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The burden of tuberculosis
:
Measuring uncertainty
F R AN K VAN L E T H
A S S O C I A T E P R O F E S S O R O F G L O B A L H E A L T H
A M S T E R D A M U N I V E R S I T Y M E D I C A L C E N T E R S , U N I V E R S I T Y O F A M S T E R D A M
A M S T E R D A M I N S T I T U T E F O R G L O B A L H E A L T H A N D D E V E L O P M E N T
C H A I R T B n e t
www.aighd.org
More TB than ever?
www.aighd.org
More TB than ever?
www.aighd.org
WHO strategy and targets
www.aighd.org
Burden of tuberculosis
Key information to evaluate TB control strategies
Measurement methods develop and change over time
◦ Old estimates are updated regularly
Previous WHO reports no longer digitally available
MEASURING TB INCIDENCE
www.aighd.org
Definition and measurement
The number of new cases per time period
www.aighd.org
TB incidence
Direct Surveys Notification
Definition and measurement
The number of new cases per time period
www.aighd.org
Measuring TB incidence: direct
Assess TB
www.aighd.org
Measuring TB incidence: direct
Assess TB
www.aighd.org
Measuring TB incidence: indirect
Assess TB
migration death
Assess TB
www.aighd.org
Measuring TB incidence: indirect
Assess TB
migration death
Assess TB
www.aighd.org
Measuring TB incidence: indirect
Assess TB
Assess duration of disease
Incidence
=
Prevalence / duration
www.aighd.org
TB prevalence surveys
www.aighd.org
Surveys with low or medium TB prevalence
87,000 participants
Ukraine
17,400 cultures
97 patients
www.aighd.org
Surveys with low or medium TB prevalence
134,000 participants
Russia
26,800 cultures
83 patients
www.aighd.org
Surveys with low or medium TB prevalence
84,000 participants
Moldova
16,800 cultures
99 patients
www.aighd.org
Surveys with low or medium TB prevalence
83,000 participants
Romania
16,600 cultures
100 patients
www.aighd.org
Surveys with low or medium TB prevalence
845,000 participants
Denmark
169,000 cultures
67 patients
www.aighd.org
Measuring TB incidence: Notification
www.aighd.org
Measuring TB incidence: Notification
Incidence = notification
Incidence = notification * correction factor
Incidence = notification * opinion
www.aighd.org
Expert opinion: The onion model
All cases
Access
Presenting
Diagnosed
Reordered
www.aighd.org
Consensus on notification
www.aighd.org
Reaching consensus
Subjective
Open discussion not always possible
Error prone due to “blind spots”
Example of Tanzania
◦ WHO: 48% of cases notified
◦ Programme: 85% cases notified
◦ Applied on next year data: case detection > 100%
www.aighd.org
Capture-Recapture analysis
25
Peterson, 1894
www.aighd.org
Capture Recapture analysis
Source 1 Source 2 Total
Present Absent
Present X11 X10 n2
Absent X01 X00
Total n1 N
N
^
=
(n1 +1)(n2 +1)
(Xii +1)
www.aighd.org
Example The Netherlands
van Hest, 2007
Not notified 13%
www.aighd.org
Capture-recapture analysis
Requires multiple independent sources
Matching patients from different sources is often problematic
◦ Data protection laws
Can be repeated once system has been set up
www.aighd.org
Methods used by World Health Organization (WHO)
WHO, 2018
MEASURING TB MORTALITY
www.aighd.org
WHO strategy and targets
www.aighd.org
Measuring mortality
Count causes of death
17th Century, John Graunt
www.aighd.org
Measuring mortality
www.aighd.org
Measuring mortality
Potential sources
◦ Vital registration
◦ Verbal autopsies
◦ Mortality surveys
◦ Estimates: incidence * case fatality rate
Problems
◦ Absence of vital registration systems
◦ Classification / attribution
◦ Coverage / generalizability
www.aighd.org
Measuring TB mortality
WHO, 2018
www.aighd.org
TB mortality: Different estimates
TB mortality estimates
◦ WHO
◦ IHME (Global Burden of Disease project)
www.aighd.org
Garcia-Basteiro, 2017
www.aighd.org
Difference TB mortality estimates
CONCLUSIONS
www.aighd.org
Conclusions
Estimating TB burden requires multiple methods
Estimates are done with uncertainty
More precise estimates require improved surveillance and vital registration systems
Full insight in TB burden requires adequate
◦ Identification patients with presumptive TB
◦ Proper diagnostic procedures
◦ Complete reporting and notification to national bodies
◦ Timely reporting to international organizations (WHO)
Thank you for the attention
slides posted on frankvanleth.com

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Measuring the burden of tuberculosis

Editor's Notes

  1. We are currently reporting more TB patients that ever before. But there are differences per region. Of the six WHO regions, three report an increasing number of TB patients, while the European region shows as only region a clear decline
  2. But looking at absolute numbers is just half the story. If we look at the number of patients in relation to the population size, then we see a modest decrease in TB incidence over the last 18 years Where the absolute numbers show a complete lack of TB control, the incidence shows us a small but consistent decrease in the burden of TB But what we also see is that there is uncertainty: the green are around the estimate.
  3. The targets in WHO’s EndTB strategy are fully based on measurement of the burden of TB It is therefore important that we understand how the burden of TB is measured That is what I want to tlak about in the coming 30 to 40 minutes
  4. Having insight in the burden of TB is of importance when evaluating TB control activities. The methods of estimation change regularly, making that the estimates are also updated For that reason it s not possible to find old WHO report on-line anymore
  5. Let us start with the definition of incidence: The number of new case per time period. In the field of TB a year
  6. The important words are new and time period We can measure it in different ways: Direct, through surveys, and through notification data.
  7. The direct measurement uses a cohort approach. We have a population and we follow everybody his population for a full year. At the end of the year we assess who has a new diagnosis of TB. This proportion is then the incidence This approach is extremely difficult First: It requires large populations Second: it is impossible to have every person in direct observation for a full year This method is therefore never used in real life
  8. The direct measurement uses a cohort approach. We have a population and we follow everybody his population for a full year. At the end of the year we assess who has a new diagnosis of TB. This proportion is then the incidence This approach is extremely difficult First: It requires large populations Second: it is impossible to have every person in direct observation for a full year This method is therefore never used in real life
  9. A more feasible approach would be the survey approach We have a population in which we assess the prevalence of TB: all persons that have TB at that moment in time After a few years, we repeat this. Some persons of the first survey might be in the second, other persons are new. When we have inforamtion on who leves and who enters the first population, we can estimate the incidence. Repeat surveys are done, but the extra inforamtion to get incience is diffictlt
  10. A more feasible approach would be the survey approach We have a population in which we assess the prevalence of TB: all persons that have TB at that moment in time After a few years, we repeat this. Some persons of the first survey might be in the second, other persons are new. When we have inforamtion on who leves and who enters the first population, we can estimate the incidence. Repeat surveys are done, but the extra inforamtion to get incience is diffictlt
  11. A more feasible approach would be the survey approach We have a population in which we assess the prevalence of TB: all persons that have TB at that moment in time In the same survey we assess the duration of disease. We can then translate the prevalence of disease to the incidence of disease
  12. Such a survey is a huge undertaking. I have been directly involved in the design and implementation of two: In Tanzania and in Bangladesh. It requires knocking on doors, interviewing people, and performing laboratory tests in difficult circumstances But most of all: it requires a lot of people. Bot surveys needed over 50,000 participants to obtain a reasonable precise prevalence estimate
  13. The third methods is through notification. This is the form you use in Russia to record information on diagnosed TB patients. The formal notification data is nothing else that the total of diagnosed TB pa.tients within a time period
  14. How does this work? If we are sure that all TB patients in the country are identified and notified, the number of notifications is a direct estimate of the incidence If we know that only a few TB patients are not identified or notified, we can use a correction factor. This factor corrects the number of notifications in a way that the corrected numbers are an estimate of the incidence If we suspect a large number of patients not being identified or notified, we can not use a correction factor. Then we use detailed information from expects to correct the number of notifications
  15. To start with the expert. The WHO uses the onion model to estaimte the number of missed patients at each step. Which is not an easy task. I have been in a team that assessed this for Tanzania. It is detailed work looking at all kind of data sources and interviewing different people in the country. But in the end, you have to come up with a decision
  16. And that is just by sitting together, sharing opinions and come up with a consensus.
  17. This process is very subjective. Discussions are often not fully open, especially if the head of the TB programme is present. And there are clear blind spot on which even the experts have no reliable information. Which is specifically true if there is a large private health care system that is not engaged with the national TB program In Tanzania, the local experts decided that 85% of the TB cases was notified. This was much larger than the 48% that we as a team calculated form available data When the 85% estimate was used the next year in the official WHO report, The case det4ction rte for Tanzania was above 100%. Clearly a wrong estimate
  18. A more formal way to assess under-reporting is the use of capture recapture analyses This is a technique that stems from the field of biology to estimate the size of an animal population. First described in detail by Petersen in 1894, although there are indications that it is used even earlier Petersen needed to estimate the population size of eel at a Danish observation system. He catched fish at different places, marked them and recorded if a marked fish was captured again at a different place It very intuitive; if the population is large, you will catch only a few fish for a second time
  19. You need a minimal of two independent sources for TB patients For example the national disease register and the national laboratory system You count how many patients are in each of the sources, and how many are in. both sources The formula to estimate the total number of patients uses the total number in each of the registers and divides this by the number of those who are in both From here you can calculate how many cases are missed
  20. This was done in 2007 in the Netherlands Although a country that was considered having a very good notification system, it turned out that arounnd 13% of the TB patients were not notified. For this analysis, the investigators used 3 sources . What is striking is that only 388 patients were in all 3 sources. This was 26%
  21. The analysis looks straightforward but has some major difficulties. But it is not always easy to prove that the sources are really independent Matching can be a problem given the absence of personal data or restrictions by data protection laws. In an analyses to assess under-reporting of TB-HIV co-infection it took me almost 3 years to get permission to merge two national databases. But if a system is in place, it can easily be repeated for updated estimates and measure the impact of strategies for improved reporting
  22. Having discussed the different methodologies, we can see which one is used where. There are clear differences with the poorest method of expert opinion used in the majority of African countries While formal capture-recapture analyses are performed in just a few countries. And this does not mean that these studies are done very year. In general: estimating TB incidence is guess work leading to uncertain estimates
  23. Apart from incidence, the EndTB strategy has a target on TB mortality
  24. compared to 1990, the number of deaths need to be decreased by 35% in 2020, and 95% in 2035
  25. Mortality is measured for a long time. The first systematic appoach was in the 17th century by John Graunt. A parish priest who recorded all births and death in the parishes in London. But not he added the causes of death and published this in the famous book: Bills of Mortality
  26. Here is just a page, and we notice that cough and consumption is listed, with clearly the largest numbers of deaths form the disease. This is tuberculosis
  27. We do nothing different today and just want to count the number of deaths form tuberculosis. For that we use different data sources Vital registration refers to official government records Verbal autopsies are interviews in which we try to identify from what disease relatives have died We can perform formal surveys or just come up with a wild guess by using other data like incidence and death rate Assessing TB mortality ahs some major problems. Quite a number of countries do not have a reliable vital registration Difficult to assign a cause of death, as all of doctors might relate to. A good example is TB in HIV. This is recorded often as an HIV death, not a TB death Suveys are always a small sample making coverage an important issue
  28. The diffent methods are use in different parts of the world The two types of red refer to the use of vital registration
  29. Tb mortality estimates are produced by two different sources. The WHO and the Institute for Health Metrics and Evaluation. Known from the Global Burden of Disease project
  30. And these measures can differed greatly. This is the result form an analysis from a colleague at AIGHD There are countries where the WHO estimates are higher (the left side of the graph) And counties where the IHME estimates are higher (right side) More importantly: there is not an single correction factor that can bring the estimates in line
  31. This graph shows the differences between the two methods In the orange countries the WHO estimates are highest and in the green countries the estimates from IHME Estimating TB mortality becomes very difficult
  32. In conclusion. We need different methods to estimate the burden of TB in the world This leads to uncertain estimates For more precise estimates we need better surveillance and vital registration systems But it starts with adequate identification of patients with presumptive TB Proper diagnostic procedures Good record keeping And timely reporting to international organizations.