REVIEW
Epidemiology of invasive Haemophilus influenzae type b disease and the susceptibility of aggregate hosts Wanda Alexandra Danuz, DNP, FNP-BC (Certified Advanced Practice Registered Nurse, Doctor of Nursing Practice) University of Massachusetts, Amherst, Massachusetts
Keywords Evidence-based practice; immunization; infectious disease; older adult; vaccine. Correspondence Wanda Alexandra Danuz, DNP, FNP-BC, Center for Bone and Joint Surgery of the Palm Beaches, 10131 W. Forest Hill Blvd., Suite 206, Wellington, FL 33414-6109. E mail: [email protected], [email protected] Received: 20 May 2012; accepted: 4 March 2013 doi: 10.1002/2327-6924.12145 Disclosure The author reports no competing interests.
Abstract Purpose: Haemophilus influenzae type b bacteria has been responsible for recent increase in invasive disease in the adult population of the United States. This increase in H. influenzae infections is greatest in individuals above 65 years of age. A plausible explanation for this increase may be the changes observed in the epidemiology of invasive H. influenzae type b (Hib) disease and the susceptibility of aggregate hosts. Data sources: A comprehensive literature review was conducted from multiple data sources, such as PubMed, MEDLINE, CDC, journal articles, reference texts, and Internet websites. Conclusions: The increase in infectious disease caused by H. influenzae type b bacteria is affecting individuals 65 years and older and is preventable. However, Hib vaccines are currently approved for the pediatric population and susceptible adults with certain immune deficiencies. New trends in this invasive disease require reevaluation of current guidelines to include individuals 65 years and older as target population for the polysaccharide Hib vaccine. Implications for practice: The changing epidemiology of H. influenzae type b bacteria requires reevaluation of current immunization guidelines regarding Hib vaccination so that it is included in the immunization schedule for adults aged 65 and above.
Introduction Recent trends of invasive disease among susceptible adults, especially those 65 years and above, indicate an increase in Haemophilus influenzae type b (Hib) infections (Dworkin, Park, & Borchardt, 2007). Invasive Hib disease is quite prevalent in underdeveloped countries where vaccinations are not easily available (Schuchat & RosensteinMessonier, 2007). However, an increasing trend of Hib invasive disease has been observed in the United States (Rubach et al., 2011). This trend is associated with several factors, including underimmunization in children, the waning effects of “herd” immunity, complications of comorbidities and immune deficiencies, and lack of research related to Hib vaccination among the adult population (Bockhold, 2011; Farley et al., 1992; Schuchat & Rosenstein-Messonier, 2007). Since 1985, the vaccination against Hib disease has been readily available in the United States (Beattie, 2008). However, this vaccine
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is available for children less than 5 years of age (WHO, 2005).
A short history of this disease Hib is a Gram-negative coccobacillus first identified by Robert Pfeiffer in 1892 (Mansnerus, 2009). The name “Haemophilus influenzae” literally refers to “blood-loving” (hemo is blood and philus is loving). In 1931, Margaret Pittman successfully identified the distinct strains of the bacteria as a cause of meningitis (Mansnerus, 2009). Before the availability of Hib vaccination, the incidence of invasive disease because of Hib bacteria increased by 399% in cases that were reported during 1942–1950 (Beattie, 2008). Similar trends were observed during 1951–1959 and during 1960–1968 (Beattie, 2008). Today, most H. influenzae infections occur in underdeveloped countries where routine vaccination is not
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available (Schuchat & Rosenstein-Messonier, 2007). Although there are six different serotypes of polysaccharide capsules identified (A through F), 95% of invasive disease are caused by type b (CDC, 2002). Haemophilus influenzae bacteria may colonize in the nasopharynx and in some individuals the organism invades the bloodstream leading to more severely invasive disease (CDC, 2002). Transmission of the organism occurs through respiratory droplets from an infected host. Serious ramifications of this condition include pneumonia, septicemia, epiglottis, and meningitis (Beattie, 2008).
Epidemiology of H. influenzae It is estimated that 50,000 adults die each year from vaccine-preventable diseases and their complications (Bockhold, 2011). Although immunization schedules have been updated throughout the years to widen the span of adult vaccinations, research has been limited in regard to recommendations concerning Hib vaccines for adults (Bockhold, 2011). Elderly individuals with comorbidities, such as lung disease, diabetes mellitus, and cardiovascular disease, have even higher risks (Hak, Rovers, Kuyvenhoven, Shelves, & Verhelj, 2006). Individuals aged 65 and above are at increased risk for respiratory infections, especially infections of the lower respiratory tract. Respiratory tract infections (RTIs) are recognized as a leading cause of death among this age group (Hak et al., 2006). Aging, comorbidities, and exogenous environmental factors, such as smoking and exposure to pollutants, contribute to the susceptibility of elderly adults (Hak et al., 2006). Prevention of RTIs among this population has been improved with vaccination against Streptococcus pneumoniae bacteria since the approval of the pneumococcal vaccine for individuals 65 years and older (Hak et al., 2006). It has been proved that the pneumococcal vaccine is 60%–70% effective, in preventing invasive disease because of the S. pneumoniae bacteria among the elderly (Munroe Cohen, 2010). Incidence rates because of pneumococcal disease have decreased 37% in individuals more than 65 years since the emergence of the vaccine (Zangeneh, Baracco, & Al-Tawfiq, 2011). Incidence rates related to H. influenzae type b bacteria reflect the epidemiology of the S. pneumoniae bacteria (Gessner & Adegbola, 2008). Learning about disease prevention through the history of pneumococcal vaccination may lead to the development of new guidelines on Hib vaccination of older adults. The case fatality among this age group has increased to 29% because of H. influenzae infection versus 15% for those younger than 65 years of age (Rubach et al., 2011). Invasive diseases caused by H. influenzae bacteria have been steadily on the rise in adults in the United States (Dworkin et al., 2007) with
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a higher incidence observed in individuals aged 65 and above (Rubach et al., 2011). One study reported a surreptitious rise in H. influenzae disease from seven cases in 1996 to 53 cases in 2004 (Dworkin et al., 2007). A nontypeable H. influenzae disease (35.8%–61.5%) was found to be the predominant cause in large proportion of the cases. In this study, H. influenzae disease was confirmed through isolation of the bacteria from normally sterile sites, such as blood, CSF, or joint, pleural and pericardial fluid. Results revealed that a substantial increase in cases was observed in individuals more than 65 years of age. The reported number of cases was found to be greater during winter months than in summer months. Rubach et al. (2011) identified an increase in H. influenzae disease among adults in Utah over the past 10 years accounting for 51% of cases and 67% of deaths. From changes in the epidemiology of the invasive disease, it has been observed that H. influenzae affliction shifted from children to adults. This study isolated H. influenzae from normally sterile sites using standard culture techniques that identified bacteria types a–f (Rubach et al., 2011). Once again, the results revealed that the increasing trends were similar among men and women, but invasive disease was observed markedly higher in individuals more than 65 years of age. The serotype distribution of infectious episodes discovered that type b strains, nonb encapsulated strains, type f strains, and type a strains accounted for 9%, 49%, 25%, and 15% of infections, respectively (Rubach et al., 2011). Type b strain is associated with disease that is more invasive, such as meningitis, than the nontypeable strains of the bacteria. The presence of comorbidities such as diabetes, immunosuppression, malignancy, lung, heart, liver disease, and renal disease were found to be influencing factors among those susceptible to infection (Rubach et al., 2011). Twothirds of H. influenzae related deaths occurred in the 65 years and older age group (Rubach et al., 2011). The observed increases in H. influenzae related disease may determine the future need for Hib vaccination in adults, especially for those more than 65 years of age.
Immunology Further research is required to understand the dynamics of H. influenzae transmission among adults and to determine the evolution of vaccination and immunity. Although H. influenzae is transmitted person-toperson through secretions from the respiratory tract, some individuals may remain asymptomatic while being infected with the bacteria (Mansnerus, 2009). Mandatory childhood vaccination is expected to protect adults against invasive disease through “herd” immunity. Herd
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immunity postulates that when diseases are transmitted among individuals, it is difficult to transmit disease when a large population is immune (Mansnerus, 2009). The concept of herd immunity was first introduced in 1923 by the scientists Topley and Wilson, who studied infectious epidemics in laboratory mice (Mansnerus, 2009). A herd immunity threshold refers to the stage where the percentage of vaccinated individuals is at a level at which the spread of infection is effectively eliminated (Mansnerus, 2009). The rise in this infectious disease may indicate a decreased herd threshold. A plausible explanation for the increases in trends of H. influenzae disease may be the recent controversy linking childhood vaccination to autism; this has led to an increase in the number of children not receiving the recommended vaccinations. Although this theory has recently been debunked, some parents are still hesitant to vaccinate their children. Day care and school-aged children are at increased risk of exposure to other nonimmunized children. Adults exposed to school-aged children are also susceptible to the disease. Usually the adult healthy immune system can fight off invasive disease caused by H. influenzae, but this may not be the case in adults with compromised immune systems, in elderly individuals, and in persons with chronic disease. Some aspects of a seemingly healthy adult immune system may go unnoticed and individuals with antibody deficiencies may not be diagnosed. Adults with Hib antibody deficiency present seemingly inoffensive recurrent RTIs requiring frequent antibiotics (Munroe Cohen, 2010). Individuals with recurrent acute episodes of sinusitis, otitis media, bronchitis, and pneumonia should be thoroughly checked for antibody deficiencies. Clinical experience in managing individuals with H. influenzae specific antibody deficiencies has led to the construct that episodes of recurrent RTIs requiring antibiotics in this targeted population should decrease once protected antibody levels are obtained through Hib vaccination. Although this antibody deficiency may be easily corrected by administering an Hib vaccine, primary care providers do not promote adult Hib boosters (WHO, 2005). Because insufficient data exist regarding the benefits of vaccinating older children and adults with Hib vaccines, individuals with H. influenzae antibody deficiencies remain susceptible to these recurrent infections. Many adults who seek the vaccine are confronted with the dilemma that these vaccines are only for the pediatric population (CDC, 2010). In addition, practitioners are not up-to-date with the issues related to antibody deficiencies and misinform their patients regarding the need for vaccination. Many primary care providers do not offer Hib vaccines, pediatricians do not administer the vaccine to adults, nor do local health departments; there-
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fore, adults requiring Hib boosters cannot receive the vaccine. The multiple barriers that exist preventing these individuals from receiving this vaccine are because of the lack of knowledge as this is not an extensively researched subject. Providers need to acknowledge this condition in order to shift the general concept that this vaccine is solely for the pediatric population. Serum antibody titers are measured to determine deficiencies. Typically, antibody levels to these bacteria would be protective in individuals who have been vaccinated during their childhood. However, this is not the case for some individuals, because they have never been immunized, newer vaccines may have not been available to them when they were children, immunity has faded over the years, or an incompetent immune system did not stimulate adequate protection. Haemophilus influenzae serum antibody titer concentrations above 1.0 μg/mL have been regarded as predictors of long-term protection after Hib vaccination (van den Hof, Melker, Berbers, van der Kraal, & Conyn-van Spaendonck, 2001). Individuals of all ages having less than 1.0 μg/mL serum antibody levels with recurrent RTIs and frequent antibiotic use should receive Hib boosters. Few studies have been conducted to measure antibody levels in individuals who experience recurrent RTIs. In a study conducted in 1996, scientists concluded that further investigations were necessary for the development of specific antibodies against vaccine serotypes in normal populations of different ages (Hidalgo, Moore, Leiva, & Sorensen, 1996). The researchers’ work was conducted primarily on individuals with S. pneumococcal antibody deficiencies. Research on this subject remained limited even after a decade and a half later. Measurement of antibody-specific titers in serum is performed using commercial latex agglutination testing on undiluted serum of suspected individuals (Storch & Myers, 1984). Antigen detection is a noninvasive approach to sensitive and specific diagnosis of deficiencies performed by mixing antibody-coated particles with specimens collected from targeted individuals and determining visible agglutination reaction if the antigen is present (Ajello et al., 1987). This technique of antibody response to H. influenzae was applied in a Dutch study conducted after the introduction of routine vaccination in the Netherlands from October 1995 to December 1996 on individuals of different ages (van den Hof et al., 2001). Decline in antibody titers among vaccinated individuals created a concern among the authors regarding the persistence of memory immunity in vaccinated individuals and proposed continuous surveillance of invasive H. influenzae disease in relation to vaccination status (van den Hof et al., 2001). In a study conducted by Perdue et al. (2000), 109 Alaskan residents aged 10 and above were surveyed from
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1980 through 1996. Until 1991, Hib statewide vaccination for infants was not initiated in Alaska. The objective of the study was to characterize trends in incidence and mortality because of H. influenzae disease in individuals more than 10 years of age before and after the introduction of the Hib vaccine in Alaska. The results observed were a dramatic 80% decrease in overall H. influenzae disease among those aged 10 and above once the children less than 10 years of age were immunized with the newly introduced Hib vaccine (Perdue et al., 2000). The decline in adult disease is suspected to be related to herd immunity (Jin, Romero-Steiner, Carlone, Robbins, & Schneerson, 2007). However, the study failed to immunize individuals more than 10 years of age, track the incidence of disease in this age group, or monitor H. influenzae antibody serum titers in older, high-risk adults. In a separate study performed in the United Kingdom, serum antibody levels in children less than 2 years of age were evaluated after observing a decline in antibody levels in infants having received all three Hib series (Heath et al., 2000). The study proposed to evaluate long-term clinical protection against H. influenzae disease and H. influenzae antibody concentrations following vaccination to determine the necessity of a fourth booster dose. The study determined that the decline in clinical protection was minimal and concluded that a fourth booster was not necessary. The limitation of this study is the fact that serum antibody levels were measured in a pediatric population from infancy to 6 years of age who had completed the Hib series of vaccination quite recently and did not study effects of decreases in levels over a prolonged period of time.
Surveillance Although limited, some studies following trends in invasive H. influenzae disease have been conducted and demonstrate increases in infectious episodes to the point that guidelines regarding vaccination status may need to be revised. A study conducted in the metropolitan Atlanta, Georgia area from 1988 to 1990, following trends in H. influenzae disease in the adult population, was a prospective, population-based surveillance of hospital and referral bacteriology laboratories (Farley et al., 1992). The findings concluded that 25% of all invasive H. influenzae disease occurred in adults. The majority of adults at higher risks of H. influenzae infection were females (79%), followed by persons with chronic lung disease, pregnancy, HIV infection, and malignancy (Farley et al., 1992). This study proposed that H. influenzae was an important cause of bacteremia in compromised adults. In another study, McVernon, Trotter, Slack, and Ramsay (2004) conducted a prospective, laboratory-based surveillance of invasive H. influenzae infections and a cross-sectional seroprevalence
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study among English individuals from 30 to 39 years of age. The purpose was to describe invasive H. influenzae infection among individuals aged 15 or older. Their results revealed a resurgence in reported cases in adults from 2002 to 2003 (399–424 cases). Perhaps one of the most important studies supporting the evidence was the study conducted by Dworkin et al. (2007), which demonstrated a significant increase, from 1.1 to 3.9 cases per 100,000 persons, in invasive H. influenzae disease in adults more than 65 years of age. This represented an increase in 42 cases statewide each year (Dworkin et al., 2007). The study was conducted through public health surveillance and hospital discharge data in Illinois and compared with data from other states. The purpose of the study was to determine descriptive epidemiological characteristics and trends of invasive H. influenzae disease among adults. It concluded that trends and characteristics of H. influenzae disease have changed from an illness predominantly serotype b found in pediatric population to one predominantly because of atypical strains found in adults (Dworkin et al., 2007). Currently in 2011, a study conducted by Rubach et al. (2011) determined that incidence of invasive H. influenzae disease was considered more complex among adults than in children. The authors isolated H. influenzae from normally sterile sites found in suspected Utah residents from 1998 to 2008 aged 18 or more (Rubach et al., 2011). The results revealed 121 invasive H. influenzae cases during this period increasing from 0.54/100,000 persons/year in 1998 to 1.27/100,000 persons/year in 2008 with the increase observed markedly higher in individuals more than 65 years of age (Rubach et al., 2011). In the article by Schuchat and Rosenstein-Messonier (2007), the authors suspect that risk factors for the increased incidence of H. influenzae disease observed by Dworkin, Park, and Borchardt were because of advanced age, immunosuppression, pulmonary manifestations, and chronic lung disease brought on by waning immunity from childhood exposure to this bacteria (Schuchat & Rosenstein-Messonier, 2007). In the Rubach et al. (2011) study conducted in Utah over a period of 10 years (1998– 2008), the increase in H. influenzae disease specifically among the group of individuals aged 65 and above was 2.74 cases per 100,000 in 1998 to 6.14 cases per 100,000 in 2008. These cases were observed predominantly during winter season and among those with comorbidities.
Professional considerations Healthcare professionals can assist the detection, monitoring, education, and research issues related to invasive H. influenzae disease. Nurse practitioners must become alert for possible H. influenzae infections while 117
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treating patients with recurrent respiratory tract conditions that require multiple use of antibiotics. There is extensive literature regarding excessive use of antibiotics and it is clear that overusage of these drugs can create problems on their own. Antibiotics increase the likelihood of repeat infections, destroy beneficial bacteria necessary and vital to promote health, and cause serious infectious disease resistance (Sheppard, 2011). For more in-depth information on this issue, we can refer to http://emedicine.medscape.com/article/218271medication#2. Identifying causes for a patient’s recurrent need for antibiotics, such as antibody deficiencies, is necessary to safeguard the use of these drugs. Increases in H. influenzae disease pose a threat to overusage of antibiotics in individuals who remain incorrectly diagnosed. Advanced practice registered nurses treating individuals more than 65 years of age with multiple comorbidities need to assess the requirement of vaccine booster doses when multiple infectious episodes occur. Public health nurses must work closely with infectious disease coordinators to assure correct monitoring and identification of H. influenzae cases are done properly. Disease tracking and monitoring assist in acquiring evidence-based data that may change current guidelines. Professionals in acute care setting need to be aware of increased incidences of invasive H. influenzae disease while treating patients with conditions such as recurrent pneumonias, bronchitis, meningitis, and septicemia because antibody deficiencies may be an underlying cause for their recurrent episodes. Nurses working in long-term care facilities treating susceptible elderly individuals may be able to alert providers regarding antibody deficiencies in residents who are treated for multiple RTIs and the possible need for booster vaccines to those identified as immunocompromised. As healthcare providers and coordinators, nurses are able to create awareness regarding childhood and adult vaccination status, follow infectious disease episodes, and alert for the indication of prophylactic treatment when required. Continuous educational activities regarding invasive H. influenzae and signs and symptoms of disease state are essential for the proper identification of susceptible individuals by those who are in caregiving positions. Nurses in advanced practices may contribute to the development of newer guidelines that include Hib vaccination for susceptible adults and those 65 years and older through evidenced-based practice.
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extensive investigation has been conducted on this subject for the pediatric population, insufficient data exist regarding the benefits of vaccinating adults with Hib vaccines. In 1985, the United States licensed a pure polysaccharide vaccine against H. influenzae (Mansnerus, 2009). However, it was not until December 1987 with the introduction of a Hib polysaccharide–protein conjugate vaccine that the incidence of H. influenzae dramatically dropped (Mansnerus, 2009). This was because of an improved protein carrier in the vaccine that made a more effective antigen (CDC, 2002). This indicates that individuals born before 1987 may have inadequate protection against H. influenzae, because vaccination did not exist for this organism prior to this year. In healthy individuals, one would suspect that adults would have obtained immunological memory against this invading organism and would react rapidly to subsequent exposures because of their adaptive immune system. Further studies are necessary to evaluate adequate protection in other age groups to determine the need for booster doses in adults 65 years and older because of waning protection from the vaccine. It is important for individuals to understand the seriousness of this issue and the complications involved with invasive H. influenzae disease. In order to create awareness for prevention, individuals and practitioners must understand the seriousness, susceptibility, barriers, and benefits of Hib vaccination. This state of awareness can lead to policy changes to include insurance coverage for Hib administration to susceptible adults. Current evidence-based guidelines regarding adult Hib vaccinations must be reassessed to include susceptible adults and those more than 65 years who have an H. influenzae antibody deficiency manifesting with recurrent RTIs and frequent antibiotic use. Consideration should be given to changing guidelines associated with Hib vaccines to include susceptible individuals, such as those more than 65 years of age, because this invasive disease may be easily controlled through vaccination (Beattie, 2008).
Acknowledgments The author would like to acknowledge Mary Christine King, PhD, and Gabriel Gonzalez, MD, for their helpful comments on this manuscript.
Conclusion Haemophilus influenzae disease has been considered a disease of the past since the emergence of a polysaccharide Hib vaccine introduced in the United States in 1985 (Beattie, 2008). It is now recommended by the CDC as one of the scheduled childhood vaccines (CDC, 1985). Although 118
References Ajello, G. W., Bolan, G.A., Hayes, P.S.,Lehmann, D., Montgomery, J., Feeley, J.C., Broome, C.V. (1987). Commercial latex agglutination tests for detection of Haemophilus influenzae Type b and Streptococcus pneumoniae antigens in patients with bacteremic pneumonia. Journal of Clinical Microbiology, 25, 1388–1391.
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Beattie, G. (2008). What is Hib disease? Vaccination risk awareness network. Retrieved from http://vran.org/about-vaccines/specific-vaccines/ influenza-vaccine Bockhold, K. (2011). Vaccines aren’t just for kids. Advance for NPs and PAs. Retrieved from http://nurse-practitioners-and-physician-assistants. advanceweb CDC. (1985). Recommendation for the Immunization Practices Advisory Committee (ACIP) Polysaccharide Vaccine for Prevention of Haemophilus influenzae Type b Disease. Morbidity and Mortality Weekly Report, 34, 201–205. CDC. (2002). Haemophilus influenzae Type b. Morbidity and Mortality Weekly Report, 51(11), 234–237. CDC. (2010). Prevention of pneumococcal disease among infants and children—Use of valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine. Recommendations of the advisory committee on immunization practices. Morbidity and Mortality Weekly Report, 59, RR-11, 1–24. Dworkin, M. S., Park, L., & Borchardt S. M. (2007). The changing epidemiology of invasive Haemophilus influenzae disease, especially in persons >65 years old. Clinical Infectious Disease, 44(6), 810 –816. Farley, M. M., Stephens, D. S., Brachman, P. S., Harvey, R. C., Smith, J. D., & Wenger, J. D. (1992). Invasive Haemophilus influenzae disease in adults. A prospective, population based surveillance. CDC Meningitis Surveillance Group. Annals of Internal Medicine, 117(7), 621–622. Gessner, B. D., & Adegbola, R. A. (2008). The impact of vaccines on pneumonia: Key lessons from Haemophilus influenzae type B conjugate vaccines. Retrieved from http://www.elsevier.com/locate/vaccine Hak, E., Rovers, M. M., Kuyvenhoven, M. M., Shelves, F. G., & Verhelj, T. J. M. (2006). Incidence of GP-diagnosed respiratory tract infections according to age, gender and high risk co-morbidity: The Second Dutch National Survey of General Practice. Family Practice, 23, 291–294. doi:10.1093/fampra/cmi121 Heath, P. T., Booy, R., Azzopardi, H. J., Slack, M. P., Bowen-Morris, J., Griffiths, H., . . . Moxon, R. (2000). Antibody concentration and clinical protection after HIB conjugate vaccination in the United Kingdom. Journal of the American Medical Association, 284(18), 34–2340. doi:10.1001/jama.284.18.2334 Hidalgo, H., Moore, C., Leiva, L. E., & Sorensen, R. U. (1996). Preimmunization and postimmunization pneumococcal antibody titers in children with
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recurrent infections. Annals of Allergy, Asthma & Immunology, 76(4), 341–346. Jin, Z., Romero-Steiner, S., Carlone, G. M., Robbins, J. B., & Schneerson, R. (2007). Haemophilus influenzae type a Infection and Its Prevention. Infection and Immunity, 75(6), 2650–2654. doi:10.1128/IAI.01774-06 Mansnerus, E. (2009). The lives of “Facts” in mathematical models: A story of population-level disease transmission of Haemophilus influenzae type B bacteria. Biosocieties, 4, 207–222. doi:10.1017/51745855209990111 McVernon, J., Trotter, C.L., Slack, M.P.E., & Ramsey, M.E. (2004). Trends in Haemophilus influenzae type b infections in adults in England and Wales: surveillance study. BMJ, 2004;329:655. doi:10.1136/bmj.329.7467.655 Munroe Cohen, S. (2010). Pneumococcal vaccination and specific polysaccharide antibody deficiency syndrome. Journal for Nurse Practitioners, 6(7), 534–539. Purdue, D. G., Bulkow, L. R., Gellin, B. G., Davidson, M., Peterson, K. M., Singleton, R. J., & Parkingson, A. J. (2000). Journal of the American Medical Association, 283(23), 3089–3094. doi:10.1001/jama.283.23.3089 Rubach, M. P., Bender, J.M., Mottice, S., Hanson, K., Cindy Weng, H. Y., Korgenski, K., Pavia, A.T. (2011). Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA. Emerging Infectious Diseases. Retrieved from wwwnc.cdc.gov/eid/r/content/17/9/101991.htm Schuchat, A., & Rosenstein-Messonnier, N. (2007). From pandemic suspect to the postvaccine era: The Haemophilus influenzae story. Clinical Infectious Disease, 44, 817–819. doi:10.1086/511886 Sheppard, J. (2011). Consequences of excessive antibiotic use. Healthy Child. Retrieved from http://www.healthychild.com/pharmaceuticaldrugs/consequences-of-excessive-antibiotic-use Storch, G. A., & Myers, N. (1984). Latex-agglutination test for rubella antibody: Validity of positive results assessed by response to immunization and comparison to other tests. Journal of Infectious Disease, 149(3), 459–464. Van den Hof, S., Melker, H. E., Berbers, G. A. M., van der Kraal, P. H., & Conyn-van Spaendonck, M. A. E. (2001). Antibodies to Haemophilus influenzae serotype B in the Netherlands a few years after the introduction of routine vaccination. Clinical Infectious Disease, 32, 2–8. WHO. (2005). Haemophilus influenzae type B. World Health Organization Department of Immunization. Retrieved from http://www.who.int/ mediacentre/factsheet/fs294/en/index.html Zangeneh, T. T., Baracco, G., & Al-Tawfiq, A. (2011). Impact of conjugate pneumococcal vaccines on the changing epidemiology of pneumococcal infections. Expert Reviews Vaccines 10(3), 345–353.
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Epidemiology of invasive Haemophilus influenzae type b disease and the susceptibility of aggregate hosts Wanda Alexandra Danuz, DNP, FNP-BC (Certified Advanced Practice Registered Nurse, Doctor of Nursing Practice) University of Massachusetts, Amherst, Massachusetts
Keywords Evidence-based practice; immunization; infectious disease; older adult; vaccine. Correspondence Wanda Alexandra Danuz, DNP, FNP-BC, Center for Bone and Joint Surgery of the Palm Beaches, 10131 W. Forest Hill Blvd., Suite 206, Wellington, FL 33414-6109. E mail: [email protected], [email protected] Received: 20 May 2012; accepted: 4 March 2013 doi: 10.1002/2327-6924.12145 Disclosure The author reports no competing interests.
Abstract Purpose: Haemophilus influenzae type b bacteria has been responsible for recent increase in invasive disease in the adult population of the United States. This increase in H. influenzae infections is greatest in individuals above 65 years of age. A plausible explanation for this increase may be the changes observed in the epidemiology of invasive H. influenzae type b (Hib) disease and the susceptibility of aggregate hosts. Data sources: A comprehensive literature review was conducted from multiple data sources, such as PubMed, MEDLINE, CDC, journal articles, reference texts, and Internet websites. Conclusions: The increase in infectious disease caused by H. influenzae type b bacteria is affecting individuals 65 years and older and is preventable. However, Hib vaccines are currently approved for the pediatric population and susceptible adults with certain immune deficiencies. New trends in this invasive disease require reevaluation of current guidelines to include individuals 65 years and older as target population for the polysaccharide Hib vaccine. Implications for practice: The changing epidemiology of H. influenzae type b bacteria requires reevaluation of current immunization guidelines regarding Hib vaccination so that it is included in the immunization schedule for adults aged 65 and above.
Introduction Recent trends of invasive disease among susceptible adults, especially those 65 years and above, indicate an increase in Haemophilus influenzae type b (Hib) infections (Dworkin, Park, & Borchardt, 2007). Invasive Hib disease is quite prevalent in underdeveloped countries where vaccinations are not easily available (Schuchat & RosensteinMessonier, 2007). However, an increasing trend of Hib invasive disease has been observed in the United States (Rubach et al., 2011). This trend is associated with several factors, including underimmunization in children, the waning effects of “herd” immunity, complications of comorbidities and immune deficiencies, and lack of research related to Hib vaccination among the adult population (Bockhold, 2011; Farley et al., 1992; Schuchat & Rosenstein-Messonier, 2007). Since 1985, the vaccination against Hib disease has been readily available in the United States (Beattie, 2008). However, this vaccine
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is available for children less than 5 years of age (WHO, 2005).
A short history of this disease Hib is a Gram-negative coccobacillus first identified by Robert Pfeiffer in 1892 (Mansnerus, 2009). The name “Haemophilus influenzae” literally refers to “blood-loving” (hemo is blood and philus is loving). In 1931, Margaret Pittman successfully identified the distinct strains of the bacteria as a cause of meningitis (Mansnerus, 2009). Before the availability of Hib vaccination, the incidence of invasive disease because of Hib bacteria increased by 399% in cases that were reported during 1942–1950 (Beattie, 2008). Similar trends were observed during 1951–1959 and during 1960–1968 (Beattie, 2008). Today, most H. influenzae infections occur in underdeveloped countries where routine vaccination is not
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available (Schuchat & Rosenstein-Messonier, 2007). Although there are six different serotypes of polysaccharide capsules identified (A through F), 95% of invasive disease are caused by type b (CDC, 2002). Haemophilus influenzae bacteria may colonize in the nasopharynx and in some individuals the organism invades the bloodstream leading to more severely invasive disease (CDC, 2002). Transmission of the organism occurs through respiratory droplets from an infected host. Serious ramifications of this condition include pneumonia, septicemia, epiglottis, and meningitis (Beattie, 2008).
Epidemiology of H. influenzae It is estimated that 50,000 adults die each year from vaccine-preventable diseases and their complications (Bockhold, 2011). Although immunization schedules have been updated throughout the years to widen the span of adult vaccinations, research has been limited in regard to recommendations concerning Hib vaccines for adults (Bockhold, 2011). Elderly individuals with comorbidities, such as lung disease, diabetes mellitus, and cardiovascular disease, have even higher risks (Hak, Rovers, Kuyvenhoven, Shelves, & Verhelj, 2006). Individuals aged 65 and above are at increased risk for respiratory infections, especially infections of the lower respiratory tract. Respiratory tract infections (RTIs) are recognized as a leading cause of death among this age group (Hak et al., 2006). Aging, comorbidities, and exogenous environmental factors, such as smoking and exposure to pollutants, contribute to the susceptibility of elderly adults (Hak et al., 2006). Prevention of RTIs among this population has been improved with vaccination against Streptococcus pneumoniae bacteria since the approval of the pneumococcal vaccine for individuals 65 years and older (Hak et al., 2006). It has been proved that the pneumococcal vaccine is 60%–70% effective, in preventing invasive disease because of the S. pneumoniae bacteria among the elderly (Munroe Cohen, 2010). Incidence rates because of pneumococcal disease have decreased 37% in individuals more than 65 years since the emergence of the vaccine (Zangeneh, Baracco, & Al-Tawfiq, 2011). Incidence rates related to H. influenzae type b bacteria reflect the epidemiology of the S. pneumoniae bacteria (Gessner & Adegbola, 2008). Learning about disease prevention through the history of pneumococcal vaccination may lead to the development of new guidelines on Hib vaccination of older adults. The case fatality among this age group has increased to 29% because of H. influenzae infection versus 15% for those younger than 65 years of age (Rubach et al., 2011). Invasive diseases caused by H. influenzae bacteria have been steadily on the rise in adults in the United States (Dworkin et al., 2007) with
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a higher incidence observed in individuals aged 65 and above (Rubach et al., 2011). One study reported a surreptitious rise in H. influenzae disease from seven cases in 1996 to 53 cases in 2004 (Dworkin et al., 2007). A nontypeable H. influenzae disease (35.8%–61.5%) was found to be the predominant cause in large proportion of the cases. In this study, H. influenzae disease was confirmed through isolation of the bacteria from normally sterile sites, such as blood, CSF, or joint, pleural and pericardial fluid. Results revealed that a substantial increase in cases was observed in individuals more than 65 years of age. The reported number of cases was found to be greater during winter months than in summer months. Rubach et al. (2011) identified an increase in H. influenzae disease among adults in Utah over the past 10 years accounting for 51% of cases and 67% of deaths. From changes in the epidemiology of the invasive disease, it has been observed that H. influenzae affliction shifted from children to adults. This study isolated H. influenzae from normally sterile sites using standard culture techniques that identified bacteria types a–f (Rubach et al., 2011). Once again, the results revealed that the increasing trends were similar among men and women, but invasive disease was observed markedly higher in individuals more than 65 years of age. The serotype distribution of infectious episodes discovered that type b strains, nonb encapsulated strains, type f strains, and type a strains accounted for 9%, 49%, 25%, and 15% of infections, respectively (Rubach et al., 2011). Type b strain is associated with disease that is more invasive, such as meningitis, than the nontypeable strains of the bacteria. The presence of comorbidities such as diabetes, immunosuppression, malignancy, lung, heart, liver disease, and renal disease were found to be influencing factors among those susceptible to infection (Rubach et al., 2011). Twothirds of H. influenzae related deaths occurred in the 65 years and older age group (Rubach et al., 2011). The observed increases in H. influenzae related disease may determine the future need for Hib vaccination in adults, especially for those more than 65 years of age.
Immunology Further research is required to understand the dynamics of H. influenzae transmission among adults and to determine the evolution of vaccination and immunity. Although H. influenzae is transmitted person-toperson through secretions from the respiratory tract, some individuals may remain asymptomatic while being infected with the bacteria (Mansnerus, 2009). Mandatory childhood vaccination is expected to protect adults against invasive disease through “herd” immunity. Herd
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immunity postulates that when diseases are transmitted among individuals, it is difficult to transmit disease when a large population is immune (Mansnerus, 2009). The concept of herd immunity was first introduced in 1923 by the scientists Topley and Wilson, who studied infectious epidemics in laboratory mice (Mansnerus, 2009). A herd immunity threshold refers to the stage where the percentage of vaccinated individuals is at a level at which the spread of infection is effectively eliminated (Mansnerus, 2009). The rise in this infectious disease may indicate a decreased herd threshold. A plausible explanation for the increases in trends of H. influenzae disease may be the recent controversy linking childhood vaccination to autism; this has led to an increase in the number of children not receiving the recommended vaccinations. Although this theory has recently been debunked, some parents are still hesitant to vaccinate their children. Day care and school-aged children are at increased risk of exposure to other nonimmunized children. Adults exposed to school-aged children are also susceptible to the disease. Usually the adult healthy immune system can fight off invasive disease caused by H. influenzae, but this may not be the case in adults with compromised immune systems, in elderly individuals, and in persons with chronic disease. Some aspects of a seemingly healthy adult immune system may go unnoticed and individuals with antibody deficiencies may not be diagnosed. Adults with Hib antibody deficiency present seemingly inoffensive recurrent RTIs requiring frequent antibiotics (Munroe Cohen, 2010). Individuals with recurrent acute episodes of sinusitis, otitis media, bronchitis, and pneumonia should be thoroughly checked for antibody deficiencies. Clinical experience in managing individuals with H. influenzae specific antibody deficiencies has led to the construct that episodes of recurrent RTIs requiring antibiotics in this targeted population should decrease once protected antibody levels are obtained through Hib vaccination. Although this antibody deficiency may be easily corrected by administering an Hib vaccine, primary care providers do not promote adult Hib boosters (WHO, 2005). Because insufficient data exist regarding the benefits of vaccinating older children and adults with Hib vaccines, individuals with H. influenzae antibody deficiencies remain susceptible to these recurrent infections. Many adults who seek the vaccine are confronted with the dilemma that these vaccines are only for the pediatric population (CDC, 2010). In addition, practitioners are not up-to-date with the issues related to antibody deficiencies and misinform their patients regarding the need for vaccination. Many primary care providers do not offer Hib vaccines, pediatricians do not administer the vaccine to adults, nor do local health departments; there-
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fore, adults requiring Hib boosters cannot receive the vaccine. The multiple barriers that exist preventing these individuals from receiving this vaccine are because of the lack of knowledge as this is not an extensively researched subject. Providers need to acknowledge this condition in order to shift the general concept that this vaccine is solely for the pediatric population. Serum antibody titers are measured to determine deficiencies. Typically, antibody levels to these bacteria would be protective in individuals who have been vaccinated during their childhood. However, this is not the case for some individuals, because they have never been immunized, newer vaccines may have not been available to them when they were children, immunity has faded over the years, or an incompetent immune system did not stimulate adequate protection. Haemophilus influenzae serum antibody titer concentrations above 1.0 μg/mL have been regarded as predictors of long-term protection after Hib vaccination (van den Hof, Melker, Berbers, van der Kraal, & Conyn-van Spaendonck, 2001). Individuals of all ages having less than 1.0 μg/mL serum antibody levels with recurrent RTIs and frequent antibiotic use should receive Hib boosters. Few studies have been conducted to measure antibody levels in individuals who experience recurrent RTIs. In a study conducted in 1996, scientists concluded that further investigations were necessary for the development of specific antibodies against vaccine serotypes in normal populations of different ages (Hidalgo, Moore, Leiva, & Sorensen, 1996). The researchers’ work was conducted primarily on individuals with S. pneumococcal antibody deficiencies. Research on this subject remained limited even after a decade and a half later. Measurement of antibody-specific titers in serum is performed using commercial latex agglutination testing on undiluted serum of suspected individuals (Storch & Myers, 1984). Antigen detection is a noninvasive approach to sensitive and specific diagnosis of deficiencies performed by mixing antibody-coated particles with specimens collected from targeted individuals and determining visible agglutination reaction if the antigen is present (Ajello et al., 1987). This technique of antibody response to H. influenzae was applied in a Dutch study conducted after the introduction of routine vaccination in the Netherlands from October 1995 to December 1996 on individuals of different ages (van den Hof et al., 2001). Decline in antibody titers among vaccinated individuals created a concern among the authors regarding the persistence of memory immunity in vaccinated individuals and proposed continuous surveillance of invasive H. influenzae disease in relation to vaccination status (van den Hof et al., 2001). In a study conducted by Perdue et al. (2000), 109 Alaskan residents aged 10 and above were surveyed from
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1980 through 1996. Until 1991, Hib statewide vaccination for infants was not initiated in Alaska. The objective of the study was to characterize trends in incidence and mortality because of H. influenzae disease in individuals more than 10 years of age before and after the introduction of the Hib vaccine in Alaska. The results observed were a dramatic 80% decrease in overall H. influenzae disease among those aged 10 and above once the children less than 10 years of age were immunized with the newly introduced Hib vaccine (Perdue et al., 2000). The decline in adult disease is suspected to be related to herd immunity (Jin, Romero-Steiner, Carlone, Robbins, & Schneerson, 2007). However, the study failed to immunize individuals more than 10 years of age, track the incidence of disease in this age group, or monitor H. influenzae antibody serum titers in older, high-risk adults. In a separate study performed in the United Kingdom, serum antibody levels in children less than 2 years of age were evaluated after observing a decline in antibody levels in infants having received all three Hib series (Heath et al., 2000). The study proposed to evaluate long-term clinical protection against H. influenzae disease and H. influenzae antibody concentrations following vaccination to determine the necessity of a fourth booster dose. The study determined that the decline in clinical protection was minimal and concluded that a fourth booster was not necessary. The limitation of this study is the fact that serum antibody levels were measured in a pediatric population from infancy to 6 years of age who had completed the Hib series of vaccination quite recently and did not study effects of decreases in levels over a prolonged period of time.
Surveillance Although limited, some studies following trends in invasive H. influenzae disease have been conducted and demonstrate increases in infectious episodes to the point that guidelines regarding vaccination status may need to be revised. A study conducted in the metropolitan Atlanta, Georgia area from 1988 to 1990, following trends in H. influenzae disease in the adult population, was a prospective, population-based surveillance of hospital and referral bacteriology laboratories (Farley et al., 1992). The findings concluded that 25% of all invasive H. influenzae disease occurred in adults. The majority of adults at higher risks of H. influenzae infection were females (79%), followed by persons with chronic lung disease, pregnancy, HIV infection, and malignancy (Farley et al., 1992). This study proposed that H. influenzae was an important cause of bacteremia in compromised adults. In another study, McVernon, Trotter, Slack, and Ramsay (2004) conducted a prospective, laboratory-based surveillance of invasive H. influenzae infections and a cross-sectional seroprevalence
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study among English individuals from 30 to 39 years of age. The purpose was to describe invasive H. influenzae infection among individuals aged 15 or older. Their results revealed a resurgence in reported cases in adults from 2002 to 2003 (399–424 cases). Perhaps one of the most important studies supporting the evidence was the study conducted by Dworkin et al. (2007), which demonstrated a significant increase, from 1.1 to 3.9 cases per 100,000 persons, in invasive H. influenzae disease in adults more than 65 years of age. This represented an increase in 42 cases statewide each year (Dworkin et al., 2007). The study was conducted through public health surveillance and hospital discharge data in Illinois and compared with data from other states. The purpose of the study was to determine descriptive epidemiological characteristics and trends of invasive H. influenzae disease among adults. It concluded that trends and characteristics of H. influenzae disease have changed from an illness predominantly serotype b found in pediatric population to one predominantly because of atypical strains found in adults (Dworkin et al., 2007). Currently in 2011, a study conducted by Rubach et al. (2011) determined that incidence of invasive H. influenzae disease was considered more complex among adults than in children. The authors isolated H. influenzae from normally sterile sites found in suspected Utah residents from 1998 to 2008 aged 18 or more (Rubach et al., 2011). The results revealed 121 invasive H. influenzae cases during this period increasing from 0.54/100,000 persons/year in 1998 to 1.27/100,000 persons/year in 2008 with the increase observed markedly higher in individuals more than 65 years of age (Rubach et al., 2011). In the article by Schuchat and Rosenstein-Messonier (2007), the authors suspect that risk factors for the increased incidence of H. influenzae disease observed by Dworkin, Park, and Borchardt were because of advanced age, immunosuppression, pulmonary manifestations, and chronic lung disease brought on by waning immunity from childhood exposure to this bacteria (Schuchat & Rosenstein-Messonier, 2007). In the Rubach et al. (2011) study conducted in Utah over a period of 10 years (1998– 2008), the increase in H. influenzae disease specifically among the group of individuals aged 65 and above was 2.74 cases per 100,000 in 1998 to 6.14 cases per 100,000 in 2008. These cases were observed predominantly during winter season and among those with comorbidities.
Professional considerations Healthcare professionals can assist the detection, monitoring, education, and research issues related to invasive H. influenzae disease. Nurse practitioners must become alert for possible H. influenzae infections while 117
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treating patients with recurrent respiratory tract conditions that require multiple use of antibiotics. There is extensive literature regarding excessive use of antibiotics and it is clear that overusage of these drugs can create problems on their own. Antibiotics increase the likelihood of repeat infections, destroy beneficial bacteria necessary and vital to promote health, and cause serious infectious disease resistance (Sheppard, 2011). For more in-depth information on this issue, we can refer to http://emedicine.medscape.com/article/218271medication#2. Identifying causes for a patient’s recurrent need for antibiotics, such as antibody deficiencies, is necessary to safeguard the use of these drugs. Increases in H. influenzae disease pose a threat to overusage of antibiotics in individuals who remain incorrectly diagnosed. Advanced practice registered nurses treating individuals more than 65 years of age with multiple comorbidities need to assess the requirement of vaccine booster doses when multiple infectious episodes occur. Public health nurses must work closely with infectious disease coordinators to assure correct monitoring and identification of H. influenzae cases are done properly. Disease tracking and monitoring assist in acquiring evidence-based data that may change current guidelines. Professionals in acute care setting need to be aware of increased incidences of invasive H. influenzae disease while treating patients with conditions such as recurrent pneumonias, bronchitis, meningitis, and septicemia because antibody deficiencies may be an underlying cause for their recurrent episodes. Nurses working in long-term care facilities treating susceptible elderly individuals may be able to alert providers regarding antibody deficiencies in residents who are treated for multiple RTIs and the possible need for booster vaccines to those identified as immunocompromised. As healthcare providers and coordinators, nurses are able to create awareness regarding childhood and adult vaccination status, follow infectious disease episodes, and alert for the indication of prophylactic treatment when required. Continuous educational activities regarding invasive H. influenzae and signs and symptoms of disease state are essential for the proper identification of susceptible individuals by those who are in caregiving positions. Nurses in advanced practices may contribute to the development of newer guidelines that include Hib vaccination for susceptible adults and those 65 years and older through evidenced-based practice.
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extensive investigation has been conducted on this subject for the pediatric population, insufficient data exist regarding the benefits of vaccinating adults with Hib vaccines. In 1985, the United States licensed a pure polysaccharide vaccine against H. influenzae (Mansnerus, 2009). However, it was not until December 1987 with the introduction of a Hib polysaccharide–protein conjugate vaccine that the incidence of H. influenzae dramatically dropped (Mansnerus, 2009). This was because of an improved protein carrier in the vaccine that made a more effective antigen (CDC, 2002). This indicates that individuals born before 1987 may have inadequate protection against H. influenzae, because vaccination did not exist for this organism prior to this year. In healthy individuals, one would suspect that adults would have obtained immunological memory against this invading organism and would react rapidly to subsequent exposures because of their adaptive immune system. Further studies are necessary to evaluate adequate protection in other age groups to determine the need for booster doses in adults 65 years and older because of waning protection from the vaccine. It is important for individuals to understand the seriousness of this issue and the complications involved with invasive H. influenzae disease. In order to create awareness for prevention, individuals and practitioners must understand the seriousness, susceptibility, barriers, and benefits of Hib vaccination. This state of awareness can lead to policy changes to include insurance coverage for Hib administration to susceptible adults. Current evidence-based guidelines regarding adult Hib vaccinations must be reassessed to include susceptible adults and those more than 65 years who have an H. influenzae antibody deficiency manifesting with recurrent RTIs and frequent antibiotic use. Consideration should be given to changing guidelines associated with Hib vaccines to include susceptible individuals, such as those more than 65 years of age, because this invasive disease may be easily controlled through vaccination (Beattie, 2008).
Acknowledgments The author would like to acknowledge Mary Christine King, PhD, and Gabriel Gonzalez, MD, for their helpful comments on this manuscript.
Conclusion Haemophilus influenzae disease has been considered a disease of the past since the emergence of a polysaccharide Hib vaccine introduced in the United States in 1985 (Beattie, 2008). It is now recommended by the CDC as one of the scheduled childhood vaccines (CDC, 1985). Although 118
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