In children, a male predominance in the incidence of symptomatic disease has been reported for some infectious agents and not for others. Not only are the factors underlying these sex differences poorly understood, but it is also not clear why the differences are described only for selected infectious diseases. In this study of sex- and age-specific incidence of infectious diseases in children, a possible explanation for the inconsistencies in the literature was explored. The sex ratio in reported disease incidence in Israel during a period of about 20 years was examined for various viral and bacterial infections. In addition, an hypothetical mathematical model was developed which assumes increased susceptibility to infectious disease (such as in relative immune deficiency) in a proportion of males. In children aged under 4 years, a higher incidence among males was consistently observed for all diseases, and the sex ratio varied between 1.16 (95% confidence interval (CI): 1.13-1.18) for shigellosis to 1.98 (95% CI: 1.79-2.17) for viral meningitis. The highest ratios were associated with the diseases which tend to present asymptomatically most often, which is consistent with the predictions of the model. The male excess in symptomatic disease appears to be present for most infectious diseases and this should be taken into account in studies comparing observed disease incidence between groups with different sex ratios. The inconsistencies in reports on the excess male morbidity for infectious diseases may be due to variations in symptomatic to asymptomatic infection ratios.
PIP: An explanation is provided for the male predominance in incidence of infectious diseases in children. A theoretical and mathematical model for predicting sex ratios for different prevalences of increased susceptibility to infectious disease in males is presented. The theoretical model states that males are more likely to experience symptomatic disease due to an increased prevalence of a factor such as immune deficiency. Variables are the proportion infected, the ratio of symptomatic (clinical) to asymptomatic (subclinical) infections, and the prevalence of males with increased susceptibility to infectious disease. Data included incidence of viral hepatitis, shigellosis and salmonellosis between 1966-85 and viral meningitis between 1971-85 by age and sex for Israeli Jews and nonJews. Other data for shorter time periods included poliomyelitis (1958-62), measles (1976-85), and diphtheria (1958-70). Single years of age were used for those 0-4 years. In diseases where vaccination has reduced the case load, the male to female incidence ratio was estimated with incidence density computed for the whole time period. The results of the analysis showed that male incidence 5 years in all 3 bacterial and 4 viral diseases was higher. The incidence ratios showed an excess of 20-100% for infectious diseases. This consistent pattern is not apparent in the literature because sex differences may be difficult to detect among symptomatic diseases; i.e., measles. There is also a lower symptomatic to nonsymptomatic infection ratio and small sex incidence ratio for shigellosis, salmonellosis and viral hepatitis. Where the symptomatic to nonsymptomatic ratio is about 1:50 or 1:100, the male to female incidence ratio will be much higher at about 2:1 and more readily detected. The immunodeficiency prevalence among males as an explanation for the susceptibility of males for diseases was not supported by an excess frequency of 2-3% in overt symptoms, although it is still considered a viable hypothesis. It is suggested that the inconsistencies in reports on male predominance in infectious diseases may be an artifact of statistics showing variability in the proportion of symptomatic infectious diseases. The implications are that comparisons should be made between the sexes. The disease rates may be biased by different proportions of males in the study and placebo groups in vaccine testing. Sex differences and disease should be examined further.