When a new disease is recognized, it may be of interest to describe the nature of the disease and to evaluate the probable means of transmission, reservoir, and natural history. Sometimes a new disease can be quickly linked to a specific organism, such as staphylococcal toxic shock syndrome. More often, however, epidemiologic studies contribute to the discovery and characterization of new pathogens, as with hantavirus pulmonary syndrome, Legionnaires’ disease, and AIDS.
Early studies may consist of descriptions of cases that may be linked by a route of transmission or common exposure. Descriptive studies do not typically make inferential comparisons of cases to individuals without disease (controls); rather, they only describe aspects of the disease and circumstances surrounding the acquisition and occurrence of disease. Surveillance methods capture cases of disease and are an excellent source for identifying individuals for further follow-up. At times, case reports or case series provide considerable insight into the epidemiology of an infectious disease.
Ecologic Studies
Ecologic studies utilize populations with different levels of exposure and examine the correlation of exposure levels with population-level disease frequency. In a typical ecologic study, data are not available at the individual level to determine whether those individuals who are truly exposed have a higher (or lower) occurrence of disease; the researcher simply knows that in the population with greater exposure, there is more (or less) disease.
Ecologic studies may be useful in exploring hypothesized associations by comparing disease frequencies among populations from different geographic regions or from different time periods. Population-level data may be available from national
or community-wide surveys of exposure frequencies and disease rates, which can often be obtained inexpensively. Ecologic studies also allow for comparisons where the range of exposure in one particular population may be too narrow to correlate with a disease outcome at the individual level. For example, the association of vitamin A deficiency with an infectious outcome would be difficult to evaluate in a population consisting of only vitamin A-deficient individuals. Alternatively, an ecologic study comparing infection outcomes across populations with varying prevalence of vitamin A deficiency would permit a better assessment of the correlation. Similarly, studies of the relationship between infectious agents and unusual outcomes—such as the liver fluke
Opisthorchis viverrini and bile duct cancer, and
Helicobacter pylori and stomach cancer—can be strengthened by ecologic data from populations with widely varying levels of infections and cancer.
Two ecologic studies, one of rheumatic fever and one of HIV infection, are described here.
Crowding and Rheumatic Fever Early studies led to the hypothesis that household crowding was an important environmental factor in the transmission of group A streptococci and high rates of acute rheumatic fever. Moreover, it has been hypothesized that the reduction in household crowding may have been one factor leading to the decreased rates of acute rheumatic fever in the last half of the 1900s in comparison with earlier periods.
20 The data in
Figure 3-6 show the association between the incidence of rheumatic heart disease and crowding (as measured by household size) in various districts in the city of Bristol, England, 1927-1930. Compared to districts with high household crowding, those with low crowding show lower rates of disease.
Circumcision and HIV Transmission Male circumcision (removal of the foreskin) is a common surgical procedure undertaken for a variety of cultural and medical reasons. Biologically, the foreskin is rich in immune cells and may develop micro-tears that may
serve as an entry point for HIV. The foreskin may also trap HIV in a warm moist environment, allowing more time for infection to occur. Given these factors, it is not surprising that circumcised men have been found to have lower rates of sexually transmitted diseases.
21
In the late 1990s, data began to emerge suggesting that circumcised men were at lower risk for HIV infection. An ecologic study contributed to this evidence by examining the association of the prevalence of circumcision and HIV in several African countries.
22 Data on circumcision practices were extracted from an ethnographic database and were combined with published HIV seroprevalence data. By mapping these data, the authors identified a strong correlation between the practice of male circumcision and the prevalence of HIV infection among males (
Figure 3-7).
The challenge in conducting this analysis was that a variety of behavioral, cultural, and religious
differences between ethnic groups may alter the risk of HIV acquisition. Most notably, circumcised men in the study were more likely to be Muslim, and it was possible that behavioral factors may have contributed to their lower risk of infection. As noted by Gray:
[M]arried Muslim men are predominantly polygamous, and polygamous unions may provide a closed sexual network reducing the risk of HIV introduction. Also, Muslim men abstain from alcohol consumption, and alcohol is associated with high-risk behaviors. Key informant interviews suggest that penile hygiene may be important. Under Islam, individuals are considered unclean after intercourse, and Muslim men and women are required to perform post-coital ablutions. In addition, observant Muslims will often wash before daily prayer. Hygienic practices
associated with religion may thus partly explain the protective effects of circumcision among Muslims.
23
Because an ecologic study design does not collect individual-level data, it cannot account for differences in cultural or hygienic practices that may differ between those men who are and are not circumcised.
Based on the strength of the ecologic studies and other emerging data, three randomized clinical trials of male circumcision were initiated in 2001 in Kenya, South Africa, and Uganda. The results of these studies demonstrated convincingly that male circumcision reduced the incidence of HIV acquisition by more than 50%.
24,
25 and
26 Although no benefits were seen for circumcision of HIV-infected men in protecting against transmission to their female partners,
27 additional studies have demonstrated benefits of circumcision for genital ulcer disease
28 and high-risk human papillomavirus.
29 The next generation of studies will need to evaluate the expansion of circumcision as part of national HIV prevention strategies and the impact on regional HIV incidence—again requiring further ecologic designs.