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Measuring the burden of tuberculosis

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Measuring the burden of tuberculosis

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Estimates of the incidence of tuberculosis (TB) and TB-related mortality are key indicators in the evaluation of B-control activities. But how are these estimates derived? The presentation highlights the key methods, and focuses on the uncertainties around the estimates.

Estimates of the incidence of tuberculosis (TB) and TB-related mortality are key indicators in the evaluation of B-control activities. But how are these estimates derived? The presentation highlights the key methods, and focuses on the uncertainties around the estimates.

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Measuring the burden of tuberculosis

  1. 1. 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
  2. 2. www.aighd.org More TB than ever?
  3. 3. www.aighd.org More TB than ever?
  4. 4. www.aighd.org WHO strategy and targets
  5. 5. 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
  6. 6. MEASURING TB INCIDENCE
  7. 7. www.aighd.org Definition and measurement The number of new cases per time period
  8. 8. www.aighd.org TB incidence Direct Surveys Notification Definition and measurement The number of new cases per time period
  9. 9. www.aighd.org Measuring TB incidence: direct Assess TB
  10. 10. www.aighd.org Measuring TB incidence: direct Assess TB
  11. 11. www.aighd.org Measuring TB incidence: indirect Assess TB migration death Assess TB
  12. 12. www.aighd.org Measuring TB incidence: indirect Assess TB migration death Assess TB
  13. 13. www.aighd.org Measuring TB incidence: indirect Assess TB Assess duration of disease Incidence = Prevalence / duration
  14. 14. www.aighd.org TB prevalence surveys
  15. 15. www.aighd.org Surveys with low or medium TB prevalence 87,000 participants Ukraine 17,400 cultures 97 patients
  16. 16. www.aighd.org Surveys with low or medium TB prevalence 134,000 participants Russia 26,800 cultures 83 patients
  17. 17. www.aighd.org Surveys with low or medium TB prevalence 84,000 participants Moldova 16,800 cultures 99 patients
  18. 18. www.aighd.org Surveys with low or medium TB prevalence 83,000 participants Romania 16,600 cultures 100 patients
  19. 19. www.aighd.org Surveys with low or medium TB prevalence 845,000 participants Denmark 169,000 cultures 67 patients
  20. 20. www.aighd.org Measuring TB incidence: Notification
  21. 21. www.aighd.org Measuring TB incidence: Notification Incidence = notification Incidence = notification * correction factor Incidence = notification * opinion
  22. 22. www.aighd.org Expert opinion: The onion model All cases Access Presenting Diagnosed Reordered
  23. 23. www.aighd.org Consensus on notification
  24. 24. 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%
  25. 25. www.aighd.org Capture-Recapture analysis 25 Peterson, 1894
  26. 26. 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)
  27. 27. www.aighd.org Example The Netherlands van Hest, 2007 Not notified 13%
  28. 28. 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
  29. 29. www.aighd.org Methods used by World Health Organization (WHO) WHO, 2018
  30. 30. MEASURING TB MORTALITY
  31. 31. www.aighd.org WHO strategy and targets
  32. 32. www.aighd.org Measuring mortality Count causes of death 17th Century, John Graunt
  33. 33. www.aighd.org Measuring mortality
  34. 34. 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
  35. 35. www.aighd.org Measuring TB mortality WHO, 2018
  36. 36. www.aighd.org TB mortality: Different estimates TB mortality estimates ◦ WHO ◦ IHME (Global Burden of Disease project)
  37. 37. www.aighd.org Garcia-Basteiro, 2017
  38. 38. www.aighd.org Difference TB mortality estimates
  39. 39. CONCLUSIONS
  40. 40. 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)
  41. 41. Thank you for the attention slides posted on frankvanleth.com

Editor's Notes

  • 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
  • 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.
  • 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
  • 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
  • Let us start with the definition of incidence: The number of new case per time period.

    In the field of TB a year

  • The important words are new and time period

    We can measure it in different ways:

    Direct, through surveys, and through notification data.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • And that is just by sitting together, sharing opinions and come up with a consensus.
  • 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
  • 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
  • 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
  • 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%
  • 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
  • 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
  • Apart from incidence, the EndTB strategy has a target on TB mortality
  • compared to 1990, the number of deaths need to be decreased by 35% in 2020, and 95% in 2035
  • 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
  • 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
  • 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
  • The diffent methods are use in different parts of the world
    The two types of red refer to the use of vital registration
  • 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
  • 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
  • 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
  • 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.

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