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Pneumococcal disease is predominantly caused by Streptococcus pneumoniae and affects people across all ages. The risk of pneumococcal disease increases distinctly with age.
- pneumococcal disease
- high-risk adults
- pneumococcal vaccine
1. Introduction—Risk of Pneumococcal Disease in Adults
Pneumococcal disease is predominantly caused by Streptococcus pneumoniae and affects people across all ages [1,2]. The risk of pneumococcal disease increases distinctly with age [1,3]. Concurrent conditions such as alcoholism, cigarette smoking, chronic heart/liver/lung disease, diabetes, asthma, neuromuscular disorders, rheumatoid arthritis, Crohn’s disease, and any other condition or medicine that weakens the immune system, such as oral corticosteroids, increase the risk of contracting pneumococcal pneumonia or pneumococcal disease among adults. Patients with these conditions are classified as an “at-risk” population. The “high-risk” population includes patients with immunocompromising conditions such as chronic renal failure, nephrotic syndrome, congenital or acquired immunodeficiency (HIV), iatrogenic immunosuppression, malignancy, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies. Patients taking immunosuppressive drugs and having a cochlear implant or a cerebrospinal fluid leak are also classified as “high-risk” [3,4,5]. Multiple risk factors impart a cumulative risk of contracting invasive pneumococcal disease (IPD) or community-acquired pneumonia (CAP) [4]. The increase in risk for pneumococcal diseases due to present comorbidities can be justified by the increased and dysregulated inflammation from aging, the delayed response of the immune system, and augmented expression of bacterial ligands in the lung [6]. A meta-analysis of 26 studies conducted in various countries reported the overall mortality rate due to IPD as 20.8%. Factors such as older age (>64 years old), septic shock, immunocompromising condition, underlying chronic diseases, solid organ tumors, alcohol abuse, nursing homes, and nosocomial infection were determined to be prognostic factors determining the mortality rate from IPD [7].
2. Burden of Pneumococcal Disease in Middle East/Lebanon
In 2015, the Global Burden of Disease (GBD) study reported a total of 1,517,388 deaths due to pneumococcal pneumonia in all ages. The disease claimed 693,041 people aged ≥70 years [8]. A systematic review and meta-analysis conducted on articles published from Southern Europe reported an incidence of invasive pneumococcal disease (IPD) in adults to be 15.08 per 100,000 in Spain and 2.56 per 100,000 in Italy. The same study reported an incidence of 19.59 per 100,000 in Spain and 2.19 per 100,000 in Italy for pneumococcal pneumonia [9]. An Australian study reported hospitalization incidence due to pneumococcal pneumonia to be 274 per 100,000 population in 2011–2012 in adults aged ≥65 years. They also reported a case fatality rate of 6.1% between 2004 to 2012 [1]. A decline in the burden of pneumococcal disease has been reported by various studies due to the introduction of vaccination [2,9].
The overall mortality due to lower respiratory tract infections (LRTIs) has been reported to be 10% in the Middle East and North Africa (MENA) region, as opposed to 4% in developed regions of the world [10]. There are limited studies reporting the epidemiology and disease burden for pneumococcal disease in the region. However, the studies support a general consensus that there is a high burden of pneumococcal disease among adults and older adults in the region [11].
An epidemiological study conducted between 2006 to 2015 retrospectively reviewed the clinical course and outcomes of 103 adult patients infected with Streptococcus pneumoniae at Makassed General Hospital, Beirut, Lebanon. Among the 103 patients, 65% were ≥65 years of age and 35% had invasive isolates. The mortality rate was 21.6%; kidney disease and septic shock were significant mortality predictors. Superinfections, caused by extremely drug resistant (XDR) Gram-negative bacteria were developed by 19% of the patients and included ventilator-associated pneumonia (13%), hospital-acquired pneumonia (2.9%), bacteremia (1.0%), urinary tract infection (1.0%), and wound infection (1.0%) [12,13]. The serotypes identified in the 37 IPD isolates were 1, 3, 4, 7F, 9V/9A, and 19F, which are covered by the PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23); 9N, 15B/C, and 33F is covered by PPV23; 16F, 18, and 29 are not covered by vaccines [13].
The Lebanese Inter-Hospital Pneumococcal Surveillance Program (LIPSP) conducted a prospective 6-year study between October 2005 to December 2011 at 78 hospitals distributed all over Lebanon. During the study duration, 257 isolates of Streptococcus pneumoniae were identified from patients who fulfilled the IPD criteria. There was a predominance of male patients (56%), mostly above 60 years of age (33.1%) followed by patients aged <2 years (24.1%) and patients between 21 to 60 years (16.3%). A total of 119 patients (46.5%) were diagnosed with pneumonia, 17.2% patients were diagnosed with meningitis and 14.8% had other diagnoses. The highest mortality was reported in patients above 60 years of age (25%) [14].
Further, the LIPSP highlighted the serotype distribution in Lebanon during the study period across all age groups. The serotypes identified were 19F (n = 31), 6 (n = 23), 14 (n = 18), 9V/9A (n = 13), 23F (n = 9), 4 (n = 9), 18C (n = 8), 1 (n = 16), 5 (n = 10), 7F (n = 6), 3 (n = 18), 19A (n = 15), 22F (n = 7), 33F (n = 6), 11A/D (n = 5), 9N (n = 5), 10A (n = 4), 12F (n = 4), 8 (n = 4), 15A (n = 3), 15 B/C (n = 3), 16F (n = 3), 23A (n = 2), 29 (n = 2), 29 (n = 2), 35B (n = 2), 38 (n = 2), and others (n = 12). The antimicrobial susceptibility testing reported 82.6% isolates to be susceptible to penicillin G using Clinical and Laboratory Standards Institute (CLSI) breakpoints. Among the isolates that were MDR, 19F (17 isolates) and 14 (5 isolates) were the most prevalent serotypes [14].
3. Immunization Recommendations and Challenges
In Lebanon, the 13-valent pneumococcal conjugate vaccine (PCV13) is included in the routine immunization schedule for children. The Lebanese Ministry of Public Health (MOPH) encourages vaccination for children with the approved vaccines. However, guidance for adult immunization is absent from the nation immunization schedule. Private practices and community pharmacies offer the pneumococcal vaccine to adults as per the international guidelines [13].
Until 2021, the United States Advisory Committee on Immunization Practices (ACIP) recommended the use of either one dose of PCV13 or one or two doses of PPSV23 in adults between 19 to 64 years who have not been previously vaccinated and carry an additional risk factor or have any underlying medical conditions. For adults aged above 65 years, PCV13 was recommended as one dose for those who have not been previously vaccinated and carry an additional risk factor or have any underlying medical conditions. The population above 65 years of age who do not have any risk factors or comorbid conditions can be vaccinated based on shared clinical decision-making. PPSV23 is recommended as a single dose for adults above 65 years of age who do not have a record of pneumococcal vaccination or do not have a documented medical history of past infection [15]. In its 2022 update, the ACIP recommends the use of either one dose of 15-valent pneumococcal conjugate vaccine (PCV15) followed by the pneumococcal polysaccharide vaccine (PPSV23), or one dose of the 20-valent pneumococcal conjugate vaccine (PCV20) in adults between 19 to 64 years who have not been previously vaccinated and carry an additional risk factor or have any underlying medical conditions. In adults aged above 65 years who have not been previously vaccinated, the ACIP recommends the use of either one dose of PCV15 followed by PPSV23 or one dose of PCV20 [16].
As of 2019, all 42 European countries have a vaccination program for adults, and 30 countries among these have recommended the PCV and/or pneumococcal polysaccharide vaccine (PPV) in the national vaccination policies for adults. The PCV is mandatory for specific groups in Czech Republic, Slovakia and Serbia, while the PPV is mandatory for specific groups in Serbia. The PCV is recommended for all adults in Austria, Belgium, Denmark, Finland, Greece, Hungary, Iceland, Italy, Luxemburg, Malta, Poland, Russia, Slovenia, and Spain. The PPV is recommended for all adults in Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxemburg, Norway, Russia, Slovenia, Spain, Sweden, and the United Kingdom. Countries such as Bosnia and Herzegovina, France, Monaco, Montenegro, and North Macedonia have recommended the PPV while France and Lithuania have recommended the PCV for specific groups of patients. The other European countries have not recommended pneumococcal vaccination for adults [17].
There is limited updated information available on the disease burden of vaccine-preventable invasive bacterial diseases among adults from the Middle East and North Africa region. Although the available literature emphasizes the importance of enhanced surveillance efforts for these diseases within the region, there is an urgent need to develop and implement the surveillance systems to enable the integration of the healthcare sector with respect to epidemiology, laboratory, and data management [11]. This would support in developing robust vaccination strategies with more favorable outcomes. The other factors significantly influencing the clinical applicability of vaccination in adults include gaps in recommendations and limited or absent information on the risks and benefits of vaccination. The cost of vaccination and availability only in the private sector can lead to low voluntary uptake of vaccine by patients, especially those who are not covered by insurance.
4. Cost-Effectiveness of Pneumococcal Vaccines
Apart from the morbidity and mortality associated with vaccine-preventable diseases, they are also associated with economic burden. It was estimated that missed vaccination opportunities in adults above 50 years cost USD 26.5 billion for managing influenza, pneumococcal disease, herpes zoster, and pertussis in the United States [18]. A systematic review conducted on cost evaluation studies on pneumococcal vaccines for adults above 50 years noted that individually the included studies either concluded the pneumococcal vaccination (both PCV13 and PPSV23) to be either cost-saving or cost-effective as compared to no vaccination. The review evaluated 18 studies conducted in low- and middle-income countries [19].
There are no cost-effectiveness studies published from Lebanon. It is imperative to understand the economic burden of pneumococcal disease in adults, with and without comorbidities, to further convince policymakers and patients about the importance of vaccination.
This entry is adapted from the peer-reviewed paper 10.3390/vaccines10101650
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