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Journal articleHoward SC, Donnelly CA, 2000,
Estimation of a time-varying force of infection and basic reproduction number with application to an outbreak of classical swine fever.
, J Epidemiol Biostat, Vol: 5, Pages: 161-168, ISSN: 1359-5229BACKGROUND: A method was developed for stochastically reconstructing the pattern of infection from observed epidemic data. This allowed for estimation of a time-dependent force of infection, or transmission rate, during an epidemic. METHODS: A discrete-time mechanistic model was used to describe the spread of infection and a stochastic procedure, which utilised the latent and infectious period distributions, was used to reconstruct the dates of infection, becoming infectious and removal from the given data. The four equations describing the model were then solved to obtain least squares estimates of the transmission rate and the basic reproduction number (R0) throughout the epidemic. This process was repeated in order to assess the variability in these key epidemiological parameters. The stochastic epidemic reconstruction procedure was developed to account for changes in the distribution of the survival period over the course of the epidemic and adapted for application to epidemic data where not all infected individuals have yet been observed as cases. RESULTS: The method was applied to a set of epidemic data from an outbreak of classical swine fever in Pakistan. Constant and time-varying estimates of the transmission rate were derived and compared. There was some evidence to suggest that the force of infection varied over time. DISCUSSION: The method described can be applied to data from epidemics where observations are incomplete. The confidence limits obtained for the estimated force of infection provide a means of assessing the evidence for time variation in this parameter.
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Journal articleSchwartlander B, Garnett G, Walker N, et al., 2000,
AIDS in a new millennium.
, Science, Vol: 289, Pages: 73-77 -
Journal articleBrooker S, Donnelly CA, Guyatt HL, 2000,
Estimating the number of helminthic infections in the Republic of Cameroon from data on infection prevalence in schoolchildren
, BULLETIN OF THE WORLD HEALTH ORGANIZATION, Vol: 78, Pages: 1456-1465, ISSN: 0042-9686- Author Web Link
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- Citations: 33
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Journal articleGhani AC, Donnelly CA, Ferguson NM, et al., 2000,
Assessment of the prevalence of vCJD through testing tonsils and appendices for abnormal prion protein
, Proc Biol Sci, Vol: 267, Pages: 23-29, ISSN: 0962-8452The objective of this study was to determine the age group or groups which will provide the most information on the potential size of the vCJD epidemic in Great Britain via the sampling of tonsil and appendix material to detect the presence of abnormal prion protein (PrP(Sc)). A subsidiary aim was to determine the degree to which such an anonymous age-stratified testing programme will reduce current uncertainties in the size of the epidemic in future years. A cohort- and time-stratified model was used to generate epidemic scenarios consistent with the observed vCJD case incidence. These scenarios, together with data on the age distribution of tonsillectomies and appendectomies, were used to evaluate the optimal age group and calendar time for undertaking testing and to calculate the range of epidemic sizes consistent with different outcomes. The analyses suggested that the optimal five-year age group to test is 25-29 years, although a random sample of appendix tissue from all age groups is nearly as informative. A random sample of tonsil tissue from all age groups is less informative, but the information content is improved if sampling is restricted to tissues removed from those over ten years of age. Based on the assumption that the test is able to detect infection in the last 75% of the incubation period, zero detected infections in an initial random sample of 1000 tissues would suggest that the epidemic will be less than 870,000 cases. If infections are detected, then the model prediction suggests that both relatively small epidemics (800+ cases if one is detected or 8300+ if two are detected) and larger epidemics (21,000+ cases if three or more are detected) are possible. It was concluded that testing will be most informative if undertaken using appendix tissues or tonsil tissues removed from those over ten years of age. Large epidemics can only be excluded if a small number of infections are detected and the test is able to detect infection early in the incubat
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Journal articleGhani AC, Ferguson NM, Donnelly CA, et al., 2000,
Predicted vCJD mortality in Great Britain
, Nature, Vol: 406, Pages: 583-584, ISSN: 0028-0836 -
Journal articleFraser C, Ferguson NM, Ghani AC, et al., 2000,
Reduction of the HIV-1-infected T-cell reservoir by immune activation treatment is dose-dependent and restricted by the potency of antiretroviral drugs
, AIDS, Vol: 14, Pages: 659-669, ISSN: 0269-9370BACKGROUND: Treatments combining T-cell activating agents and potent antiretroviral drugs have been proposed as a possible means of reducing the reservoir of long-lived HIV-1 infected quiescent CD4 T-cells. OBJECTIVE: To analyse the effect of such therapies on HIV-1 dynamics and T-cell homeostasis. DESIGN AND METHODS: A mathematical framework describing HIV-1 dynamics and T-cell homeostasis was developed. Three patients who were kept on a particularly potent course of highly active antiretroviral therapy (HAART) were treated with the anti-CD3 monoclonal antibody OKT3 and interleukin (IL)-2. Plasma HIV-RNA, and HIV-RNA and DNA in peripheral blood mononuclear cells and lymph node mononuclear cells were measured. These results and other published studies on the use of IL-2 alone were assessed using our mathematical framework. RESULTS: We show that outcome of treatment is determined by the relative rates of depletion of the infected quiescent T-cell population by activation and of its replenishment through new infection. Which of these two processes dominates is critically dependent on both the potency of HAART and also the degree of T-cell activation induced. We demonstrate that high-level T-cell stimulation is likely to produce negative outcomes, both by failing to reduce viral reservoirs and by depleting the CD4 T-cell pool and disrupting CD4/CD8 T-cell homeostasis. In contrast, repeated low-level stimulation may both aid CD4 T-cell pool expansion and achieve a substantial reduction in the long-lived HIV-1 reservoir. CONCLUSIONS: Our analysis suggests that although treatment that activates T-cells can reduce the long-lived HIV-1 reservoir, caution should be used as high-level stimulation may result in a negative outcome.
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Journal articlePutter H, Prins JM, Jurriaans S, et al., 2000,
Slower decline of plasma HIV-1 RNA following highly suppressive antiretroviral therapy in primary compared with chronic infection
, AIDS, Vol: 14, Pages: 2831-2839, ISSN: 0269-9370OBJECTIVES: To study the effect of highly suppressive antiretroviral therapy on the slopes of HIV-1 RNA decline in primary compared with chronic HIV-1 infection. METHODS: Slopes of HIV-1 RNA decline in plasma were compared before and after the start of highly suppressive antiretroviral therapy from five acutely infected patients who started treatment 2 to 5 weeks following the onset of clinical symptoms. Slopes of decline after the initiation of therapy were also compared with those found in 12 chronically infected individuals on the same therapy. Numbers and percentages of activated CD4 and CD8 T cells at baseline were compared as well. RESULTS: The pre-treatment slopes of HIV-1 RNA decline in the acutely infected individuals increased significantly (P = 0.0001) after the start of anti-retroviral therapy. However, these post-treatment slopes were lower than those found in the chronically infected individuals (P= 0.012). Slopes were inversely correlated (P= 0.012) with baseline HIV-1 RNA. Although the number of CD38+HLA-DR+ CD4 cells was higher in primary infection (P= 0.02), the percentage did not differ between primary and chronic infection. CONCLUSIONS: These findings indicate that antiretroviral therapy contributes significantly to the clearance of HIV-1 during primary infection. Based on the mathematical model the less steep RNA slope following the start of treatment in primary infection can be predicted to be the result of lower clearance of productively infected cells and higher burst size per cell per unit time. This may indicate a growing immune response to HIV-1 in this very early stage of infection.
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Journal articleTuyttens FAM, Macdonald DW, Delahay R, et al., 1999,
Differences in trappability of European badgers <i>Meles meles</i> in three populations in England
, JOURNAL OF APPLIED ECOLOGY, Vol: 36, Pages: 1051-1062, ISSN: 0021-8901- Author Web Link
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- Citations: 84
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Journal articleGupta S, Anderson RM, 1999,
Population structure of pathogens: The role of immune selection
, PARASITOLOGY TODAY, Vol: 15, Pages: 497-501, ISSN: 0169-4758- Cite
- Citations: 80
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Journal articleJames CS, Eaton JW, Hardwick K, 1999,
Competition between three submerged macrophytes, <i>Elodea canadensis</i> Michx, <i>Elodea nuttallii</i> (Planch.) St John and <i>Lagarosiphon major</i> (Ridl.) moss
, HYDROBIOLOGIA, Vol: 415, Pages: 35-40, ISSN: 0018-8158
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