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Biomedical subjects

J C Koella

Publications and source records attributed to J C Koella.

31 records · Page 2Linked to original sources

Malaria parasites enhance blood-feeding of their naturally infected vector Anopheles punctulatus.

We investigated the blood-feeding behaviour of a natural population of the human-feeding mosquito Anopheles punctulatus in Iguruwe, Papua New Guinea. In particular we investigated the relationship between the mosquitoes' blood-feeding behaviour and their infection by the malaria parasites Plasmodium falciparum and P. vivax. Female mosquitoes were caught at 4 times of the night, the amount of blood they had obtained was measured and their status of infection was evaluated. Among uninfected mosquitoes the bloodmeal size steadily increased through the night, possibly because they were progressively less likely to be disturbed by human activity as the night drew on. Infected mosquitoes, on the other hand, tended to feed maximally at all times of the night. This suggests that infected mosquitoes were more tenacious in their blood-feeding behaviour, being either less readily disturbed during a bout of feeding (and thus feeding longer) or more likely to return to continue their feed following disturbance (and thus feeding several times). Either change would increase the parasites' rate of transmission. We conclude that in this natural situation the two species of malaria parasites modified the mosquitoes' behaviour with the effect of increasing their own transmission.

Animals↗

Variability in the relationship between weight and wing length of Anopheles gambiae (Diptera: Culicidae).

The relationship between wing length and body weight of female Anopheles gambiae Giles reared at 3 densities and at 3 temperatures was examined. Although overall, weight was proportional to wing length raised to the 4th power, the relationship within treatments was linear. The slope of the regression line varied significantly among treatments. Therefore, wing length of mosquitoes caught from field populations may not be an adequate measure of body weight if the conditions under which the mosquitoes have developed are not known.

Animals↗

A model of non-specific immunity.

Though the importance of the non-specific immune response is well known, it has often been neglected in theoretical studies. Whereas adaptive or antigen-specific immune responses arise from the proliferation of clones of antigenic-specific cells to form populations sufficiently large to control the parasite, the non-specific response involves the activation of cells such as macrophages from a reservoir consisting of a fixed number of cells. In this paper, we use simple mathematical models to investigate the dynamics of the non-specific immune response to parasites. In particular we describe the conditions under which the non-specific immune response can clear a parasite, control a parasite, or merely reduce the growth rate of a parasite. We also show that non-specific response to concurrent infections of hosts with two parasites can lead to competitive exclusion of one of the parasites. The model incorporating non-specific immunity is then expanded to include specific immune responses. This more complex model, is used to investigate the relative roles of non-specific and specific immunity in dealing with parasites and shows that the non-specific immune system may control the density of parasites prior to the generation of specific immune responses which are capable of clearing them. Finally we show that the predictions of the models conform with results from published experiments on listeria infections.

Animals↗

Variability and its implications for host-parasite interactions.

Variability in host-parasite interactions has considerable impact on the ecology and evolution of parasites and on the epidemiology of disease. The nature of the impact depends largely on the level of ecological organization where variability occurs: variability of parasites within their individual hosts, variability of host individuals within populations, or variability of hosts and parasites among populations. In this review, Paul Schmid-Hempel and Jacob Koella give some examples of variability at each of these levels, with particular emphasis on microparasites (defined broadly as viruses, bacteria and protozoa), consider the maintenance of the variability, and describe the implications of variability for the epidemiology of disease and the ecology of host parasite associations. In particular, they describe how variability at each level of ecological organization can affect the perception of AIDS and the evolution of virulence.

Journal Article↗

Epidemiological evidence for an association between chloroquine resistance of Plasmodium falciparum and its immunological properties.

The appearance of chloroquine-resistant genotypes o f Plasmodium falciparum has thwarted the goal of global eradication of malaria. Although much effort has been put into understanding the molecular mechanisms of chloroquine resistance, many questions about its distribution remain open: Why, some 30 years after the emergence o f chloroquine resistance, have resistant genotypes not taken over the population? Why have many parasites remained sensitive? Why, after its first appearance in Africa, has chloroquine resistance spread so rapidly through sub-Saharan Africa? In this paper Jacob Koella reviews epidemiological data that suggest that an answer to these questions may involve an association between chloroquine resistance and immunological properties o f malaria parasites.

Journal Article↗

Relationship between body size of adult Anopheles gambiae s.l. and infection with the malaria parasite Plasmodium falciparum.

The influence of adult female body size of Anopheles gambiae s.l. on development of midgut and salivary gland infections by the parasite Plasmodium falciparum was investigated in a field study carried out in Tanzania. The proportion of mosquitoes infected during a blood meal was independent of size. However, the number of oocysts harboured by infected mosquitoes increased with size of the mosquito. The proportion of mosquitoes with sporozoites, and thus potentially infective to humans, was highest in intermediate-sized mosquitoes, whereas the largest and smallest mosquitoes were less likely to have sporozoites. This pattern is interpreted as a combination of high survival rate of large, uninfected mosquitoes and of low survival rate of mosquitoes infected with many oocysts.

Animals↗

Population genetics and dynamics of Plasmodium falciparum: an ecological view.

Molecular characterization of the Plasmodium falciparum genome has led to identification of polymorphic loci and the mechanisms generating genetic diversity in this parasite. This information has resulted in the development of molecular methods to type parasite diversity in the field. Consequently, we are now in a position to describe the population genetics and dynamics of P. falciparum. The limited number of field studies that have been conducted to date have revealed an extraordinary degree of genetic diversity in natural parasite populations. Heterozygous recombination which occurs during meiosis appears to be one mechanism for generating genetic diversity. The rate at which such recombination occurs in natural parasite populations defines the genetic structure of the parasite population and can influence the ability of the parasite to respond to selection pressure. The high frequency of single genotype infections and the female-biased gametocyte sex ratios found in hyperendemic malaria areas suggest that self-fertilization occurs frequently. Population-wide surveys of allele frequencies in endemic areas have, however, shown no evidence of linkage disequilibrium and are consistent with a panmictic population structure. We argue that these studies have only sampled symptomatic infections, within which rare or recombinant genotypes may be disproportionately represented. They also take no account of the spatial structure of P. falciparum populations. Systematic investigations of the amount of heterozygosity in small areas as part of population-wide surveys are required to define the genetic structure of P. falciparum populations. Population dynamic studies which consider genetic heterogeneity of P. falciparum have shown fluctuations of different serotypes in space and time. The host immune response appears to play an important role in generating these dynamics. Integrated field and laboratory studies, which consider the interaction between population genetics and dynamics, will be necessary to describe the population biology of P. falciparum.

Animals↗

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.

Animals↗

In vitro resistance patterns of Plasmodium falciparum to chloroquine--a reflection of strain-specific immunity?

Studies in vitro among children on the response of Plasmodium falciparum to chloroquine were conducted as part of the national long-term monitoring of drug resistance in a holo- to hyperendemic malarious area of Tanzania between 1983 and 1989. Overall, no significant increase in chloroquine resistance was observed. However, in children under 5 years old resistance increased during this period, whereas in schoolchildren resistance decreased from 1986 to 1989. A hypothesis based on antigenic differences between resistant and sensitive strains is proposed to explain this age-specific pattern. If immunity develops principally against the most frequent parasite strains, then as it develops the numbers of the most frequent strains will be reduced, whilst, the rare strains may become predominant and thus be detected in the blood of immune patients. Thus, in an endemic area, the observed resistance pattern in non-immune infants will differ from that in immune schoolchildren, as was observed in the present study. These findings may have important implications for the control of malaria and the development of vaccines.

Adolescent↗

Ultrasound scanning for detecting morbidity due to Schistosoma haematobium and its resolution following treatment with different doses of praziquantel.

A study to assess the resolution of urinary tract morbidity due to Schistosoma haematobium was conducted on 2 cohorts of schoolchildren attending neighbouring schools in Kilombero District, southern Tanzania. Schoolchildren were screened for S. haematobium infection using the standard World Health Organization filtration technique and subsequently examined for urinary tract pathology using a portable 3.0 MHz sector scanner (Siemens Sonoline 1300). Treatment with praziquantel was given to all infected children. Children with observed urinary tract pathology received either 20 (n = 52) or 40 (n = 79) mg/kg body weight and were sonographically re-examined one, 2, 3 and 6 months following treatment. Geometric mean outputs of 21 and 19 eggs/ml of urine were detected in the 2 cohorts before treatment. Urinary tract pathology correlated positively with egg output (chi 2, P = 0.02) and microhaematuria (P = 0.0001). Bladder (wall irregularities and polyps) and kidney (congestive changes) pathologies were found in 81% and 36%, respectively, of the group that received 20 mg/kg of praziquantel, and in 78% and 46% of the group that received 40 mg/kg. Six months after treatment, 90.4% and 88.0% parasitological cure rates were obtained using 20 or 40 mg praziquantel/kg body weight. The respective pathology clearances were 88% and 91%. 20 mg/kg of praziquantel was as effective with regard to cure rates and reversibility of morbidity as 40 mg/kg.

Adolescent↗