Jacob C. Koella

THE EVOLUTION OF PHENOTYPIC PLASTICITY IN LIFE‐HISTORY TRAITS: PREDICTIONS OF REACTION NORMS FOR AGE AND SIZE AT MATURITY

We used life‐history theory to predict reaction norms for age and size at maturation. We assumed that fecundity increases with size and that juvenile mortality rates of offspring decrease as ages‐at‐maturity of parents increase, then calculated the reaction norm by varying growth rate and calculating an optimal age at maturity for each growth rate. The reaction norm for maturation should take one of at least four shapes that depend on specific relations between changes in growth rates and changes in adult mortality rates, juvenile mortality rates, or both. Most organisms should mature neither at a fixed size nor at a fixed age, but along an age‐size trajectory. The model makes possible a clear distinction between the genetic and phenotypic components of variation. The evolved response to selection is reflected in the shape and position of the reaction norm. The phenotypic response of a single organism to rapid or slow growth is defined by the location of its maturation event as a point on the reaction norm.

The role of evolution in the emergence of infectious diseases

It is unclear when, where and how novel pathogens such as human immunodeficiency virus (HIV), monkeypox and severe acute respiratory syndrome (SARS) will cross the barriers that separate their natural reservoirs from human populations and ignite the epidemic spread of novel infectious diseases. New pathogens are believed to emerge from animal reservoirs when ecological changes increase the pathogens opportunities to enter the human population and to generate subsequent human-to-human transmission. Effective human-to-human transmission requires that the pathogens basic reproductive number, R0, should exceed one, where R0 is the average number of secondary infections arising from one infected individual in a completely susceptible population. However, an increase in R0, even when insufficient to generate an epidemic, nonetheless increases the number of subsequently infected individuals. Here we show that, as a consequence of this, the probability of pathogen evolution to R0 > 1 and subsequent disease emergence can increase markedly.

Malaria infection increases attractiveness of humans to mosquitoes

Do malaria parasites enhance the attractiveness of humans to the parasites vector? As such manipulation would have important implications for the epidemiology of the disease, the question has been debated for many years. To investigate the issue in a semi-natural situation, we assayed the attractiveness of 12 groups of three western Kenyan children to the main African malaria vector, the mosquito Anopheles gambiae. In each group, one child was uninfected, one was naturally infected with the asexual (non-infective) stage of Plasmodium falciparum, and one harboured the parasites gametocytes (the stage transmissible to mosquitoes). The children harbouring gametocytes attracted about twice as many mosquitoes as the two other classes of children. In a second assay of the same children, when the parasites had been cleared with anti-malarial treatment, the attractiveness was similar between the three classes of children. In particular, the children who had previously harboured gametocytes, but had now cleared the parasite, were not more attractive than other children. This ruled out the possibility of a bias due to differential intrinsic attractiveness of the children to mosquitoes and strongly suggests that gametocytes increase the attractiveness of the children.

THE MALARIA PARASITE, PLASMODIUM FALCIPARUM, INCREASES THE FREQUENCY OF MULTIPLE FEEDING OF ITS MOSQUITO VECTOR, ANOPHELES GAMBIAE

It has often been suggested that vector–borne parasites alter their vectors feeding behaviour to increase their transmission, but these claims are often based on laboratory studies and lack rigorous testing in a natural situation. We show in this field study that the malaria parasite, Plasmodium falciparum, alters the blood–feeding behaviour of its mosquito vector, Anopheles gambiae s.l., in two ways. First, mosquitoes infected with sporozoites, the parasite stage that is transmitted from the mosquito to a human, took up larger blood meals than uninfected mosquitoes. Whereas 72% of the uninfected mosquitoes had obtained a full blood meal, 82% of the infected ones had engorged fully. Second, mosquitoes harbouring sporozoites were more likely to bite several people per night. Twenty–two per cent of the infected mosquitoes, but only 10% of the uninfected mosquitoes, contained blood from at least two people. We conclude that the observed changes in blood–feeding behaviour allow the parasite to spread more rapidly among human hosts, and thus confirm that the parasite manipulates the mosquito to increase its own transmission.

On the use of mathematical models of malaria transmission.

The key conclusions of several mathematical models of malaria are reviewed with emphasis on their relevance for control. The Ross-Macdonald model of malaria transmission has had major influence on malaria control. One of its main conclusions is that endemicity of malaria is most sensitive to changes in mosquito imago survival rate. Thus malaria can be controlled more efficiently with imagicides than with larvicides. An extension of this model shows that the amount of variability in transmission parameters strongly affects the outcome of control measures and that predictions of the outcome can be misleading. Models that describe the immune response and simulate vaccination programs suggest that one of the most important determinants of the outcome of a vaccine campaign is the duration of vaccine efficacy. Apparently malaria can be controlled only if the duration of efficacy is in the order of a human life-span. The models further predict that asexual stage vaccines are more efficient than transmission-blocking vaccines. Directions for further applications of mathematical models are discussed.

Concurrent Evolution of Resistance and Tolerance to Pathogens

Recent experiments on plant defenses against pathogens or herbivores have shown various patterns of the association between resistance, which reduces the probability of being infected or attacked, and tolerance, which reduces the loss of fitness caused by the infection or attack. Our study describes the simultaneous evolution of these two strategies of defense in a population of hosts submitted to a pathogen. We extended previous approaches by assuming that the two traits are independent (e.g., determined by two unlinked genes), by modeling different shapes of the costs of defenses, and by taking into account the demographic and epidemiological dynamics of the system. We provide novel predictions on the variability and the evolution of defenses. First, resistance and tolerance do not necessarily exclude each other; second, they should respond in different ways to changes in parameters that affect the epidemiology or the relative costs and benefits of defenses; and third, when comparing investments in defenses among different environments, the apparent associations among resistance, tolerance, and fecundity in the absence of parasites can lead to the false conclusion that only one defense trait is costly. The latter result emphasizes the problems of estimating trade‐offs and costs among natural populations without knowledge of the underlying mechanisms.

Host genotype by parasite genotype interactions underlying the resistance of anopheline mosquitoes to Plasmodium falciparum

BackgroundMost studies on the resistance of mosquitoes to their malaria parasites focus on the response of a mosquito line or colony against a single parasite genotype. In natural situations, however, it may be expected that mosquito-malaria relationships are based, as are many other host-parasite systems, on host genotype by parasite genotype interactions. In such systems, certain hosts are resistant to one subset of the parasites genotypes, while other hosts are resistant to a different subset.MethodsTo test for genotype by genotype interactions between malaria parasites and their anopheline vectors, different genetic backgrounds (families consisting of the F1 offspring of individual females) of the major African vector Anopheles gambiae were challenged with several isolates of the human malaria parasite Plasmodium falciparum (obtained from naturally infected children in Kenya).ResultsAveraged across all parasites, the proportion of infected mosquitoes and the number of oocysts found in their midguts were similar in all mosquito families. Both indices of resistance, however, differed considerably among isolates of the parasite. In particular, no mosquito family was most resistant to all parasites, and no parasite isolate was most infectious to all mosquitoes.ConclusionsThese results suggest that the level of mosquito resistance depends on the interaction between its own and the parasites genotype. This finding thus emphasizes the need to take into account the range of genetic diversity exhibited by mosquito and malaria field populations in ideas and studies concerning the control of malaria.

Epidemiological models for the spread of anti-malarial resistance

BackgroundThe spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance.MethodsWe present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance.ResultsIn our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population.ConclusionsThe models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

Host life history responses to parasitism

Parasites and their infections can adversely effect a hosts growth, reproduction and survival. These effects are often not immediate, but increase with time since infection. A general prediction from evolutionary biology is that hosts suffering from this type of infection should preferentially allocate resources towards reproduction, even if this is at the expense of their growth and survival. This review illustrates this argument with several empirical studies showing hosts behaving in this manner. These studies indicate that one way for hosts to reduce the costs of parasitism is by altering their life history traits to bring forward their schedule of reproduction.

Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l.

There is some evidence that pathology induced by heavy malaria infections (many oocysts) increases mortality of infected mosquitoes. However, there is little or no published evidence that documented changes in feeding behaviour associated with malaria infection also contribute to higher mortality of infected mosquitoes relative to uninfected individuals. We show here for the first time that, in a natural situation, infection by the sporozoites of the malaria parasite Plasmodium falciparum significantly reduced survival of blood-feeding Anopheles gambiae, the major vector of malaria in sub-Saharan Africa. To estimate feeding-associated mortality of infected mosquitoes, we compared the percentage of sporozoite infection in host-seeking mosquitoes caught before and after feeding. The infection rate was 12% for mosquitoes caught during the night as they were entering a tent to feed; however, only 7.5% of the surviving members of the same cohort caught after they had had the opportunity to feed were infected. Thus, Plasmodium falciparum sporozoites increased the probability of dying during the night-time feeding period by 37.5%. The increase in mortality was probably due to decreased efficiency in obtaining blood and by increased feeding activity of the sporozoite-infected mosquitoes that elicited a greater degree of defensive behaviour of hosts under attack.