James S. Koopman

Modeling and analyzing HIV transmission: the effect of contact patterns

A compartmental model is presented for the spread of HIV in a homosexual population divided into subgroups by degree of sexual activity. The model includes constant recruitment rates for the susceptibles in the subgroups. It incorporates the long infectious period of HIV-infected individuals and allows one to vary infectiousness over the infectious period. A new pattern of mixing, termed preferred mixing, is defined, in which a fraction of a group’s contacts can be reserved for within-group contacts, the remainder being subject to proportional mixing. The fraction reserved may differ among groups. In addition, the classic definition of reproductive number is generalized to show that for heterogeneous populations in general the endemic threshold is BDc,, where cr is the mean number of contacts per infective. The most important finding is that the pattern of contacts between the different groups has a major effect on the spread of HIV, an effect inadequately recognized or studied heretofore.

Role of the primary infection in epidemics of HIV infection in gay cohorts.

A review of the data on infectivity per contact for transmission of the HIV suggests that the infectivity may be on the order of 0.1-0.3 per anal intercourse in the period of the initial infection, 10(-4) to 10(-3) in the long asymptomatic period, and 10(-3) to 10(-2) in the period leading into AIDS. The pattern of high contagiousness during the primary infection followed by a large drop in infectiousness may explain the pattern of epidemic spread seen in male homosexual cohorts in the early years of the epidemic. Simulations of cohorts of homosexual males, using that range of parameter values, indicate the following: (a) The initial fast rise and then more or less rapid flattening of the incidence curve of seropositives is primarily due to rapid initial spread, yielding a group of infecteds all of whom pass into the low infectivity asymptomatic period at close to the same time. All this occurs only if the basic reproduction number for the primary infection is > 1. (b) The behavioral changes that have been reported all started after the incidence of new infections began to fall, too late to have a major effect on the initial rise. The behavioral changes had a major effect in slowing down the subsequent rise in the number of seropositives. (c) High activity groups play an important role in the early rapid rise of the epidemic. However, it is not likely that the rapid decrease in rate of growth of seropositives is solely due to saturation of these very high activity groups. Although the evidence for this interpretation of the role of the primary infection is not conclusive, its implications for prevention and for vaccine trials are so markedly different from those of other interpretations that we consider it to be an important hypothesis for further testing.

Declining hepatitis A seroprevalence: a global review and analysis.

Hepatitis A virus (HAV) is spread by faecal-oral contact or ingestion of contaminated food or water. Lifelong immunity is conferred by infection or vaccination, so anti-HAV seroprevalence studies can be used to indicate which populations are susceptible to infection. Seroprevalence rates are highly correlated with socioeconomic status and access to clean water and sanitation. Increasing household income, education, water quality and quantity, sanitation, and hygiene leads to decreases in HAV prevalence. Japan, Australia, New Zealand, Canada, the United States, and most European nations have low anti-HAV rates. Although anti-HAV rates remain high in most Latin American, Asian, and Middle Eastern nations, average seroprevalence rates are declining. Surveys from Africa generally indicate no significant decline in anti-HAV rates. Because the severity of illness increases with age, populations with a high proportion of susceptible adults should consider targeted vaccination programmes.

The role of early HIV infection in the spread of HIV through populations

The combination of two factors gives early HIV infection an especially strong influence on transmission dynamics: (a) increased transmission probabilities and (b) increased transmission potential of partners infected during this period. Most attention has been focused on the first factor because it fits the way we usually think about risk factors affecting individuals. The second factor acts not on individuals, but across chains of transmission. It is missed by models with constant partnership formation rates over an individuals life or with random mixing. It cannot be assessed from available data collected from individuals. Its assessment requires data from both individuals in a partnership. We demonstrate that this second effect can be so strong that early infection can dominate transmission dynamics even when transmission probabilities are only modestly increased. This second effect is not directly parameterized in our models but arises from two realistic types of temporal variation in partnership formation: (a) Partnership formation rates vary by age with preferential partnership formation in ones own age group, and (b) individuals of any age can experience transient periods of high-risk partnership formation. In a model with only the age-related effect, early infection is observed to dominate transmission dynamics when 20% of transmissible virus is allocated to the first 6 weeks of infection, 7% to middle infection, and 73% to late infection. This domination occurs both early in the course of an epidemic and later when endemic infection levels have been reached. When the second effect is added, early infection is seen to dominate transmission in a model allocating 10% of transmissible virus to the first 6 months, 40% to middle infection, and 50% to late infection. In this model, transmission probabilities during early infection are only 4.17 times those of middle infection and half those of late-stage infection.

Household and Community Transmission Parameters from Final Distributions of Infections in Households

A model is devised for the distribution of the total number of cases in households from a homogeneous community. In the model, community-acquired infection serves as a source of initial infection within households as well as of possible further cases. In addition, infected household members can infect others in the household. Maximum likelihood procedures for the model parameters are given. The model is fitted to symptom data on influenza and the common cold. Influenza seems to spread more easily in the community than within the household, while the opposite may be the case for the common cold. The model, which does not require specification of the time of onset of infection for individuals, can be fitted to serological data; this would provide a more accurate measure of household infection than the symptom data used.

Percolation on heterogeneous networks as a model for epidemics

We consider a spatial model related to bond percolation for the spread of a disease that includes variation in the susceptibility to infection. We work on a lattice with random bond strengths and show that with strong heterogeneity, i.e. a wide range of variation of susceptibility, patchiness in the spread of the epidemic is very likely, and the criterion for epidemic outbreak depends strongly on the heterogeneity. These results are qualitatively different from those of standard models in epidemiology, but correspond to real effects. We suggest that heterogeneity in the epidemic will affect the phylogenetic distance distribution of the disease-causing organisms. We also investigate small world lattices, and show that the effects mentioned above are even stronger.

First-time urinary tract infection and sexual behavior.

We studied the relation between sexual and health behaviors of women and first-time urinary tract infection (UTI). The study population was women using a university health service who were unmarried, had no UTI history, and who had engaged in sexual activity at least once. We found 86 cases of UTI, defined as one or more urinary symptoms and & 1,000 colony-forming units per ml urine of a known pathogen. We randomly sampled 288 controls from the student body. Vaginal intercourse increased the risk of UTI; this risk was further increased with condom use. After adjusting for vaginal intercourse with other birth control methods and recentness of current sexual partnership, a single sex act with a condom in the past 2 weeks increased UTI risk by 43%. Having a sex partner for less than 1 year vs 1 year or more, after adjustment for frequency of vaginal intercourse and birth control method, was associated with about twice the risk of UTI [odds ratio (OR) = 1.97; 95% confidence interval (CI) = 1.04–3.74]. After adjusting for frequency of vaginal intercourse, regular drinking of cranberry juice was protective against UTI (OR = 0.48; 95% CI = 0.19–1.02), whereas drinking carbonated soft drinks appeared to be associated with increased risk (OR = 2.37; 95% CI = 0.75–7.81). Using deodorant sanitary napkins or tampons was associated with a slight increase in risk of UTI (OR = 1.51; 95% CI = 0.74–3.06). Blacks had five times greater risk of UTI than whites after adjusting for frequency of vaginal intercourse (OR = 5.2; 95% CI = 1.89–24.63). We observed only modest differences in health behavior between racial groups.

Transmission Clustering Drives the Onward Spread of the HIV Epidemic Among Men Who Have Sex With Men in Quebec

Phylodynamic analysis and epidemiologic data identified 3 patterns of spread of primary human immunodeficiency virus type 1 infection (PHI) among men who have sex with men (2001-2009): 420 unique PHIs, 102 small clusters (2-4 PHIs per cluster, n = 280), and 46 large clusters (5-31 PHIs per cluster, n = 450). Large clusters disproportionately increased from 25.2% of PHIs in 2005 to 39.1% in 2009 (χ(2) = 33.9, P < .001). Scalar expansion of large clusters over 11 months (interquartile range, 3.5-25.5 months) correlated with cluster membership size (r(2) = 0.174, F = 4.424, P = .047). PHI cohort data revealed variations in social networks and risk behaviors among the 3 groups, suggesting the need for tailored prevention measures.

Choosing an appropriate bacterial typing technique for epidemiologic studies

A wide variety of bacterial typing systems are currently in use that vary greatly with respect to the effort required, cost, reliability and ability to discriminate between bacterial strains. No one technique is optimal for all forms of investigation. We discuss the desired level of discrimination and need for a biologic basis for grouping strains of apparently different types when using bacterial typing techniques for different epidemiologic applications: 1) confirming epidemiologic linkage in outbreak investigations, 2) generating hypotheses about epidemiologic relationships between bacterial strains in the absence of epidemiologic information, and 3) describing the distributions of bacterial types and identifying determinants of those distributions. Inferences made from molecular epidemiologic studies of bacteria depend upon both the typing technique selected and the study design used; thus, choice of typing technique is pivotal for increasing our understanding of the pathogenesis and transmission, and eventual disease prevention.

Transmission of Uropathogens between Sex Partners

Epidemiologic evidence and several case reports suggest that Escherichia coli causing urinary tract infection (UTI) may be transmitted between sex partners. In order to test this hypothesis, urinary, vaginal, and fecal E. coli isolates from 19 women with UTI were compared with E. coli found in random initial voids from their most recent male sex partner. E. coli was isolated from 4 of 19 male sex partners. In each case, the E. coli isolated from the man was identical by pulsed-field gel electrophoresis and bacterial virulence profile to the urinary E. coli from his sex partner.