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Biomedical subjects

R M Anderson

Publications and source records attributed to R M Anderson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Density-dependent processes in the transmission of human onchocerciasis: relationship between the numbers of microfilariae ingested and successful larval development in the simuliid vector.

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of 'initial facilitation' and 'limitation' described in culicid vectors of lymphatic filariases. A maximum mean number of 1-3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibaria.

Africa, Western↗
PubMed1995

Evolutionary pressures in the spread and persistence of infectious agents in vertebrate populations.

Infectious agents have considerable potential to regulate or constrain the population growth of vertebrate hosts in natural habitats. A broad theoretical framework provides many insights into how the biology of the parasite and the demography of the host interact to determine this impact. It may manifest itself as a steady influence over time via stable endemic infection or in a recurrent epidemic fashion, sometimes with unpredictable intervals between epidemics depending on the generation time of the pathogen (time from infection to recovery or host death), its ability to induce lasting immunity and the population growth rate of the host species. Building on these notions, the paper focuses on recent work on the population dynamics of genetically variable pathogen populations and examines the factors that determine the evolution of virulence and the maintenance of genetic diversity in both host and pathogen. Recent research extends conventional theoretical templates to include population genetic elements and the within-host dynamics of the parasite and its interaction with the vertebrate immune system.

Animals↗
PubMed1995

Predicting the impact of measles vaccination in England and Wales: model validation and analysis of policy options.

Measles incidence in England and Wales has fallen to an all-time low. Attention is now focused on preventing local outbreaks, and, in the long run, on the elimination of indigenous measles. A realistic age-structured (RAS) mathematical model of measles transmission is used to reconstruct the impact of measles vaccination in England and Wales from 1968 to the present and to evaluate the merits of future policy options. In general, the predictions of the model show good agreement with long-term age stratified case reports and seroprevalence surveys. The model underestimates the proportion of cases that are notified in 0-2-year-old children. However, recent work suggests a high degree of misdiagnosis in this age group. Projections on the basis of the existing vaccination strategy in the UK suggest that the present level of measles vaccine coverage will be insufficient to eliminate small seasonal outbreaks of measles. This result is, however, sensitive to the assumed level of vaccine efficacy. Explorations of a variety of changes to current vaccination strategy favour a 2-dose schedule with the second dose administered at age 4 years irrespective of vaccination history. A vaccination campaign in school-age children, to reduce deficits in herd immunity, would accelerate progress towards measles elimination.

Adolescent↗
PubMed1995

Early onset of multiple sclerosis with autopsy confirmation.

A female had her first generalized epileptic seizure at age 11 yrs. Apart from intermittent seizures she remained well until 15 yrs of age when she developed double vision, unsteadiness and bilateral plantar responses which resolved spontaneously. Brain MRI scan at this stage revealed changes typical of multiple sclerosis. She died at 17 yrs of age from asthma and epilepsy. Autopsy confirmed the presence of multiple sclerosis and showed the disease to be very active. We consider it likely that multiple sclerosis was present at the age of 11 yrs when she had her first epileptic seizure. This case of multiple sclerosis is presented because of the rarity of the early age of onset, unusual presentation with epilepsy, marked activity of disease and early death. Also it is uncommon to have autopsy confirmation of such disease.

Adolescent↗
PubMed1995

Sudden death due to undiagnosed medullary-pontine astrocytoma.

A 20-year-old woman died suddenly and unexpectedly from low-grade medullary pontine fibrillary astrocytoma. She had experienced neurological symptoms including coughing and choking thought to be asthma, poor motor coordination, nasopharyngeal incompetence, and arm pain since the age of 11 months. Despite the long history of symptoms, the tumor remained clinically undiagnosed. This case demonstrates the minor, nonlocalizing, and relapsing remitting nature of symptoms and signs related to this slow-growing tumor. To the best of our knowledge, this is the first case of sudden, unexpected death due to brainstem glioma in the English-language literature. Since autopsy disclosed a 5-7 week pregnancy, this case is also an example of a rare cause of maternal death.

Adult↗
PubMed1995

Patient empowerment. Results of a randomized controlled trial.

OBJECTIVE: The purpose of this study was to determine if participation in a patient empowerment program would result in improved psychosocial self-efficacy and attitudes toward diabetes, as well as a reduction in blood glucose levels. RESEARCH DESIGN AND METHODS: This study was conducted as a randomized, wait-listed control group trial. The intervention group received a six-session (one session per week) patient empowerment education program; the control group was assigned to a wait-list. At the end of 6 weeks, the control group completed the six-session empowerment program. Six weeks after the program, both groups provided follow-up data. RESULTS: The intervention group showed gains over the control group on four of the eight self-efficacy subscales and two of the five diabetes attitude subscales. Also, the intervention group showed a significant reduction in glycated hemoglobin levels. Within groups, analysis of data from all program participants showed sustained improvements in all of the self-efficacy areas and two of the five diabetes attitude subscales and a modest improvement in blood glucose levels. CONCLUSIONS: This study indicated that patient empowerment is an effective approach to developing educational interventions for addressing the psychosocial aspects of living with diabetes. Furthermore, patient empowerment is conducive to improving blood glucose control. In an ideal setting, patient education would address equally blood glucose management and the psychosocial challenges of living with diabetes.

Adaptation, Psychological↗
PubMed1995

Age and religion selection biases in HIV-1 prevalence data from antenatal clinics in Manicaland, Zimbabwe.

Sera from 487 women attending antenatal clinics in two areas of Manicaland were tested for the presence of HIV-1 infection. In the Honde Valley and Rusitu Valley areas, 24,3 pc and 14 pc respectively, were found to be infected. HIV-1 infection was found to be associated with age, marital status and location. Younger women, non-married women and women living in the Honde Valley were all more likely to be infected. There was also a weak association with level of education, with women with secondary education being at greater risk of being infected. The unadjusted overall figures for HIV-1 prevalence from the antenatal clinics were shown to provide a poor indication of the relative levels of prevalence of infection in the two study areas because of differences in the age structure and religious affiliations of the antenatal clinic and study populations. Similar problems may exist in sentinel surveillance data and would distort comparisons between locations and over time, especially during periods of rapid fertility change. In particular, the age bias is liable to exaggerate differences between urban and rural populations in developing societies. Where comparable information is available for the general population and sample sizes permit, this problem may be overcome by collecting basic socio-demographic data on the individuals tested and then applying standardization techniques. In the Honde Valley and Rusitu Valley example, the levels of HIV-1 prevalence after adjusting for age differences are 18,4 pc and 13,2 pc respectively.

Adolescent↗
PubMed1994

The Croonian Lecture, 1994. Populations, infectious disease and immunity: a very nonlinear world.

The interaction between the variables that determine the typical course of infection in an individual patient and those that determine transmission in communities of people is often complex and very nonlinear in form. Mathematical models of infection and immunity are used to study the interaction in a wide variety of problems including the role of antigenic variation in pathogen persistence in the host, the design of vaccination policies for the control of childhood viral infections, the role of heterogeneity in sexual behaviour as a determinant of the epidemiology of sexually transmitted diseases and the demographic impact of infectious disease on human population growth. The themes of dynamical complexity in outcome deriving from simple biological assumptions, the evolution of the parasite under selection by the immune system, heterogeneities in the interacting systems, and the necessity of comparing prediction with observation reoccur in each problem. It is argued that much is to be gained from the use of mathematics in biology, concomitant with experiment and observation, in providing precision in interpretation and in facilitating the formulation and testing of hypotheses to explain observed pattern. Special emphasis is placed on the need for interdisciplinary research on the epidemiology of infectious diseases that combines molecular, immunological, field study and theoretical approaches.

Adult↗
PubMed1994

Two signal activation as an explanation of high zone tolerance: a mathematical exploration of the nature of the second signal.

Much work on the induction of non-responsiveness in lymphocytes suggests that it takes two signals to activate a cell correctly, and that receipt of the first signal alone not only causes suboptimal response, but also subsequent non-responsiveness or anergy. This paper discusses not anergy, but the original suboptimal response in the context of the well known but poorly understood phenomenon of high zone tolerance in experiments studying immunological responses to a range of antigen concentrations (low to high "zones"). We proceed to ask specific questions about the nature and timing of the signals involved. We construct three different models describing how the second signal might be received and use them to predict the shapes of dose-response curves. Comparison with data enables us to select, from a dynamical perspective, the most likely mechanism and to tentatively exclude a number of proposed mechanisms for high zone tolerance. We suggest that the stage at which a cell becomes susceptible to anergy is crucial and that it is over-contact, rather than lack of contact, which is important in the induction of tolerance.

Antigens↗
PubMed1994

Mathematical studies of parasitic infection and immunity.

The techniques that underpin modern molecular biology have been rapidly adopted by those interested in the major parasitic infections of humans. The parasitological literature is full of reports of genes and their amino acid sequences, of molecules, of cell membrane receptors and channels, and of the fine details of the immunological responses mounted by the host to combat infection. Much less enthusiasm has been shown for the mathematical techniques that facilitate the analysis and interpretation of dynamical processes such as transmission, evolution, and the interplay between parasite population growth and immunological responses within the host. Molecular techniques provide enormous opportunities for description, but ultimately, understanding biological systems with the precision that physicists and engineers aspire to in their own fields will require quantitative description of the many rate processes that dictate both an observed pattern and the dynamics of its change.

Animals↗
PubMed1994

Theoretical studies of the effects of heterogeneity in the parasite population on the transmission dynamics of malaria.

Periodicity in malaria transmission has generally been ascribed to seasonal fluctuations in mosquito population density or spatial heterogeneity with periodic migration. In this paper we demonstrate that simple models of strain heterogeneity can generate periodic behaviour as a consequence of the interaction between parasite strains and host immunological defences. As the degree of cross-immunity between strains increases, the system moves from a régime of independent strain transmission and coexistence, through increasingly coupled behaviour, to the displacement of the strain of lower transmissibility by the strain with a higher basic reproductive rate (R0). Cross-immunity thus serves both to bring the strains into competition, and also to couple the dynamics. We find analytical and numerical results on strain coexistence to show how the range of possible outcomes may be read as an effect of the tension between these two effects of cross-protection.

Animals↗
PubMed1994

Antigenic diversity and the transmission dynamics of Plasmodium falciparum.

The average age of humans at their first infection with Plasmodium falciparum is typically less than 1 year in most endemic areas. This has been interpreted as evidence of the high transmissibility of the parasite, with the implication that control of malaria will require high levels of coverage with a potential vaccine. This interpretation is challenged by mathematical models that demonstrate that the long period required to develop immunity to malaria permits a high risk (or low average age) of infection even when parasite transmissibility is low. Patterns of seroconversion to five antigenically distinct isolates of P. falciparum in a highly malarious area of Papua New Guinea indicate that each is only mildly transmissible and that malaria, as a construct of several such independently transmitted strains, has a basic reproductive rate (or transmissibility) that is an order of magnitude lower than other estimates.

Aging↗
PubMed1994

Generalised nuclear and cytoplasmic inclusion disease: a rare case investigated by microscopy and immunohistochemistry.

A Caucasian female who was noted to be mildly microcephalic at birth was diagnosed as having cerebral palsy at the age of 1 year. Her development was delayed and she never walked or talked. She appeared relatively stable neurologically until the age of 17 years when she had an illness with fever thought to be due to a virus. She was noted to deteriorate from this time on until her death at the age of 19 years. Autopsy revealed intranuclear and cytoplasmic inclusions wide-spread throughout the brain and visceral organs. There was no evidence of inflammation. Immunohistochemistry revealed strong immunoreactivity for tau protein and neurofilament protein. Electron microscopy revealed the inclusions to be composed of homogeneous finely granular material. Scattered within the granular material in the cytoplasmic bodies were crystalline structures with a honeycomb appearance. The possibility of these changes representing an old viral infection or a primary metabolic disorder are discussed.

Adult↗
PubMed1994

Density-dependent processes in the transmission of human onchocerciasis: intensity of microfilariae in the skin and their uptake by the simuliid host.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum s.l.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestion by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.

Africa, Central↗
PubMed1994

Primary meningeal glioma.

A 59 yr old man presented with headaches and was shown to have a posterior fossa tumor arising from the inferior surface of the tentorium cerebelli. At operation the tumor was discrete from the cerebellum and was thought to be a meningioma. Pathological examination showed the tumor had features similar to those of a meningioma. It consisted of interlacing bundles of spindle cells with a considerable amount of connective tissue. Some mitoses were present. The tumor cells, however, showed abundant staining for glial fibrillary acidic protein indicating their astrocytic nature. The tumor was diagnosed as astrocytoma Grade 2. The tumor 'recurred' 4 mths later and a second surgical removal was attempted. Pathological examination showed features similar to those in the first operative specimen but this time invasion of the cerebellum was present. Deep x-ray treatment (D.X.R.T.) did not alter the tumor growth which proved fatal 7 mths after presentation. The differential diagnosis of an apparently meningeal-based tumor includes the rare entity of primary meningeal glioma. The case is presented as an example of this rare entity which both clinically and pathologically may be mistaken for a meningioma. The prognosis of intracranial solitary primary leptomeningeal gliomas is variable with recurrence and survival being months to years.

Glioma↗
PubMed1994

Balancing sexual partnerships in an age and activity stratified model of HIV transmission in heterosexual populations.

A mathematical model of the transmission dynamics of HIV-1 in a heterosexual population stratified by age, sex, and sexual activity (defined by rates of sexual partner acquisition) is presented. The model represents an extension of previous studies with a special focus on patterns of mixing or contact between sexual activity and different age classes of the two sexes. A range of mixing patterns between these groups is specified for both sexes. Mixing is described on two scales from fully assortative to fully disassortative, with random defined either according to numbers of sexual partnerships or numbers of people. The sexual partnerships in the model are balanced by changes in the rates of sexual partner acquisition between particular groups and a range of changes, from only women changing behaviour to only men changing behaviour, are analysed. The pattern of mixing is most influential in determining the shape and magnitude of the epidemic, but the manner in which people choose partners (i.e. dependent on numbers or proportions in the population) is also important. The relative importance of variation in transmission probabilities and mean rates of partner change on the course of the HIV epidemic is also illustrated. The analysis of the sensitivity of predictions to changing parameters in the force of infection term of the model provides a theoretical basis from which the influence of control strategies and the demographic effects of HIV can be analysed.

Acquired Immunodeficiency Syndrome↗