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The Children’s Vaccine Initiative: Continuing Activities: A Summary of Two Workshops Held September 12–13 and October 25–26, 1994 Scientists and public health authorities need a much better understanding of ARI epidemiology. Specific areas of focus might be the roles of malnutrition, crowding, and inhaled pollutants in contributing to respiratory illness. Special attention should be paid to ARI in very young children, in whom the incidence of severe disease is so much higher than the rest of the population. Effective, affordable vaccines against H. influenzae and S. pneumoniae will clearly be important in prevention efforts. Short of preventing illness through vaccination or other means, health care providers must be prepared to treat those who become sick. Case management of respiratory disease could benefit from operational studies of oxygen delivery systems, bronchodilators, and fluid maintenance. Antibiotics are a key tool used to treat ARI in the developing world. However, appropriate drug schedules and doses for developing-world populations have not been adequately formulated. In addition, extensive resistance to some antimicrobial drugs has limited their usefulness in this context. In the developing world, infections of the lower respiratory tract are interwoven with a number of other health problems; they are also influenced by the host of well-known social and economic hardships borne by many living in these regions of the world. While there is no single or easy solution to the problems posed by ARI and N. meningitides-caused meningitis, the value of more and better laboratory and epidemiologic data cannot be underestimated. DETERMINING VACCINE NEED3 Reliable information about the health status of a population is key to designing effective vaccine trials and evaluating their results. The need for such data does not end once a vaccine is proved effective in a particular group of volunteers, however. In order for a vaccine to be broadly useful, country-specific data on overall disease incidence and age-specific rates of infection are vital. Without such epidemiologic information, health ministries may be reluctant to devote scarce government dollars to the purchase and administration of vaccines. The rather unexpected results of a disease surveillance study in Cairo, Egypt, illustrate this last point. During this recent 18-month project, investigators collected blood and nasopharyngeal samples from 1,635 preschool children admitted with pneumonia to two of the city’s communicable diseases hospitals. Serotyping of blood isolates from patients and ARI-free controls revealed a roughly even split in each group between H. influenzae type b and H. influenzae 3 Unless otherwise noted, material in this section is based on presentations by Mark Steinhoff, Catherine Oyejide, Mona Assad, and Jay Wenger.
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The Children’s Vaccine Initiative: Continuing Activities: A Summary of Two Workshops Held September 12–13 and October 25–26, 1994 non-type b. In a pneumonia surveillance study conducted in Pakistan by the CDC, over 90 percent of children bacteremic with H. influenzae were infected with nontypeable organisms.4 In addition, there is some evidence suggesting that nonencapsulated Hib strains can be responsible for serious disease in older children. 5 These and other similar data suggest that in certain settings, a conjugate Hib vaccine is likely to prevent only a moderate proportion of Haemophilus disease. Given the relative high cost of such vaccines, these data argue strongly for further epidemiologic testing to determine the prevalence of Haemophilus types in settings in which immunization programs are being contemplated. It is worth noting that H. influenzae serotype data in the United States come primarily from isolates of cerebrospinal fluid from children with meningitis and from blood samples from children with high fevers, not pneumonia. In contrast, serotype data from the developing world derive mainly from children with cough who meet World Health Organization diagnostic criteria for pneumonia. These differences have important implications for vaccine testing and reinforce the need for rigorous vaccine trials in the developing world.6 In the case of S. pneumoniae, considerable data have accumulated in the United States over the past decade regarding infection with this pathogen. Studies in various areas of the country reveal that somewhere between 90 and 2,000 cases of pneumococcal disease occur each year per 100,000 persons, predominantly among the very young. In general, much less is known about pneumococcal incidence in the developing world. For example, in Nigeria, Africa ’s most populous nation, pneumonia accounts for some 30 to 40 percent of all visits to the doctor and roughly 12 percent of pediatric hospital admissions. About 30 percent of all childhood mortality can be attributed to pneumonia. Likewise, in the United Arab Emirates, a small developed nation at the eastern tip of the Arabian peninsula, ARI is a major cause of morbidity and mortality. In neither country, however, are there many hard data on the etiology of these infections. In addition to variations in disease incidence between and even within certain regions of the world, there are differences in the pneumococcal serotypes present. A review of the published literature found that in the United States and a number of other developed nations, the seven most prevalent serotypes were (in rank order) 14, 6, 19, 18, 9, 23, and 7.7 In many developing nations, the top 4 Benjamin Schwartz. 5 Dan Granoff. 6 Joel Ward. 7 Sniadac D, Bogaerts J, Butler J, et al. Geographic variation on pneumococcal serotypes in children with invasive disease: Implications for conjugate vaccine use [Abstract 1651]. 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993.
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The Children’s Vaccine Initiative: Continuing Activities: A Summary of Two Workshops Held September 12–13 and October 25–26, 1994 seven serotypes (also in rank order) were 14, 6, 5, 1, 19, 9, and 23. Thus, frequency of infection with pneumococcal types 1 and 5 appears to distinguish developing-world populations from those in developed nations. This was not always the case. Some 40 years ago, pneumococcal serotype 1 was the most common serotype in the United States. Likewise, serotype 5 was once much more prevalent in the United States than it is now. This sort of shift, or “secular change,” is not limited to the dramatic alteration in U.S. pneumococcal distribution. Temporary, year-to-year fluctuations in serotype prevalence have been documented in many developing countries. Although estimates of serotype prevalence in the developing world are fairly good, data from certain regions (particularly South Asia and much of sub-Saharan Africa) are less complete than those from others. A number of efforts are underway to fill these data gaps. One such initiative, funded by the Rockefeller Foundation and USAID, is tracking invasive pneumococcal and haemophilus disease in six sites in India. The SIREVA project of the Pan American Health Organization is undertaking similar research, focused only on S. pneumoniae, in Latin America and the Caribbean. In the India project, some 8 percent of 1,000 blood cultures collected initially were positive for S. pneumoniae, and preliminary subtyping indicates types 1 and 5 are the most common on the subcontinent. Data gathered over the past several years from Pakistan, Bangladesh, and India indicate that, compared with the United States, pneumococcal disease disproportionately strikes the very young, those less than 5 months old. Therefore, a vaccine that is immunogenic only in older infants may prevent disease in U.S. infants while having much less of an impact in the developing world. This reinforces the need to design vaccine trials in the developing world that look specifically at efficacy in young infants. With respect to meningococcal meningitis, lack of solid data on disease incidence outside of the established market economies has played out in a different way. In a number of recent outbreaks—in Ethiopia (1989), Brazil (1989–1990), Cameroon (1991–1992), and Mongolia (1994)—actual disease burden has been poorly quantified. Health officials have often reacted by initiating mass immunizations with polysaccharide vaccines. Although necessary under the circumstances, such actions cannot prevent death and illness during the first few weeks of an epidemic, and they have tended to divert funds and personnel from routine public health services. The availability of an effective conjugate meningococcal vaccine that could be given to young children would probably prevent such scenarios from occurring.
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