|Year : 2019 | Volume
| Issue : 3 | Page : 216-225
Pneumococcal disease burden from an Indian perspective: Need for its prevention in pulmonology practice
Parvaiz A Koul1, Sudhir Chaudhari2, Ramesh Chokhani3, D Christopher4, Raja Dhar5, Kumar Doshi6, A Ghoshal7, SK Luhadiya8, Ashok Mahashur9, Ravindra Mehta10, Amita Nene11, Md Rahman12, Rajesh Swarnakar13
1 Department of Internal & Pulmonary Medicine, SKIMS Hospital, Srinagar, Jammu and Kashmir, India
2 Department of T.B. & Chest, Dr. Murari Lal Chest Hospital, GVSM Medical College, Kanpur, Uttar Pradesh, India
3 Department of Pulmonary, Critical Care & Sleep Medicine, Norvic International Hospital, Kathmandu, Nepal
4 Department of Pulmonary Medicine, Christian Medical College Hospital, Vellore, Tamil Nadu, India
5 Department of Respiratory Medicine, Fortis Hospital, Kolkata, West Bengal, India
6 Department of Pulmonary Medicine, Dr. Kumar Doshi Clinic, Kolkata, West Bengal, India
7 Department of Pulmonary Medicine, National Allergy Asthma Bronchitis Institute, Kolkata, West Bengal, India
8 Department of T.B. & Chest, Geetanjali Medicity, Eklingpura, Rajasthan, India
9 Department of Chest Medicine, Hinduja Hospital, Mumbai, Maharashtra, India
10 Department of Pulmonary, Critical Care and Sleep Medicine, Apollo Speciality Hospital, Mumbai, Maharashtra, India
11 Department of Chest Medicine, Bombay Hospital, Mumbai, Maharashtra, India
12 Department of Medicine, Anwer Khan Modern Medical College, Dhaka, Bangladesh
13 Respiratory, Critical Care & Sleep Medicine, Getwell Hospital, Nagpur, Maharashtra, India
|Date of Web Publication||24-Apr-2019|
Dr. Parvaiz A Koul
SKIMS Hospital, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Globally, pneumococcal diseases are a significant public health concern. They are preventable and frequently occur among older adults. Major risk factors for the disease are extremes of age, alcohol intake, smoking, air pollution, and comorbid conditions (diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, and heart disease). Risk factors, coupled with limited disease-burden data and the emergence of antibiotics resistance, are hindering the effective management of the disease in older adults. Various global guidelines recommend pneumococcal vaccines for the prevention of pneumococcal diseases, as they reduce disease burden, hospitalization, and mortality rates among patients with comorbid conditions. Besides being an integral part of childhood immunization, these vaccines are advocated by various Indian healthcare bodies/groups for older and younger adults with certain medical conditions. The article presents an overview of the closed-door discussion by the Indian pulmonary experts on the scientific evidence and clinical practice followed for the prevention of pneumococcal disease in India.
Keywords: Chronic obstructive pulmonary disease, community-acquired pneumonia, comorbidity, mortality, pneumococcal conjugate vaccine, Streptococcus pneumoniae
|How to cite this article:|
Koul PA, Chaudhari S, Chokhani R, Christopher D, Dhar R, Doshi K, Ghoshal A, Luhadiya S K, Mahashur A, Mehta R, Nene A, Rahman M, Swarnakar R. Pneumococcal disease burden from an Indian perspective: Need for its prevention in pulmonology practice. Lung India 2019;36:216-25
|How to cite this URL:|
Koul PA, Chaudhari S, Chokhani R, Christopher D, Dhar R, Doshi K, Ghoshal A, Luhadiya S K, Mahashur A, Mehta R, Nene A, Rahman M, Swarnakar R. Pneumococcal disease burden from an Indian perspective: Need for its prevention in pulmonology practice. Lung India [serial online] 2019 [cited 2019 Sep 18];36:216-25. Available from: http://www.lungindia.com/text.asp?2019/36/3/216/256933
| Introduction|| |
Pneumococcal diseases are a global health-care concern caused by the pathogen, Streptococcus pneumoniae umococcus); however, these diseases are preventable.,, Pneumococcal diseases are broadly classified into invasive and noninvasive forms. Invasive pneumococcal disease (IPD) is diagnosed when the pathogen is identified in normally sterile body fluids (cerebrospinal fluid, blood, and pericardial fluid) of an affected individual, for example, bacteremia, meningitis, etc., Non-IPD includes sinusitis, acute otitis media, and community-acquired pneumonia (CAP); the noninvasive form of pneumonia can change into the invasive form when coupled with bacteraemia.,,S. pneumoniae exists in about 93 serotypes, characterized by a distinct polysaccharide capsule. Different serotypes present variations in colonizing and tissue invasiveness, thus leading to a difference in the biological behavior of the serotype. The pathogen colonizes the nasopharynx and through the transmission to the lower respiratory tract, leads to the development of pneumonia. Vaccination is used for disease prevention.,,
For this article, PubMed served as the primary electronic literature search engine. The international guidelines and Indian recommendations on pneumococcal disease prevention were also consulted. A thorough literature search was conducted to identify scientific literature written in English published between November 8, 1999 and November 9, 2018 using keywords antibiotics, comorbidity, consensus statement, COPD, epidemiology, for pneumococcal infections that were paired with terms such as S. pneumoniae, herd immunity, immunogenicity, India, mortality, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, pollution, prevention, recommendations and guidelines, risk stacking, safety, and serotype.
In a pioneer attempt, we intend to summarize the scientific evidence on pneumococcal disease burden and its prevention through vaccination in India, discussed by a group of pulmonologists in a closed-door discussion. However, clinical judgment should rely upon the individual's condition.
| Burden of Pneumococcal Diseases|| |
According to the Global Burden of Disease (GBD) 2016 estimates, lower respiratory tract infections (LRI), defined as pneumonia or bronchiolitis, were the leading cause of mortality and morbidity worldwide. Approximately 2.38 million deaths resulted from LRI in 2016.S. pneumoniae emerged as the leading cause of LRI morbidity and mortality globally, contributing to more deaths compared to all other etiologies combined in 2016 (1,189,937 deaths). The prevalence of LRI in all age groups was found to be highest in Sub-Saharan Africa, South Asia, and Southeast Asia. The number of deaths due to LRI among adults aged >70 years increased from 746,700 to 1,080,958 from the year 2000 to 2016. However, a reduction in mortality was observed in the under-5-year age group. In the 2017 GBD estimates, the incidence and mortality further registered substantial increases of about 26% and 33% among those aged 50–69 years and >70 years, respectively. According to the World Health Organization (WHO), IPD (e. g., meningitis, pneumonia, and sepsis) accounts for an estimated 600,000–800,000 cases of mortality among adults every year. The invasive form of the disease predominantly affects older adults with underlying comorbidities.,
A recent population-based study conducted among American adults revealed the substantial burden of CAP in the country and estimated that >1.5 million adults are hospitalized annually due to the disease in the country. Of the hospitalized patients, an estimated 100,000 die during hospitalization, and approximately one out three patients die during subsequent years of hospitalization. Epidemiological studies from the European region conducted among the adult population reported the incidence rate of CAP in the range of 1.6–11.6/1000 individuals. Data available for the adult population report an IPD case fatality rate in the range of 26%–30% in the region. The WHO 2008 report revealed Asia to have the highest burden of pneumonia, with the Indian subcontinent contributing the largest share of the disease burden. Furthermore, results from an Indian prospective study revealed CAP to be the second-most common reason of death from infectious diseases in the region.
| Epidemiology of Pneumococcal Diseases in India|| |
Various studies evaluating the clinical and bacteriological profiles for IPD across various parts of India showed the predominance of S. pneumoniae in the region. Meningitis and pneumonia emerged as the most common clinical conditions and were found to have a high case fatality rate despite their treatment in hospital settings.,,,,, A recent laboratory-based surveillance study on IPD conducted in a tertiary care setting among the adult population of India showed that S. pneumoniae-positive cultures were characterized by serotype prevalence and antimicrobial resistance patterns. In line with the findings from the previous studies, pneumonia and meningitis were found to be the most common clinical conditions, accounting for 39% and 24.3% of total IPD cases, respectively. Furthermore, the highest IPD case fatality rates were observed for pneumococcal septicemia, with an unknown focus on infection, pneumonia, and meningitis. In contrast to previously reported findings, the most common serotypes found in the study were 1, 3, 5, 19F, 8, 14, 23F, 4, 19A, and 6B. These serotypes accounted for 54.9% of IPD cases, which shows a clear need for the addition of the 13-valent pneumococcal conjugate vaccine (PCV13) to cover all prevalent serotypes and provide the necessary protective serotype coverage in the country.
The study further noted an overall high resistance to erythromycin and co-trimoxazole antibiotics. Nonsusceptibility to penicillin and cefotaxime was observed for pneumococcal meningitis, thus making cephalosporin the drug of choice for the treatment of pneumococcal diseases. The susceptibility profiles of various antibiotics, over the study duration, are presented in [Figure 1].
|Figure 1: Antimicrobial susceptibility trend in the adult population of India over time. SXT: Sulfamethoxazole/trimethoprim (co-trimoxazole). Cited from: Jayaraman J, et al. J Microbiol Immunol Infect 2018|
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Other studies have also reported an overall high nonsusceptibility to co-trimoxazole and the slow emergence of resistance to penicillin, tetracycline, and erythromycin.,,,
| Risk Factors Associated With Higher Incidence of Pneumococcal Diseases|| |
Pneumococcal diseases are more prevalent in extremes of age, under-5-years, and older adults. With aging, complex changes in the immune system are seen in older adults (immunosenescence), which make them more vulnerable to pneumococcal and other infectious diseases. Moreover, compared to young adults, the aged adult population tends to have one or more chronic comorbidities that make the disease more severe.
In addition to age, an interplay of various risk factors places an individual at a higher risk of developing pneumococcal diseases. A case–control study by Jackson et al. conducted among immunocompetent older adults with CAP showed that factors such as low body weight, smoking, existing lung and heart diseases, and impaired body functions were independent risk factors for CAP. The study revealed that, if current smokers in the study stopped smoking, the burden of CAP would reduce by 2.4%. A systematic review including seven observational studies further highlighted smoking and intake of alcohol to be independent risk factors for IPD. The analysis indicated at least a two-times-higher risk for IPD among current smokers compared to nonsmokers. Alcohol intake was also a significant risk for IPD, with the risk of IPD ranging between 2.9 and 11.4 in adult individuals.
Environmental factors have a substantial impact on the pulmonary system. In a population-based study conducted among older adults, long-term exposure to pollutants (nitrogen dioxide and fine particulate matter) was found to be an independent risk factor for hospitalization due to CAP. Furthermore, in India, the detrimental impact of indoor pollution (biomass fuel combustion, tobacco smoke, and bioaerosols) cannot be ignored. Indoor pollutants aggravate lower respiratory tract ailments, further increasing the incidence of pneumonia among adults.
| Effect of Underlying Comorbid Conditions|| |
A study by Jackson et al. revealed chronic cardiopulmonary disease to account for 42% of pneumonia cases in their study population. Furthermore, the severity of the underlying comorbid disease was found to be directly proportional to the risk of CAP among older adults. A nationwide cohort study based on a European registry assessed the 30-day mortality, hospitalization rate, and risk of subsequent hospitalization for COPD exacerbations with and without pneumonia in patients >40 years of age.
The study showed that around 36% of patients who were hospitalized for a first-time COPD exacerbation were diagnosed with pneumonia. This first-time pneumonic exacerbation further increased the hospitalization rate for successive COPD exacerbation and was associated with a high 30-day mortality rate among older adults. Similar findings were reflected in another prospective observational study, wherein mortality rates were found to be significantly higher for pneumonia-related exacerbations compared to pneumonia-unrelated exacerbations (P < 0.001).
A population-based study showed a significant association between asthma and the risk of IPD. Patients with asthma had a threefold increased risk of developing IPD, compared with patients without asthma. In another retrospective study, adults with asthma were found to have a more than six-fold higher risk of developing IPD and pneumococcal pneumonia compared to patients without asthma. A retrospective study by Shea et al. conducted in an adult population (>65 years) revealed that patients with asthma are at a 5.9- and 16.7-time higher risk of developing pneumococcal pneumonia and IPD, respectively, compared to healthy individuals.
While assessing the impact of various lung diseases on CAP outcomes, a Swiss case–control study conducted in an adult population showed a comparable occurrence rate of CAP complications in IPD patients and the control group; however, a significantly higher in-hospital mortality rate was observed among IPD patients compared to patients in the control group (16.3% vs. 6.8%).
In another retrospective, longitudinal American study, diabetic patients were found to be at higher risk of conditions, such as fibrosis, pneumonia, and COPD, compared to healthy individuals. The risk of pneumonia significantly increased with increasing HbA1c values. This rise in the risk of pneumococcal diseases in diabetic patients was due to the decrease in pulmonary function and immune response. A retrospective cohort study conducted among the Asian population highlighted CKD as another comorbid condition contributing to a higher risk of pneumonia. The study showed pneumonia incidence rates of 65.6 and 28.4/1000 person-years for patients with and without CKD, respectively. The comorbid condition served as an independent contributor and increased the risk of both outpatient and inpatient pneumonia. The increased infection risk among CKD patients can be attributed to immune cell impairment (increased cytokines and neutrophil phagocytosis) observed in uremia. In a retrospective study by Shea et al., episodes of pneumococcal pneumonia and IPD were assessed for a duration of 1 year.
The study population consisted of healthy individuals, immunocompetent adults with chronic medical conditions (”at-risk” group), and immunocompromised adults (”high-risk” group). All-cause pneumonia rates were higher for the at-risk and high-risk populations when compared to healthy individuals across all age groups. In addition, all-cause pneumonia rates increased significantly with the accumulation of multiple risk factors/comorbidities (risk-stacking). The effect of various risk factors in the study is presented in [Figure 2].
|Figure 2: Impact of various risk factors on the incidence rate of pneumonia. Adapted from Shea KM, et al. Open Forum Infect Dis 2014|
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Findings from another retrospective study conducted among an adult population showed that individuals with two or more concurrent comorbid diseases had higher pneumococcal disease incidence rates compared to individuals with chronic high-risk conditions. In addition, the incidence rates of pneumococcal pneumonia, IPD, and all-cause pneumonia increased significantly with the accumulation of concurrent at-risk conditions. In a case–control American study conducted among unvaccinated adults (>50 years), the mortality rate increased with the stacking of risk factors (up to 6 factors), with each additional risk factor increasing the mortality rate by approximately 55%.
| Unmet Needs and Treatment Challenges in Pneumococcal Diseases|| |
Prior to formulating policies on the management of a disease, a precise estimate of the disease burden and seroprevalence, as well as the antimicrobial susceptibility profile data for the region, is essential. Certainly, data on pneumococcal diseases in India are limited, especially for the older adult population., As the majority of CAP forms can be treated, accurate and timely diagnosis is required to optimize treatment. A sound understanding of causative pathogens is warranted. However, due to inadequate resources and the inconsistent quality of laboratory tests for disease-causing pathogens, diagnosis is a major challenge in the region. Advanced and speedy diagnostic tools will not only ensure selection of the correct treatment agent but will also ensure timely hospitalization in severe cases.,,
Apart from the challenges encountered in diagnosis, the prevalence of antibiotic-resistant strains of S. pneumoniae is increasing at an alarming rate in India proving to be the primary obstacle in the effective treatment of CAP.,,, Despite resistance to penicillin being comparatively lower in India compared to the rest of the world, recent data indicate an increase in resistance to the treatment agent. In a surveillance study conducted over a period of 11 years in India, nonsusceptibility to penicillin among meningeal IPD cases was found to be 27.4%. Resistant strains lead to high rates of treatment failure, increase in the length of hospital stay, and increase in the risk of mortality among elderly individuals with underlying comorbid conditions.,,, In the absence of new antibiotics, the treatment of pneumococcal diseases is a major challenge among older adults.
Against this backdrop, the prevention of risk factors assumes vital importance. The measures consist of reducing childhood wasting; lessening indoor and ambient air pollution; infection control practices; and attempts at mitigating the susceptibility to pneumococcal diseases by vaccination. Vaccination against pneumococcal diseases is a crucial preventive strategy and should be regarded as the key focus.
| Pneumococcal Vaccines in Pulmonary Practice|| |
Pneumococcal vaccines vary based on the number of S. pneumoniae serotypes they contain and whether these serotypes are conjugated to a protein carrier or not. At present, two vaccines are used clinically and recommended globally; the previously introduced unconjugated 23-valent pneumococcal polysaccharide vaccine (PPSV23), introduced in 1983, and the recently introduced conjugated PCV13, introduced in 2009. The detailed characteristics of both vaccines are presented in [Table 1].,,,
| What Do the Various Pneumococcal Vaccines Have to Offer?|| |
Vaccination has several benefits. In a population-based study conducted over a span of 2 years, CAP patients previously vaccinated with the PPSV23 were found to have a 40% lower rate of mortality or intensive care unit admission compared with nonvaccinated patients. The value of pneumococcal vaccination goes beyond the purview of clinical outcomes and has a potential economic impact as well. As the PCV decreases the usage of antibiotics, the total health-care expenditure decreases.
In a retrospective study conducted among elderly patients with COPD, vaccinated COPD patients had reduced hospitalization, lower mortality, and reduced direct medical care costs. The vaccine was associated with a 43% reduction in hospitalization for pneumonia.
| Place of Unconjugated and Conjugated Vaccines in the Wake of Emerging Recommendations|| |
Before discussing various recommendations and the schedule of pneumococcal immunization for adults in detail, it is pertinent to acknowledge the difference between the effectiveness of the PPSV23 and PCV13.
PPSV23 has been available for more than three decades and found to have a consistent protective effect against IPD and all-cause pneumonia among healthy adults. Evidence shows an effectiveness of 50%–80% against preventing IPD in adults with comorbid conditions. The vaccine has not shown risk reduction of CAP associated with seasonal influenza in adults. Furthermore, there is a dearth of robust evidence supporting protective effect of PPV23 in adults at highest risk of pneumococcal disease.
The key limitations associated with PPSV23 isolated us include the following: uncertain effectiveness for prevention against nonbacteremic pneumococcal pneumonia, hypo-responsiveness upon repeated administration, and a decrease in clinical protection with age (>65 years) in the adult population.,
The PPSV23 is unable to provide long-lasting immunity to adult patients, with no anamnestic effect occurring postrevaccination. Immune response to the vaccine is also found to be specifically low in immunocompromised adults and adults with various underlying comorbid conditions. According to a meta-analysis conducted by Huss et al. including 22 trials and assessing the clinical outcome of death and rates of pneumonia, little evidence was found in favor of the effectiveness of PPSV23 against pneumonia in elderly patients or adults with chronic illness.
The combined limitations of PPSV23 make the protection of the aging adult population from IPD a challenge.
PCV13, a relatively new vaccine, has proven its safety and efficacy in various clinical trials. In addition, it can address the unmet medical need of the PPSV23 by serving as a valuable pneumococcal vaccination option in older adults. The findings of the clinical trials summarized in [Table 2] highlight how PCV13 exhibits a more robust or greater immune response compared to the PPSV23 in majority of shared pneumococcal serotypes.
The 5-year, randomized controlled, CAP Immunization Trial in Adults was a landmark study that highlighted the importance of PCV13 vaccine in adult immunization. The trial, conducted among > 80,000 adults (aged > 65 years), showed an efficacy of 46% (95% confidence interval [CI] 22%–63%) and 75% (95% CI 41%–91%) for PCV13 in relation to the prevention of vaccine-type pneumonia and IPD, respectively. The overall efficacy of PCV13 against pneumonia caused by S. pneumoniae was 31% (95% CI 10%–47%). The study helped in justifying the need for PCV13 in addition to the PPSV23 and served as the foundation for various recommendations for protecting the older adult population against pneumococcal diseases.,
Findings from a study by Greenberg et al. conducted among treatment-naive adults revealed that an initial single dose of PCV13 amplifies the anti-pneumococcal response to subsequent administration of PPSV23 for many common vaccine serotypes. This occurs due to a recalled and augmented immune response by the conjugated PCV13 vaccine when followed upon by sequential administration of PPSV23. On the contrary, an initial administration of PPSV23 before PCV13 results in a diminished response to subsequent administration of PCV13 for all the serotypes. The study helped in providing a reasonable rationale for the recommendation on first administering PCV13 followed by PPSV23.
Furthermore, results from a double-blind, randomized trial evaluating the immunogenic response and safety profile of PCV13 coadministered with trivalent, inactivated influenza vaccine showed that both the vaccines could be safely coadministered in the adult population (>50 years).
In light of increasing evidence that S. pneumoniae might be a coinfection or a follow-up infection to viral infections, it is pertinent to note that permissible immunogenic response and safety profile was shown by the coadministered PCV-13 and trivalent, inactivated influenza vaccine was demonstrated in older adults.,
The results from both the studies add value in a comprehensive immunization schema for older adults. As acceptable immunogenicity and tolerability profile are demonstrated by both the coadministered influenza vaccine and PCV, immunization for older adults becomes convenient with enhanced compliance.
PCV13 also has the potential to slow the rate of antibiotic resistance. The vaccine exerts this effect by slowing the spread of resistant pneumococcal serotypes (19A) and by preventing the disease in the first place, thereby eliminating the need for antibiotics. A reduction in the rate of antibiotic-resistant infection among older adults was also observed in a laboratory-based study. The incidence rate of pneumococcal diseases caused by penicillin-resistant strains reduced to 8.4 from 16.4 cases/100,000. Furthermore, the rates of resistant pneumococcal disease caused by vaccine serotypes reduced by 87%.
PCV13 immunization was also found to be relatively more cost-effective for immunocompromised individuals than the previously recommended vaccinations. This benefit is especially noteworthy for developing nations such as India.
Hence, based on the overall scientific evidence for the PCV13 vaccine in the adult population, the Advisory Committee on Immunization Practices guidelines recommend administration of one dose of PCV13 in a sequential manner with the PPSV23 in high-risk individuals and all individuals aged >65 years (with or without risk conditions).
Despite several limitations of PPSV23 vaccine in older adult, it is recommended along with PCV13 as a part of comprehensive immunization schema. It is sequentially administered after PCV13, in order to provide maximum coverage of disease-specific serotypes to healthy or at risk, immunocompromised older adults with underlying comorbid conditions.
| Evolution of Guidelines from a Global Perspective|| |
Various guidelines have advocated the use of pneumococcal vaccines sequentially for preventing disease occurrence among older adults. The chronological evolution of pneumococcal vaccine recommendations from global advocacy groups is detailed in [Table 3].,,,
|Table 3: Chronological evolution of pneumococcal vaccine recommendations|
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| Where Does India Stand With Respect to Pneumococcal Disease Prevention in Pulmonology Practice?|| |
India has the highest mortality and morbidity due to IPD among adults aged >50 years. With the increase in the aging population and the rise in the incidence of comorbid conditions in the country, vaccination can play a crucial role in the prevention of pneumococcal diseases and in improving the quality of life of the at-risk population., Both PPSV23 and PCV13 are available in the country. At present, PCV13 is approved for use only in adults aged >50 years. Although the vaccines are recommended and advocated globally for the at-risk elderly population, their usage is suboptimal in the region and is majorly dependent on clinicians' awareness of guidelines.,
Hence, despite the increasing global clinical evidence on the benefits of these vaccines, India is lagging in implementing preventive steps for protecting its at-risk population from pneumococcal diseases.
In addition, there are several factors, leading to neglect of preventive care for the older population in the country. As with advancing age, the immunity is decreased, older adults are at higher risk of acquiring the pneumococcal infections. However, on the contrary, there is no defined immunization schedule for the older population in India. Furthermore, region specific evidence on modest coverage (57.9%) of S. pneumoniae serotypes by PPV23 vaccine in the adult population cannot be ignored.
In the light of the above discussion, it is crucial to set forth a comprehensive immunization schedule (PCV13/PPSV23) tailored to the Indian region, for protecting the elderly population of the country.
| Guidelines by Indian Bodies for the Prevention of Pneumococcal Diseases|| |
Acknowledging the fact that adult immunization is as essential as childhood immunization, various Indian health-care groups, and bodies have proposed recommendations for pneumococcal vaccination among adults [Table 4].,,,
|Table 4: Pneumococcal immunization recommendations by various Indian groups|
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Although the recommendations described above are put forward considering the global guideline and evidence perspective, it is pertinent to state that, these recommendations give due weightage to the current Indian clinical practice and consider the regulatory requirements in the country. In the absence of evidence-based India-specific guidelines for pneumococcal vaccination and scarcity of robust evidence for effectiveness and safety of pneumococcal vaccines in varied Indian population, the importance of these recommendations for limiting the consequences of pneumococcal disease in the region cannot be disregarded.
Furthermore, these recommendations will serve as an excellent base for structuring formal evidence-based guidelines by the pulmonary associations of the country for use in patients attended by pulmonary physicians, especially those with chronic pulmonary diseases.
| Future Directions for Pneumococcal Disease Prevention|| |
Vaccination has an indisputable potential to reduce the global pneumococcal disease burden. Serotype-switching and replacement are significant causes of vaccine ineffectiveness., With >90 pneumococcal serotypes for the disease, the development of broad-spectrum vaccines covering the majority of serotypes would be a future direction for the effective prevention of pneumococcal diseases. In addition, the development of serotype-independent protein vaccines, which is still in the nascent stage and would further require the construction of a defined regulatory and licensing framework, is of paramount importance. Recent GBD data show a moderate reduction in mortality due to LRI among children aged <5 years, after the introduction of PCV in many countries. The finding, thus, suggests that a great deal of LRI burden could be averted by universal coverage of PCV.
| Summary and Conclusion|| |
Timely prevention is better than treatment for any disease; this is especially true for pneumococcal diseases. Pneumococcal diseases are a major challenge for developing countries such as India, which is already burdened with other communicable and noncommunicable diseases. Further, it is necessary to acknowledge that the presence of certain comorbid conditions places patients at high risk of developing pneumonia. Pneumococcal diseases can be prevented by offering effective vaccination. Pneumococcal vaccines have demonstrated safety and efficacy in various global clinical trials conducted among both children and adults. Consistent with global guideline recommendations, Indian health-care groups/bodies have recommended vaccination in diverse older adult population. However, pneumococcal vaccination usage is suboptimal in the region, which could be attributed to the absence of structured region-specific guidelines for the use of pneumococcal vaccine. This unmet need requires a primary address to not only reduce the burden of pneumococcal diseases, its associated mortality, its consequences on the Indian economy but also to empower the practicing clinicians in the country.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Ludwig E, Bonanni P, Rohde G, Sayiner A, Torres A. The remaining challenges of pneumococcal disease in adults. Eur Respir Rev 2012;21:57-65.
Randle E, Ninis N, Inwald D. Invasive pneumococcal disease. Arch Dis Child Educ Pract Ed 2011;96:183-90.
Drijkoningen JJ, Rohde GG. Pneumococcal infection in adults: Burden of disease. Clin Microbiol Infect 2014;20 Suppl 5:45-51.
Dockrell DH, Whyte MK, Mitchell TJ. Pneumococcal pneumonia: Mechanisms of infection and resolution. Chest 2012;142:482-91.
GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: A systematic analysis for the global burden of disease study 2016. Lancet 2017;390:1151-210.
GBD 2016 Lower Respiratory Infections Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: A systematic analysis for the global burden of disease study 2016. Lancet Infect Dis 2018;18:1191-210.
Muley VA, Ghadage DP, Yadav GE, Bhore AV. Study of invasive pneumococcal infection in adults with reference to penicillin resistance. J Lab Physicians 2017;9:31-5.
] [Full text]
GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: A systematic analysis for the global burden of disease study 2017. Lancet 2018;392:1736-88.
Thomas K, Mukkai Kesavan L, Veeraraghavan B, Jasmine S, Jude J, Shubankar M, et al.
Invasive pneumococcal disease associated with high case fatality in India. J Clin Epidemiol 2013;66:36-43.
Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, et al.
Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis 2017;65:1806-12.
Ghoshal AG. Burden of pneumonia in the community. J Assoc Physicians India 2016:64;8-11.
Daganokar RS, Udwadia ZF, Sen T, Nene A, Joshi J, Rastogi SA, et al
. Severe community acquired pneumonia in Mumbai, India: Etiology and predictive value of the modified British thoracic society rule. Am J Respir Crit Care Med 185;2012:A6060.
Shah BA, Singh G, Naik MA, Dhobi GN. Bacteriological and clinical profile of community acquired pneumonia in hospitalized patients. Lung India 2010;27:54-7.
] [Full text]
Oberoi A, Aggarwal A. Bacteriological profile, serology and antibiotic sensitivity pattern of micro-organisms from community acquired pneumonia. JK Sci 2006;8:79-82.
Bansal S, Kashyap S, Pal LS, Goel A. Clinical and bacteriological profile of community acquired pneumonia in Shimla, Himachal Pradesh. Indian J Chest Dis Allied Sci 2004;46:17-22.
Para RA, Fomda BA, Jan RA, Shah S, Koul PA. Microbial etiology in hospitalized North Indian adults with community-acquired pneumonia. Lung India 2018;35:108-15.
] [Full text]
Jayaraman R, Varghese R, Kumar JL, Neeravi A, Shanmugasundaram D, Ralph R, et al.
Invasive pneumococcal disease in Indian adults: 11 years' experience. J Microbiol Immunol Infect 2018. pii: S1684-1182(18) 30113-0.
Shariff M, Choudhary J, Zahoor S, Deb M. Characterization of Streptococcus pneumoniae
isolates from India with special reference to their sequence types. J Infect Dev Ctries 2013;7:101-9.
Jackson ML, Nelson JC, Jackson LA. Risk factors for community-acquired pneumonia in immunocompetent seniors. J Am Geriatr Soc 2009;57:882-8.
Cruickshank HC, Jefferies JM, Clarke SC. Lifestyle risk factors for invasive pneumococcal disease: A systematic review. BMJ Open 2014;4:e005224.
Neupane B, Jerrett M, Burnett RT, Marrie T, Arain A, Loeb M, et al.
Long-term exposure to ambient air pollution and risk of hospitalization with community-acquired pneumonia in older adults. Am J Respir Crit Care Med 2010;181:47-53.
Kankaria A, Nongkynrih B, Gupta SK. Indoor air pollution in India: Implications on health and its control. Indian J Community Med 2014;39:203-7.
] [Full text]
Søgaard M, Madsen M, Løkke A, Hilberg O, Sørensen HT, Thomsen RW, et al.
Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia. Int J Chron Obstruct Pulmon Dis 2016;11:455-65.
Steer J, Norman EM, Afolabi OA, Gibson GJ, Bourke SC. Dyspnoea severity and pneumonia as predictors of in-hospital mortality and early readmission in acute exacerbations of COPD. Thora×2012;67:117-21.
Kwak BO, Choung JT, Park YM. The association between asthma and invasive pneumococcal disease: A nationwide study in Korea. J Korean Med Sci 2015;30:60-5.
Juhn YJ, Kita H, Yawn BP, Boyce TG, Yoo KH, McGree ME, et al.
Increased risk of serious pneumococcal disease in patients with asthma. J Allergy Clin Immunol 2008;122:719-23.
Shea KM, Edelsberg J, Weycker D, Farkouh RA, Strutton DR, Pelton SI, et al.
Rates of pneumococcal disease in adults with chronic medical conditions. Open Forum Infect Dis 2014;1:ofu024.
Dusemund F, Chronis J, Baty F, Albrich WC, Brutsche MH. The outcome of community-acquired pneumonia in patients with chronic lung disease: A case-control study. Swiss Med Wkly 2014;144:w14013.
Ehrlich SF, Quesenberry CP Jr., Van Den Eeden SK, Shan J, Ferrara A. Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes Care 2010;33:55-60.
Chou CY, Wang SM, Liang CC, Chang CT, Liu JH, Wang IK, et al.
Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings: A nationwide population-based study. Medicine (Baltimore) 2014;93:e174.
Pelton SI, Shea KM, Weycker D, Farkouh RA, Strutton DR, Edelsberg J, et al.
Rethinking risk for pneumococcal disease in adults: The role of risk stacking. Open Forum Infect Dis 2015;2:ofv020.
Morton JB, Morrill HJ, LaPlante KL, Caffrey AR. Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae
infections. Vaccine 2017;35:1692-7.
Kanungo R. Challenges to pneumococcal vaccine in India. Indian J Med Microbiol 2013;31:1-2.
] [Full text]
Nangia V. Treatment of community-acquired pneumonia and pitfalls. J Assoc Physicians India 2016;64:17-22.
Mathai D, Shamsuzzaman AM, Feroz A, Virani AR, Hasan A, Kumar KL, et al
. Consensus recommendation for India and Bangladesh for the use of pneumococcal vaccine in mass gatherings with special reference to Hajj pilgrims. J Glob Infect Dis 2016;8:129.
Muruganathan A. Community-acquired pneumonia: Challenges and solutions. J Assoc Physicians India 2016;64:6-7.
File T. Current challenges in the treatment of community-acquired pneumonia. Clin Infect Dis 2004;38:1-4.
Hayward S, Thompson LA, McEachern A. Is 13-valent pneumococcal conjugate vaccine (PCV13) combined with 23-valent pneumococcal polysaccharide vaccine (PPSV23) superior to PPSV23 alone for reducing incidence or severity of pneumonia in older adults? A clin-IQ. J Patient Cent Res Rev 2016;3:111-5.
Cafiero-Fonseca ET, Stawasz A, Johnson ST, Sato R, Bloom DE. The full benefits of adult pneumococcal vaccination: A systematic review. PLoS One 2017;12:e0186903.
Johnstone J, Marrie TJ, Eurich DT, Majumdar SR. Effect of pneumococcal vaccination in hospitalized adults with community-acquired pneumonia. Arch Intern Med 2007;167:1938-43.
Bärnighausen T, Bloom DE, Cafiero-Fonseca ET, O'Brien JC. Valuing vaccination. Proc Natl Acad Sci U S A 2014;111:12313-9.
Nichol KL, Baken L, Wuorenma J, Nelson A. The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease. Arch Intern Med 1999;159:2437-42.
23-valent pneumococcal polysaccharide vaccine. WHO position paper. Wkly Epidemiol Rec 2008;83:373-84.
Sings HL. Pneumococcal conjugate vaccine use in adults – Addressing an unmet medical need for non-bacteremic pneumococcal pneumonia. Vaccine 2017;35:5406-17.
Swaminathan S, Balajee G. Pneumococcal vaccines – A real world perspective cost-effectiveness of pneumococcal vaccination. J Assoc Physicians India 2015;63:25-8.
Huss A, Scott P, Stuck AE, Trotter C, Egger M. Efficacy of pneumococcal vaccination in adults: A meta-analysis. CMAJ 2009;180:48-58.
McLaughlin JM, Jiang Q, Isturiz RE, Sings HL, Swerdlow DL, Gessner BD, et al.
Effectiveness of 13-valent pneumococcal conjugate vaccine against hospitalization for community-acquired pneumonia in older US adults: A Test-negative design. Clin Infect Dis 2018;67:1498-506.
Prato R, Fortunato F, Cappelli MG, Chironna M, Martinelli D. Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: A case-control study in a 2-year prospective cohort. BMJ Open 2018;8:e019034.
Solanki BB, Juergens C, Chopada MB, Supe P, Sundaraiyer V, Le Dren-Narayanin N, et al.
Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine in adults 50 to 65 years of age in India: An open-label trial. Hum Vaccin Immunother 2017;13:2065-71.
Jackson LA, Gurtman A, Rice K, Pauksens K, Greenberg RN, Jones TR, et al.
Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine 2013;31:3585-93.
Jackson LA, Gurtman A, van Cleeff M, Jansen KU, Jayawardene D, Devlin C, et al.
Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults. Vaccine 2013;31:3577-84.
Jackson LA, Gurtman A, van Cleeff M, Frenck RW, Treanor J, Jansen KU, et al.
Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older. Vaccine 2013;31:3594-602.
Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al.
Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N
Engl J Med 2015;372:1114-25.
Greenberg RN, Gurtman A, Frenck RW, Strout C, Jansen KU, Trammel J, et al.
Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naïve adults 60-64 years of age. Vaccine 2014;32:2364-74.
Frenck RW Jr., Gurtman A, Rubino J, Smith W, van Cleeff M, Jayawardene D, et al.
Randomized, controlled trial of a 13-valent pneumococcal conjugate vaccine administered concomitantly with an influenza vaccine in healthy adults. Clin Vaccine Immunol 2012;19:1296-303.
Malosh RE, Martin ET, Ortiz JR, Monto AS. The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine 2018;36:141-7.
Schwarz TF, Flamaing J, Rümke HC, Penzes J, Juergens C, Wenz A, et al.
Arandomized, double-blind trial to evaluate immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given concomitantly with trivalent influenza vaccine in adults aged≥65 years. Vaccine 2011;29:5195-202.
Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J, Reingold A, et al.
Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae
Engl J Med 2006;354:1455-63.
Smith KJ, Nowalk MP, Raymund M, Zimmerman RK. Cost-effectiveness of pneumococcal conjugate vaccination in immunocompromised adults. Vaccine 2013;31:3950-6.
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease; 2017. Available from: https://www.goldcopd.org
. [Last accessed on 2018 Sep 05].
American Diabetes Association. Diabetes management guidelines. Diabetes Care 2015;38:S1-93.
Swaminathan S, Mathai D. Protocols for pneumococcal vaccination understanding the term. J Assoc Physicians India 2016;64:52-62.
Dhar R. Review of guidelines for the use of vaccines to prevent community-acquired pneumonia in Indian adults. J Assoc Physicians India 2016;64:45-51.
Verma R, Khanna P, Chawla S. Vaccines for the elderly need to be introduced into the immunization program in India. Hum Vaccin Immunother 2014;10:2468-70.
Wattal C, Goel N, Byotra SP. Prevalence of pneumococcal serotypes in adults≥50 years of age. Indian J Med Microbiol 2017;35:95-100.
] [Full text]
Bajaj S. RSSDI clinical practice recommendations for the management of type 2 diabetes mellitus 2017. Int J Diabetes Dev Ctries 2018;38:1-15.
Indian Society of Nephrology Vaccination Work Group. Guidelines for vaccination in patients with chronic kidney disease. Indian J Nephrol 2016;26, Suppl S1:15-8.
Torres A, Bonanni P, Hryniewicz W, Moutschen M, Reinert RR, Welte T, et al.
Pneumococcal vaccination: What have we learnt so far and what can we expect in the future? Eur J Clin Microbiol Infect Dis 2015;34:19-31.
Wantuch PL, Avci FY. Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them. Hum Vaccin Immunother 2018;14:2303-9.
Rodgers GL, Klugman KP. The future of pneumococcal disease prevention. Vaccine 2011;29 Suppl 3:C43-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]