Читать книгу Tuberculosis and War - Группа авторов - Страница 40

To take the potential uncertainty about the correct denominator out of the equation, we can examine only numerators where they exist. For example, we can examine either the ratio of TB cases to TB deaths or the ratio of the respective rates, as both likely used the same denominator, and thus cancel out the influence of potentially faulty denominators. One problem with this is that for simplicity we have to use incident cases from a given year and deaths from the same year. Yet, patients dying from M. tuberculosis were incident cases not just in the current but also in earlier years as we know from the survival curves discussed earlier.

Fig. 8. Tuberculosis case-to-death ratio in 3 different United Kingdom jurisdictions in the pre-chemotherapy era [66–69], reproduced with permission from Elsevier. Underlying data to calculate ratios were abstracted from graphs, where those for England and Wales showed numbers, and those for Lancaster and Worcestershire rates derived from much smaller numbers than for England and Wales.

While morbidity data are available only for some countries in their entirety, some sub-country jurisdictions have notifications of both pulmonary TB cases and deaths for multiple sequential years. Three jurisdictions with such data were chosen from the United Kingdom to exemplify the use of case-to-death ratios. These were England and Wales over 2 time periods [66, 67], Lancaster [68], and Worcestershire [69]. None of the 3 studies revealed a marked change during the war years as far as they were included (Fig. 8). The data from England and Wales are based on large case numbers (60,000–70,000 per year), whereas the data from Lancaster and Worcestershire yielded rates based on much smaller case and population numbers (cities as opposed to 2 entire regions of the United Kingdom). The case-to-death ratio is remarkably constant over all the observation years with an average of about 1.6 for England and Wales, and Lancaster. The ratio in Worcester is higher at approximately 2.0 on average, but it also fluctuates much more as might be expected for the smallest among the 3 jurisdictions. This example demonstrates that in the pre-chemotherapy era, the case-to-death ratio – an approximation to the reciprocal of case fatality – was fairly constant in the inter-war years and was similar during wartime when TB, in Worcester for instance, did not increase [69].

Lewis-Faning examined specifically the interval between TB notification and death from M. tuberculosis and the effect of WWII on it, but could not find any difference, suggesting an effect of the war on acceleration of progression to death in Middlesex County, United Kingdom [70]. Rist noted that TB case notifications in Paris continued to decline during WWII, yet reported that the number of deaths increased in parallel [28]. Unfortunately, he did not provide the numbers to define this relationship more precisely.

Fig. 9. Reported notifications of cases of infectious tuberculosis and tuberculosis deaths (all forms) per 100,000 population, Norway, 1924–1950. Data to reproduce figures were abstracted from graph in [71], reproduced with the permission of the European Respiratory Society.

Norway, as mentioned earlier, is one of the few countries that has collected comprehensive TB morbidity data since the beginning of the 20th century. Figure 9 shows national notification rates of infectious respiratory TB and TB mortality rates (all forms) from 1924 through 1950 [71]. Tuberculosis cases declined to a nadir in 1941, then increased slowly to a peak in 1945, subsequently to resume the pre-war decline. The increase in cases during war years was a relatively modest 17.5%. A similar increase is not discernible for mortality. Calculating the case-to-death ratio from these data (Fig. 10) [71] shows a fairly flat course hovering around an average of about 1.6 from 1920 through 1943. Subsequently, the ratio gradually increases to 3.5 in 1950 in the wake of the progressively successive introduction of chemotherapy that reduced case fatality. The data from Norway do not confirm Rist’s hypothesis of accelerated progression from disease to death, which might be attributable to the relatively small effect the war seems to have had on TB in Norway.

Like Norway, Denmark introduced systematic notification of TB cases early on [72]. Figure 11 shows the comparison of notified pulmonary TB cases and TB deaths from 1921 through 1957 [72]. The first nadir of cases was reached in 1940, then increased to a peak in 1946, resulting in an increase of 53.4%; in other words, a much larger increase than reported from Norway during the war years. Over the same period, the number of deaths remained essentially unchanged. Calculating the case-to-death ratio, the ratio hovers around an average of slightly over 1.5 during the 11 years from 1921 through 1931. Subsequently, there is a regular, virtually exponential increase in the ratio by an average 5.2% annual increase until the end of the observation period (Fig. 12). The ratio had substantially increased to 3.1 in 1946 when the peak morbidity was reported. By the end of the observation period, the ratio had risen to over 5.5, testifying the power of chemotherapy in saving lives. In the period from 1940 to 1946, when cases increased, the ratio also increased. This is quite the opposite of what would be expected if Rist’s hypothesis for France holds good. In other words, there is no evidence in Denmark that cases of TB succumbed at an accelerated pace during the war years; in fact, it was just the reverse.

Fig. 10. Case-to-death ratio of notified infectious respiratory tuberculosis case rates to tuberculosis mortality (all forms) rates, Norway, 1924–1950. Underlying data to calculate ratios were abstracted from the graph in [71].

Fig. 11. Reported notifications of pulmonary tuberculosis cases and tuberculosis deaths (all forms), Denmark, 1921–1957. Data to draw graph were abstracted from [72], reproduced with the permission of the World Health Organization.

Fig. 12. Case-to-death ratio of notified pulmonary tuberculosis cases to tuberculosis deaths (all forms), Denmark, 1921–1957. Data to calculate ratios were abstracted from graph in [72], reproduced with the permission of the World Health Organization. The dashed line to the left of the 1931 vertical line is the average ratio during that period, the line to the right the regression from that year onwards through the end of the observation period.

Fig. 13. Reported cases and deaths from pulmonary tuberculosis, per 100,000 population, London and Paris, 1934–1944. Data to reproduce graph were abstracted from [73], reproduced with permission from Elsevier. For better proportional comparison, data are shown semi-logarithmically.

Finally, we turn to Paris and London for which comparative rates for pulmonary cases and deaths are available for the period 1934 through 1944 (Fig. 13) [73]. The reported burden is larger in Paris than in London, and the course is parallel for the observation period, except that in the final year of observation TB cases in Paris declined while in London they continued to increase. The case-to-death ratio (Fig. 14) is generally higher in London than in Paris, but there are major fluctuations in the ratio over the observation period. However, there seems to be no indication in either city that, while there are fluctuations, the ratio is getting systematically smaller during the war years compared to the pre-war years. On the contrary, should one like to construe an interpretation, if anything, the ratio may tend to get larger with time. Again this does not suggest accelerated progression to death during WWII.

Fig. 14. Case-to-death ratio of notified pulmonary tuberculosis cases and deaths, per 100,000 population, London and Paris, 1934–1944. Underlying data to calculate ratios were abstracted from graph in [73], reproduced with permission from Elsevier. For better proportional comparison, data are shown semi-logarithmically.

In summary, the examination of comparative morbidity and mortality data in various settings does not give any indication that TB tends to progress faster to death at times when TB morbidity increases during wartime. The data examined here were almost exclusively from Western European countries of the inter-war years and WWII, because morbidity data from WWI seem to be rarely available. Tuberculosis epidemiology during and in the aftermath of WWII is, however, not at all comparable with that during and after WWI. The reported excess peak in mortality in Germany reported in WWII was not anywhere nearly as large as that reported for WWI. Second, the period after WWII brought chemotherapy, which had a substantial impact on the duration of infectiousness of cases and case fatality. The 2 post-war situations cannot thus possibly be compared. The phenomenon reported by Redeker [62] of a seeming resumption of the pre-war (WWI) secular trend without a ratchet effect after the hyperinflation period (Fig. 4 chapter 1) stands out as a unique puzzle. A similar phenomenon has been reported for some countries, but few had actually a sufficiently long observation period before WWI and/or did collect data during the war years [74, 75]. Among those countries with longer series of mortality data before and during WWI, there are indications, however, that in countries with particularly large mortality spikes (such as Belgium, Denmark or The Netherlands), a similar phenomenon [76, 77] as that reported by Redeker for Germany [62] is discernible. The “Rist hypothesis” – formulated on unfortunately sketchily reported observations of an accelerated progression from disease to death – has still the greatest appeal, at least for WWI, even if there is scarce if any evidence for it that could be found in other settings and other times. That such a shortening of lifespan could take place in the pre-chemotherapy era was reported from Chemnitz, Germany [78]. Deaths occurring in the years 1938 to 1943 were taken, and the average number of years elapsed since diagnosis were calculated (Fig. 6 in chapter 3). The regression on years surviving and death year then shows a substantial average decrease in survival years of 7.5% annually. Because these are averages and the events cover both pre-war and war years, it remains impossible to tease out the actual role of the war years on the observed accelerated case fatality. It also points to some of the difficulties discussed in this chapter in the epidemiologic assessment as diagnosis of incident cases and their ultimate death do not occur in the same calendar year. Perhaps the hypothesis that the influenza pandemic of 1918 contributed to hastening the decline of TB [65] not just in the United States will deserve further scrutiny.