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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
4
Comparison of Disease Burdens
The objective of any vaccine development program is to reduce morbidity, mortality, and costs resulting from disease. Unfortunately, time and resource limitations make it impossible to pursue intensive development programs for all vaccines simultaneously. Priorities must be set in a manner that is consistent both with the needs of the population the vaccine is intended to benefit and the capabilities of current technologies. The committee sought a methodology that would allow quantitative comparison of the burdens of morbidity and mortality resulting from diseases that afflict populations in developing countries.
The classification of developing countries used in this study is in accordance with that used by the United Nations. Table 4.1 shows the regions, their populations, and other population features. Table 4.2 further defines the population estimates for the developing regions. Population estimates used throughout this volume were adapted from the 1984 World Population Data Sheet (Population Reference Bureau, Inc., 1984). Population estimates by age group were derived with the assistance of the Population Reference Bureau.
In the proposed system for comparing diseases, information on morbidity and mortality are combined with value judgments on the undesirability of various generic conditions into a single numerical score for each disease.* The same principles have been used in the comparisons of potential health benefits anticipated from individual vaccine candidates in Chapter 7. It is possible to use the same system to compare diseases identified in Appendix A that are candidates for long-term rather than accelerated vaccine development.
For the first phase of this study, setting vaccine priorities for the United States, the committee developed a method to calculate and compare the costs associated with various diseases. This method is described briefly in the latter portion of this chapter. For the reasons explained below, no attempt is made in this analysis to compare total treatment costs for diseases or the potential cost savings from
*
See Appendix F for information on the computer software used in this analysis.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.1 World Population Data
Region or Country
Population as of Mid-1984 (millions)
Crude Birth Rate (per 1,000 population)
Infant Mortality Rate (per 1,000 live births)
Percent Population Under Age 15
Percent Population Over Age 64
Urban Population (percent)
Worlda
4,762
28
84
35
6
40
Less developed
3,596
32
94
38
4
32
Africa
531
45
119
45
3
29
Asiab
2,662
30
91
38
4
25
Latin Americac
397
31
65
39
4
65
Oceaniad
5
41
89
43
3
18
More developed
1,116
16
19
23
12
71
Europe
491
14
15
22
13
72
North Americae
262
15
11
22
12
74
USSR
274
20
32
25
10
64
Australia, New Zealand
19
16
11
25
10
85
Japan
120
13
7
23
9
76
aError in total population due to rounding.
bJapan is excluded. China is included.
cMexico, Central America, and South America are included.
dAustralia and New Zealand are not included.
eCanada and the United States are included.
SOURCE: Population Reference Bureau, Inc. (1984).
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.2 Estimated 1984 Population by Age Groups for Regions in Which Developing Countries Predominate (thousands)
Age Group (years)
Region
Under 1
1–4
Under 5
5–14
15–59
60 and Over
Total
Latin America
12,736
44,499
57,235
100,220
214,415
25,130
397,000
Africa
23,040
73,762
96,802
141,459
265,451
27,288
531,000
Asia
73,400
270,300
343,700
666,402
1,472,242
179,656
2,662,000
Oceania
187
635
822
1,285
2,620
273
5,000
Total
109,363
389,196
498,559
909,366
1,954,728
232,347
3,595,000
(Percentage)
(3)
(11)
(14)
(25)
(54)
(6)
treatment averted by vaccine candidates in the developing world. This does not mean that these techniques cannot be applied in developing regions. Individuals setting priorities for a single country or region who have access to information (or reliable estimates) necessary to calculate treatment costs and potential cost savings from vaccines could employ the methods presented in Volume I (Institute of Medicine, 1985).
ELEMENTS OF THE SYSTEM FOR COMPARING MORBIDITY AND MORTALITY BURDENS ARISING FROM VARIOUS DISEASES
The system described below was designed not only to incorporate information relating to a disease (i.e., incidence, severity, complications, sequelae, duration, and distribution), but also to allow expression of individual value judgments on the undesirability (disutility) of various consequences resulting from that disease. Such value judgments are an inevitable part of the ranking process, whether they are explicit or implicit. The committee chose to make them explicit.
A format was devised with generic categories for estimates of the annual number of cases, complications, sequelae, and deaths associated with each disease. The scheme was designed to cover all major conditions that result from infectious diseases. Three levels of severity were established for both acute and chronic morbidity, and provision was made for recording the duration of an acute illness. The scheme also was designed to allow distribution of cases, complications, sequelae, and deaths among four age groups. An example of the matrix used to compile these estimates is shown in Table 4.3; the methods used to determine the entries are described below. Data on individual diseases are presented in Appendixes D-1 through D-19.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.3 Examples of the Format Used to Compile Information on the Burden of Illness Arising from infectious Diseases: Hepatitis A Virusa
Under 5 Years
5–14 Years
15–59 Years
60 Years and Over
Morbidity Category
Description
Condition
Number of Cases
Duration (days)
Number of Cases
Duration (days)
Number of Cases
Duration (days)
Number of Cases
Duration (days)
A
Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
139,843
7
635,651
7
2,256,561
7
149,378
7
C
Severe pain, severe short-term impairment, or hospitalization
Jaundice, nausea, malaise
31,735
14
158,675
14
1,221,794
14
206,277
14
D
Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)
Severe jaundice, fulminant hepatitis
n.a.
n.a.
n.a.
n.a.
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)
n.a.
n.a.
n.a.
n.a.
F
Total impairment
n.a.
n.a.
n.a.
n.a.
G
Reproductive impairment resulting in infertility
n.a.
n.a.
n.a.
n.a.
H
Death
n.a.
1,144
n.a.
5,146
n.a.
8,005
n.a.
aSee Appendix D-4 for derivation.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
Trade-Off Values
Individual value judgments (trade-off values)* on the undesirability of particular disease states were elicited through a questionnaire (see Appendix E) completed by a range of health professionals in developing countries. Respondents to the questionnaire were first asked to judge the undesirability of one unit of each acute and chronic morbidity category against death within a specific age group. The units were specified as 1 day for each state of acute illness and 1 case for each type of chronic illness (assumed to last a lifetime). Respondents then were asked to evaluate the undesirability of deaths across age groups. An example is shown in Table 4.4. The morbidity/ mortality and age categories in the questionnaire were the same as those used to develop estimates of disease incidence.
With these trade-offs, a set of values was derived for each respondent that represented on a single numeric scale the individual’s feelings about various disease consequences. The unit of comparison was designated as the “infant mortality equivalence” (IME) value. The IME value of a morbidity category/age group combination was calculated by multiplying the trade-off value for that combination by the trade-off value assigned to a death in that age group compared with the death of a child under 5 years of age (for an example derived from Table 4.4, see Table 4.5).
Expression of Morbidity and Mortality Burdens
Specific infant mortality equivalence values can be combined with disease burden estimates, such as those given in Appendixes D-1 through D-19, to generate scores that express the seriousness of a disease relative to others as viewed by the individual making the trade-off decisions.
The procedure begins with the calculation of a subtotal for each morbidity category/age group combination, as shown:
*
A trade-off value expresses an individual’s perception of the undesirability or disutility of a morbidity state compared with a death in the same age group.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.4 Example of an Individual Scheme of Trade-off Values
Trade-Off Values
Morbidity Category
Description
Unit
Under 5 Years
5–14 Years
15–59 Years
60 Years and Over
A
Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity
Days
20,000
15,000
10,000
5,000
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
Days
10,000
10,000
5,000
500
C
Severe pain, severe short-term impairment, or hospitalization
Days
1,000
500
200
100
D
Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)
Cases
100
100
200
200
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)
Cases
5
5
10
2
F
Total impairment
Cases
1
1
1
2
G
Reproductive impairment resulting in infertility
Cases
5
5
2
100
H
Death
Cases
1
1
1
1
Deaths adjusted for age group
1
0.5
0.3
3
The total score or total disease burden value (TDBV) is then a summation of the subtotals. A sample calculation sheet is shown in Table 4.6.
The views of various individuals on the relative importance of diseases can be compared by ranking diseases based on their TDBVs or by normalizing values so that the highest value represents some arbitrary common number, such as 100.
Prior to presenting the results of the disease burden comparison performed by this committee, some discussion of the method is desirable.
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TABLE 4.5 Example of an Individual Scheme of Infant Mortality Equivalence Values
Infant Mortality Equivalence Values
Morbidity Category
Description
Unit
Under 5 Years
5–14 Years
15–59 Years
60 Years and Over
A
Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity
Days
20,000
7,500
3,000
15,000
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
Days
10,000
5,000
1,500
1,500
C
Severe pain, severe short-term impairment, or hospitalization
Days
1,000
250
60
300
D
Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)
Cases
100
50
60
600
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)
Cases
5
2.5
3
6
F
Total impairment
Cases
1
0.5
0.3
6
G
Reproductive impairment resulting in infertility
Cases
5
2.5
0.6
300
H
Death
Cases
1
0.5
0.3
3
Procedures Used in Deriving Disease Estimates
The committee solicited information that would enable estimates to be made in the format shown in Table 4.3 from individuals knowledgeable about particular diseases. If the disease was not one for which the World Health Organization collects information, the committee used other sources. Committee staff integrated information from various sources with the assistance of consultants. Reviews of preliminary estimates were obtained from initial sources and other individuals. Revised estimates were generated on the basis of reviews, with committee members arbitrating if reviewers made conflicting recommendations for modification of preliminary efforts.
Estimates of disease burden for the diseases that are candidates for accelerated vaccine development are included in Appendixes D-1 through D-19. For some of the diseases included in this comparison, only limited data exist on their incidence in developing countries. Estimates sometimes had to be made on the basis of reports from a few
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
developing countries and the assumption that extrapolation to the entire developing world was reasonably valid.
Certain general procedures and assumptions were adopted to promote consistency in the derivation of estimates:
Cases were included under chronic categories (D through G) only if the condition would persist for the remainder of the individual’s life; convalescence or protracted initial illness (even possibly leading to death) from which the individual eventually might recover was not considered chronic disability.
To simplify implementation of the scheme, acute episodes of illness usually were assigned entirely to the morbidity category representing the most severe signs and symptoms present, although the episode might include periods of recovery at less severe levels.
Category C was interpreted as morbidity for which hospitalization was desirable, even if probably not accessible.
For diseases in which the pathogen produces a broad spectrum of illness severity rather than reasonably discrete conditions, estimates of the portions falling into different morbidity categories were obtained from individuals familiar with the disease’s clinical symptoms and epidemiology. In some cases, estimates were made from the most recent epidemiologic surveys of the disease; in other cases previously reported incidence rates were applied to 1984 population figures (Population Reference Bureau, Inc., 1984).
It was judged that trends in the patterns of diseases under consideration (see Appendixes D-1 through D-19) were generally not of sufficient magnitude to obscure differences among diseases, that is, that the relative impact of diseases when vaccines were likely to become available would be similar to that in 1984. This is amenable to verification. The effect of trends in population numbers and disease incidence on future vaccine benefits is discussed in Chapter 7. The impact of certain diarrheal diseases (especially mortality) probably will be decreased by the increased use of oral rehydration therapy. Two scenarios are therefore included in the calculations of disease burdens and vaccine benefits for these pathogens; they are described in Appendix C.
For epidemic diseases, the approximate average annual incidence was calculated using epidemic incidence and the average length of the inter-epidemic period.
Limitations of the Current Estimates
Limitations on the accuracy of estimates included in Appendixes D-1 through D-19 need to be recognized. The extent to which the estimates represent true disease patterns varies among diseases for the following reasons.
The quality and availability of data on specific diseases vary.
The types of data from which estimates were made vary. (For some diseases, infection rates for certain populations could be coupled
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.6 Example of Total Disease Burden Value Calculations: Hepatitis A Virus
Age Group
Under 5 Years
5–14 Years
Morbidity Category
Description
Cases
Duration (days)
Infant Mortality Equivalence Value
Subtotal
Cases
Duration (days)
Infant Mortality Equivalence Value
Subtotal
A
Moderate localized pain and/or mild systemic reaction or impairment requiring minor change in normal activities, and associated with some restriction of work activity
40,000
0
32,500
0
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
139,843
7
23,713
41
635,651
7
17,500
254
C
Severe pain, severe short-term impairment, or hospitalization
31,735
14
2,000
222
158,675
14
2,244
990
D
Mild chronic disability (not requiring hospitalization, institutionalization or other major limitation of normal activity, and resulting in minor limitation of ability to work)
n.a.
75
0
n.a.
62.5
0
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity and seriously restricting ability to work)
n.a.
5.5
0
n.a.
5.5
0
F
Total impairment
n.a.
1
0
n.a.
0.4
0
G
Reproductive impairment resulting in infertility
n.a.
100
0
n.a.
22.5
0
H
Death
0
n.a.
1
0
1,144
n.a.
0.5
2,288
TOTALS
263
3,532
aInfant mortality equivalence values represent the median of responses from individuals in developing countries.
with estimates of the proportion of clinically symptomatic infections to yield numbers of cases displaying symptoms. For other diseases, estimates were based on surveillance data, on prospective or retrospective studies in certain populations, or on reported disease incidence.) The reliability of data from such disparate sources varies considerably, even within countries.
It is almost universally accepted that, with few exceptions, reliable surveillance data from developing countries are unavailable. (Underreporting or overreporting may occur for many reasons, and it is
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
15–59 Years
60 Years and Over
Cases
Duration (days)
Infant Mortality Equivalence Value
Subtotal
Cases
Duration (days)
Infant Mortality Equivalence Value
Subtotal
Subtotal by Category
8,750
0
50,000
0
0
2,256,561
7
5,650
2,796
149,378
7
25,000
42
3,133
1,221,794
14
2,000
8,553
206,277
14
5,000
578
10,342
n.a.
30
0
n.a.
550
0
0
n.a.
2.75
0
n.a.
23.125
0
0
n.a.
0.309
0
n.a.
5
0
0
n.a.
16.5
0
n.a.
300
0
0
5,146
n.a.
0.4
12,865
8,005
n.a.
5
1,601
16,754
24,213
2,220
30,229
generally not practical to determine the extent of the error. Therefore, raw data on reported disease incidence were rarely used as a sole basis for disease estimates.)
Conditions affecting disease incidence are not uniform. Therefore, the exceptionally broad scope of the attempted estimates and the occasional need to extrapolate data from very few countries or studies to the entire developing world led to numerical estimates of uncertain validity.
For certain conditions, the estimates (both absolute numbers
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
and distributions) were based on individuals’ clinical and epidemiological experience and judgment, for which no means of verification existed.
The resources and time available to generate estimates were limited.
As noted above, many of the estimates used in this report are highly uncertain. However, the data-based approach presented here can be refined as epidemiological information increases. The committee believes that its method ensures the optimal use of available information and is preferable to qualitative measures (e.g., high, intermediate, or low) or scaling methods (e.g., assigning scores to incidence on a scale of 1 to 10).
The committee cautions that while the current estimates have been judged sufficient for the purposes of this report, efforts to collect additional data on relative disease burdens and to refine estimates from available data would be highly desirable. Discussions of the uncertainty of each disease’s estimates appear in Appendixes D-1 through D-19.
VALUE JUDGMENTS IN QUANTIFYING MORBIDITY AND MORTALITY
The use of infant mortality equivalence (IME) values in quantifying disease burdens (as in Table 4.6) intentionally introduces into the system for comparing diseases a component that reflects variations among individuals on the relative undesirability of disease consequences within and among age groups. Each individual’s perspective is equally valid; hence, there can be no single, correct set of trade-off or IME values.
Several composite or hypothetical perspectives are worth considering, however, because they illustrate how differences in perspectives are reflected in the ultimate rankings of disease burdens and benefits expected from vaccines.
The intent of selecting priorities for accelerated vaccine development is to benefit health—in the case of this report, the health of the populations in developing countries. Hence, the perspectives of medical or public health experts in those countries are of interest. Perspectives of the population at large, the intended beneficiaries, also are important.
If a representative sample from each group (health practitioners or the general populations in developing countries) were polled, the range of trade-offs or IMEs probably would be extensive. It would be possible to calculate a median perspective for the range, but other clusters also might exist. To illustrate, consider the way individuals rate mortality at different ages: while most group members might consider an adult death (15–59 years) more undesirable than an infant death, a fairly large minority might believe just the opposite. Acute morbidity of severity sufficient to interfere with producing food or earning a living might also be relatively highly ranked for undesirability in
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developing countries. In comparison, the economic impact of illness on the individual in developed countries is usually less immediate. The aggregation of these preferences is a complex issue both methodologically and ethically and needs careful consideration.
To help set IME values for this report, the committee polled a wide range of public health professionals and medical researchers from regions where developing countries predominate. Time and resource constraints did not permit polling representatives of the general population. The committee recognized that the responses obtained probably did not include the full range of perspectives required by an analysis of this type. However, the composite perspective described below was adopted to illustrate application of the system and to describe the qualitative effects of using different perspectives.
IME Perspective Used in This Study
For IME values in its calculations, the committee used a median of IME perspectives derived from the responses of health professionals in developing countries. Trade-off values elicited from these individuals were distributed over a considerable range.
The median IMEs, shown in Table 4.7, are used here and in Chapter 7 solely to illustrate the operation of the system, not to suggest the most appropriate or correct IME values. Choosing IME values to guide policy formulation is discussed at the end of this chapter.
The Effect of Adopting Other IME Perspectives
Other sets of IME values might reflect the view that morbidity and mortality in young age groups, chronic disability in adults, hospitalizations (at any age), or infertility is relatively more undesirable than expressed by the median perspective. Adopting this perspective would cause diseases inflicting or vaccines preventing a particularly disfavored morbidity or mortality to rise in the rankings of disease importance and vaccine priority. The extent of the rise would depend on the numbers of disfavored cases and the extent to which the relevant IME values differed from the median.
The committee’s first report on vaccine priorities for important diseases in the United States (Institute of Medicine, 1985) compared the effect of adopting the median of committee member perspectives with an age-neutral perspective. In the former perspective, death in the 25–59* years age group was most disfavored (and in the over 60 years age group, the least disfavored), while in the latter perspective, deaths at any age were judged equally undesirable. For the diseases in this study, the ranking was generally similar, but influenza (which causes many deaths in the over 60 years age group) ranked relatively
*
In that analysis narrower age ranges were considered.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE 4.7 The Median Infant Mortality Equivalence Values for Respondents from Developing Countries
Infant Mortality Equivalents
Morbidity Category
Description
Unit
Under 5 Years
5–14 Years
15–59 Years
60 Years and Over
A
Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity
Days
40,000
32,500
8,750
50,000
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
Days
23,713
17,500
5,650
25,000
C
Severe pain, severe short-term impairment, or hospitalization
Days
2,000
2,244
2,000
5,000
D
Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)
Cases
75
62.5
30
550
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)
Cases
5.5
5.5
2.75
23.125
F
Total impairment
Cases
1
0.4
0.309
5
G
Reproductive impairment resulting in infertility
Cases
100
22.5
16.5
n.a.
H
Death
Cases
1
0.5
0.4
5
higher in the age-neutral perspective. When fetal deaths from ectopic pregnancy were considered equal in undesirability to all other deaths/ gonorrhea also ranked relatively higher in the age-neutral perspective.
The committee derived a second set of IME values for this study based on trade-off questionnaires (see Appendix E) completed by individuals in the United States who are involved in improving health in developing countries. Table 4.8 presents these values. (The committee recognizes that the medians shown in Tables 4.7 and 4.8 were not drawn from statistically valid samples.) Adopting the perspective represented in Table 4.8 rather than Table 4.7 would lower the relative rankings for diseases that primarily cause mild acute morbidity, but would raise the rankings of diseases that cause very severe (total) chronic disability.
Adopting particular IME perspectives is comparable in some ways to ranking diseases or vaccines for particular age groups in the population. For example, an IME perspective that highly disfavors diseases affecting children would emphasize the relative ranking of pediatric
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vaccines. Chapter 8 presents further discussion of the grouping of vaccine candidates.
COMPARISON OF COSTS ASSOCIATED WITH DISEASES
Another way to compare candidates for accelerated vaccine development would be to compare the extent to which they would render unnecessary expenditures for treating diseases or avert other disease-related economic losses, for example, lost work productivity, and their cost-effectiveness in doing so. To make such comparisons it is necessary to know (or to obtain reliable estimates on) the costs associated with each disease. The costs incurred in vaccine development and in vaccination programs are discussed in Chapters 5 and 7, respectively.
TABLE 4.8 The Median Infant Mortality Equivalence Values for Respondents from the United States
Infant Mortality Equivalents
Morbidity
Category Description
Unit
Under 5 Years
5–14 Years
15–59 Years
60 Years and Over
A
Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity
Days
300,000
140,000
50,000
10,000,000
B
Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work
Days
80,000
10,000
4,000
100,000
C
Severe pain, severe short-term impairment, or hospitalization
Days
8,000
1,000
500
10,000
D
Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)
Cases
500
80
25
5,000
E
Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)
Cases
5
1
0.6
50
F
Total impairment
Cases
0.2
0.05
0.025
1
G
Reproductive impairment resulting in infertility
Cases
300
150
50
n.a.
H
Death
Cases
1
0.5
0.1
10
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Estimating Aggregate Direct Costs of Diseases in the Developing World
The committee did not attempt to predict the cost associated with treating diseases included in this analysis. It would be extremely difficult and probably unrealistic to estimate, for the developing world as a whole, the proportion of cases, complications, and sequelae that receive treatment; the nature of those treatments; and their average costs. No data exist on these questions, and the committee judged that convening a group sufficiently large to develop reliable estimates of these costs would not be practical.
Estimating Costs for Diseases in Specific Countries or Regions
Although it was not feasible to include disease cost comparisons in this analysis, it might be possible to compare the costs of treating various diseases in a particular region or country in the developing world. The procedures used by the committee to estimate the direct costs (mostly treatment-related) associated with important diseases in the United States can be adopted for this purpose. Those procedures are described fully in the first volume of the committee’s report (Institute of Medicine, 1985). Excluded from those calculations are costs resulting from loss of work, loss of future earnings, and public health measures to prevent further spread of illness (e.g., contact tracing for sexually transmitted diseases).
Indirect Costs
How best to calculate indirect costs associated with disease, such as loss of work time or loss of future earnings, is quite controversial. For its analysis of vaccine priorities for the United States, the committee did not believe that monetization of health benefits was either necessary or appropriate. Reduction of the overall economic burden imposed by certain diseases is definitely an important health goal; however, if these indirect economic aspects of disease burden were included among the costs, then interpretation of the disease burden figures would have to be modified to ensure that health benefits were not double counted (because IMB and trade-off values already incorporate some psycho-social considerations). In contrast, costs associated with contact tracing, quarantine, etc., are not currently reflected in the disease burden figures; these could be addressed in future applications of the model. These considerations are also pertinent to the assessment described in this report.
FINDINGS
Application of the procedures described above to derive burden estimates for the diseases that are candidates for accelerated vaccine
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TABLE 4.9 Morbidity and Mortality Burdens Resulting from Various Diseases
Disease
Total Disease Burden Valuea (IME units)b
Normalized (percent)
Dengue virus
34,365
0.52
Escherichia coli
978,248
14.79
(550,248)c
(8.32)
Hemophilus influenzae type b
471,336
7.13
Hepatitis A virus
30,229
0.46
Hepatitis B virus
2,394,256
36.21
Japanese encephalitis virus
18,075
0.27
Mycobacterium leprae
657,349
9.94
Neisseria meningitidis
68,252
1.03
Parainfluenza virus
145,954
2.21
Plasmodium spp.
2,111,795
31.94
Rabies virus
67,821
1.03
Respiratory syncytial virus
183,326
2.77
Rotavirus
925,042
13.99
(488,542)c
(7.39)
Salmonella typhi
1,308,121
19.78
Shigella spp.
828,068
12.52
Streptococcus Group A
811,477
12.27
Streptococcus pneumoniae
6,612,261
100.00
Vibrio cholera
229,217
3.47
Yellow fever virus
32,887
0.50
aSee Appendixes D-1 through D-19 for derivations of disease burden estimates used to calculate TDBVs.
bInfant mortality equivalence units.
cValues in parentheses represent the anticipated disease burden from certain diarrheal pathogens if a plausible increase in oral rehydration therapy is assumed (see Appendix C).
development is described in Appendixes D-1 through D-19. Various assumptions were entailed in deriving such estimates. Table 4.9 shows the total disease burden values calculated for each disease (using disease burden estimates and the median of perspectives from public health professionals in developing countries). Use of these total disease burden values to rank the diseases is demonstrated in Table 4.10.
Chapter 7 describes application of the disease comparison system to the calculation of potential health benefits from candidate vaccines.
LIMITATIONS OF THE PROPOSED SYSTEM
The proposed system assesses the most obvious feature of infectious diseases, morbidity, and mortality. The aggregate nature of the total
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TABLE 4.10 Ranking of Diseases by Total Disease Burden Values
Disease
Total Disease Burden Value (IME units)a
Streptococcus pneumoniae
6,612,261
Hepatitis B virus
2,394,256
Plasmodium spp.
2,111,795
Salmonella typhi
1,308,121
Escherichia coli
978,248
Rotavirus
925,042
Shigella spp.
828,068
Streptococcus Group A
811,477
Mycobacterium leprae
657,349
(Escherichia coli)
(550,248)b
(Rotavirus)
(488, 542)b
Hemophilus influenzae type b
471,336
Vibrio cholera
229,217
Respiratory syncytial virus
183,326
Parainfluenza virus
145,954
Neisseria meningitidis
68,252
Rabies virus
67,821
Dengue virus
34,365
Yellow fever virus
32,887
Hepatitis A virus
30,229
Japanese encephalitis virus
18,075
aInfant mortality equivalence units.
bValues represent the anticipated disease burden from certain diarrheal pathogens if a plausible increase in oral rehydration therapy is assumed (see Appendix C) .
disease burden value for each disease may be regarded by some as obscuring important differences among disease consequences. Although they are assigned to the same generic morbidity category, some disease conditions may be regarded as more severe (more undesirable) than those of another disease. This problem exists with any category system; to assign trade-off (or IME) values to the whole spectrum of conditions arising from all diseases would be too complex and unmanageable.
Additionally, the system does not, as presently conceived, permit differentiation of diseases on the basis of episode duration. That is, it does not indicate whether hospitalization of 100 individuals for 2 days each is more or less desirable than 1 individual for 200 days, or 10 individuals for 20 days.
Other disease characteristics not recognized by the proposed system include the following:
The epidemic potential of the disease: the average annual incidence is used for comparative purposes, but certain epidemic
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diseases may overwhelm available medical services and engender particular concern in the at-risk populations.
The potential for synergistic interaction with other diseases: the committee evaluated the possibility of incorporating into the disease burden estimates of the effects of known synergism, such as between diarrheal disease and measles. The committee concluded that current knowledge of these phenomena did not permit reliable quantification of their consequences, but that they should be recognized in the ultimate selection of priorities.
These issues are discussed further in Chapter 8.
Problems in obtaining accurate estimates of disease incidence and difficulties in deciding which IME perspectives to adopt also limit the usefulness of the system. Nevertheless, the system has the potential to be a useful tool for selecting priorities for accelerated vaccine development. Recommendations that might remedy some of the problems are made below.
SUMMARY AND CONCLUSIONS
The system described in this chapter allows quantitative comparison of the morbidity and mortality caused by various diseases. It takes into account specific information about each disease (number of cases, complications, sequelae, deaths) and can accommodate various perspectives on the undesirability of various disease consequences.
To illustrate use of the proposed system, diseases that are candidates for accelerated vaccine development have been ranked according to a median of trade-off perspectives elicited from public health experts in developing countries. The effects of adopting alternative perspectives are also discussed. Considerable uncertainty surrounds some of the estimates of disease burdens because data of the desired reliability are not available.
No attempt has been made to calculate the costs of treating diseases in the developing world as a whole because of the many uncertainties involved in such aggregate estimates. However, the committee believes that estimates of total direct costs for certain diseases could be used to help set vaccine priorities in specific countries or regions of the developing world.
RECOMMENDATIONS
The capacity to make rational choices of vaccine development priorities and vaccine formulation would be enhanced by better information on disease incidence and the pathogen serotypes prevalent in particular regions. Therefore, the National Institute of Allergy and Infectious Diseases and other national and international agencies should consider ways to improve the epidemiologic information on infectious diseases.
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REFERENCES
Institute of Medicine. 1985. New Vaccine Development: Establishing Priorities, Volume I. Diseases of Importance in the United States. Washington, D.C.: National Academy Press.
Population Reference Bureau. 1984. World Population Data Sheet. Washington, D.C.: Population Reference Bureau.
Representative terms from entire chapter:
infant mortality
