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Case fatality designates the proportion of people with TB who succumb to it: thus, the numerator is deaths, and the denominator is TB cases among whom the deaths occurred. Tuberculosis mortality has the same numerator as fatality, but the denominator is the entire population (rather than just TB cases) from which the TB cases arose and it has an observation time (usually 1 year). These 3 components make the definition of a “rate” [56].

Tuberculosis case fatality from untreated sputum smear-positive TB was large in the pre-chemotherapy era. One of the earliest long-term observations from a sanatorium in Switzerland showed a cumulative fatality of 70% after 17 years of follow-up (Fig. 6) [57]. What was designated “open tuberculosis” are patients excreting tubercle bacilli, and is thus largely synonymous with sputum smear-positive TB, because cultures were rarely used in routine testing at that time. By contrast, “closed tuberculosis” referred to any other form of TB (both pulmonary and extrapulmonary). “Sputum” is also almost uniformly “direct,” which means spontaneously produced rather than induced or via bronchoscopy. Clearly, the “closed” form with 18% fatality was substantially less deadly than “open” (pulmonary) TB. Similarly, high fatality ratios were determined in Denmark (68% after 10 years) [58], in Sweden (84% after 18 years) [59], and in the United Kingdom (86% after 11 years) [60]. A meta-analysis put the weighted mean after 10 years at 70% [61]. To obtain a reasonable estimate of case fatality, a longer observation period improves the estimate, but it is not required. For instance, it is perfectly justified to have only an approximate observation time for each case in treatment outcome analysis. Therefore, it suffices to state that a certain number of all patients who should have completed treatment died prematurely from M. tuberculosis. According to the WHO/Union definition, those who died of other causes are added to this numerator. Without observation time, we then get a simple proportion rather than a rate.

Fig. 6. Fate of untreated pulmonary tuberculosis, long-term follow-up, Barmelweid Sanatorium, Switzerland, reproduced by permission from Springer [57].

The variation in case fatality at the end of long observation time is relatively large: 68–86% in the four pre-chemotherapy studies mentioned here. For better comparability of these studies, the observation end point was fixed at ten years as in the meta-analysis. The median is then very narrow: between 1.2 and 1.7 years (Fig. 7) [57–60]. In other words, about half of the deaths occur within the first 1.5 years, while the other half occurs over the next 8.5 years. As the final cumulative fatality is so high, it cannot get much higher under the influence of an adverse situation, such as wartime. What could change substantially was the speed at which patients died, as suspected by Rist [28]. Whether this hypothesis can be confirmed or has to be refuted will be examined shortly.

Fig. 7. Cumulative case fatality from untreated sputum smear-positive tuberculosis in four studies from Denmark [58], Sweden [59], Switzerland [57], and the United Kingdom [60], with permission from Elsevier.

The determination of case fatality poses no problems with the denominator (patients with TB) as the cases are known and all that is needed is to learn about their outcome (e.g., the number of deaths among the cases). In contrast, the determination of mortality can be complex as it requires knowledge of both the correct numerator and denominator, that is, the accurate enumeration of deaths (numerator) and population (denominator) from which the cases arose as discussed above.

The famous compilation of data by Redeker about mortality in Germany (Fig. 4 in chapter 1), includes the years 1892–1940 [62]. In many ways, these are the most remarkable data. For one, there is a huge spike commencing shortly after the beginning of WWI in 1914, then rapidly accelerating to a peak lasting from 1917 to 1919, then precipitously falling to less than pre-war levels by 1921; the second smaller peak denotes the period of hyperinflation in 1923. It is difficult to reconcile what actually happened. One must always consider the succinct possibility of errors in the numerator and denominator, as discussed above. The last pre-war census was held in 1910, enumerating a population of 65 million. Two wartime censuses were held in 1916 and 1917, both covering a population of around 62 million. A census in 1919 reported a population of 61 million and the next regular census of 1925 counted 62 million inhabitants (https://en.wikipedia.org/wiki/Census_in_Germany). During this 15-year interval, the population appeared to have been much too stable to account for a gross denominator error in the calculation of the mortality rates. Potentially more biased might have been the numerator data, obtained by counting deaths from M. tuberculosis, particularly among males. The Spanish influenza pandemic beginning in early 1918 cost millions of lives and could have contributed to misattributing influenza deaths to TB or actually be co-responsible for causing TB deaths [63, 64] or that indeed the H1N1 1918 influenza epidemic removed TB sources of transmission [65]. Tuberculosis mortality in Germany had actually peaked in 1917, one year before the influenza pandemic, thus this type of misclassification could not account for the observation in that year, but influenza could have accounted at least partially for the subsequent decline in TB mortality. If one removes the years 1915 through 1923 and regresses linearly on the remaining data, the regression line suggests that the pre-war secular trend resumed its projection from 1924 onwards, as if the 10-year epidemic surge had had no influence whatsoever.

If we recall the discussion of the epidemiologic transitions in the model discussed at the beginning of this chapter, it suggests probably only one rational explanation: the decline in the transmission of M. tuberculosis at the core of the TB epidemic continued uninterrupted throughout the period of WWI and afterward. There was no ratchet effect in that a declining trend was resumed at a higher level after the 10-year epidemic was over: it continued as if the epidemic had never happened. This may imply that in the final analysis, any excess sources of infection that might have arisen as a result of the war, influenza, and post-war miseries did not contribute equally to the excess transmission as one would normally have expected. As morbidity data are unavailable for Germany during this period, one must thus conclude that either there was no excess morbidity, only excess fatality (as Rist implied [28]) or that both “usual” plus excess cases all died at an accelerated speed. The latter hypothesis is considerably more likely as the untreated case fatality of 70% [61] can simply not double, which would have to be postulated in the former case.