. This was most likely related to the highprevalence found in local populations, rubber plantationworkers and palm grove estates. The work from the

    Table 2 Summary of Chrysops spp. immature and adult stages, and associated vector control measures

    Stage Target Aim Activity Target area Category(after Gordon [28])

    Larvae Environmental modification Reduce or kill pupae/ larvaldevelopment and emergence

    Drainage of water, vegetationclearing to remove shade; flood

    Community andsurrounds

    Defensive

    Insecticide treatment Reduce or kill pupae/ larvaldevelopment and emergence

    Apply insecticide to mudbreeding sites

    Community andsurrounds

    Aggressive

    Adult Personal repellents Prevent biting by repelling withskin/ clothing impregnatedinsecticide

    Apply insecticide to skin/impregnateclothes of humans

    Humans Defensive

    Household screens, curtains Prevent indoor biting by aphysical barrier/ infrastructure

    Wired/meshed windows and doorsof houses

    Houses Defensive

    Environmental modification Reduce abundance by eliminatingvegetation/ canopy resting sites

    Vegetation clearing around houses/village surrounds

    Community andsurrounds

    Defensive

    Insecticidal treatment To kill or knock down hostseeking

    Spraying of foliage near ovipositionsites

    Community andsurrounds

    Aggressive

    Indoor residual spraying Houses Aggressive

    Traps alone, or withinsecticide or wood fire

    Reduce abundance by capturingor killing

    Proximity to emerging larvae or hostseeking

    Community andsurrounds

    Aggressive

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 10 of 15

  • Helminthiasis Research Scheme in Kumba, Cameroon,and the significant body of related work published inseveral series of research papers, has provided an im-portant and comprehensive foundation from which tobuild further work in this field, specifically in relation tothe distribution, ecology and epidemiology in high riskareas [2], and methods of targeted vector control, whichcould be integrated with other vector-borne diseases[107]. However, this will require a further significantsurge in interest, funding and purpose for capacitystrengthening, as currently there is a general shortage ofmedical entomologists in Africa, and only a small poolof scientists currently working on L. loa.Moving forward with any form of Chrysops control is

    likely to be multifaceted given that C. silacea and C.dimidiata are day-biting vectors that breed in denselyshaded muddy streams and swamps, and rest in forestcanopies high above ground-level. While these charac-teristics pose significant challenges, several studies indi-cated that vector control activities can impact on L. loatransmission. Therefore, Chrysops control or repellingthe biting of humans, should be considered as an add-itional approach to be used in conjunction with otherstrategies. While this may not be a solution to reducingthe risk of SAEs in the short-term given the duration ofthe transmission cycle, it would provide long-term bene-fits by reducing the number and intensity of infections,and thereby reducing the frequency of individuals withhigh Mf loads. The use of modern tools and technologyto identify local hotspots and initiate vector control/ re-pellency studies could be successful if targeted at theright place, at the right time, with the right intervention.However, understanding spatial and temporal patterns ofthe local distributions will be key [108], and not neces-sary complicated, given that these vectors have readilyidentifiable physical characteristics, and are primarilyassociated with forested or plantation areas, with clearseasonality, all of which can be effectively targeted.For the immature stages of Chrysops, the use of

    community-based environmental management and lar-viciding with new formulations may be considered.Environmental management including drainage, filling,or removal of vegetation around breeding sites may bepossible on a small scale, but is not practical in vastforested areas. The application of insecticide-based lar-vicides such as temephos (Abate) or biological controlagents such as Bacillus thuringiensis (Bti) that specific-ally kill dipteran larvae through regular spraying offersan alternative method. These interventions have lowtoxicity and have been used widely in Africa for thecontrol of onchocerciasis (Simulium spp.), control ofDracunculus (guinea worm) intermediate hosts cope-pods and malaria (Anopheles spp.) control [109112].The application requires little technical skill, so that

    community members may be trained to target key siteswithin vector flight range of 12 km, at high risk timesbased on peak seasonality. Further potential lies with newchemical formulations being developed by the InnovativeVector Control Consortium (IVCC) [113, 114], and in-novative field application methods being considered forhard-to-reach places by using smart drones to apply larvi-cides and adulticides in remote locations using unmannedaerial vehicles (UAV) [115]. However, this approach usingUAVs could also focus on the forest edge close to humansettlements, to deploy insecticide avoiding the problemsof operating within a dense forest environment.For the Chrysops adult stages, the use of personal

    protection, household screening, IRS, and community-based insecticide spraying or trapping may all help toreduce vector-human contact and transmission. Stand-ard insect repellents have been shown to provide pro-tection to people if applied regularly, especially in themorning peak biting times, however, new methods in-volving transfluthrin-impregnated hessian strips beingtrialled against outdoor exposure of malaria (Anopheles),urban filariasis (Culex) and Zika (Aedes) vectors may alsobe promising for loiasis (Chrysops) [116, 117]. Windowscreening, insecticide-impregnated curtains, and IRScould provide household-level protection, while other in-novative community-based approaches such as the bluetiny targets/ traps being used for human African trypano-somiasis (Gambian sleeping sickness) (tsetse) control, mayalso be capable of reducing transmission by readily placingthe targets as key visual stimuli around disease hotspotswithin high risk communities at relatively low cost [118].These examples also provide insights into the potential

    for integrated vector management (IVM), with multiplediseases potentially being targeted simultaneously withshared human and financial resource and multiple im-pact. However, it will be important to first conduct asituational analysis of each disease, including an assess-ment of the epidemiology and entomology, the extent ofgeographical overlap, vector control needs and availableresources [107]. A systematic review and field assess-ments of tabanid trapping and control methods in otherregions of the world may also help to determine whatcould realistically be trialled and used in Africa [119121]. Different trapping methods such as the Nzi traphave been used to monitor species abundance, and at-tractants such as carbon dioxide (CO2) and octanol haveshown to potentially improve capture rates, which maybe better than the use of wood fires. The developmentof a trapping-attractant method for the loiasis vectors inAfrica could also help with large-scale monitoring. Chry-sops xenomonitoring has never previously been pro-posed as tool to determine community risk, but may bea more cost-effective option than labour intensive hu-man seroprevalence surveys or RAPLOA.

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 11 of 15

  • Further examination of the current loiasis distributionrisk should also be undertaken using the newest remotesensing satellite data sets. Since the initial mapping andremote sensing studies were conducted some 1015years ago [2, 4], it is likely that significant deforestationhas taken place with human infrastructure develop-ment, which will have impacted on the distribution ofChrysops in West and Central Africa. It is urgent toutilise remote sensing data to define such risk areasand environmental factors driving transmission, since itis not considered feasible for financial and resource rea-sons to undertake further RAPLOA studies across such anextensive region, especially in hypo-endemic onchocercia-sis hotspots [12]. Further, there is a need to better definethe areas and extent of risk of SAEs when the implemen-tation of programmes is becoming increasingly urgent ifthe NTD Roadmap targets are to be met [18].

    ConclusionThis review provides the most recent summary on thecurrent knowledge on the two main Chrysops vectors,highlighting main field and laboratory procedures, speciesdistributions, ecology, habitats and potential methods ofvector control. Importantly, these factors may help deter-mine the feasibility of how vector control may be imple-mented to reduce L. loa transmission and microfilariaeloads in high prevalence communities, and if as a conse-quence, could also reduce the risk of SAEs associated withthe drug ivermectin for LF and onchocerciasis elimination.This is particularly important in areas where high preva-lence of L. loa are co-endemic with hypo-endemic oncho-cerciasis hotspots and the need for alternative strategiesand novel approaches is critical if elimination targets areto achieved. Focussing on those already infected ignoresthe role that the vector plays in driving the epidemiologyand the consequent risk of SAEs.

    Additional files

    Additional file 1: Chrysops literature database. (XLSX 45 kb)

    Additional file 2: Photographs of breeding sites and apparatus forcollecting larvae (PDF 626 kb)

    Additional file 3: Historical maps of Chrysops distributions (PDF 674 kb)

    AbbreviationsAPOC: African Programme for Onchocerciasis Control; CDTi: Community-directed treatment with ivermectin; DDT: Dichlorodiphenyltrichloroethane;DEC: Diethylcarbamazine citrate; DRC: Democratic Republic of Congo;GPELF: Global Programme to Eliminate Lymphatic Filariasis;ICT: Immunochromatographic test; IRS: Indoor residual spraying;IVCC: Innovative Vector Control Consortium; IVM: Integrated vectormanagement; LF: Lymphatic filariasis; LLIN: Long-lasting insecticidal net;MDA: Mass drug administration; MF: Microfilaria; NTDs: Neglected tropicaldiseases; RAPLOA: Rapid Assessment Procedure for Loiasis; SAE: Severeadverse event; UAV: Unmanned aerial vehicles; WHO: World HealthOrganization

    AcknowledgementsWe are grateful to Louise Harbour from the Liverpool School of TropicalMedicine for assistance with the collation and chronological listing ofarticles. LKH and BT acknowledge the support from the Department forInternational Development (DFID), and DHM support from DFID andGlaxoSmithKline through the CouNTDown operational projects to theLiverpool School of Tropical Medicine.

    DedicationThis study is dedicated to those staff of the Liverpool School of TropicalMedicine and others who worked in West Africa during the 1950s on Loaloa, notably the late Professor William Kershaw and the late Dr Brian Dukeand particularly Dr Bill Crewe whose thesis was a major stimulus for ourstudies and this review. We are grateful to have benefitted from discussionswith Bill Crewe, which provided an insight into the ecology of L. loa andChrysops derived from many years of direct experience.

    FundingThe authors received no specific funding for this study.

    Availability of data and materialsThe datasets supporting the conclusions of this article are included in thearticle and its additional files.

    Authors contributionsLKH and DHM conceived the idea for review. LKH and RP collated themajority of documents, summarised the information and drafted of the firstversion of the manuscript. BT contributed to the collation and summary ofdocuments. DHM, TRU and MB provided important intellectual content andcontributed the editing and finalising the manuscript. All authors read andapproved the final manuscript.

    Competing interestsThe authors declare that they have no competing interests.

    Consent for publicationNot applicable.

    Ethics approvalNot applicable.

    Publishers NoteSpringer Nature remains neutral with regard to jurisdictional claims in publishedmaps and institutional affiliations.

    Author details1Department of Parasitology, Liverpool School of Tropical Medicine,Liverpool, UK. 2CISA, Health Research Centre of Angola, Caxito, Angola.3Lisbon School of Health Technology, Lisbon, Portugal. 4College of PublicHealth, Department of Global Health, University of South Florida, Tampa,USA.

    Received: 27 October 2016 Accepted: 23 March 2017

    References1. Boussinesq M. Loiasis. Ann Trop Med Parasitol. 2006;100:71531.2. Zour HGM, Wanji S, Noma M, Amazigo UV, Diggle PJ, Tekle AH, et al. The

    geographic distribution of Loa loa in Africa: results of large-scale implementationof the Rapid Assessment Procedure for Loiasis (RAPLOA). PLoS Negl Trop Dis.2011;5:e1210.

    3. Takougang I, Meremikwu M, Wandji S, Yenshu EV, Aripko B, Lamlenn SB,et al. Rapid assessment method for prevalence and intensity of Loa loainfection. Bull World Health Organ. 2002;80:8528.

    4. Thomson MC, Obsomer V, Dunne M, Connor SJ, Molyneux DH. Satellitemapping of Loa loa prevalence in relation to ivermectin use in West andCentral Africa. Lancet. 2000;356:10778.

    5. Kelly-Hope LA, Bockarie MJ, Molyneux DH. Loa loa ecology in Central Africa:Role of the Congo River system. PLoS Negl Trop Dis. 2012;6:e1605.

    6. Boussinesq M, Gardon J. Prevalences of Loa loa microfilaraemia throughoutthe area endemic for the infection. Ann Trop Med Parasitol. 1997;91:57389.

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 12 of 15

    dx.doi.org/10.1186/s13071-017-2103-ydx.doi.org/10.1186/s13071-017-2103-ydx.doi.org/10.1186/s13071-017-2103-y

  • 7. Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP,Boussinesq M. Serious reactions after mass treatment of onchocerciasis withivermectin in an area endemic for Loa loa infection. Lancet. 1997;350:1822.

    8. Chesnais CB, Takougang I, Pagul M, Pion SD, Boussinesq M. Excessmortality associated with loiasis: a retrospective population-based cohortstudy. Lancet Infect Dis. 2017;17:10816.

    9. van den Berg H, Kelly-Hope LA, Lindsay SW. Malaria and lymphatic filariasis: thecase for integrated vector management. Lancet Infect Dis. 2013;13:8994.

    10. Reimer LJ, Thomsen EK, Tisch DJ, Henry-Halldin CN, Zimmerman PA, BaeaME, et al. Insecticidal bed nets and filariasis transmission in Papua NewGuinea. N Engl J Med. 2013;369:74553.

    11. Rebollo MP, Sambou SM, Thomas B, Biritwum NK, Jaye MC, Kelly-Hope L,et al. Elimination of lymphatic filariasis in The Gambia. PLoS Negl Trop Dis.2015;9:116.

    12. Kelly-Hope LA, Unnasch TR, Stanton MC, Molyneux DH. Hypo-endemiconchocerciasis hotspots: defining areas of high risk through micro-mappingand environmental delineation. Infect Dis Poverty. 2015;4:36.

    13. Molyneux DH, Hopkins A, Bradley MH, Kelly-Hope LA. Multidimensionalcomplexities of filariasis control in an era of large-scale mass drugadministration programmes: a can of worms. Parasit Vectors. 2014;7:363.

    14. Bakajika DK, Nigo MM, Lotsima JP, Masikini GA, Fischer K, Lloyd MM, et al.Filarial antigenemia and Loa loa night blood microfilaremia in an areawithout bancroftian filariasis in the Democratic Republic of Congo. Am JTrop Med Hyg. 2014;91:11428.

    15. Wanji S, Amvongo-Adjia N, Koudou B, Njouendou AJ, Chounna NdongmoPW, Kengne-Ouafo JA, et al. Cross-reactivity of filariais ICT cards in areas ofcontrasting endemicity of Loa loa and Mansonella perstans in Cameroon:implications for shrinking of the lymphatic filariasis map in the CentralAfrican Region. PLoS Negl Trop Dis. 2015;9:e0004184.

    16. Wanji S, Amvongo-Adjia N, Njouendou AJ, Kengne-Ouafo JA, NdongmoWPC, Fombad FF, et al. Further evidence of the cross-reactivity of the BinaxNOW Filariasis ICT cards to non-Wuchereria bancrofti filariae: experimentalstudies with Loa loa and Onchocerca ochengi. Parasit Vectors. 2016;9:267.

    17. Pion SD, Montavon C, Chesnais CB, Kamgno J, Wanji S, Klion AD, et al.Positivity of antigen tests used for diagnosis of lymphatic filariasis inindividuals without Wuchereria bancrofti infection but with high Loa loamicrofilaremia. Am J Trop Med Hyg. 2016;95:141723.

    18. World Health Organization. Accelerating work to overcome the globalimpact of neglected tropical diseases: a roadmap for implementation[Internet]. Geneva: World Health Organization; 2012. Available from: http://apps.who.int/iris/handle/10665/70809.

    19. Leiper R. Report to the advisory committee of the tropical diseases researchfund, colonial office London. Trop Dis Bull. 1913;2:1956.

    20. Kleine FK. Die bertragung von Filarien durch Chrysops. The transmission ofFilaria by Chrysops. Z Hyg Infektionskr. 1915;80:3459.

    21. Connal A. Observations on filaria in Chrysops from West Africa. Trans R SocTrop Med Hyg. 1921;14:1089.

    22. Connal A, Connal SLM. A preliminary note on the development of Loa loa(Guyot) in Chrysops silacea (Austen). Trans R Soc Trop Med Hyg. 1921;15:1314.

    23. Connal A, Connal SLM. The development of Loa loa (Guyot) in Chrysopssilacea (Austen) and in Chrysops dimidiata (Van Der Wulp). Trans R Soc TropMed Hyg. 1922;16:6489.

    24. Woodman HM, Bokhari A. Studies on Loa loa and the first report of Wuchereriabancrofti in the Sudan. Trans R Soc Trop Med Hyg. 1941;35:7792.

    25. Chwatt LJ, Gordon RM, Jones CM. The breeding places of Chrysops silacea.Ann Trop Med Parasitol. 1948;42:251.

    26. Gordon RM, Chwatt LJ, Jones CM. The results of a preliminaryentomological survey of loiasis at Kumba, British Cameroons, together witha description of the breeding-places of the vector and suggestions forfuture research and possible methods of control. Ann Trop Med Parasitol.1948;42:36476.

    27. Woodman HM. Filaria in the Anglo-Egyptian Sudan. Trans R Soc Trop MedHyg. 1949;42:54358.

    28. Gordon RM, Kershaw WE, Crewe W, Oldroyd H. The problem of loiasis inWest Africa with special reference to recent investigations at Kumba in theBritish Cameroons and at Sapele in Southern Nigeria. Trans R Soc Trop MedHyg. 1950;44:1147.

    29. Kershaw WE. Studies on the epidemiology of filariasis in West Africa, with specialreference to the British Cameroons and the Niger Delta. II. The influence of townand village evolution and development on the incidence of infections with Loaloa and Acanthocheilone. Ann Trop Med Parasitol. 1951;45:26183.

    30. Davey J, ORourke F. Observations on Chrysops silacea and C. dimidiata atBenin, Southern Nigeria. I. Ann Trop Med Parasitol. 1951;45:307.

    31. Davey J, ORourke F. Observations on Chrysops silacea and C. dimidiata atBenin, Southern Nigeria. II. Ann Trop Med Parasitol. 1951;45:6672.

    32. Davey J, ORourke F. Observations on Chrysops silacea and C. dimidiata atBenin, Southern Nigeria. Part III. Ann Trop Med Parasitol. 1951;45:1019.

    33. Crewe W, ORourke FJ. The biting habits of Chrysops silacea in the forest atKumba, British Cameroons. Ann Trop Med Parasitol. 1951;45:3850.

    34. Crewe W. The effect of light on the biting activity of Chrysops silacea in theforest at Kumba, British Cameroons. Ann Trop Med Parasitol. 1953;47:3403.

    35. Kettle DS. The effect of light on the biting activity of Chrysops silacea(Diptera Tabanidae). Ann Trop Med Parasitol. 1953;47:3359.

    36. Kershaw WE, Keay RW, Nicholas WL, Zahra A. Studies on the epidemiologyof filariasis in West Africa, with special reference to the British Cameroonsand the Niger Delta. IV. The incidence of Loa loa and Acanthocheilonemaperstans in the rain-forest, the forest fringe and the mountain grasslands ofthe British Cameroons, with observations on the species of Chrysops andCulicoides found. Ann Trop Med Parasitol. 1953;47:40624.

    37. Gordon RM, Crewe W. The deposition of the infective stage of Loa loa byChrysops silacea, and the early stages of its migration to the deeper tissuesof the mammalian host. Ann Trop Med Parasitol. 1953;47:7485.

    38. Kershaw WE, Crewe W, Beesley WN. Studies on the intake of microfilariae bytheir insect vectors, their survival, and their effect on the survival of theirvectors. II. The intake of the microfilariae of Loa loa and Acanthocheilonemaperstans by Chrysops spp. Ann Trop Med Parasitol. 1954;48:1029.

    39. Kershaw WE, Nicholas WL. Studies on the epidemiology of filariasis inWest Africa, with special reference to the British Cameroons andthe Niger Delta. V. The intensity of infections with Loa loa and withAcanthocheilonema perstans in the rain-forest, the forest fringe. AnnTrop Med Parasitol. 1954;48:11020.

    40. Kershaw WE, Chalmers TA, Duke BO. Studies on the intake of microfilariaeby their insect vectors, their survival, and their effect on the survival of theirvectors. IV. The survival-rate of Chrysops under laboratory conditions, andthe effect upon it of Loa loa. Ann Trop Med Parasitol. 1954;48:32939.

    41. Kershaw WE, Duke BO. Studies on the intake of microfilariae by their insectvectors, their survival, and their effect on the survival of their vectors. V. Thesurvival of Loa loa in Chrysops silacea under laboratory conditions. Ann TropMed Parasitol. 1954;48:3404.

    42. Crewe W. Studies on Ethiopian Chrysops as possible vectors of loiasis. I.Chrysops langi Bequaert. Ann Trop Med Parasitol. 1954;48:2169.

    43. Duke BOL. The transmission of loiasis in the forest-fringe area of the BritishCameroons. Ann Trop Med Parasitol. 1954;48:34955.

    44. Kershaw WE, Beesley WN, Crewe W. Studies on the intake of microfilariae bytheir insect vectors, their survival, and their effect on the survival of theirvectors. VI. Further observations on the intake of the microfilariae of Loa loaand Acanthocheilonema perstans by Chrysops silacea. Ann Trop MedParasitol. 1955;49:11420.

    45. Kershaw WE, Plackett RL, Beesley W. Studies on the epidemiology offilariasis in West Africa, with special reference to the British Cameroons andthe Niger Delta. VI. The chance of infection with Loa loa incurred byChrysops in feeding on different age-groups of the human population. AnnTrop Med Parasitol. 1955;49:6679.

    46. Crosskey R, Crosskey M. The horse-flies (Diptera : Tabanidae) of Nigeria andthe British Cameroons. London: Royal Entomological Society; 1955.

    47. Gordon RM. Symposium on Loiasis. Trans R Soc Trop Med Hyg. 1955;49:97157.48. Rageau J, Grenier P, Adam J. Tabanidae du Cameroun Francais. Ann

    Parasitol Hum Comp. 1955;3.49. Woodman H. African filariasis. Cent Afr J Med. 1955;1:28994.50. Duke BOL. Studies on the biting habits of Chrysops. I. The biting-cycle of

    Chrysops silacea at various heights above the ground in the rain-forest atKumba, British Cameroons. Ann Trop Med Parasitol. 1955;49:193202.

    51. Duke BOL. Studies on the biting habits of Chrysops. II. The effect of woodfires on the biting density of Chrysops silacea in the rain-forest at Kumba,British Cameroons. Ann Trop Med Parasitol. 1955;49:26072.

    52. Duke BOL. Studies on the biting habits of Chrysops. III. The effect of groupsof persons, stationary and moving, on the biting density of Chrysops silaceaat ground level in the rain-forest at Kumba, British Cameroons. Ann TropMed Parasitol. 1955;49:3627.

    53. Duke BOL. Studies on the biting habits of Chrysops. IV. The dispersal ofChrysops silacea over cleared areas from the rain-forest at Kumba, BritishCameroons. Ann Trop Med Parasitol. 1955;49:36875.

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 13 of 15

    http://apps.who.int/iris/handle/10665/70809http://apps.who.int/iris/handle/10665/70809

  • 54. Duke BOL. Studies on the biting habits of Chrysops. V. The biting-cycles andinfection rates of C. silacea, C. dimidiata, C. langi and C. centurionis atcanopy level in the rain-forest at Bombe, British Cameroons. Ann Trop MedParasitol. 1958;52:2435.

    55. Duke BOL. Studies on the biting habits of Chrysops. VI. A comparison of thebiting habits, monthly biting densities and infection rates of C. silacea andC. dimidiata (Bombe form) in the rain-forest at Kumba, SouthernCameroons, U.U.K.A. Ann Trop Med Parasitol. 1959;53:20314.

    56. Duke BOL. Studies on the biting habits of Chrysops. VII. The biting-cycles ofnulliparous and parous C. silacea and C. dimidiata (bombe form). Ann TropMed Parasitol. 1960;54:14755.

    57. Crewe W. The bionomics of Chrysops silacea: its life history and role in thetransmission of filariasis. PhD Thesis. University of Liverpool; 1956.

    58. Beesley WN, Crewe W, Duke BOL. The relationship between the size of theblood-meal taken in by Chrysops silacea, the development of the flysovaries, and the development of the microfilariae of Loa loa taken in withthe blood-meal. Ann Trop Med Parasitol. 1956;50:28390.

    59. Kershaw WE, Deegan T, Moore PJ, Williams P. Studies on the intake ofmicrofilariae by their insect vectors, their survival, and their effect on thesurvival of their vectors. VIII. The size and pattern of the bloodmeals takenin by groups of Chrysops silacea and C. dimidiata. Ann Trop Med Parasitol.1956;50:959.

    60. Kershaw WE, Plackett RL, Moore PJ, Williams P. Studies on the intake ofmicrofilariae by their insect vectors, their survival, and their effect on thesurvival of their vectors. IX. The pattern of the frequency of the blood-mealstaken in by Chrysops silacea and of the survival of the fly in naturalconditions in the rain-forest of the British Cameroons and on a rubberestate in the Niger delta. Ann Trop Med Parasitol. 1957;51:2637.

    61. Oldroyd H. The horse-fly (Diptera: Tabanidae) of the Ethiopian Region.Subfamilies Chrysopinae, Scepaidinae and Pangoniinae, and a revisedclassification. London: British Museum (Natural History); 1957.

    62. Lavoipierre MM. Studies on the hostparasite relationships of filarialnematodes and their arthropod hosts. I. The sites of development and themigration of Loa loa in Chrysops silacea, the escape of the infective formsfrom the head of the fly, and the effect of the worm. Ann Trop MedParasitol. 1958;52:10321.

    63. Williams P. Studies on Ethiopian Chrysops as possible vectors of loiasis. II.Chrysops silacea Austen and human loiasis. Ann Trop Med Parasitol.1960;54:43959.

    64. Williams P. Studies on Ethiopian Chrysops as possible vectors of loiasis. II.Chrysops silacea Austen and human loiasis. Ann Trop Med Parasitol. 1961;55:117. contd.

    65. Duke BO, Moore PJ. A trial of banocide as a means of controlling thetransmission of loiasis on a Rubber Estate in Nigeria. 1961. p. 26377.

    66. Crewe W, Oldroyd H. The life-history of Chrysops silacea Austen, 1907. I.Introduction and outlines of the life-history, with a note on the taxonomicstatus of C. dimidiata and C. silacea. Ann Trop Med Parasitol. 1961;55:35762.

    67. Crewe W. The rate of development of larvae of Loa loa in Chrysops silaceaat Kumba, and the effect of temperature upon it. Ann Trop Med Parasitol.1961;55:2116.

    68. Crewe W, Williams P. The bionomics of the tabanid fauna of streams in therain-forest of the Southern Cameroons. I. Oviposition. Ann Soc Belges MedTrop Parasitol Mycol. 1961;55:36378.

    69. Williams P. The bionomics of the tabanid fauna of streams in the rain-forestof the Southern Cameroons. II. The species collected as larvae or pupae atKumba. Ann Trop Med Parasitol. 1961;55:45262.

    70. Williams P. The bionomics of the tabanid fauna of streams in the rain-forestof the Southern Cameroons. III. The distribution of immature tabanids atKumba. Ann Trop Med Parasitol. 1962;56:14960.

    71. Williams P. The bionomics of the tabanid fauna of streams in the rain-forestof the Southern Cameroons. IV. Seasonal fluctuations in the numbers ofimmature tabanids at Kumba. Ann Trop Med Parasitol. 1962;27483.

    72. Beesley WN, Crewe W. The bionomics of Chrysops silacea Austen, 1907. II.The biting-rhythm and dispersal in rain-forest. Ann Trop Med Parasitol. 1963;57:191203.

    73. Duke BO. The Transmission by Chrysops spp. (Diptera) of the human andsimian strains of Loa. Med Vet Entomol. 1965;7723.

    74. Fain A. Notes sur la distribution gographique de la filaire Loa loa et destabanides du genre Chrysops au Congo et au Rwanda. Ann Soc Belg MedTrop. 1969;49:499530. Geographic distribution of the filaria Loa loa and ofthe tabanid Chrysops in the Congo and Rwanda.

    75. Williams P. Studies on the control of the vectors of loiasis in West Africa. I.Introduction. Ann Trop Med Parasitol. 1962;56:2848.

    76. Beesley WN, Williams P. Studies on the control of the vectors of loiasis inWest Africa. II. The effect of clearing vegetation from tabanid breeding-places. Ann Trop Med Parasitol. 1962;56:28991.

    77. Williams P. Studies on the control of the vectors of loiasis in West Africa. III.Comparison of the toxicities of DDT, dieldrin, aldrin and gamma-BHC to latein-star tabanid larvae. Ann Trop Med Parasitol. 1963;57:18290.

    78. Williams P, Vickars MA, Park PO, Crewe W, Mesmer ET. Studies on the controlof the vectors of loiasis in West Africa. IV. The persistence of DDT, dieldrin,aldrin and gamma-BHC in the mud of natural tabanid breeding-sites in therain-forest of the Cameroons. Ann Trop Med Parasitol. 1963;57:28399.

    79. Williams P, Crewe W. Studies on the control of the vectors of loiasis in WestAfrica. V. The effects of DDT, dieldrin, aldrin and gamma-BHC in the mud ofnatural tabanid breeding-sites in the rain-forest of the Cameroons. AnnTrop Med Parasitol. 1963;57:3006.

    80. Williams P. Studies on the control of the vectors of loiasis in West Africa. VI.The effects of water emulsions of dieldrin on late-instar Chrysops larvae inthe laboratory. Ann Trop Med Parasitol. 1963;57:4304.

    81. Crewe W, Williams P. Studies on the control of the vectors of loiasis in WestAfrica. VII. The effect of low concentrations of dieldrin in the mud of naturaltabanid breeding-sites in the rain-forest of the Cameroons. Ann Trop MedParasitol. 1964;58:3436.

    82. Williams P, Crewe W. Studies on the control of the vectors of loiasis in WestAfrica. 8. An attempt to control loiasis at Kumba, West Cameroon. Ann TropMed Parasitol. 1967;61:14858.

    83. Williams P, Crewe W. Studies on the control of the vectors of loiasis in WestAfrica. IX. Some conclusions drawn from the attempt to control loiasis at Kumba,West Cameroon. Ann Soc Belges Med Trop Parasitol Mycol. 1967;61:15966.

    84. Sasa M. Human filariasis - A global survey of epidemiology and control.Baltimore: University Park Press; 1976.

    85. Fain A. Les Problemes Actuels De La Loase. Bull World Health Organ.1978;56:15567.

    86. Inaoka T, Hori E, Yamaguchi K, Watanabe M, Yoneyama Y, Ogunba EO.Morphology and identification of Chrysops larvae from Nigeria. Med VetEntomol. 1988;2:14152.

    87. Gouteux JP, Noireau F, Staak C. The host preferences of Chrysops silacea andC. dimidiata (Diptera: Tabanidae) in an endemic area of Loa loa in theCongo. Ann Trop Med Parasitol. 1989;83:16772.

    88. Noireau F, Nzoulani A, Sinda D, Itoua A. Chrysops silacea and C. dimidiata: flydensities and infection rates with Loa loa in the Chaillu mountains, CongoRepublic. Trans R Soc Trop Med Hyg. 1990;84:1535.

    89. Grove D. A history of human helminthology. Wallingford: CAB International; 1990.90. Noireau F, Nzoulani A, Sinda D, Itoua A. Transmission indices of Loa loa in

    the Chaillu Mountains, Congo. Am J Trop Med Hyg. 1990;43:2828.91. Noireau F, Nzoulani A, Sinda D, Caubre P. Chrysops silacea and C. dimidiata

    seasonality and loiasis prevalence in the Chaillu mountains, Congo. Med VetEntomol. 1991;5:4139.

    92. Pinder M. The improvement of maintenance conditions for wild-caughtChrysops silacea and the production of infective larvae of Loa loa. Acta Trop.1991;49:30511.

    93. Caubere P, Noireau F. Effect of attraction factors on the sampling ofChrysops silacea and C. dimidiata (Diptera: Tabanidae), vectors of Loa loa(Filaroidea: Onchocercidae) filariasis. J Med Entomol. 1991;28:2635.

    94. Chippaux J, Bouchite B, Demanou M, Legoff G, Rangue S, Morlais I, et al.Biologie des vecteurs de la loase dans un village forestier du centre duCameroun. Estude de la dispersion. Document de lAntenne ORSTOMaupres di Centre Pasteur No. 8/94 1994. 1994.

    95. Demanou M, Bernard B, Baldet T. Biocologie de deux vecteurs de la loasehumaine (Chrysops dimidiata et C. silacea) Ngat (sud-Cameroun). Bulletinde Liaison et de. Confrence Tech. lOCEAC, 18, vol. 30 (3). Yaound: Bulletinde Liaison et de Documentation - OCEAC, 1997; 1997. p. 1489.

    96. Chippaux JP, Bouchit B, Boussinesq M, Ranque S, Baldet T, Demanou M.Impact of repeated large scale ivermectin treatments on the transmission ofLoa loa. Trans R Soc Trop Med Hyg. 1998;92:4548.

    97. Chippaux J-P, Bouchit B, Demanou M, Morlais I, Le Goff G. Density anddispersal of the loaiasis vector Chrysops dimidiata in southern Cameroon.Med Vet Entomol. 2000;14:33944.

    98. Demanou M, Pion SD, Boussinesq M. Entomologic study of loaiasistransmission in the Lekie area (Cameroon). Bull Soc Pathol Exot. 2001;94:34752 (In French).

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 14 of 15

  • 99. Wanji S, Tendongfor N, Esum ME, Enyong P. Chrysops silacea biting densitiesand transmission potential in an endemic area of human loiasis in south-west Cameroon. Trop Med Int Health. 2002;7:3717.

    100. Cheke RA, Mas J, Chainey JE. Potential vectors of loiasis and other tabanidson the Island of Bioko, Equatorial Guinea. Med Vet Entomol. 2003;17:2213.

    101. Mavoungou JF, Makanga BK, Acapovi-Yao G, Desquesnes M, MBatchi B.Abundance and species diversity of tabanids (Diptera) in the biospherereserve Ipassa-Makokou (Gabon) during the rainy season. Institut deRecherches en Ecologie Tropicale (IRET), BP 13354, Libreville, Gabon.Parasite. 2012;19:16571 (In French).

    102. Iboh CL, Okon OE, Arong GA, Asor JE, Opara KN. Occurrence anddistribution of Chrysops species in Akamkpa community of Cross River State,Nigeria. Pak J Biol Sci. 2012;15:113943.

    103. Kouam MK, Tchatchueng-Mbougua JB, Demanou M, Boussinesq M, PionSDS, Kamgno J. Impact of repeated ivermectin treatments againstonchocerciasis on the transmission of loiasis: an entomologic evaluation incentral Cameroon. Parasit Vectors. 2013;6:283.

    104. Hopkins AD. Neglected tropical diseases in Africa: a new paradigm. IntHealth. 2016;8 Suppl 1:i2833.

    105. Walker M, Specht S, Churcher TS, Hoerauf A, Taylor MJ, Basez MG.Therapeutic efficacy and macrofilaricidal activity of doxycycline for thetreatment of river blindness. Clin Infect Dis. 2015;60:1199207.

    106. Klarmann-Schulz U, Specht S, Debrah AAY, Batsa L, Ayisi-Boateng NK, Osei-Mensah J, et al. Comparison of doxycycline, minocycline, doxycycline plusalbendazole and albendazole alone in their efficacy against onchocerciasisin a randomized, open-label, pilot trial. Clin Infect Dis. 2014;60:e0005156.

    107. World Health Organization. A toolkit for integrated vector management insub-Saharan Africa [Internet]. Geneva, Switzerland; 2016. Available from:http://www.who.int/neglected_diseases/resources/9789241549653/en/.

    108. Kelly-Hope L, Thomson MC. Climate and infectious diseases. In: ThomsonMC, Garcia-Herrera R, Beniston M, editors. Seasonal forecasts, climaticchange and human health. Health and climate. [Internet]. Dordrecht:Springer; 2008. p. 3170. Available from: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.424.2946&rep=rep1&type=pdf.

    109. Monnerat R, Pereira E, Teles B, Martins E, Praca L, Queiroz P, et al. Synergisticactivity of Bacillus thuringiensis toxins against Simulium spp. larvae. JInvertebr Pathol USA. 2014;121:703.

    110. Lakwo T, Garms R, Wamani J, Tukahebwa EM, Byamukama E, Onapa AW,et al. Interruption of the transmission of Onchocerca volvulus in theKashoya-Kitomi focus, western Uganda by long-term ivermectin treatmentand elimination of the vector Simulium neavei by larviciding. Acta Trop.2017;167:12836.

    111. Biswas G, Sankara DP, Agua-Agum J, Maiga A. Dracunculiasis (Guinea wormdisease): eradication without a drug or a vaccine. Philos Trans R Soc Lond BBiol Sci. 2013;368:20120146.

    112. The Open University. Malaria prevention: environmental management andlarviciding for vector control, Communicable Disease Module 9. 2016.

    113. IVCC. Innovative Vector Control Consortium [Internet]. 2016. Available from:http://www.ivcc.com/.

    114. Vontas J, Moore S, Kleinschmidt I, Ranson H, Lindsay S, Lengeler C, et al.Framework for rapid assessment and adoption of new vector control tools.Trends Parasitol. 2014;30:191204.

    115. Knapp J, Macdonald M, Malone D, Hamon N, Richardson JH. Disruptivetechnology for vector control: the Innovative Vector Control Consortium andthe US Military join forces to explore transformative insecticide applicationtechnology for mosquito control programmes. Malar J. 2015;14:371.

    116. Govella NJ, Ogoma SB, Paliga J, Chaki PP, Killeen G. Impregnating hessianstrips with the volatile pyrethroid transfluthrin prevents outdoor exposureto vectors of malaria and lymphatic filariasis in urban Dar es Salaam,Tanzania. Parasit Vectors. 2015;8:322.

    117. Ogoma SB, Ngonyani H, Simfukwe ET, Mseka A, Moore J, Killeen GF. Spatialrepellency of transfluthrin-treated hessian strips against laboratory-rearedAnopheles arabiensis mosquitoes in a semi-field tunnel cage. Parasit Vectors.2012;5:54.

    118. Lehane M, Alfaroukh I, Bucheton B, Camara M, Harris A, Kaba D, et al. Tsetsecontrol and the elimination of Gambian sleeping sickness. PLoS Negl TropDis. 2016;10:e0004437.

    119. Mizell III RF, Mizell IV RF, Mizell RA. Trolling: a novel trapping method forChrysops spp. (Diptera: Tabanidae). Florida Entomol. 2002;85:35666.

    120. Mihok S, Carlson DA, Krafsur ES, Foil LD. Performance of the Nzi and othertraps for biting flies in North America. Bull Entomol Res. 2006;96:38797.

    121. Van Hennekeler K, Jones RE, Skerratt LF, Fitzpatrick LA, Reid SA, Bellis GA.A comparison of trapping methods for Tabanidae (Diptera) in NorthQueensland, Australia. Med Vet Entomol. 2008;22:2631.

    We accept pre-submission inquiries Our selector tool helps you to find the most relevant journal We provide round the clock customer support Convenient online submission Thorough peer review Inclusion in PubMed and all major indexing services Maximum visibility for your research

    Submit your manuscript atwww.biomedcentral.com/submit

    Submit your next manuscript to BioMed Central and we will help you at every step:

    Kelly-Hope et al. Parasites & Vectors (2017) 10:172 Page 15 of 15

    http://www.who.int/neglected_diseases/resources/9789241549653/en/http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.424.2946&rep=rep1&type=pdfhttp://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.424.2946&rep=rep1&type=pdfhttp://www.ivcc.com/

    AbstractBackgroundResultsConclusions

    BackgroundMethodsResultsPublication profileStudy features: location, type and periodField and laboratory proceduresCollection methodsSpecies identificationInfection detection

    Species distribution, ecology and habitatsDistribution and ecologyImmature stage habitatsAdult habitatsAdult host-seekingHost preference and patternsFlight range

    Factors influencing spatial-temporal transmissionAbundance pattern measuresSpatial environmental factorsTemporal environmental factorsWood fires

    Methods of vector controlDefensive control measuresAggressive control methods

    Areas of potential future research

    DiscussionConclusionAdditional filesAbbreviationsAcknowledgementsDedicationFundingAvailability of data and materialsAuthors contributionsCompeting interestsConsent for publicationEthics approvalPublishers NoteAuthor detailsReferences