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New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries (1986)

Chapter: Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness

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Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

Appendix B
The Burden of Disease Resulting from Acute Respiratory Illness

This appendix reports estimates of the burden of illness (particularly mortality) associated with three vaccine development candidates that cause acute respiratory illness (ARI) in children in developing countries. These pathogens are respiratory syncytial virus (RSV), the parainfluenza viruses, H. influenzae type b, and S. pneumoniae.

Table B.1 shows the population distribution in regions where developing countries predominate. Table B.2 shows the estimated mortality resulting from acute respiratory infections. Application of the rates in Table B.2 to the population data in Table B.1 yields the ARI mortality distribution shown in Table B.3.

The number of ARI deaths estimated by this method accounts for about 13.5 percent of the 10.4 million infant deaths (under 1 year of age) and 22 percent of the 4.4 million child deaths (1 to 4 years of age) estimated to occur in developing countries in 1984 (United Nations Children’s Fund, 1983). Combined, they represent about 18 percent of all deaths in the under 5 years age group.

Bulla and Hitze (1978) reported that about 10 percent of all ARI deaths were attributable to influenza. Of the remainder, most were viral and bacterial pneumonias (80 percent), and the balance involved acute upper respiratory tract infections. Table B.4 shows the estimated total noninfluenza ARI mortality for children.

Little information from developing countries is available on the etiology of lower respiratory tract infections or their impact on mortality rates. Even less is available on serious or fatal upper respiratory tract infections. One of the difficulties in obtaining data on the etiology of lower respiratory tract infections is that ethical requirements dictate that lung aspiration (to identify pathogens) is performed only for medical indications (e.g., to aid in selection of appropriate treatment of patients with selected bacterial pneumonia). Accordingly, this procedure is not used routinely.

The committee gratefully acknowledges the advice and assistance of F.W.Denny, W.P.Glezen, and A.S.Monto. The committee assumes full responsibility for all judgments and assumptions.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.1 Population Distribution in Regions Where Developing Countries Predominate (thousands)

 

Age Group (years)

Region

Under 1

1–4

Total Under 5

5–14

15–59

60 and Over

Africa

23,040

73,762

96,802

141,459

265,451

27,288

Asia

73,400

270,300

343,700

666,402

1,472,242

179,656

Latin America

12,736

44,499

57,235

100,220

214,415

25,130

Oceania

187

635

822

1,285

2,620

273

Total

109,363

389,196

498,559

909,366

1,954,728

232,347

TABLE B.2 Estimated Mortality in Developing Countries Due to Acute Respiratory Infections (deaths/100,000 population/yeara)

 

Age Group (years)

Region

Under 1

1–4

5–14

15–59b

60 and Over

Africa

1,500

500

20

150

Asia

1,200

200

20

150

Latin America

1,300

130

13

400

Oceania

200

10

1

100

aModified from Bulla and Hitze (1978). Rates in some categories are based on a small number of reporting countries.

bNot calculated.

Pio et al. (1985) reviewed the results of bacteriological studies on lung aspirates from children (birth to 8 years of age) in developing countries who had pneumonia and no previous antimicrobial treatment. About 55 percent of these aspirates were culture positive for bacteria. Of these, 22.5 percent contained S. pneumoniae, and 11.5 percent contained H. influenzae. Staphylococcus aureus (4.4 percent), mixed infections, or other bacteria accounted for the balance of positive cultures. These proportions may be underestimates because the appropriate lung lesion may not have been reached with the aspiration needle or because laboratory methods may have been inadequate. Lung aspirate sampling may overestimate the significance of bacterial pathogens because of the kinds of patients selected for testing (see above). However, it is not possible to estimate how much these considerations affect the accuracy of available data.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.3 Deaths due to Acute Respiratory Infections in Developing Countries (thousands)a

 

Age Group (years)

Region

Under 1

1–4

Total Under 5

5–14

Africa

345.6

368.810

714.41

28.3

Asia

880.8

540.6

1,421.4

133.3

Latin America

165.6

57.8

223.4

13.0

Oceania

0.374

0.064

0.44

0.0129

Total

1,392.4

967.3

2,359.7

174.6

aDerived by application of the rates shown in Table B.2 to the population estimates shown in Table B.1.

Few studies have been undertaken on viruses as a cause of lower respiratory tract infection or mortality in developing countries. Denny and Clyde (1983) reported on the isolation of viruses and mycoplasma from children with lower respiratory tract disease in the United States. No isolate was obtained in 74 percent of cases. Parainfluenza viruses were isolated in 9.4 percent of cases and RSV in 5.2 percent of cases. A variety of other viruses and Mycoplasma pneumoniae accounted for the balance of identified agents.

TABLE B.4 Annual Deaths from Acute Respiratory Infections Other than Influenza

 

 

Age Group (years)

Pathogen

Proportion of Deaths (percent)a

Under 5

5–14

H. influenzae

 

11.5

244,260

18,071

Parainfluenza viruses

5.5

116,820

8,643

Respiratory syncytial virus

7

148,680

11,000

S. pneumoniae

22.5

477,900

35,357

Totalb

 

2,124,000

157,140

aThese proportions are based on a very limited number of reports and assume that the distribution of deaths parallels the isolation of pathogens from individuals with lower respiratory tract infection.

bThe total includes deaths caused by other pathogens for which vaccine prospects are considered poor, or for which an etiologic agent is not yet identified.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

Berman et al. (1983) reported data on acute lower respiratory tract infections in children under 5 years of age attending ambulatory clinics in Colombia. A viral diagnosis was reported in 20 percent of cases: RSV was found in 9 percent and parainfluenza viruses in 2.1 percent. Serologic data reported by Monto and Johnson (1968) for three areas in Latin America suggest that the behavior and distribution of viral respiratory disease agents in the tropics are generally similar to those of the same agents in the temperate zones.

The data discussed above appear to be the best basis on which to estimate the disease burden proportion of noninfluenza ARI that can be attributed to the pathogens that are candidates for vaccine development. No direct information is available on the proportions of deaths due to the various pathogens incriminated in ARIs. To estimate deaths, it is therefore assumed that the proportion of deaths due to each agent parallels its isolation in lower respiratory tract illness/pneumonia cases. This assumed relationship is likely to be imprecise because certain agents, like respiratory syncytial virus, are more virulent than others, such as parainfluenza virus type 1.

The proportion of lower respiratory tract illness/pneumonia cases attributed to a particular pathogen sometimes differed between studies. In these instances, intermediate values have been used in the calculations if reported figures vary considerably. The resulting distribution of deaths due to noninfluenza ARI is assumed to be as follows: RSV, 7 percent; parainfluenza viruses, 5.5 percent; H. influenzae, 11.5 percent; and S. pneumoniae, 22.5 percent.

Table B.4 shows the results of combining the above assumptions with the estimates of annual noninfluenza ARI mortality.

To complete the disease burden estimates in the format required for the disease comparison method used in this report, it is necessary to estimate the number of disease episodes at various levels of severity. No specific information on the ratio of deaths to severe cases of ARI is available. However, the number of severe cases of parainfluenza and RSV disease can be calculated by presuming a case fatality rate of 10 percent for severe cases of these diseases. The relative distributions of less severe episodes are assumed to be the same as those estimated

TABLE B.5 Relative Case Frequenciesa

Category

H. influenzae

Parainfluenza Viruses

Respiratory Syncytial Virus

S. pneumoniae

Mild (A)

 

500

300

 

Moderate (B)

 

100

100

 

Severe (C)

7

10

10

7

Death (H)

1

1

1

1

aThese ratios are assumed from limited data (see text).

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.6 Disease Burden Estimates by Morbidity Category, Disease, and Age Group (years)

 

H. influenzae

Parainfluenza Viruses

Respiratory Syncytial Virus

S. pneumoniae

Morbidity Category

Under 5

5–14

Under 5

5–14

Under 5

5–14

Under 5

5–14

A

58,410,000

4,321,500

44,604,000

3,300,000

B

11,682,000

864,300

14,868,000

1,100,000

C

1,709,820

126,497

1,168,200

86,430

1,486,800

110,000

3,345,300

247,500

H

244,260

18,071

116,820

8,643

148,680

11,000

477,900

35,357

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.7 Disease Burden: Hemophilus influenzae—Respiratory Component

 

 

Under 5 Years

5–14 Years

15–59 Years

60 Years and Over

Morbidity Category

Description

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

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

 

 

 

 

 

 

 

 

C

Severe pain, severe short-term impairment, or hospitalization

1,709,820

7

126,497

7

 

 

 

 

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.

 

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

244,260

n.a.

18,071

n.a.

 

n.a.

 

n.a.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.8 Disease Burden: Parainfluenza Viruses

 

 

Under 5 Years

5–14 Years

15–59 Years

60 Years and Over

Morbidity Category

Description

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

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

58,410,000

3

4,321,500

3

 

 

 

 

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

11,682,000

5

864,300

5

 

 

 

 

C

Severe pain, severe short-term impairment, or hospitalization

1,168,200

7

86,430

7

 

 

 

 

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.

 

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

116,820

n.a.

8,643

n.a.

 

n.a.

 

n.a.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.9 Disease Burden: Respiratory Syncytial Virus

 

 

Under 5 Years

5–14 Years

15–59 Years

60 Years and Over

Morbidity Category

Description

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

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

44,604,000

3

3,300,000

3

 

 

 

 

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

14,868,000

5

1,100,000

5

 

 

 

 

C

Severe pain, severe short-term impairment, or hospitalization

1,486,800

7

110,000

7

 

 

 

 

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.

 

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 resticting 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

148,680

n.a.

11,000

n.a.

 

n.a.

 

n.a.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE B.10 Disease Burden: S. Pneumoniae—Respiratory Component in Children

 

 

Under 5 Years

5–14 Years

15–59 Years

60 Years and Over

Morbidity Category

Description

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

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

 

 

 

 

 

 

 

 

C

Severe pain, severe short-term impairment, or hospitalization

3,345,300

 

247,500

 

 

 

 

 

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.

 

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

477,900

n.a.

35,357

n.a.

 

n.a.

 

n.a.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

for the diseases domestically (Institute of Medicine, 1985): for parainfluenza, 50 mild and 10 moderate episodes for each severe case, and for RSV, 30 mild and 10 moderate episodes for each severe case. In the absence of pathogen-specific data for developing countries, a case fatality rate (CFR) of 15 percent is assumed for H. influenzae and S. pneumoniae (based on CFRs for untreated and hospitalized ARIs; Pio et al., 1985). Hence, seven severe cases are presumed to occur for each death. All H. influenzae and S. pneumoniae episodes are assumed to be severe.

The relative case frequencies shown in Table B.5 are based on these assumptions. They were used to derive the disease burden distributions shown in Table B.6, and in Tables B.7, B.8, B.9, and B.10 for the individual pathogens.*

UNCERTAINTY IN THE DISEASE BURDEN ESTIMATES

Advisers to the committee expressed concerns about the limited knowledge from which the estimates described above are derived. Certain features of acute respiratory infections led the committee to conclude that the available data are probably not entirely reliable because of suspected bias.

For example, many children with pneumonia may not reach the hospital, and those who do may represent a skewed sample. How to adjust available data for suspected biases is not known; hence, the procedures described above represent the only practical approach to developing the disease burden estimates needed for the overall assessment.

REFERENCES

Berman, S., A.Duenas, A.Bedoya, V.Constain, S.Leon, I.Borrero, and J.Murphy. 1983. Acute lower respiratory tract illness in Cali, Colombia: A two-year ambulatory study. Pediatrics 71:210–218.

Bulla, A., and K.L.Hitze. 1978. Acute respiratory infections: a review. Bull. WHO 56:481–498.


Denny, F.W., and W.A.Clyde. 1983. Acute respiratory tract infections: An overview. Pediatr. Res. 17:1026–1029.


Institute of Medicine. 1985. New Vaccine Development: Establishing Priorities, Volume 1. Diseases of Importance in the United States. Washington, D.C.: National Academy Press.


Monto, A.S., and K.M.Johnson. 1968. Respiratory infections in the American tropics. Am. J.Trop. Med. Hyg. 17:867–874.


Pio, A., J.Leowski, and H.G.ten Dam. 1985. The magnitude of the problem of acute respiratory infections. Pp. 3–16 in Acute Respiratory Infections in Childhood, R.M.Douglas and E.Kerby-Eaton, eds. Adelaide, Aust.: University of Adelaide.


United Nations Children’s Fund. 1983. Statistics. Pp. 174–197 in The State of the World’s Children 1984. New York: Oxford University Press.

*  

The disease burdens for disease caused by H. influenzae type b and S. pneumonia have also been computed separately in Appendixes D-3 and D-17.

Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 149
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 150
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 151
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 152
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 153
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 154
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 155
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 156
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 157
Suggested Citation:"Appendix B: The Burden of Disease Resulting from Acute Respiratory Illness." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 158
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Common diseases cost the developing world an enormous amount in terms of human life, health, and productivity, as well as lost economic potential. New and effective vaccines could not only improve the quality of life for millions of residents in developing countries, they could also contribute substantially to further economic development. Using data from the World Health Organization and other international agencies, this book analyzes disease burdens, pathogen descriptions, geographic distribution of diseases, probable vaccine target populations, alternative control measures and treatments, and future prospects for vaccine development. New Vaccine Development provides valuable insight into immunological and international health policy priorities.

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