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• Journal article
  Austion DJ, Anderson RM, 1999,

  Transmission Dynamics of Epidemic Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci in England and Wales.

  , The Journal of Infectious Diseases, Vol: 179, Pages: 883-891
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• Journal article
  Ferguson NM, Donnelly CA, Ghani AC, Anderson RMet al., 1999,

  Predicting the size of the epidemic of the new variant Creutzfeldt-Jakob disease.

  , British Food Journal: an international multi-disciplinary journal for the dissemination of food-related research, Vol: 101, Pages: 86-98
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• Journal article
  Ferguson N, Anderson R, Gupta S, 1999,

  The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens

  , Proc Natl Acad Sci U S A, Vol: 96, Pages: 790-794, ISSN: 0027-8424

  Cross-reactive antibodies produced by a mammalian host during infection by a particular microparasitic strain usually have the effect of reducing the probability of the host being infected by a different, but closely related, pathogen strain. Such cross-reactive immunological responses thereby induce between-strain competition within the pathogen population. However, in some cases such as dengue virus, evidence suggests that cross-reactive antibodies act to enhance rather than restrict the severity of a subsequent infection by another strain. This cooperative mechanism is thought to explain why pre-existing immunity to dengue virus is an important risk factor for the development of severe disease (i.e., dengue shock syndrome and dengue hemorrhagic fever). In this paper, we explore the effect of antibody-dependent enhancement on the transmission dynamics of multistrain pathogen populations. We show that enhancement frequently may generate complex and persistent cyclical or chaotic epidemic behavior. Furthermore, enhancement acts to permit the coexistence of all strains where in its absence only one or a subset would persist.

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• Journal article
  Donnnelly CA, MaWhinney S, Anderson RM, 1999,

  A Review of the BSE Epidemic in British Cattle.

  , Aquatic Ecosystem Health and Management, Vol: 5, Pages: 164-173
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• Journal article
  Ferguson NM, Donnelly CA, Anderson RM, 1999,

  Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys

  , Philos Trans R Soc Lond B Biol Sci, Vol: 354, Pages: 757-768, ISSN: 0962-8436

  The relationship between infection with the four major serotypes of dengue virus and the occurrence of different forms of disease is complex and not fully understood. Interpreting longitudinal records of the incidence of serious disease to gain insight into the transmission dynamics and epidemiology of the virus is therefore complicated. Since age reflects duration of exposure, age-stratified, strain-specific serological surveys carried out at one point in time, or over a short time interval, can potentially provide a rich source of information on longitudinal patterns. This paper describes the development and application (to data collected in Thailand) of statistically rigorous methods designed to estimate time-varying, strain-specific forces of infection, and thus basic reproduction numbers, from cross-sectional serological data. The analyses provide support for the hypothesis that antibody-dependent enhancement of transmission influences observed epidemiological pattern. Age-stratified serological data also reveal evidence of a propensity for the annual incidence of infection to oscillate over time with a frequency of several years. The latter observation is consistent with the predictions of simple mathematical models of the transmission dynamics of the virus. The estimates of the basic reproduction numbers obtained are similar in magnitude for each dengue serotype, being in the range of four to six. Such values are higher than those obtained from earlier analyses, and the implications of this for dengue control are discussed.

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• Journal article
  Gregson S, Zaba B, Garnett GP, 1999,

  Low fertility in women with HIV and the impact of the epidemic on orphanhood and early childhood mortality in sub-Saharan Africa

  , AIDS, Vol: 13, Pages: S249-S257, ISSN: 0269-9370
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  • Citations: 23
• Journal article
  Ferguson NM, deWolf F, Ghani AC, Fraser C, Donnelly CA, Reiss P, Lange JM, Danner SA, Garnett GP, Goudsmit J, Anderson RMet al., 1999,

  Antigen-driven CD4+ T cell and HIV-1 dynamics: residual viral replication under highly active antiretroviral therapy

  , Proc Natl Acad Sci U S A, Vol: 96, Pages: 15167-15172, ISSN: 0027-8424

  Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are consistent with a mathematical model in which host cell redistribution between lymph nodes and peripheral blood is a function of viral burden. Model fits to patient data suggest that, although therapy reduces HIV replication below replacement levels, substantial residual replication continues. This residual replication has important consequences for long-term therapy and the evolution of drug resistance and represents a challenge for future treatment strategies.

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• Journal article
  Ferguson NM, Donnelly CA, Woolhouse ME, Anderson RMet al., 1999,

  Estimation of the basic reproduction number of BSE: the intensity of transmission in British cattle

  , Proc Biol Sci, Vol: 266, Pages: 23-32, ISSN: 0962-8452

  The basic reproduction number, R0, of an infectious agent is a key factor determining the rate of spread and the proportion of the host population affected. We formulate a general mathematical framework to describe the transmission dynamics of long incubation period diseases with complex pathogenesis. This is used to derive expressions for R0 of bovine spongiform encephalopathy (BSE) in British cattle, and back-calculation methods are used to estimate R0 throughout the time-course of the BSE epidemic. We show that the 1988 meat and bonemeal ban was effective in rapidly reducing R0 below 1, and demonstrate that this indicates that BSE will be unable to become endemic in the UK cattle population even when case clustering is taken into account. The analysis provides some insight into absolute infectiousness for bovine-to-bovine transmission, indicating maximally infectious animals may have infected up to 400 animals each. The relationship between R0 and the early stages of the BSE epidemic and the requirements for additional research are also discussed.

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• Journal article
  Raab GM, Donnelly CA, 1999,

  Information on sexual behaviour when some data are missing

  , JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS, Vol: 48, Pages: 117-133, ISSN: 0035-9254
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  • Citations: 11
• Journal article
  Donnelly CA, Santos R, Ramos M, Galo A, Simas JPet al., 1999,

  BSE in Portugal: anticipating the decline of an epidemic.

  , J Epidemiol Biostat, Vol: 4, Pages: 277-283, ISSN: 1359-5229

  BACKGROUND: Attention throughout Europe continues to focus on bovine spongiform encephalopathy (BSE), with increasing evidence linking it to the new variant of Creutzfeldt-Jakob disease in humans. In particular, recent attention has been directed at Portugal, where the incidence of confirmed BSE cases continues to rise. METHODS: We modelled the age-specific incidence of BSE in Portuguese-born cattle by birth cohort as a function of: the survival distribution; the cohort-specific incidence of BSE infection; the age-specific probability, conditional on survival, that an infected animal will experience clinical onset; and the under-reporting rate of BSE cases prior to 1998. RESULTS: We obtained good fits to the age-specific incidence of BSE by birth cohort in Portugal. Under a range of assumptions, the estimated incidence of BSE infection was relatively low initially, except possibly in the 1989 cohort, and then rose gradually between the 1992 and 1994 cohorts. The estimated decrease in infection incidence between the 1994 and 1995 cohorts probably reflects the effectiveness of the ban on the use of mammalian meat and bone-meal introduced in Portugal in mid-1994. Assuming no infections in animals born after June 1995, the models predict that the incidence of BSE cases in Portugal will peak in 1999 with BSE case-incidence declining thereafter. DISCUSSION: Our results illustrate the power of epidemiological analysis to detect decreasing trends in infection incidence prior to the resulting decrease in case incidence. The findings should inform the deliberations of the European Commission, which recently reported concerns about the sharp increase in case incidence from 1997 to 1998.

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