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I Maudlin

Publications and source records attributed to I Maudlin.

At least 19 recordsLinked to original sources
PubMed2001

Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene.

BACKGROUND: The expansion of sleeping sickness caused by Trypanosoma brucei rhodesiense beyond its traditional focus in southeast Uganda has been linked with large-scale livestock restocking. To assess the risk presented to the human population by domestic livestock, human-infective T b rhodesiense must be distinguished from non-human-infective T brucei brucei, since both parasites can be present in cattle. We investigated the use of a simple genetic marker to characterise parasites collected from cattle in villages within the new sleeping sickness focus in Soroti District, Uganda. METHODS: 70 T brucei sl samples of known human infectivity status collected from human beings and cattle in Tororo District, Uganda, from 1989 to 1991 were screened for the presence of the human-serum-resistance-associated (SRA) gene by conventional PCR. In 2000-01, blood samples from 200 randomly selected cattle in six villages and two markets in Soroti District were screened for T brucei sl parasites by PCR; positive samples were screened for the presence of the SRA gene. FINDINGS: The SRA gene was present in all 29 samples from patients with sleeping sickness in Tororo District. Of the 41 samples collected from cattle at the same time, the SRA gene was present in the eight samples that tested resistant to human serum in vitro, whereas it was absent from all 33 isolates that were sensitive to human serum in vitro. Of the 200 cattle sampled in Soroti District, we estimated that up to 18% (95% CI 12-23) were infected with T b rhodesiense. INTERPRETATION: Detection of the SRA gene could provide the basis for a simple diagnostic test to enable targeted control of T b rhodesiense in the domestic livestock reservoir, thereby reducing the public-health burden of sleeping sickness in east Africa.

Animals↗
PubMed2001

Trypanosomiasis control.

In July 2000, Heads of State of the 36th Session of the Organisation for African Unity signed a potentially important declaration on African trypanosomiasis, urging member states "to act collectively to rise to the challenge of eliminating the problem through concerted efforts in mobilising the necessary human, financial and material resources required to render Africa tsetse-free within the shortest time possible". To many, such an ambitious dream is received with some scepticism, recalling the doubts that surrounded a similar declaration signed in Brasilia in 1991, which paved the way for the Southern Cone Initiative against American trypanosomiasis (Chagas disease). True, the two diseases are quite different. But the operational challenges are quite similar, and there are sufficient biological parallels to suggest that the Latin American experience in controlling Chagas disease may provide a useful model for the control of African trypanosomiasis.

Africa South of the Sahara↗
PubMed2001

Evidence for multiple origins of human infectivity in Trypanosoma brucei revealed by minisatellite variant repeat mapping.

In recent years a wide variety of biochemical and molecular typing systems has been employed in the study of parasite diversity aimed at investigating the level of genetic diversity and delineating the relationship between different species and subspecies. However, such methods have failed to differentiate between two of the classically defined subspecies of the protozoan parasite Trypanosoma brucei: the human infective, T. b. rhodesiense, which causes African sleeping sickness, and the non-human infective T. b. brucei. This has led to the hypothesis that T. b. rhodesiense is a host range variant of T. b. brucei. In this paper we test this hypothesis by examining highly polymorphic tandemly repeated regions of the trypanosome genome, i.e., minisatellite loci. We have employed the technique of minisatellite variant repeat mapping by PCR (MVR-PCR), which determines the distribution of variant repeat units along the tandem array of one minisatellite, MS42. The maps generated by this technique not only allow unequivocal allele identification but also contain within them cladistic information which we used to determine the possible genetic relationship between the different subspecies of T. brucei. Our findings revealed that human infective (T. b. rhodesiense) isolates from Uganda are more closely related to the local non-human infective isolates (T. b. brucei) than they are to other human infective stocks from different regions, suggesting that human infectivity has originated independently in these different geographical regions. This would infer that the separate classification of all human infective stocks from East Africa into the subspecies T. b. rhodesiense is genetically inappropriate and it would be better to consider geographically separate populations as host range variants of T. brucei brucei or perhaps as a series of different subspecies. Based on these data, it is clear that MVR mapping is a very useful tool for the analysis of zoonotic eukaryotic pathogens where delineation of the origins of outbreaks of disease and definition of human infective strains are key questions.

Africa↗
PubMed2001

Sleeping sickness: a tale of two diseases.

Sleeping sickness presents clinically as two distinct diseases, reflecting the fact that two very different trypanosomes are responsible. The African Rift separating East and West Africa defines the distribution of the two diseases. In this review, Susan Welburn, Eric Fèvre, Paul Coleman, Martin Odiit and Ian Maudlin discuss the biology and distribution of these two diseases in relation to the evolution of hominids in Africa.

Animals↗
PubMed2001

Prospects for control of African trypanosomiasis by tsetse vector manipulation.

The extensive antigenic variation phenomena African trypanosomes display in their mammalian host have hampered efforts to develop effective vaccines against trypanosomiasis. Human disease management aims largely to treat infected hosts by chemotherapy, whereas control of animal diseases relies on reducing tsetse populations as well as on drug therapy. The control strategies for animal diseases are carried out and financed by livestock owners, who have an obvious economic incentive. Sustaining largely insecticide-based control at a local level and relying on drugs for treatment of infected hosts for a disease for which there is no evidence of acquired immunity could prove extremely costly in the long run. It is more likely that a combination of several methods in an integrated, phased and area-wide approach would be more effective in controlling these diseases and subsequently improving agricultural output. New approaches that are environmentally acceptable, efficacious and affordable are clearly desirable for control of various medically and agriculturally important insects including tsetse. Here, Serap Aksoy and colleagues discuss molecular genetic approaches to modulate tsetse vector competence.

Animals↗
PubMed2000

Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures.

The African trypanosome, Trypanosoma brucei, has been shown to undergo genetic exchange in the laboratory, but controversy exists as to the role of genetic exchange in natural populations. Much of the analysis to date has been derived from isoenzyme or randomly amplified polymorphic DNA data with parasite material from a range of hosts and geographical locations. These markers fail to distinguish between the human infective (T. b. rhodesiense) and nonhuman infective (T. b. brucei) "subspecies" so that parasites derived from hosts other than humans potentially contain both subspecies. To overcome some of the inherent problems with the use of such markers and diverse populations, we have analyzed a well-defined population from a discrete geographical location (Busoga, Uganda) using three recently described minisatellite markers. The parasites were primarily isolated from humans and cattle with the latter isolates further characterized by their ability to resist lysis by human serum (equivalent to human infectivity). The minisatellite markers show high levels of polymorphism, and from the data obtained we conclude that T. b. rhodesiense is genetically isolated from T. b. brucei and can be unambiguously identified by its multilocus genotype. Analysis of the genotype frequencies in the separated T. b. brucei and T. b. rhodesiense populations shows the former has an epidemic population structure whereas the latter is clonal. This finding suggests that the strong linkage disequilibrium observed in previous analyses, where human and nonhuman infective trypanosomes were not distinguished, results from the treatment of two genetically isolated populations as a single population.

Animals↗
PubMed2000

Trypanosoma brucei: identification of trypanosomes with genotypic similarity to human infective isolates in tsetse isolated from a region free of human sleeping sickness.

In previous work, we have developed a molecular method that defines genotypes of Trypanosoma brucei and allows distinction of the human-infective subspecies T. b. rhodesiense from the non-human-infective T. b. brucei without recourse to measurement of resistance to lysis by human serum. Using this approach, we are also able to determine the geographical range of specific genotypes associated with a particular focus. In this study, we have characterised T. brucei isolates collected from tsetse in a region where human sleeping sickness has never been reported and which is some 500 km from the Busoga sleeping sickness focus of Uganda. We show that some of the trypanosome isolates taken from tsetse in this region have considerable genotypic similarity to trypanosomes from the Busoga focus, demonstrating a surprisingly wide dispersal of these trypanosome genotypes. Furthermore, the similarity of these genotypes to human-infective trypanosomes in the Busoga focus suggest the possible circulation of human-infective trypanosomes in this location. We also demonstrate that the genetic diversity in trypanosomes isolated from tsetse is significantly higher than that in those isolated from humans, confirming other studies that show that there exists a significant restriction in the range of genotypes that can be transmitted to humans.

Animals↗
PubMed1999

Tsetse-trypanosome interactions: rites of passage.

Trypanosomes that cause sleeping sickness (Trypanosoma brucei rhodesiense and T. b. gambiense) are entirely dependent on tsetse for their transmission between hosts, but the flies are not easily infected. This situation has not arisen by chance - the tsetse has evolved an efficient defence system against trypanosome invasion. In this review, Susan Welburn and Ian Maudlin chart the progress of trypanosomes through the fly and identify some of the hazards faced by both parasite and fly that affect vector competence of tsetse.

Animals↗
PubMed1999

Sodalis gen. nov. and Sodalis glossinidius sp. nov., a microaerophilic secondary endosymbiont of the tsetse fly Glossina morsitans morsitans.

A secondary intracellular symbiotic bacterium was isolated from the haemolymph of the tsetse fly Glossina morsitans morsitans and cultured in Aedes albopictus cell line C6/36. Pure-culture isolation of this bacterium was achieved through the use of solid-phase culture under a microaerobic atmosphere. After isolation of strain M1T, a range of tests was performed to determine the phenotypic properties of this bacterium. Considering the results of these tests, along with the phylogenetic position of this micro-organism, it is proposed that this intracellular symbiont from G. m. morsitans should be classified in a new genus Sodalis gen. nov., as Sodalis glossinidius gen. nov., sp. nov. Strain M1T is the type strain for this new species.

Aedes↗
PubMed1998

Trypanosoma brucei: comparison of circulating strains in an endemic and an epidemic area of a sleeping sickness focus.

Human sleeping sickness in East Africa is characterized by periods of long-term endemicity interspersed with short-term epidemics. The factors generating these huge changes are largely uncharacterized but probably reflect complex interactions among socioeconomic factors, ecological factors, and the movement and diversity of trypanosome strains. To investigate the role of trypanosome strains in the generation of these epidemics, we addressed two important questions. (1) Are the trypanosome strains circulating within a focus the same during times of endemicity and during an epidemic? (2) How stable are trypanosome strains within a single animal reservoir host? Using restriction fragment length polymorphism analysis of repetitive DNA, we have examined the relationship between Trypanosoma brucei isolates, taken from the Busoga focus of human sleeping sickness, during an endemic period (Busia, Kenya, 1993-1994) and stocks isolated during an epidemic period (Tororo, Uganda, 1988-1990). We show that similar strains, including human infective strains, are circulating in domestic cattle (the most significant animal reservoir) in both epidemic and endemic areas of the Busoga focus. Furthermore, we show the important finding that individual animals harbor the same genotype of T. brucei for a period of time and may be clonal for a given parasite strain.

Animals↗
PubMed1998

Trypanosome infections and survival in tsetse.

The effect of trypanosome infection on vector survival was observed in a line of Glossina morsitans selected for susceptibility to trypanosome infection. The differential effects of midgut and salivary gland infections on survival were examined by exposing flies to infection with either Trypanosoma congolense which colonizes midgut and mouthparts or Trypanosoma brucei rhodesiense which colonizes midgut and salivary glands. A comparison of the survival distributions of uninfected flies with those exposed to infection showed that salivary gland infection significantly reduces tsetse survival; midgut infection had little or no effect on the survival of tsetse. The significance of these findings is discussed in relation to the vectorial capacity of wild flies.

Animals↗
PubMed1997

Control of Trypanosoma brucei brucei infections in tsetse, Glossina morsitans.

Numbers of immature Trypanosoma brucei brucei within a tsetse midgut remain remarkably constant after establishment throughout the course of an infection, irrespective of whether the infection eventually matures. These results suggest a system of self regulation of the parasite population in the insect gut based on a form of programmed cell death which would carry advantages for both the parasite and the vector.

Animals↗
PubMed1995

Trypanozoon: infectivity to humans is linked to reduced transmissibility in tsetse. I. Comparison of human serum-resistant and human serum-sensitive field isolates.

The transmissibility of recent isolates of human serum-sensitive (HSS) and human serum-resistant (HSR) Trypanozoon was compared by transmission of 37 stocks through an inbred line of Glossina m. morsitans. As in previous studies maturation was found to be dependent on fly sex with males producing significantly greater proportions of salivary gland infections than females. HSS stocks were, however, 1.8 times more likely to mature to mammalian infective form than HSR stocks in male tsetse and 2.7 times more likely to mature than HSR stocks in female tsetse. Infectivity to man has apparently evolved at the expense of transmissibility in tsetse. The likelihood of sexual processes occurring in Trypanosoma b. rhodesiense in wild flies is discussed.

Animals↗
PubMed1995

Trypanozoon: infectivity to humans is linked to reduced transmissibility in tsetse. II. Genetic mechanisms.

Trypanozoon infections are less likely to mature in female tsetse than in males. Analysis of maturation data from 37 Trypanozoon isolates in Glossina m. morsitans showed that while the proportion of mature infections (salivary gland infections as a proportion of established midgut infections) varied from isolate to isolate, the proportion of mature infections in female flies was consistently smaller than the proportion in male flies. The log of the probability of maturation in females is, on average, twice the log of the probability in males (estimate of the ratio of the logged proportions is 2.09, 95% confidence interval (CI) 1.8 to 2.5). Human serum-resistant isolates were less likely to mature than human serum-sensitive isolates (ratio of logged proportions maturing was 1.5, 95% CI 1.3 to 1.8, in both male and female tsetse). Data for four other trypanosome stocks show that the probability of maturation decreases as the maturation time (the delay between the infected bloodmeal and maturation) increases. The decrease is approximately exponential with twice the half-life in male flies compared to that in female flies (estimate of the ratio of the exponential parameters is 1.97, 95% CI 0.7 to 3.3). A model is proposed to explain these observations which assumes that product(s) from an X-linked gene(s) kills or otherwise prevents migrating parasites from establishing a mature infection. Longer maturation times are associated with a heavy penalty in terms of transmissibility as measured by the vectorial capacity.

Animals↗
PubMed1995

The kinetics of maturation of trypanosome infections in tsetse.

Estimates of the time delay between the infective bloodmeal and maturation (incubation or maturation time) for 4 trypanosome stocks (2 Trypanozoon and 2 Trypanosoma congolense) show that maturation time in tsetse is not a parasite species-specific constant. The mean incubation time of a Trypanosoma brucei rhodesiense stock (EATRO 2340 - 18 days) was not significantly different from one T. congolense stock (SIKUDA88 - 15.5 days) but was significantly greater than another (1/148 FLY9 - 12.5 days). There was no significant difference in incubation times between male and female Glossina morsitans morsitans for any of the stocks but in both of the Trypanozoon stocks the proportion of female flies producing mature infections was significantly less than in males. However, estimates of gene frequency, assuming a model in which maturation is controlled by an X-linked recessive allele, gave inconsistent results indicating that maturation cannot be controlled by a single sex-linked gene. Maturation was shown to be a tsetse sex-dependent phenomenon in Trypanozoon but not in T. congolense infections. Incubation time was quite variable even for a single trypanosome stock (e.g., standard deviation of 5 days for one Trypanozoon stock); we discuss how this variability can affect disease transmission, and the interpretation of age-prevalence data.

Alleles↗