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The results of the meta-analyses of the occurrence of combined chronic disease, hydrocele only (for males) and lymphoedema only in mf-positives, are displayed graphically in Figures 2.8-2.10. In each figure, the estimated ORs from
PRINCIPLES AND PRACTICE OF CLINICAL PARASITOLOGY
Fig 2-8 Odds ratios (mf-positives to mf-negatives) and 95% confidence intervals for 23 studies of the relation between the presence of mf and combined chronic disease (hydrocele and lymphoedema) in bancroftian filariasis. Two studies (marked with asterisk) provided data only for males. See text for explanation of the figure and interpretation of the results. aIvory Coast; bKoupela; cMali; dTingrela. For references, see source. From Michael et al. (1994), with permission
individual studies are plotted in descending order of magnitude, together with their respective 95% confidence intervals. Ratios lying to the right of the unity line (OR> 1) denote a positive association, or a higher observed probability of disease in mf-positives. By contrast, an OR located to the left (OR< 1) represent a negative relationship for that study, with a higher chance of disease in mf-negatives. Studies in which the 95% confidence interval of the estimated OR include 1 signify equal chance of disease in their respective mf-positive and mf-negative populations. The results show that, contrary to the expectation of a negative association between mf and chronic disease, most studies had ORs that did not differ significantly from unity (12/21 for combined chronic disease, 8/14 for hydrocele, and 8/12 for lymphoedema), and thus provide no evidence for a significant association between the presence or absence of patent infection and the occurrence of disease. Indeed, the overall results suggest a bias towards a positive association, with more studies
in each disease category showing significantly higher rather than lower odds of disease in mf-positives (Figures 2.8-2.10). However, for all three meta-analyses, there was significant between-study variability which precluded the computation of a common OR for these studies. Michael and colleagues, however, showed that although there could be regional effects, the observed between-study variability could be explained by the local incidence of infection; in general, there was a trend for the odds of patent infection in diseased individuals to increase positively with increasing prevalence of infection (Figure 2.11). The authors concluded that, on balance, these results supported the prediction of the dynamic model of disease (proportion of individuals with both chronic disease and microfilaraemia increase with increasing prevalence of infection because of higher probabilities of reinfection) rather than the immunological model of infection and disease development in lymphatic filariasis.
F'g2-9 Meta-analysis of 14 studies of the relation between the presence of mf and hydroceles in males. The individual study odds ratios (mf-positives to mf-negatives) are plotted together with their 95% confidence intervals. aTingrela; bKoupela; cMali. For references, see source. From Michael et al. (1994), with permission
Fig 2.10 Meta-analysis of 14 studies. Two studies provided data for males only (marked with asterisk) of the relation between the presence of mf and lymphoedema. aKoupela; aTingrela. For references, see source. From Michael et al. (1994), with permission
PRINCIPLES AND PRACTICE OF CLINICAL PARASITOLOGY
Fig 2.11 The relationship between individual study odds ratios (ORs) of disease in mf-positives relative to mf-negatives by region and the prevalence of infection in each study. Note that the natural logarithms of the ORs are plotted—negative ratios indicate more disease in mf-negatives for that study, while positive ratios signify greater probability of disease in the mf-positive subpopulation of the presenting study. Asterisks denote the estimated ORs from studies from the Indian subcontinent, closed squares represent ORs from the South Pacific islands, and diamonds are ORs estimated for studies from Africa. Vertical bars denote the estimated 95% confidence intervals (natural log scale) of each study OR. From Michael et al. (1994), with permission
These examples demonstrate that with careful application, meta-analysis can provide a tractable and powerful tool for arriving at general conclusions regarding major epidemiological questions in parasitic infections. Recent developments in incorporating randomization and bootstrap tests into meta-analysis, in order to determine the significance level of a given statistic, have the potential to further enhance the applicability of this technique to nonrandomized observational field data (Adams et al., 1997). We predict that meta-analysis will have a substantial impact in uncovering broad patterns in the accumulated body of epidemiological research over the next few years.
EMERGING TECHNOLOGIES IN EPIDEMIOLOGY: REMOTE SENSING AND GEOGRAPHICAL INFORMATION SYSTEMS