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case_images: PMC7693426_02
case_images: PMC7693426_03
case_images: The international decline of rheumatic fever, with incidence data from Denmark (1862-1963) and mortality data from the United States (1921-1970). Correlation: r = 0.928, r2 = 0.81. Penicillin was introduced in 1943, in the US and in Denmark. Data for Denmark extracted from Figure 1 in Steer, and data for the US extracted from Figure 4 in Massell et al.. Both graphs changed from logarithmic to a linear scale (Note, the data for mortality before 1949 has been modified to attempt to compensate for a discontinuity in the data series related to change of the ICD criteria for diagnosis, see details in Data Sheet 1 in the Supplementary Material).
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case_images: F1
case_images: Annual incidence data for rheumatic fever is available from Denmark, and mortality data from the US, see Figure 1. In Figure 1 the decrease had already begun in 1888 and was almost linear until 1963. I and II there was a problem of epidemics of rheumatic fever among young men in the military, who were living close to one another. Increases in the incidence in Denmark during these two wars can be seen in Figure 1. It would be reasonable to expect that penicillin had a major effect on the incidence of rheumatic fever, however, as shown in Figure 1, the decline began about 50 years earlier. It is striking that this pattern of change and timing almost exactly describes the pattern for rheumatic fever (see Figure 1), with a steady decline beginning in the late 1800s and reaching a floor level in the early 1960s.
case_images: The parallel decline of stuttering and rheumatic fever, after the introduction of penicillin in 1943. The blue markers show the decline of the mortality due to rheumatic fever age 5-19, in the United States. The brown diamonds show the annual prevalence of stuttering in Palo Alto schools, California, grades 1-6 (Jackson, 1967, as reprinted in Van Riper,). A polynomial trend line is fitted to the stuttering time series. The correlation is r = 0.954, r2 = 0.91, p = 6.0E-1 (Note, as mentioned in Figure 1, the data for mortality before 1949 has been modified. The correlation without the data before 1949 is r = 0.898 with p = 4.2E-07).
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case_images: The data shows a dramatic decrease in the prevalence of stuttering in the Palo Alto schools, from about 2.56% in 1945 to a mean level of about 0.61% from 1955 to 1966, see Figure 2. Further, as shown in Figure 2, the prevalence of stuttering appears to have followed the same trajectory as rheumatic fever between 1945 and the early 1960s. The high correlation after 1945 suggested by Figure 2 is likely to have been caused by the specific effect of the introduction of penicillin on the frequency and severity of GAS tonsillitis.
case_images: The parallel decline of stuttering and rheumatic fever in different continents, after the introduction of penicillin in 1943, in the US and in Denmark. The correlation is r = 0.945, r2 = 0.89, p = 1.2E-9.
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case_images: F3
case_images: The prevalence data for stuttering from Palo Alto can also be compared to the incidence data from Denmark, see Figure 3. Does this mean that we can expect that the prevalence of stuttering followed the trajectory of rheumatic fever already from the early 1900s (as illustrated in Figure 3)? If this was the case, it would imply that the rate of stuttering was very high in the late 1800s.
case_images: Result of multiple regression analysis of the possible confounding effect of the increasing number of students in Palo Alto schools, hypothetically resulting in reduced detection rate for stuttering. The unfilled diamonds show the stuttering data adjusted according to the multiple regression model, with the possible effect of an increasing number of students on the rate of detection of stuttering students removed, resulting in a more conservative estimate of a decline of stuttering. The correlation between the mortality due to rheumatic fever, and the prevalence of stuttering, according to the multiple regression, is r = 0.92, with p = 1E-9.
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case_images: F4
case_images: The resulting estimated prevalence series is plotted in Figure 4, unfilled diamonds.