Cover Image

PAPERBACK
$43.50



View/Hide Left Panel

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.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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).

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.

OCR for page 149
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries 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.