Indices of onchocerciasis transmission by different members of the Simulium damnosum complex conflict with the paradigm of forest and savanna parasite strains
Graphical abstract
Highlight
► More than 48,800 flies belonging to 10 different members of the Simulium damnosum complex were dissected. ► Numbers of Onchocerca volvulus larvae in the flies from forest and savanna zones were analysed. ► Blindness was positively correlated with transmission rates in a forest vector. ► Conversion rates to third stage larvae were equivalent in different taxa. ► The results do not concur with the paradigm of forest and savanna strains of the parasite.
Introduction
Onchocerciasis, caused by the nematode worm Onchocerca volvulus, is spread from person to person in much of sub-Saharan Africa by the blackfly Simulium damnosum s.l. It has been estimated that in 37 countries worldwide 120,000,000 people are at risk of infection, 99% of whom live in Africa where at least 37,000,000 people are infected (Amazigo et al., 2006, Hotez and Kamath, 2009, WHO, 2009). Symptoms of the disease vary from mild itching caused by sub-dermal microfilariae, serious skin conditions such as leopard skin, sowda and depigmentation, to eye diseases including bilateral blindness. The severe outcome of blindness led to the abandonment of villages, particularly in savanna areas of West Africa, and so extensive areas became unsuitable for agriculture and village life.
The severity of the disease is usually worse in savanna when compared with the pathology of onchocerciasis in the forest, with more microfilariae present in the cornea and anterior chamber of the eye, more anterior uveitis, choroidal retinitis and sclerosing keratitis (Budden, 1963). In a comparison between Sudan-savanna and rain-forest onchocerciasis in Cameroon, Anderson et al. (1974) found more nodules per person and more depigmentation in the forest but less bilateral blindness (2% versus 5.1%). The more severe ocular complications were also reflected in the higher savanna rates for sclerosing keratitis (6.6% in savanna, 1.6% in forest) and iritis. In general, there are more irreversible ocular complications due to involvement of the anterior segment of the eye in savanna zones, whereas in the forest anterior lesions are rarer, with the posterior segment more often affected and with some lesions reversible. In the savanna the severity of symptoms such as sclerosing keratitis, advanced iridocyclitis, post-neuritic optic atrophy and choroido-retinitis are related to the intensity of the infection as measured by the Community Microfilarial Load (CMFL) (Remme et al., 1989), but in the forest there is no such clear relationship with CMFL (Dadzie et al., 1990).
The vector S. damnosum s.l. is a complex of approximately 60 different sibling species and cytoforms (Adler et al., 2010, Adler and Crosskey, 2011), originally described on the basis of chromosomal variation (Vajime and Dunbar, 1975), which differ in their geographical distribution, ecologies, degree of anthropophily and vectorial efficiency (Adler et al., 2010). The flies’ immature stages from egg to pupae are aquatic, with the larvae reliant on fast-flowing stretches of streams and rivers. Emerging female adults seek host blood meals when they may acquire infections by ingesting microfilariae from an infected person. The aquatic stages are targets for vector control achieved by applying larvicides to selected sections of rivers.
Duke and colleagues developed the concept of Onchocerca–Simulium complexes involving forest and savanna strains of the parasite (Duke, 1966, Duke, 1967, Duke, 1970, Duke et al., 1966, Duke et al., 1967, Lewis and Duke, 1966) because (a) patterns of the disease's pathology differed between samples from populations infected in savanna zones of West Africa from those in the forest (see above); (b) the vectors also differed according to bioclimatic zone, and (c) experiments involving taking vectors and patients from one zone to another revealed incompatibilities between vectors and parasites from different zones. Additional support came from experiments involving injecting microfilariae from both forest- and savanna-based patients into rabbits and examining the subsequent pathology (Duke and Anderson, 1972, Duke and Garner, 1973, Garner et al., 1973) and from vector studies showing differences in vectorial efficiencies of forest and savanna flies (Philippon, 1977).
The greater severity of the disease and the higher blindness rates in the savanna were reasons why the insecticidal treatments of the WHO Onchocerciasis Control Programme in West Africa (OCP) were initially restricted to the savanna zones (WHO, 1987). Epidemiological data from the OCP also showed that ocular manifestations of the disease were more severe in the savanna than in forest (Dadzie et al., 1989, Dadzie et al., 1990, Remme et al., 1989, Zimmerman et al., 1992). However, there were also reports of blindness at high levels (e.g. 3.4% in southern Togo) in intermediate forest-savanna mosaic areas (De Sole et al., 1991, De Sole et al., 1992, Umeh et al., 1996, Pion et al., 2002), which were influential in decisions to expand the OCP area. Furthermore, the East African forms and that from the Abu Hamed focus in Sudan are not assignable to either typical forest or savanna strains (Fischer et al., 1996, Higazi et al., 2001) and even in West Africa variation in the prevalence of blindness does not accord neatly with the two strains hypothesis (Little et al., 2003). Furthermore there are epidemiological data revealing high blindness rates in forest zones in, for instance, Liberia (up to 8.9%, Frentzel-Beyme, 1973; and 2.4% blind in one or both eyes, Newland et al., 1991) and Cameroon (9 blind eyes found amongst 88 people at Bombe, giving 5.7% assuming a minimum of 5 people involved, Duke et al., 1972) and in deforested areas of Sierra Leone (5.5%, Zimmerman et al., 1992). Thus, there may be a spectrum of different strains as suggested by Fischer and Büttner (2002). They wrote “It appears reasonable to conclude that several different strains of O. volvulus occur throughout its large distribution area, but strain differences are not sufficient to explain all the geographic variation of the disease. The human host, biting habits of the vector or environmental factors may also influence the clinical picture of onchocerciasis.”
The situation is further complicated by anthropogenic changes such as deforestation that have allowed savanna forms of the fly to penetrate forest areas previously inimical to them in Liberia (Garms et al., 1991), Ghana and Togo (Wilson et al., 2002), Sierra Leone (Baker et al., 1990, Thomson et al., 1996) and Côte d’Ivoire (Adjami et al., 2004). Furthermore, members of the S. damnosum complex, but especially the savanna species S. damnosum s.str. and S. sirbanum undertake long distance movements up to 500 km (Garms et al., 1979, Cheke and Garms, 1983, Baker et al., 1990) and are thus able to bring O. volvulus back into areas where it has been thought to be eliminated or under control.
When the OCP began, all interventions relied on vector control but the advent of the microfilaricidal drug ivermectin shifted attention towards the importance of chemotherapy which became an adjunct to, and then a replacement for, vector control. Indeed the successor to OCP, the African Programme for Onchocerciasis Control (APOC) extended the area where onchocerciasis control by chemotherapy was conducted into many forested areas, in recognition of the importance of onchocerciasis even in areas without onchocercal blindness and, finally, APOC is now seeking to eliminate the disease. This ambition is currently controversial in view of increasing evidence of people who do not respond appropriately to the drug, raising fears of incipient resistance (Awadzi et al., 2004a, Awadzi et al., 2004b, Osei-Atweneboana et al., 2007, Osei-Atweneboana et al., 2011, Churcher et al., 2009).
Monitoring the success of ivermectin distribution campaigns has relied on clinical data but it has also been important to check whether any transmission by the vectors is continuing or not in treated areas. In Africa, ivermectin distribution has not led to rapid declines in transmission rates (e.g. see Kutin et al., 2004, Cheke et al., 2006), except in areas that had relatively low disease prevalence at the outset of the chemotherapy (e.g. Diawara et al., 2009). Some of the entomological monitoring that has occurred often relied, regrettably, on PCR-based tests on pooled samples of insects from which detailed transmission indices cannot be calculated.
Any evidence of reductions in transmission can only be confirmed by comparisons with pre-control data. One of the purposes of this paper is to present a review of data on onchocerciasis transmission by different forms of the vector over a wide geographical area in West Africa, and for one focus in East Africa, based on fly samples that we have dissected ourselves, to provide a baseline against which future control activities can be used for comparisons. In addition, during the course of this examination of our data we uncovered previously unrecognised links between transmission indices of the flies and blindness in forest areas. We also re-examine a previous report that both types of vectors (“forest” and “savanna”) may be involved in transmitting the disease sympatrically in a manner that we cannot explain in the context of the accepted forest-savanna dichotomy (Garms and Cheke, 1985). Also, our data confirm for some previously unstudied taxa that different vectors have their own typical parasite distribution characteristics which are independent of location and are retained even when a “savanna” fly is sympatric with a “forest” fly. Thus S. yahense and members of the S. sanctipauli sub-complex tend to have higher mean parasite loads than S. damnosum/S. sirbanum. The forest forms also have some flies that retain high numbers of parasites, which S. damnosum/S. sirbanum do not, and the parasite burdens of S. squamosum are intermediate between these two groups. The numbers of infective larvae transmitted by S. yahense and by most members of the S. sanctipauli sub-complex are higher than those transmitted by S. damnosum/S. sirbanum, yet the latter are responsible for spreading the so-called “blinding” onchocerciasis in savanna zones. This paradox was explained by the two strains hypothesis but it breaks down, as we shall show later, in forest areas where there is much blinding onchocerciasis transmitted by S. yahense, for example, and in forest-savanna mosaic zones with high blindness rates where, for instance, the Beffa form of S. soubrense retains its high parasite burdens and transmits more efficiently than S. damnosum/S. sirbanum in sympatry.
It is known that for the savanna there is a relation between intensity of transmission as measured by annual transmission potentials (ATPs) and blindness (Duke et al., 1975) and also increased ATPs are associated with increases in both microfilariae per skin snip and ocular lesions (Renz et al., 1987). Here we show, using the numbers of infective L3 larvae per 1000 parous flies as a transmission index, that a similar relation holds for onchocerciasis in the forest where S. yahense is the vector.
Section snippets
Methods
Female members of the S. damnosum complex were caught attempting to bite man as described by Walsh et al. (1978) at various sites, some within the original OCP area but most in its extension areas or outside it altogether, from Sierra Leone in the west to Uganda in the east (Table 1, Table 2, Table 3, Table 4, Table 5, Fig. 1). After capture, the flies were kept cool until separated into nulliparous and parous classes according to the absence or presence of ovarian relics (Lewis, 1958). The
Parasite burdens of different taxa
Results of dissections are presented in Table 1, Table 2, Table 3, Table 4, Table 5, from which it can be seen that there was much interspecific variation in infectivity rates, ranging from 19 L3s in the head (L3H) per 1000 parous S. damnosum/S. sirbanum at Kpoba in Benin and 35 L3s in the head per 1000 parous S. kilibanum in Uganda to 413 L3 in the head per 1000 parous S. yahense in the forest of Liberia.
Data from different areas where S. yahense occurs are given in Table 1. The transmission
Discussion
The results on transmission indices by different members of the S. damnosum complex (Table 1, Table 2, Table 3, Table 4, Table 5) in a variety of locations provide baseline information from the pre-ivermectin distribution era against which past, current and future control programmes, by either chemotherapy or vector control, can be assessed. Most general assessments to date of the success of control campaigns such as the OCP or APOC have not taken much account of the contributions to annual
Acknowledgements
We are grateful to a variety of sponsors of the original field work, in particular the WHO Onchocerciasis Control Programme, and the many people too numerous to mention individually who assisted us in the laboratory and field. Dr Stephen Young helped with statistical advice and RAC is grateful to the University of Greenwich for support (project E0187). We thank three anonymous referees for their constructive and helpful comments.
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