085 - The clinical severity of diphtheria in certain cities in Great Britain

So what is the reason all these people were trying to develop all these vaccines? This study is one that provides some justification, which is that these diseases can be pretty deadly. Hedley D. Wright looked at the clinical severity (that is, case-fatality rates, number of cases that ended in death) of diphtheria in seven cities of Great Britain over a number of years.¹

So Wright looked at the data of diphtheria cases and deaths in Liverpool, Birmingham, Manchester, Glasgow, Leeds, Hull, and Edinburgh from 1911 to 1935. Keep in mind that diphtheria antitoxin/serum treatment had been around at least 20 years in this case.

One difficulty in such a study is the issue of reporting: you don't really see things if you're not looking. And diagnostic criteria matter too: if something is not diagnosed as diphtheria, it's not reported as such, even if it should be (the same is true in reverse). Wright estimated that there could be as few as 40% of actual cases being reported, so more than half went unreported. Since deaths are more likely to be reported, this means the case-fatality rate appears higher than it actually is. But it's still possible to use it to compare cities, and also to get an idea of deadliness by death rates overall.

And this is how it seems: the average case-fatality rates ranged from 6% (Hull) to 10.1% (Manchester): this means that of 100 people who got diphtheria, 6-10 of them died. That's not great. On the other hand, looking at death rates per 100,000 people (based on 1931 census data), the rankings are almost reversed: Manchester is the lowest, with about 10 people out of each 100,000 dying (so in a population of about 800,000 that's 80 deaths), while Hull has a rate of almost 14 (so in 300,000, that's 42 deaths). The highest rate is Liverpool, with 17 (in 850,000, that's 144-145 deaths). So it seems like Hull might have a pathogen that spreads better between people but is not as deadly, compared with Manchester.

There was change over time though. Early in the data, around 1915, there was a pretty bad epidemic, and then cases and deaths fell off. But in the last five years of observation, cases and deaths picked up again. This trend was broadly similar over the seven cities, though not exactly. The new epidemic seemed to have a lot more cases but not as much death. Possibly the ability to diagnose had improved, though not everywhere.

Also important was the analysis of different age groups. In almost every case, death and case-fatality rates were worse in younger children than in older. This is consistent with what we've seen before; youth makes this disease deadlier. So ages 0-4 have case-fatalities from around 10-20%, 5-9 years have 5-10%, and 10-14 have 1-5%. 20% is a pretty high severity.

There's some good news though: the deadliness for the youngest age group went down over the period in question. It started out around 20%, and went down to about 10%. However, in the 5-9 years group, it dropped initially, after the 1915 epidemic, and then rose again. So it seemed like the later epidemic was worse for older children.

Wright and others speculated that this pattern could be due to children going to school together more, or better treatment for younger patients somehow, or changing sizes of families. Not sure. But this is the kind of disease that is why people were trying to develop vaccines.

There aren't really many studies citing this one that I can quote from, but here's one that's also by Wright, sort of an update on the Liverpool situation.²

References:
1. Wright, H. D. The clinical severity of diphtheria in certain cities in Great Britain. Journal of Pathology and Bacteriology 49, 135–155 (1939).
2. Wright, H. D. Diphtheria in Liverpool during the years 1937-40. Journal of Pathology and Bacteriology 52, 283–294 (1941).