Non-random host selection by anopheline mosquitoes

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Non-random Host Selection by Anopheline Mosquitoes T,R, Burkot

Tropical Health Program QueenslandInstitute of Medical Research Bramston Terrace, Herston Brisbane Queensland4006 Australia

Non-random (eeding of anopheline vectorson different individuals tends to increase the reproductive rate of malaria, but may either /ncreaseor decrease

malaria prevalence.

Malarm represents a complex system. Transmission depends on a multitude of factors - of which vector density may not be the most important (see Box I). The classical RossMacdonald model of malaria transmission (Box 2) reveals two dominant factors: the probability that a mosquito will survive long enough for the parasite to develop to its infective stage, and the likelihood that the mosquito will feed on man. An important assumption however, is that all individuals will be at equal risk from mosquito attack. In fact, host-vector contact is far fiom randomly distributed. In this review, Tom Burkot explains the biological causes of non-random host selection by anopheline vectors, and Chris Dye discusses some of the epidemiological implications of this selection for malaria transmission (Box 3). Malaria transmission from humans to mosquitoes and back to humans depends on a multitude of factors which affect host selection by the mosquitoes (Box 1). Clearly, if mosquitoes preferentially attack infected people for their first blood meal, survive until the parasite develops to the infective stage, and then preferentially attack uninfected people for their second and subsequent blood meals, then transmission rates will be high. Hence the distribution of bites by susceptible mosquitoes on gametocyte carriers and susceptible individuals will largely determine the effectiveness of transmission. Host selection by vectors is the result of a combination of intrinsic preferences modulated by extrinsic factors. If a mosquito prefers human hosts, a variety of selection pressures will determine whether or not a particular individual is bitten. Differential mosquito attack rates have been attributed, for example, to host race, age or size, health and use of bednets, host defensive behaviour and proximity of hosts to mosquito breeding sites. Non-random feeding of vectors on different individuals tends to increase the reproductive rate of malaria, but may either increase or decrease malaria prevalence depending on the degree of nonrandom contact and the distribution of infected individuals in different host groups (see Box 3; Refs 1, 2). Human Blood Index Of primary importance in malaria transmission, therefore, is the proportion of mosquito feeds taken from humans (rather than other hosts) and the proportion of these feeds taken from infected individuals (see Box 2). The Human Blood Index (HBI), defined by GarrettJones 3 as "the proportion of freshly fed

anophelines found to contain human blood", should therefore be estimated from a representative sample of the vector species in a particular locality at a specified time. Several techniques have been developed to analyse vector blood meals (see Parasitology Today 3, 324-326), which can then be classified as simple (from a single meal) or mixed (from two or more meals). Mixed blood meals can then be classified as patent (from two or more host species) or cryptic (from two or more individuals of the same species) 4. The proportion of blood meals derived from two or more hosts depends on the probability of a blood meal being interrupted (eg. through host defensive behaviour) and the likelihood of each host being selected by the mosquito. Most blood meal studies have not screened for mixed meals, but those that have reveal a high proportion of them. For example, Senior-White 5 found 12% of Anopheles aquasalis meals to be mixed; Boreham and Garrett-Jones 4 reported 8.9% patent mixed blood meals for An. sacharovi, and we found 4-7% of members of the An. farauti complex with patent mixed meals 6. From these data we estimated 7-19% of blood meals taken from humans to represent interrupted feeds. The proportion of cryptic mixed feeds on mother-child pairs sharing bednets ranges from 2.7-5.7% for members of the An. gambiae complex 7-9 to 13-41% for members of the An. punctulatus complex 6. The higher proportion of cryptic compared with patent mixed meals is to be expected because of the clustered distribution of humans in houses - a mosquito interrupted while feeding on a person sleeping in a house is more likely to complete its feed on another person than on an alternative host species. ~) 1988,ElsevierPublications,Cambridge0169-4758/88~2.00

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Host availability and selection The likelihood of a mosquito feeding on humans depends both on intrinsic host preference and on host availability - the latter is a function of host numbers and the ease of access to them. Migration, due to economic factors, war.,; or cultural patterns, can alter the relative availability of humans to anopheline attack. During wars for example, the influx and concentration of refugees and soldiers into a particular area - usually combined with a simultaneous decrease in numbers of alternative hosts - has often been associated with malaria epidemics 1°. Migration of Highland peoples to lowland areas in Papua New Guinea has also resulted in epidemic outbreaks (C. Jenkins, pers. commun.). Cultural practices such as type of clothing, occupation, house construction and location, can also affect the opportunity for contact with malaria vectors. Madras women, who are more fully clothed than the men, have lower spleen rates 1°. In Sierra Leone and Nigeria, many people sleep enveloped in cloth or under fine mesh nets for protection against mosquitoes, while in other areas a variety of natural repellents are'. used including smoky fires or a mixture of ash, cowdung and urine 11. The Sepik peoples of Papua New Guinea used to weave large baskets in which they slept to protect themselves against mosquitoes 12, and in the Gambia, large differences in the HBI of mosquitoes taken from different houses were attributed to differences in the use and condition of bednets 1s'14. ]In some parts of Africa, 'zooprophylaxis' is a recognized measure against mosquitoes such as An. arabiensis; cattle are deliberately impounded near (or within) houses so that the mosquitoes feed preferentially on the cattle rather than on the people. Host selection by mosquitoes can be 'opportunistic' or 'fixed' (in the latter, selection is independent of host availability). Among opportunistic feeders, a wide range in the HBI can be found even within a limited geographical area - influenced by the availability or accessibility of hosts. This appears to be the case for An. punctulatus in Papua New Guinea, where we found HBIs ranging from 7-93% among different villages within a 20 k m radius. This was attributed mainly to differences in the relative availability of different hosts 6'15. Many workers haw; demonstrated a preference in An. gambiae for feeding on adults rather than on children 7-9, and Port

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Host preferences can be assessedby the forage ratio 16and the feeding index 17.The forage ratio compares the amount of feeding on a particular host with the availability of that host compared with all others. The feeding index compares the number of feeds on one host relative to another, with the relative numbers of the two hosts in the area. Thus the forage ratio will indicate if a host is being preferentially fed upon or avoided, while the feeding index describes the relative feeding preference without requiring a full census of the host population. Feeding indexes from Papua New Guinea showed that An. punctulatus and An. koliensisprefer dogs to humans and humans to pigs, while An. farauti prefers dogs to prgsand pigs to humans6.

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et al. 9 showed that the extent of feeding on each individual was related to the proportion of the total surface area or weight contributed by that individual to the group. A similar preference for adults rather than infants has been observed for An. farauti is and An. albimanus 19(but was not found by Clyde and Shute 2° for An. gambiae or An. funestus). Nevertheless, there appear to be large variations in the attractiveness of different individuals, resulting in preferential feeding on some children rather than on adults by members of the An. punctulatus complex6. Similar large variations in individual attractiveness can be seen from studies of An. albimanus and An. gambiae. An important factor influencing host selection is the degree of defensive behaviour exhibited by individual hosts. This has been best studied in birds and small mammals attacked by culicine mosquitoes 2~-24, but can be assumed to occur in a similar way with anophelines. It appears that host behaviour in response to mosquito attack can influence the choice of host species 21. Moreover, the studies with culicines show an inverse relationship between the number of mosquitoes attacking an individual host and the proportion that obtain a blood meal. The frequency of interrupted feeds depends on host defensive behaviour which increases with the numbers of attacking mosquitoes 22. Thus, as mosquito density increases, the proportion feeding on more tolerant individuals also increases23 and consistently greater feeding success was found with mosquitoes offered groups of

hosts of the same species rather than mixed-species groups 24. It may be that with anophelines, the wide range in the proportions of cryptic mixed meals taken from mother-child pairs (see above) could reflect variation in the irritability and defensive behaviour of different individuals.

Parasite-mediated behavioural changes Studies of rodent malaria have demonstrated that infected animals exhibit reduced defensive behaviour and are preferentially fed upon by mosquitoes 25'26. Changes in activity patterns associated with symptomatic infections resulted in more tolerant hosts that were preferentially fed upon during times of gametocytaemia. Moreover, lower haematocrits in the infected animals may decrease feeding time, resulting in increased feeding success of the mosquitoes. These studies on P. berghei, P. chabaudi and P. yoelii involved parasitaemias of 9-45% in rodents, with maximum mosquito engorgement success of 33-82% during times of peak parasitaemia. Rossignol et al. z7 have also shown decreased mosquito probing time on hosts infected withP, chabaudi. In contrast, invasion of mosquito salivary glands by malaria sporozoites can induce pathology that impairs the ability of mosquitoes to engorge, resulting in increased probing. During feeding, mosquitoes secrete salivary apyrase which inhibits aggregation of host platelets, thereby enhancing the mosquitoes' ability to locate blood 28. Sporozoites - at least those of P. gallinaceum - can impair apyrase secretion (without reducing salivary output) so that infected mosquitoes tend to probe more often 29-31. But since mosquitoes salivate before ingesting blood 32, the increased probing by infected insects could result in sporozoite transmission to a greater number of hosts. Gametocyte infectivity Many studies with P. falciparum in West Africa and Papua New Guinea have demonstrated variability in infectivity at all gametocyte densities 33'34. Typically, infectivity increases with heavier gametocyte densities, yet 20% of carriers may fail to infect mosquitoes - even at the highest densities observed. However, some carriers with less than ten gametocytes per mm 3 infected more than half the mosquitoes that fed on them 33. Gametocyte infectivity also depends on other variables such as prevalence of male gametocytes and asexual parasites, presence of trans-

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mission blocking and enhancing antibodies, and the availability and usage of

antimalarials (Box 4; Refs 33-35, 36, 37). For P. falciparum, P. gallinaceum and P. kno'wlesi, there appears to be an inverse relationship between gametocyte infectivity and the level of asexual parasitaemia, regardless of gametocyte density 4°-42. This may be due to toxification of blood by the high metabolic activity of the asexual stages, or due to immune factors elaborated during high asexual parasitaemias 33. Natural transmission-blocking immunity has been shown for P. vivax in Sri Lanka 36 and P. falciparum in Papua New Guinea 37 occurring in up to 20% of people regardless of their age. The first appearance: of infective P. faldparum gametocytes generally coincides with remission of the primary asexual parasitaemia, as P. falciparum gametocytes require 10-14 days to reach maturity. In non-immune hosts, P. falciparum gametocytes can circulate for over a year, although infectivity is not continuous but follows remissions of recurrent bouts of asexual parasitaemia 43,44. P. vivax gametocytes follow a different pattern and can be infective before the first peak of asexual parasites. T]he appearance of infective P. vivax gametocytes generally coincides with the presence of asexual parasites, and with active clinical symptoms in non-immune hosts 45. However, as asexual parasitaemia declines, gametocytes continue to be produced and to infect mosquitoes even in the absence of clinical symptoms. As in P. falciparum, P. vivax gametocytes may be present for more than a year after the initial infection, but for much of this t~me infectivity coincides with undetectable or asymptomatic parasitaemia. Observations on infected individuals from endemic areas conclusively demonstrate the importance of asymptomatic parasitaemias in the: transmission of human malaria. Young et al. 46 allowed An. quadrimaculatus to feed on people in North Carolina with ]known recent histories of malaria, regardless of whether gametocytes or asexual parasites could be detected. Asymptomadc patients were as infectious as those with clinical illness. Since asymptomatic parasitaemias were five times more prevalent than symptomatic illness, these authors concluded that asymptomatic people were more important in the transmission and maintenance of both P. falciparura :and P. vivax in the area.

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Studies in Puerto R i c o 47 and Portugal 4s also found that asymptomatic parasitaemias were 9 and 4.7 times more common than symptomatic parasitaemias. Similarly in Liberia, where 95% of adults and 85% of children were parasitaemic at some time during the study, asymptomatic parasitaemias among adults were 12 times more common than symptomatic ones49. Children with P. falciparum experienced, on average, 18 asymptomatic days for each day of clinical illness. Other studies stressing the importance of asymptomatic cartiers in malaria transmission are reviewed by Covell5° for the Belgian Congo, Netherlands, Venezuela, India and Nigeria. Temperature surveys also point to the importance of asymptomatic infections. Correlations between prevalence of infection and fever tend to be weak 5~.

Epidemiological and clinical considerations The prevalence of malaria in an area is greatly influenced by the process of host selection by malaria vectors which, in turn, is influenced by many factors including the intrinsic host preferences of the mosquito species and social and cultural characteristics of the hosts. Selection of an individual host from the pool of those available will be influenced by host age, size, intrinsic attractiveness, and degree of defensive behaviour. Defensive behaviour may relate to the intensity of mosquito attack, and may be modified by the health of the individual. This effect may be more pronounced during epidemics among non-immune hosts because symptomatic parasitaemia will be more common under such conditions. However, the effect of host health on host selection by vectors must await results from field studies before its importance can be properly assessed. Given host selection by mosquitoes, the frequency of selection of gametocytaemic hosts by susceptible anophelines, and of non-immune hosts by infective anophelines, will then determine the malaria transmission rate. The efficiency of both processes will be modified by the amount of blood ingested and the frequency of mixed blood feeds. Classical vectorial capacity theory argues that the increased number of feeds taken as a result of interrupted feeding would increase the vectorial capacity of the mosquito population by increasing the chances of acquiring and transmitting the parasite. But a strong argument can be made that interrupted feeding on man

If anophelines feed preferentially on humans infected with malaria, then it will be di~cult to discern whether the presence of the malaria parasites increases the attractiveness of those individuals to vectors, or whether preferentially selected individuals are parasitaemic more often as a result of their greater attractiveness to vectors.

The time of development and the duration of infective gametocytes in man will have an important effect on the proportion of biting anophelines that become infected.If gametocytaemic episodes in humans increase human attractiveness and susceptibility to anophelines in a manner similar to that in rodent malaria models, then the emciency ofhuman malaria transmission could be significantly increased.

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does not increase (and might even reduce) transmission of malaria from man to mosquito. Interrupted feeds could result in few gametocytes being ingested, and so reduce the chance of fertilization of female gametes in the mosquito gut. Barber s2 demonstrated that partial blood meals on known gametocyte carriers could result in lower mosquito infection rates, and many studies have shown that a large proportion of infected mosquitoes may contain only one or two oocysts34'53. Similarly, although malaria can be transmitted through probing alone, experimental studies show diminished infectivity with small sporozoite inocula. When malaria is successfully transmitted by a low inoculum of sporozoites the incubation period tends to be longer and the duration of clinical attacks tends to be shorter 54. Such effects are clearly influenced by parasite strain - 100% transmission was affected wJith as few as ten sporozoites of one P. vivax strain sS, whereas other experiments with heavy intravenous inoculations of sporozoites~6 or using mosquitoes with a higher than average sporozoite load 54 were less successful. In nature, a high proportion of infected anophelines contain low sporozoite densities (estimated mode for P. falciparum sporozoites per infected mosquito: 20004000 in An. gambiae and An. funestus53"57; 2000 in the An. punctulatus complex5s. Thus if the size of the sporozoite inoculum is proportional to fi.~eding time, then increased probing and ingestion of partial bii~od meals by sporozoite-infected mosquitoes might diminish the severity of the resulting disease. If the majority of sporozoites are inoculated during the initial probes, then cryptic blood meals on humans might neither increase nor decrease malaria transmission rates. Mosquitoes with low sporozoite rates might account, in part, for the discrepancy between infant conversion and entomological inoculation rates 51. Mosquitoes may be lightly infected owing to loss of sporozoites through time and repeated f e e d i n g s 59 o r as a result of immu-

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nity depressing gametocyte production making the vectors ineffective6°. Part of the discrepancy may also be due to observation of degenerate sporozoites61, inaccuracies in measuring anopheline attack rates, and failure to appreciate the importance of non-homogeneous host selection by the anophelines.

References

1 Dye, C. and Hasibeder, G. (1986) Trans. R. Soc. Trop. Med. Hyg. 80, 69-77 2 Kingsolver, J.G. (1987)Am. Naturalist 130, 811-827 3 Garrett-Jones, C. (1964)Bull. WHO 30,241-261 4 Boreham, P.F.L. and Garrett-Jones, C. (1973) Bull. WHO 46,605-614 5 Senioro~aite, R.A. (1952) Ind.J. Malariol. 6, 29-72 6 Burkot, T.R. etal.J. Med. Entomol. (in press) 7 Boreh~m, P.F.L., Chandler, J.A. and Jolly, J. (1978) J. Trop. M ed. Hyg. 81,63-67 8 Bryan, J.H. and Smalley~M.E. (1978) Trans. R. Soc. Trop. Med. Hyg. 72,357-360 9 Port, G.R., Boreham, P.F.L. and Bryan, J.H. (1980) Bull. Entomol. Res. 70,133-144 10 Russell, P.E. et al. (1963) Practical Malariology (2nd edn), pp 451-453, London 11 MacCormack, C.P. (1984) Bull. WHO 62 (Suppl.), 81-87 12 Bateson, G. (1980) Naven (2nd edn), Wildwood House, London 13 Port, G.R. and Boreham, P.F.L. (1982) Bull. Entotool. Res. 72,483-488 14 Boreham, P.F.L. and Port, G.R. (1982) Bull. Entotool. Res. 72,489-495 15 Charlwood, J.D., Dagoro, H. and Paru, R. (1985) Bull. Entomol. Res. 75,463-475 16 Hess, A.D., Hays, R.O. and Tempelis, C.H. (1968) Mosq. News 28,386-389 17 Kay, B.H., Boreham, P.F.L. and Edman, J.D. (1979) Mosq. News 39, 68-72 18 Spencer, M. (1967) Papua New GuineaMed.J. 10, 75 19 Muirhead-Thomson, R.C. (1951) Brit. Med. J. 1, 1114-1117 20 Clyde, D.F. and Shute, G.T. (1958) Am. J. Trop. Med. Hyg. 7,543-545 21 Edman, J.D. and Kale, H.W. (1971) Ann. Entomol. Soc. Am. 64,513-516 22 Edman, J.D., Webber, L.A. and Kale, H.W. (1972) Am. J. Trop. Meal. Hyg. 21,487-491 23 Edman, J.D., Webber, L.A. and Schmid, A.A. (1974)J. Parasitol. 60, 874-883

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24 Edman, J.D. and Webber, L.A. (1975) Mosq. News 35,508--512 25 Day, J.F. and Edman, J.D. (1983) J. Parasitol. 69, 163-170 26 Day, J.F., Ebert, K.M. and Edman, J.D. (1983) J. Med. Entomol. 20,120-127 27 Rossignol, P.A. et al. (1985) Proc. Natl Acad. Sci. USA 82, 7725-7727 28 Ribeiro, J.M.C., Rossignol, P.A. and Spielman, A. (1984)J. Exp. Biol. 108,1-7 29 Rossignol, P.A., Ribeiro, J.M.C. and Spielman, A. (1984) Am.J. Trpp. Med. Hyg. 33, 17-20 30 Ribeiro, J.M.C., Rossignol, P.A. and Spielman, A. (1985)J. InsectPhysiol. 31,689--692 31 Rossignol, P.A., Ribeiro, J.M.C. and Spielman, A. (1986) Ara. J. Trap. Med. Hyg. 35,277-279 32 Griftiths, R.B. and Gordon, R.M. (1952) Ann. Trap. Med. 46, 311-319 33 Carter, R. and Graves, P.M. in Textbook of Malaria (Wernsdorfer, W. and McGregor, I.A., eds), pp 253-305, Churchill Livingstone (in press) 34 Graves, P.M.etal.Parasitology(inpress) 35 Burkot, T.R., Williams, J.L. and Schneider, I. (1984) Trans. R. Sac. Trap. Med. Hyg. 78,339-341 36 Mendis, K.N. et al. (1987) Infect. lmmun. 55,369-372 37 Graves, P.M. et al. (1988) Parasite Immunol. 10, 209218 38 Cattani, J.A. et al. (1986) Am. J. Trap. Med. Hyg. 35, 3-15 39 Wilkinson, R.N., Noeypatimanondh, S. and Gould, D.J. (1976) Trans. R. Sac. Trap. Med. Hyg. 70, 306307 40 Rutledge, L.C., Gould, D.J. and Tantichareon, B. (1969) Trans. R . Sac. Trap. M ed. Hyg. 63,613--619 41 Carter, R. and Gwadz, R.W. (1980) in Malaria (Vol. 3) (Krier, J.P., ed.), pp 263-297, Academic Press

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45 Boyd, M.F., Stratman-Thomas, W.K. and Muench, H. (1936)Am.J. Trop. Med. 16, 133-138 46 Young, M.D. et al. (1948) Am. J. Trop. Med. 28, 303-311 47 Earle, W.C. et al. (1939) Puerto Rico J. Public Health Trop. M ed. 14, 391--406 48 Hill, R.B., Cambournac, F.J.C. and Simoes, M.P. (1943)Am.J. Trop. Med. Hyg. 23,147-162 49 Miller, M.J. (1958) Trans. R. Soc. Trop. Med. Hyg. 52, 152-168 50 Covell, G. (1960)Bull. WHO 22,605-619 51 Molineaux, L. and Gramiccia, G. (1980) The Garki Project, pp 253-259, WHO, Geneva 52 Barber, M.A. (1936)Am.J.Hyg. 24,45-56 53 Collins, F.H. et al. (1984) Am. J. Trop. Med. Hyg. 33, 538-543 54 Jeffery, G.M. et al. (1959) Ann. Trop. Med. Parasitol. 54, 51-58 55 Ungureanu, E.R. et al. (1976) Trans. R. Soc. Trop. Med. Hyg. 70,482-483 56 Shute, P.G. et aL (1976) Trans. R. Soc. Trop. Med. Hyg. 70,474-481 57 Pringle, G. (1966) Trans. R. Soc. Trop. Med. Hyg. 60, 626-632 58 Burkot, T.R. et al. Am. J. Trop. M ed. Hyg. (in press) 59 Boyd, M.F., Stratman-Thomas, W.K. and Kitchen, S.F. (1936)Am.J. Trop.Med. 16,157-158 60 Macdonald, G. (1955)Proc. R. Soc. Med. 48,295-302 61 Barber, M.A. and Rice, J.B. (1935) Ann. Trop. Med. 29, 329-348

The Prevalence of Ascariasis D.W.T. Crompton Department of Zoology, Universityof Glasgow GlasgowG 12 8QQ, UK

The common roundworm, Ascaris lumbricoides, /s probably the most prevalent human intestinal helminth. Previous estimates of world prevalence rangefrom around 650 million to 1000 million. By a detailed literature search, David Crompton now confirmsthe upperfigureestimating a worm prevalence of 1008 million representing about 22% of the world population. The infection is knownfrom 153 out of 218 recognizedcountries. • . . . . . . . . . . . . I, L H / ~ E K I C U S T E R E S , errant Anatomical ~

/'~rv~ti~,. t~ ltOundWorm~ d in+human/n~d/~ + B~ Edward Tyfon~ bt. D,[Col, Meal.L~d. aec non,.Rc~i f ~ i c r , Soc, ~ , . +.

Fig. I. Reproductionof the first pageof Edward Tyson'spaperentit/ed ~Lumbricus reres, or some anatomical observations on the round warm bred in human bodies." This illustration was kindly preparedby the Special Collections Departmentof the Library orthe University af Glasgow.

The scientific study ofAscaris lumbricoides was promoted by Edward Tyson some three centuries ago when he demonstrated that this worm was totally different in its structure and anatomy from earthworms1. Tyson was a physician who described A. lumbricoides as "that common round worm which children usually are troubled with" (Fig. 1). He was writing about children in London who no doubt then lived in communities characterized by poverty, poor nutrition, inadequate hygiene and sanitation, scarcity of health services, and apathy and indifference to their needs. Nowadays in the UK, less than 1000 cases of infection attributed to A. lumbricoides are being reported annually for a population of more than 50 millionz. Ascariasis has declined to an insignificant level as a consequence of developments in our health care and improvements in our standard of living. Such cases as are reported ~) 1988,ElsevierPublications,Cambridge0169-4758/88/$0200