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Biomedical subjects

H M Ferguson

Publications and source records attributed to H M Ferguson.

11 recordsLinked to original sources
PubMed2004

Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya.

Transmission of the malaria parasite Plasmodium is influenced by many different host, vector and parasite factors. Here we conducted a field study at Mbita, an area of endemic malaria in Western Kenya, to test whether parasite transmission to mosquitoes is influenced by the severity of malaria infection in its human host at the time when gametocytes, the transmission forms, are present in the peripheral blood. We examined the infectivity of 81 Plasmodium falciparum gametocyte carriers to mosquitoes. Of these, 21 were patients with fever and other malaria-related symptoms, and 60 were recruited among apparently healthy volunteers. Laboratory-reared Anopheles gambiae s.s. (local strain) were experimentally infected with blood from these gametocyte carriers by membrane-feeding. The severity of the clinical symptoms was greater in febrile patients. These symptomatic patients had higher asexual parasitaemia and lower gametocyte densities (P = 0.05) than healthy volunteers. Ookinete development occurred in only 6 out of the 21 symptomatic patients, of which only 33.3% successfully yielded oocysts. The oocyst prevalence was only 0.6% in the 546 mosquitoes that were fed on blood from this symptomatic group, with mean oocyst intensity of 0.2 (range 0-2) oocysts per mosquito. In contrast, a higher proportion (76.7%) of healthy gametocyte carriers yielded ookinetes, generating an oocyst rate of 12% in the 1332 mosquitoes that fed on them (mean intensity of 6.3, range: 1-105 oocysts per mosquito). Statistical analysis indicated that the increased infectivity of asymptomatic gametocyte carriers was not simply due to their greater gametocyte abundance, but also to the higher level of infectivity of their gametocytes, possibly due to lower parasite mortality within mosquitoes fed on blood from healthy hosts. These results suggest that blood factors and/or conditions correlated with illness reduce P. falciparum gametocyte infectivity.

Adolescent↗
PubMed2003

The energetic budget of Anopheles stephensi infected with Plasmodium chabaudi: is energy depletion a mechanism for virulence?

Evidence continues to accumulate showing that the malaria parasites (Plasmodium spp.) reduce the survival and fecundity of their mosquito vectors (Anopheles spp.). Our ability to identify the possible epidemiological and evolutionary consequences of these parasite-induced fitness reductions has been hampered by a poor understanding of the physiological basis of these shifts. Here, we explore whether the reductions in fecundity and longevity are the result of a parasite-mediated depletion or reallocation of the energetic resources of the mosquito. Mosquitoes infected with Plasmodium chabaudi were expected to have less energetic resources than uninfected mosquitoes, and energy levels were predicted to be lowest in mosquitoes infected with the most virulent parasite genotypes. Not only was there no evidence of a parasite-mediated reduction in the overall energetic budget of mosquitoes, but Plasmodium was actually associated with increased levels of glucose, a key insect nutritional and energetic resource. The data strongly suggest the existence of an increase in sugar feeding in mosquitoes infected with Plasmodium. We suggest different adaptive explanations for an enhanced sugar uptake in infected mosquitoes and call for more studies to investigate the physiological role of glucose in the Plasmodium-mosquito interaction.

Adaptation, Physiological↗
PubMed2003

The influence of malaria parasite genetic diversity and anaemia on mosquito feeding and fecundity.

Studies of invertebrate-parasite interactions frequently report that infection reduces host fecundity. The extent of the reduction is likely to be determined by a wide range of host and parasite factors. We conducted a laboratory experiment to evaluate the role of parasite genetics and infection genetic diversity on the fecundity of mosquitoes carrying malaria parasites. The malaria vector Anopheles stephensi was infected with either of 2 different genotypes of the rodent malaria parasite Plasmodium chabaudi, or by a mixture of both. Mixed genotype infections reduced mosquito fecundity by 20%, significantly more than either of the 2 single genotype infections. Mixed genotype infections were associated with high gametocyte densities and anaemia in mice, both of which were correlated with reduced bloodmeal size in mosquitoes. Bloodmeal size was the most important predictor of mosquito fecundity; the presence and number of parasites had no direct effect. Parasite density influenced the propensity of mosquitoes to feed on infected mice, with a higher percentage of mosquitoes taking a meal as asexual parasite and gametocyte density increased. Thus mosquitoes may preferentially feed on hosts who will most impair their fecundity.

Anemia↗
PubMed2003

Mosquito mortality and the evolution of malaria virulence.

Several laboratory studies of malaria parasites (Plasmodium sp.) and some field observations suggest that parasite virulence, defined as the harm a parasite causes to its vertebrate host, is positively correlated with transmission. Given this advantage, what limits the continual evolution of higher parasite virulence? One possibility is that while more virulent strains are more infectious, they are also more lethal to mosquitoes. In this study, we tested whether the virulence of the rodent malaria parasite P. chabaudi in the laboratory mouse was correlated with the fitness of mosquitoes it subsequently infected. Mice were infected with one of seven genetically distinct clones of P. chabaudi that differ in virulence. Weight loss and anemia in infected mice were monitored for 16-17 days before Anopheles stephensi mosquitoes were allowed to take a blood meal from them. Infection virulence in mice was positively correlated with transmission to mosquitoes (infection rate) and weakly associated with parasite burden (number of oocysts). Mosquito survival fell with increasing oocyst burden, but there was no overall statistically significant relationship between virulence in mice and mosquito mortality. Thus, there was no evidence that more virulent strains are more lethal to mosquitoes. Both vector survival and fecundity depended on parasite clone, and contrary to expectations, mosquitoes fed on infections more virulent to mice were more fecund. The strong parasite genetic effects associated with both fecundity and survival suggests that vector fitness could be an important selective agent shaping malaria population genetics and the evolution of phenotypes such as virulence in the vector.

Animals↗
PubMed2002

Genetic and environmental determinants of malaria parasite virulence in mosquitoes.

Models of malaria epidemiology and evolution are frequently based on the assumption that vector-parasitic associations are benign. Implicit in this assumption is the supposition that all Plasmodium parasites have an equal and neutral effect on vector survival, and thus that there is no parasite genetic variation for vector virulence. While some data support the assumption of avirulence, there has been no examination of the impact of parasite genetic diversity. We conducted a laboratory study with the rodent malaria parasite, Plasmodium chabaudi and the vector, Anopheles stephensi, to determine whether mosquito mortality varied with parasite genotype (CR and ER clones), infection diversity (single versus mixed genotype) and nutrient availability. Vector mortality varied significantly between parasite genotypes, but the rank order of virulence depended on environmental conditions. In standard conditions, mixed genotype infections were the most virulent but when glucose water was limited, mortality was highest in mosquitoes infected with CR. These genotype-by-environment interactions were repeatable across two experiments and could not be explained by variation in anaemia, gametocytaemia, blood meal size, mosquito body size, infection rate or oocyst burden. Variation in the genetic and environmental determinants of virulence may explain conflicting accounts of Plasmodium pathogenicity to mosquitoes in the malaria literature.

Animals↗
PubMed2001

Quality assurance in a Radiation Oncology Unit: the Chart Round experience.

Quality assurance ensures that planned treatments eventuate. Programmes must include feedback loops to promptly correct any shortfall in predetermined standards. In March 1999, a weekly Chart Round was introduced to verify that certain items relevant to quality care were being completed for patients of the Head and Neck Radiotherapy Unit at the Peter MacCallum Cancer Institute. The experience was reviewed after 1 year and it was found that the initiation of Chart Rounds has assisted in raising the level of item completion from 80% to 99% in similar groups of patients treated before and after the initiation of the Chart Round. Initiation of the Chart Round has also provided a useful forum for in-house peer-review, education and effective real-time communication between medical and allied health personnel, all of which has further added to the quality of patient care.

Hospital Units↗
PubMed1998

Tumour dose estimation using automated TLD techniques.

Lithium fluoride (TLD-700) dosimeters were used to measure exit surface absorbed doses in external beam radiotherapy using an automated TLD reader. Delivered tumour absorbed doses were derived from these measurements for head and neck, pelvis and breast treatments. For the head and neck treatments (first fraction only), the mean percentage difference between prescribed and delivered tumour absorbed doses was -0.15 +/- 3.0% (+/- 1 SD), for the pelvic treatments -0.83 +/- 2.8% and for the breast treatments +0.26 +/- 2.9%. The spread of results is approximately +/- 3% (+/- 1 SD). This is comparable with the estimated uncertainty in a single TLD absorbed dose measurement in phantom (+/- 2%; +/- 1 SD). Thus, ICRU recommended tolerances for absorbed dose delivery of +/- 5% may not be unequivocally detectable using this method. An action level of +/- 10% is suggested, allowing investigation of possible gross errors in treatment delivery at an early stage, before the course of treatment has progressed to a point at which absorbed dose compensation is impossible.

Breast Neoplasms↗
PubMed1997

Automated TLD system for tumor dose estimation from exit dose measurements in external beam radiotherapy.

PURPOSE: An automated TLD facility has been commissioned and calibrated, and techniques have been developed for the measurement of exit doses in external beam radiotherapy, to enable the routine estimation of delivered tumor doses. METHODS AND MATERIALS: An automated TLD system, originally intended for use in diagnostic radiology and radiation protection, has been evaluated and configured for the measurement of exit doses in radiotherapy. Linearity, optimum heating cycles and calibration procedures have been determined. At the photon energies used, encapsulated lithium fluoride chips provide insufficient buildup to ensure electronic equilibrium, necessitating calibration to allow for oblique exit surfaces. Expressions are derived to allow the calculation of delivered tumor doses. RESULTS: Under the calibration conditions described, the uncertainty in a single TLD measurement is approximately +/-2% (+/-1 standard deviation). Over the dose range 0.4-1.5 Gy, TL response is linear. The total heating cycle time, including annealing, is 75 s. Measurements of R(exit) (the ratio of exit dose with and without full backscatter), used in the estimation of tumor doses, decreases with field size for small fields and varies only slightly for field sizes greater than 7 x 7 cm. Lack of electronic equilibrium leads to a decrease in R(exit) with increasing exit surface obliquity for all energies considered. Application of the technique to a simulated treatment showed good agreement between estimated and applied tumor doses, when surface obliquity was taken into account. CONCLUSION: This work describes the commissioning and calibration of an automated TLD facility and demonstrates that exit surface measurements using TLD chips used under conditions where electronic equilibrium was not established, have the potential for identifying discrepancies in delivered tumor doses.

Calibration↗