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Biomedical subjects

J C Koella

Publications and source records attributed to J C Koella.

At least 19 recordsLinked to original sources
PubMed2005

"Clonal" population structure of the malaria agent Plasmodium falciparum in high-infection regions.

The population genetic structure of Plasmodium falciparum, the agent of malignant malaria, has been shown to be predominantly "clonal" (i.e., highly inbred) in regions of low infectivity; in high-infectivity regions, it is often thought to be panmictic, or nearly so, although there is little supporting evidence for this. The matter can be settled by investigating the parasite's genetic makeup in the midgut oocysts of the mosquito vector, where the products of meiosis can directly be observed. The developmental stages of P. falciparum are haploid, except in the oocysts of infected mosquito vectors, where two gametes fuse, diploidy occurs, and meiosis ensues. We have investigated genetic polymorphisms at seven microsatellite loci located on five chromosomes by assaying 613 oocysts in 145 mosquitoes sampled from 11 localities of Kenya, where malignant malaria is perennial and intense. There is considerable allelic variation, 16.3 +/- 2.1 alleles per locus, and considerable inbreeding, approximately 50% on the average. The inbreeding is caused by selfing (approximately 25%) and nonrandom genotype distribution of oocysts among mosquito guts (35%). The observed frequency of heterozygotes is 0.43 +/- 0.03; the expected frequency, assuming random mating, is 0.80 +/- 0.05. Linkage disequilibrium is statistically significant for all 21 pairwise comparisons between loci, even though 19 comparisons are between loci in different chromosomes, which is consistent with strong deviation from panmixia and the consequent reproduction of genomes as clones, without recombination between gene loci. This is of considerable evolutionary significance and of epidemiological consequence, concerning the spread of multilocus drug and vaccine resistance.

Animals↗
PubMed2004

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections.

BACKGROUND: Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. RESULTS: Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio) that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density) or with increased transmission. CONCLUSIONS: We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality) and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical research and adds support to the prediction that partially effective vaccines may select for increasingly virulent malaria parasite strains. By contrast, there was no consistent correlation between transmission and sub-lethal anaemia, a more common outcome of malaria infection. However, overall, the data are not inconsistent with the recent proposal that sub-lethal effects may impose an upper limit on virulence. Moreover, clone specific differences in transmission phenotypes linked to anaemia do suggest that there is considerable adaptive potential relating anaemia and transmission that may lead to uncertain consequences following intervention strategies.

Adaptation, Physiological↗
PubMed2004

The cost of immunity in the yellow fever mosquito, Aedes aegypti depends on immune activation.

Although host immunity offers the obvious benefit of reducing parasite infection, it is often traded-off with other fitness components. We investigated whether the cost of an immune response in the yellow fever mosquito, Aedes aegypti, is modulated by the antigen that activates the melanization immune response. Thus, one of three different novel antigens were injected into the mosquito's thorax--either a glass bead, a negatively charged (C-25) Sephadex bead, or a neutral (G-25) Sephadex bead--and fecundity and bead melanization were observed. Glass beads are immunologically inert and were therefore used as an inoculation control. The fecundity of mosquitoes inoculated with these beads did not differ from the fecundity of mosquitoes that did not melanize negatively charged or neutral beads. The ability of A. aegypti to melanize negatively charged Sephadex beads was associated with reduced fecundity, showing a clear cost of immunity. In contrast, melanization of the neutral beads was quite strong but had no effect on fecundity. Thus, the cost of what appeared to be the same immune response--melanization of a bead--depended on the type of bead that stimulated the immune system. Such differences might help to explain variation of immune efficacy against different parasites in natural populations.

Aedes↗
PubMed2003

Epidemiological models for the spread of anti-malarial resistance.

BACKGROUND: The 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: The 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.

Alleles↗
PubMed2002

Reduced efficacy of the immune melanization response in mosquitoes infected by malaria parasites.

Although the mosquito vectors of malaria have an effective immune system capable of encapsulating many foreign particles, they rarely encapsulate malaria parasites in natural populations. A possible reason for this apparent paradox is that infection by malaria reduces the capability of the mosquito to mount an effective immune response. To investigate this possibility, we blood-fed Aedes aegypti mosquitoes on an uninfected chicken or on one infected with Plasmodium gallinaceum, and compared the proportions of the infected and uninfected mosquitoes that melanized a negatively charged Sephadex bead injected into the thorax 1, 2 and 4 days after blood-feeding. About 40% of the uninfected mosquitoes, but less than 25% of the infected ones, melanized the bead. The difference between infected and uninfected mosquitoes was most obvious 1 day after infection (at the parasite's ookinete stage), while the difference diminished during the early oocyst stage (2 days after infection) and disappeared at the later oocyst stage (4 days after infection). These results suggest that the parasite can either actively suppress its vector's immune response or that it modifies the blood of its chicken host in away that reduces the efficacy of the mosquito's immune system. In either case, the reduction of immunocompetence can have important consequences for malaria control, in particular for the current effort being invested into the genetic manipulation of mosquitoes.

Aedes↗
PubMed2002

Effect of adult nutrition on the melanization immune response of the malaria vector Anopheles stephensi.

Two dietary resources - blood and sugar - were assessed for effects on the melanization immune response of the mosquito Anopheles stephensi Liston (Diptera: Culicidae) towards inoculated Sephadex beads (negatively charged C-25). This melanization is conferred by genetic factors capable of making the mosquito refractory to malaria parasites. If An. stephensi females had obtained a bloodmeal one day before inoculation with a bead, the efficacy of their immune response increased with the concentration of sugar ingested. At the highest sugar concentration (6%) tested, 38% of the mosquitoes completely melanized their bead, whereas at the lowest sugar concentration (2%), none of the mosquitoes were able to melanize their bead completely. Among mosquitoes not having a bloodmeal, the immuno-competence was low (c. 9% of the mosquitoes completely melanized their bead) and independent of sugar concentration. The observed interaction between these two resources indicates that both resources are required for the Anopheles female to develop an effective melanization immune response.

Aging↗
PubMed2001

Trade-offs, conflicts of interest and manipulation in Plasmodium-mosquito interactions.

A long-held view among parasitologists is that infection by malaria parasites does not harm the mosquito vector. One of the reasons for this belief is that the two partners of the association share interests in the most important life-history traits of the mosquito. Both partners benefit from increased survival and an increased rate of bloodfeeding the mosquito to increase its reproductive success and the parasite to ensure its transmission. Problems with this line of reasoning appear when one considers possible trade-offs among the mosquito's life-history parameters, which constrain the attempts by the mosquito and the parasite to maximize their success. Could these constraints differ between the two partners and thus lead to conflicts of interest and what would be the evolutionary and epidemiological consequences of conflicting interests? These questions will be investigated below.

Aedes↗
PubMed2000

The spatial spread of altruism versus the evolutionary response of egoists.

Several recent models have shown that altruism can spread in viscous populations, i.e. in spatially structured populations within which individuals interact only with their immediate neighbours and disperse only over short distances. I first confirm this result with an individual-based model of a viscous population, where an individual can vary its level of investment into a behaviour that is beneficial to its neighbours but costly to itself. Two distinct classes of individuals emerge: egoists with no or very little investment into altruism, and altruists with a high level of investment; intermediate levels of altruism are not maintained. I then extend the model to investigate the consequences of letting interaction and dispersal distances evolve along with altruism. Altruists maintain short distances, while the egoists respond to the spread of altruism by increasing their interaction and dispersal distances. This allows the egoistic individuals to be maintained in the population at a high frequency. Furthermore, the coevolution of investment into altruism and interaction distance can lead to a stable spatial pattern, where stripes of altruists (with local interactions) alternate with stripes of egoists (with far-reaching interactions). Perhaps most importantly, this approach shows that the ease with which altruism spreads in viscous populations is maintained despite countermeasures evolved by egoists.

Altruism↗
PubMed2000

Host life history responses to parasitism.

Parasites and their infections can adversely effect a host's 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.

Animals↗
PubMed2000

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.

Animals↗
PubMed1999

The effect of Plasmodium yoelii nigeriensis infection on the feeding persistence of Anopheles stephensi Liston throughout the sporogonic cycle.

Vector-borne parasites such as malaria have been shown to modify the feeding behaviour of their invertebrate hosts so as to increase the probability of transmission. However, evolutionary consideration of developmental changes in malaria within Anopheles mosquitoes suggests that the nature of altered feeding by mosquitoes should differ depending on the developmental stage of the parasite. We present laboratory evidence that the feeding persistence of female Anopheles stephensi towards a human host is decreased in the presence of Plasmodium yoelii nigeriensis oocysts (which cannot be transmitted), but increased when the malaria has developed into transmissible sporozoites in the salivary glands. In ten-minute trials, 33% of uninfected mosquitoes gave up their feeding attempt before the test period had ended, 53% of those harbouring oocysts had given up, but only 20% of those infected with sporozoites gave up by this time. We conclude that changes in feeding behaviour of mosquitoes mediated by parasite infection are sensitive to the developmental stage of the parasite and that these changes have important implications for malaria epidemiology.

Animals↗
PubMed1999

[Evolutionary ecology and epidemiology of interactions between Anopheles mosquitoes and malaria].

The transmission of malaria is largely determined by two parameters: the biting rate of the mosquito vector and its mortality. In this paper, data on the interactions among these parameters are reviewed to describe possible evolutionary mechanisms underlying the parasite's life cycle. In particular, in contrast to conventional wisdom about medical entomology, the author suggests that malaria parasites are not always expected to minimise the damage they inflict on their mosquito host. Rather, when they have developed into the infectious stage, they can increase their transmission by manipulating the mosquito to bite more frequently; this, however, is associated with a higher risk of being killed by the human host. This example illustrates that parameters determining malaria transmission can only be understood by integrating ecological and evolutionary ideas into more traditional epidemiology. Such an evolutionary view of malaria and mosquitoes will eventually lead to a better understanding of the epidemiology of malaria and may help to predict the effect of malaria control.

Animals↗
PubMed1998

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 vector's 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 sporozoited, 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.

Animals↗
PubMed1998

Costs and benefits of resistance against antimalarial drugs.

Recent experiments have suggested that resistance to antimalarial drugs, in particular chloroquine, is associated with increased transmission. However, epidemiological patterns suggest the opposite: ie. that resistance should be associated with a transmission cost. Here, Jacob Koella reviews the evidence for either a cost or a benefit of chloroquine resistance and proposes ideas from population and evolutionary biology that might explain the apparent contradiction between experimental and epidemiological evidence.

Journal Article↗
PubMed1998

Coevolutionary interactions between host life histories and parasite life cycles.

Several recent studies have discussed the interaction of host life-history traits and parasite life cycles. It has been observed that the life-history of a host often changes after infection by a parasite. In some cases, changes of host life-history traits reduce the costs of parasitism and can be interpreted as a form of resistance against the parasite. In other cases, changes of host life-history traits increase the parasite's transmission and can be interpreted as manipulation by the parasite. Alternatively, changes of host's life-history traits can also induce responses in the parasite's life cycle traits. After a brief review of recent studies, we treat in more detail the interaction between the microsporidian parasite Edhazardia aedis and its host, the mosquito Aedes aegypti. We consider the interactions between the host's life-history and parasite's life cycle that help shape the evolutionary ecology of their relationship. In particular, these interactions determine whether the parasite is benign and transmits vertically or is virulent and transmits horizontally.

Aedes↗
PubMed1997

Virulence, parasite mode of transmission, and host fluctuating asymmetry.

Horizontally transmitted parasites are broadly predicted to be more virulent, or costly to host fitness, than those with vertical transmission. This is mainly because vertical transmission, from host parent to offspring, explicitly links the reproductive interests of both parties. Underlying this prediction is a general assumption that parasite transmission success is positively correlated with its virulence. We report results where infection of larval yellow fever mosquitoes Aedes aegypti with the microsporidian Edhazardia aedis was experimentally manipulated. The parasite's complex life cycle allowed comparisons between estimates of horizontal and vertical transmission on host fitness. Our measure of virulence was the fluctuating asymmetry (FA) of adult female wings. Hosts harbouring spores showed higher FAs than controls. Horizontally transmitting spores were associated with higher FAs than vertically transmitting spores. Furthermore, within hosts FA correlated positively with the number of horizontally transmitting spores, while no relation was seen with the number of vertically transmitting spores. A developmental mechanism uncoupling the relationship between vertical transmission and virulence is proposed.

Aedes↗
PubMed1996

Models of the within-host dynamics of persistent mycobacterial infections.

We use mathematical models to investigate the within-host dynamics of mycobacterial infections. In particular, we investigate the mechanisms by which bacteria such as Mycobacterium tuberculosis and Mycobacterium leprae persist at low densities for extended periods, and attain high densities much later. We suggest that the persistence of bacteria in face of immune pressure may result from the bacteria having a very slow growth rate, or having a dormant stage. We show that whereas these mechanisms may lead to long-term persistence, this will be obtained at relatively low densities. We then suggest that the long-term persistence of bacteria may result in the loss of immunity because of the deletion of specific T-cells arriving from the thymus, and the exhaustion of the specific T-cells as these cells reach the Hayflick limit and die. This loss of immunity will allow the bacteria to attain a high density. We propose experiments capable of testing our models and discuss the implications of the models for the treatment of infected hosts.

Humans↗