Leprosy Mailing List – November 16, 2019
Ref.: (LML) What really happened in Shandong?
From: Joel Almeida, London and Mumbai
Dear Pieter and colleagues,
Thanks to Prof. Fine (LML 8 Nov 2019) for his contribution on this topic. The view expressed there is "that Shandong was similar to many populations in the world which have undergone considerable socio-economic improvement and in which leprosy declined to vanishingly low levels – even before the advent of any chemotherapy." Is this particular view about Shandong available on the evidence?
The evidence
Per capita GDP over time in Shandong and Yunnan, respectively, is shown in Figs. 1 and 2. New case detection rates of HD over time in Weifang/Shandong and Wenshan/Yunnan are shown in Fig. 3.
Figure 1. GDP per capita in Shandong, 1952 to 2018 (source: CEIC data)
Figure 2. GDP per capita in Yunnan, 1949-2018 (source: CEIC data)
Figure 3. New cases detected over time in Wenshan/Yunnan (upper line) and Weifang/Shandong (lower line). (based on ref. 1) Both areas used periodic surveys for case detection.
Prof. Fine quotes from Li et al (1) as follows: "since 1978…. Weifang has experienced rapid growth of average annual income…" However, Li et al (1) actually wrote: "With the reform and open-door policy in China since 1978, Weifang has experienced a rapid growth of average annual income (AIC) and gross prefectural product per capita (GNP) since 1985" (emphasis added). Further, Prof. Fine states that ""organised control" began in Shandong with dapsone in the 1960s". However, Li et al (2) state that "In 1949, when New China was founded, a preliminary investigation in six counties found that the prevalence was approximately 1 per 1000. A provincial leprosy control program was initiated in 1955." (emphasis added) Therefore the facts are not as Prof. Fine believed them to be.
It is helpful, for the purposes of reliable inference, to look at evidence as carefully as we can. Otherwise we might accidentally gloss over clues and unintentionally mislead ourselves. This topic is of some importance, given the implications if Shandong did indeed achieve near-zero transmission owing to a particular way of using anti-microbial chemotherapy. Nerves, limbs, eyes, minds, livelihoods and relationships are at stake.
The inferences
The evidence shows that Shandong before the 1980s had little socio-economic improvement, as measured in GDP per capita. Yet, it showed a relatively rapid decline in incidence rate during that time, starting from about 50 new cases per 100,000 population/year. At all times since 1955 Shandong used prolonged anti-microbial protection (at first with dapsone monotherapy and eventually from 1986 with prolonged MDT). Therefore Prof. Fine's view quoted at the start is contradicted by the evidence. In Shandong, prolonged anti-microbial protection contributed importantly to a relatively rapid decline of HD, ending in near-zero transmission. This argues strongly for expansion of that success to other endemic areas.
It seems important also not to disregard the evidence from Wenshan/Yunnan, nor from pre-1986 vs post-1986 in Shandong and Yunnan.(1) The stagnation in the new case detection rate in Yunnan after 1986 is shown in Figure 3. The accompanying dramatic increase in per capita GDP in Yunnan after 1986 (Fig. 2) proved insufficient to maintain the preceding decline in new cases. Yunnan's observed levelling-off in the decline of new cases after 1986 can reasonably be linked to Yunnan's reported 1986 switch from prolonged anti-microbial protection to fixed-duration MDT. Further, Yunnan's earlier steady decline in new cases from 1960 to 1986 preceded its eventual dramatic increase in per capita GDP. That decline prior to 1986, as with Shandong, can reasonably be linked to the prolonged anti-microbial protection available in Yunnan prior to 1986. Here, again, prolonged anti-microbial protection seems to play an important role in the decline of HD.
The decline of HD in Shandong accelerated in 1986, unlike in Yunnan. In Shandong, 1986 was the year when prolonged dapsone monotherapy was replaced by prolonged MDT.
The Table. Trend in new cases detected/year in two parts of China, by time period
| | Pre-1986 low income | Post-1986 increasing income |
| Weifang/Shandong maintained prolonged anti-microbial protection, first with dapsone and then from 1986 with prolonged MDT | decline | faster decline |
| Wenshan/Yunnan replaced prolonged anti-microbial protection with fixed-duration MDT in 1986 | decline | stagnation |
This improbable constellation of trends, especially given the counter-intuitive observation in Yunnan post-1986, can reasonably be attributed to prolonged anti-microbial protection having a greater impact than either income level or income increases, on new HD cases/year. The stagnation in Yunnan after 1986 is likely to be explained in part by the demonstrably important risk of recurrence (endogenous relapse or exogenous re-infection) among LLp patients 6 or more years after withdrawal of anti-microbial protection (For evidenced discussion of 20-year recurrence rates following 24 months of MDT, see LML 2 June 2019).
In summary, prolonged anti-microbial protection prior to 1986 contributed to a reasonably rapid decline in new cases in both provinces even without dramatic increases in per capita GDP. By contrast, even dramatic increases in per capita GDP in Yunnan after 1986 failed to maintain the preceding decline in new cases in Yunnan. 1986 was when prolonged anti-microbial protection was withdrawn in Yunnan and replaced by only 24 months anti-microbial protection for LL patients (among others).
Socio-economic development and even social safety nets are pursued by many governments for reasons much wider and weightier than HD control alone. We could add our voices to those of the socially-minded citizens who advocate such policies and practices. However, the evidence indicates strongly that Shandong's use of prolonged anti-microbial protection for LL patients (and incidentally others) contributed importantly to a rapid decline of HD leading to near-zero transmission.
India
Figure 4. GDP per capita in India, 1958 to 2019 (source: CEIC data)
Figure 5. GDP per capita over time in China (top) and India (bottom) (source: World Bank)
India has the world's largest number of new cases/year. GDP per capita is increasing. However, it will be small consolation to the people of India that socio-economic improvements are hypothetically sufficient to ensure a relatively rapid decline in new HD cases/year, even without any anti-microbial chemotherapy at all. There has been stagnation (or worse) in the new cases/year in India. Nor is the impact of socio-economic improvement entirely predictable. Chandigarh (India) in 2011 was the richest administrative unit in India (source: CEIC data) but had a higher newly detected prevalence of HD than Bihar, (3) the poorest state (source: CEIC data). Anti-microbials seem necessary not only to protect individuals, but also for reducing the main source of concentrated viable bacilli in India. That main source is untreated LL patients. This includes neglected previously treated LL patients with recurrent disease (owing to endogenous relapse or exogenous re-infection).
Unidentified sources of transmission are hypothesised. However, it is doubtful whether a yet-unknown source could match the overwhelmingly high concentration of viable bacilli available from untreated patients with undiagnosed or recurrent LL disease, or from anergic armadillos (the latter in the Americas only). This can be discussed in more detail at another time. For now, however, it seems wise to focus narrowly on the implications for action arising from the evidence above. The outcomes we seek, including an end to HD, ultimately depend on effective action.
Action implications
We can add prolonged anti-microbial protection of LL patients to the socio-economic development and social safety nets being pursued by the governments of several endemic countries. In so doing, we have a good chance of matching Shandong's 20%/year decline in incidence rate leading to near-zero transmission. LL patients are, in any case, entitled to such competent case management under Article 25(1) of the Universal Declaration of Human Rights. They should not have to search for well-informed private practitioners in order to access such prolonged protection, which might sometimes sink their household financially. Instead, even the poorest LL patient deserves such prolonged protection free of charge at even the most humble government-financed health facility.
We have unwittingly been emulating post-1986 Yunnan by withdrawing anti-microbial protection from even LLp patients. This unhelpful fashion has been enforced in publicly financed systems despite the demonstrably important risk of recurrent disease among LLp patients 6 or more years after release from MDT. It is better to emulate Shandong, by ensuring prolonged anti-microbial protection for all LL patients (eg., using monthly post-MDT chemoprophylaxis with 3 bactericidal drugs). Such protection will close a major gap in our defences against the bacilli, in addition to protecting vulnerable individuals. It is like closing a hole in a water levee (dyke). If this hole is left unattended, HD bacilli in high concentrations keep flooding the land. (For discussion of the importance of previously treated LLp patients relative to undiagnosed LL patients, see LML 12 May 2019 ).
Post-MDT chemoprophylaxis for LL patients is crucial if we wish to match Shandong's achievement of a 20%/year decline in incidence rate leading to near-zero transmission. Even if rapid expansion of income and social security was guaranteed in every endemic country, we would still need to use MDT and post-MDT chemoprophylaxis. In real life, such guarantees are not always available. Brazil illustrates this.
Figure 6. Brazil GDP per capita, 1962 to 2019 (source: CEIC data)
This makes post-MDT chemoprophylaxis for LL patients all the more essential if we want to treat patients humanely and end HD relatively rapidly. The example protocol for safely interrupting transmission (LML 4 Nov 2019) took into account this evidence along with other relevant evidence. In TB we (at WHO HQ) carefully analysed evidence, drew on demonstrable success, and developed a highly practical strategy that has since transformed outcomes and saved tens of millions of lives. It can be our dream similarly to transform outcomes in HD. The key in TB was to build on the foundation of Dr. Styblo's demonstrable success in saving lives at the front-lines in Tanzania. Shandong achieved a 20%/year decline in HD incidence leading to near-zero transmission, using prolonged anti-microbial protection for LL patients. That is the demonstrable success on which we can build. It would be good to spread that success across the globe, by including post-MDT chemoprophylaxis for LL patients.
Joel Almeida
References
1. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221.
2. Li HY, Pan YL, Wang Y. Leprosy control in Shandong Province, China, 1955-1983; some epidemiological features. Int J Lepr Other Mycobact Dis. 1985 Mar;53(1):79-85
3. Katoch K, Aggarwal A, Yadav VS, Pandey. A National sample survey to assess the new case disease burden of leprosy in India. Indian Journal of Medical Research, 2017; 146(5): 585-605.
- - - - - -
P.S. We can be grateful to LML for providing this uniquely valuable platform for well-informed discussions, rapid and open review of contributions, and for expert advice to those colleagues who seek assistance. Our contributions here are scrutinised, and can be openly and carefully reviewed, by nearly all of the world's knowledgeable HD experts. This allows us to help one another more rapidly to assemble the pieces of the jigsaw and evolve practical measures more securely to defeat our common enemy, the bacilli.
Interestingly, the Gates Foundation, on behalf of its funding recipients, has adopted an open rapid publication platform with open (rather than anonymous and unpublished) peer review. It is called Gates Open Research. That digital platform reproduces some of LML's helpful features.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
You received this message because you are subscribed to the Google Groups "Leprosy Mailing List" group.
To unsubscribe from this group and stop receiving emails from it, send an email to leprosymailinglist+unsubscribe@googlegroups.com.
To view this discussion on the web, visit https://groups.google.com/d/msgid/leprosymailinglist/10d31267-8227-4bba-a1fa-aef7bde2fd7a%40googlegroups.com.
