Pneumococcal conjugate vaccines for preventing otitis media

Fortanier, Alexandre C; Venekamp, Roderick P; Boonacker, Chantal Wb; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger

doi:10.1002/14651858.cd001480.pub4

Cited by 83 publications

(65 citation statements)

References 78 publications

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“…Pneumococcal conjugate vaccines have significantly reduced the rates of invasive pneumococcal disease, but their effect on nasopharyngeal colonization appears to be modest in healthy children and they seem unable to prevent further episodes (7,8). The widespread use of pneumococcal conjugate vaccines, which target the capsular polysaccharide (CPS), has led to decreased nasopharyngeal carriage of vaccine serotypes but a concomitant increase in the carriage of nonvaccine serotypes and nonencapsulated (NE) S. pneumoniae.…”

mentioning

confidence: 99%

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

Domenech

Garcı́a

2017

Antimicrob Agents Chemother

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Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and nontypeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in the carriage of nonencapsulated S. pneumoniae. Frequently, pneumococci and H. influenzae live together in the human nasopharynx, forming a self-produced biofilm. Biofilms present a global medical challenge since the inherent antibiotic resistance of their producers demands the use of large doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence. Here, we describe the development of an in vitro nonencapsulated S. pneumoniae-nontypeable H. influenzae biofilm system with polystyrene or glass-bottom plates. Confocal laser scanning microscopy and specific fluorescent labeling of pneumococcal cells with Helix pomatia agglutinin revealed an even distribution of both species within the biofilm. This simple and robust protocol of mixed biofilms was used to test the antimicrobial properties of two well-known antioxidants that are widely used in the clinical setting, i.e., N-acetyl-L-cysteine and cysteamine. This repurposing approach showed the high potency of N-acetyl-Lcysteine and cysteamine against mixed biofilms of nonencapsulated S. pneumoniae and nontypeable H. influenzae. Decades of clinical use mean that these compounds are safe to use, which may accelerate their evaluation in humans. KEYWORDS Haemophilus influenzae, Streptococcus pneumoniae, antioxidants, biofilmsA cute otitis media (AOM) is defined as the presence of inflammation in the middle ear accompanied by the rapid onset of signs and symptoms of an ear infection. Frequent suppurative complications of AOM are mastoiditis, hearing loss, and meningitis. AOM is a significant public health problem worldwide (incidence rate, ϳ11%) (1). Indeed, Ͼ80% of children suffer at least one episode of AOM by their third birthday and 40% will suffer six or more recurrences by the age of 7 years (2). Pediatric AOM, which is often treated with antibiotics (56 to 95% of cases, depending on the country) (3), represents a significant health care burden, annually accounting for some $2.88 billion in medical costs in the United States (4). A polymicrobial disease, AOM is typically caused by colonization of the middle ear space by opportunistic bacteria that normally form part of the nasopharyngeal microbiota. The most frequently involved bacterial pathogens are Streptococcus pneumoniae, nontypeable (nonencapsulated) Haemophilus influenzae (NT H. influenzae), and, to a lesser extent, Moraxella catarrhalis and other species (5). Several respiratory viruses may also cause AOM (6).

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confidence: 99%

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

Domenech

Garcı́a

2017

Antimicrob Agents Chemother

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“…The main purpose of these vaccines is to protect from invasive pneumococcal disease, but the question was soon raised of whether the vaccines would protect against pneumococcal, and in the case of the protein D conjugate vaccine, also against H. influenzae AOM. A recently updated Cochrane review [45] analysed the effect of pneumococcal conjugate vaccines on AOM. Most of the included trials used PCV7, some included infants, some included older children and some focused on children with an increased risk of AOM.…”

Section: Vaccinationmentioning

confidence: 99%

Acute Otitis Media in Children—Current Treatment and Prevention

Gisselsson-Solén

2015

Curr Infect Dis Rep

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Acute otitis media (AOM) is the most common bacterial infection in children, and has a very varied clinical spectrum, ranging from spontaneous resolutions to serious complications. The effect of antibiotics in AOM depends on the chosen outcome, but has been shown to reduce pain somewhat, and have a greater beneficial effect in severe cases of AOM. Today, not all episodes of AOM are treated with antibiotics, but most countries have issued guidelines that include an option of watchful waiting in many cases. Prevention of AOM reaches from modification of environmental risk factors to vaccinations and surgery. Conjugate pneumococcal vaccines and influenza vaccines have been shown to somewhat reduce the number of AOM episodes in different groups of children. Grommets, with or without adenoidectomy, are effective at least during the first 6 months after surgery.

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“…PCV7 had been proven effective in preventing IPD [8] and providing modest protection against all-cause acute otitis media (AOM) [10].…”

Section: Introductionmentioning

confidence: 99%

“…PCV10 prevented 570,273 AOM; 79,937 PP; 2217 PM; 3049 PS; 282 NS; 173 AS; and 7512 deaths. PCV13 prevented 419,815 AOM; 112,331 PN; 3116 PM; 4285 PS; 404 NS; 248 AS;and 10,386 deaths. Avoided DALYs were 226,370 with PCV10 and 313,119 with PCV13.…”

mentioning

confidence: 99%

Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru

Mezones‐Holguín

Canelo‐Aybar

Clark

et al. 2015

Vaccine

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a b s t r a c tObjective: To evaluate the cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine (PCV10) versus the 13-valent PCV (PCV13) to the National Immunization Schedule in Peru for prevention of pneumococcal disease (PD) in children <5 years of age. Methods: The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (version 2.0) was applied from the perspective of the Government of Peru. Twenty successive cohorts of children from birth to 5 years were evaluated. Clinical outcomes were pneumococcal pneumonia (PP), pneumococcal meningitis (PM), pneumococcal sepsis (PS) and acute otitis media from any causes (AOM). Measures included prevention of cases, neurological sequelae (NS), auditory sequelae (AS), deaths and disability adjusted life years (DALYs). A sensitivity analyses was also performed. Findings: For the 20 cohorts, net costs with PCV10 and PCV13 were US$ 363.26 million and US$ 408.26 million, respectively. PCV10 prevented 570,273 AOM; 79,937 PP; 2217 PM; 3049 PS; 282 NS; 173 AS; and 7512 deaths. PCV13 prevented 419,815 AOM; 112,331 PN; 3116 PM; 4285 PS; 404 NS; 248 AS;and 10,386 deaths. Avoided DALYs were 226,370 with PCV10 and 313,119 with PCV13. Saved treatment costs were US$ 37.39 million with PCV10 and US$ 47.22 million with PCV13. Costs per DALY averted were US$ 1605 for PCV10, and US$ 1304 for PCV13. Sensitivity analyses showed similar results. PCV13 has an extended dominance over PCV10. Conclusion: Both pneumococcal vaccines are cost effective in the Peruvian context. Although the net cost of vaccination with PCV10 is lower, PCV13 prevented more deaths, pneumococcal complications and sequelae. Costs per each prevented DALY were lower with PCV13. Thus, PCV13 would be the preferred policy; PCV10 would also be reasonable (and cost-saving relative to the status quo) if for some reason 13-valent were not feasible.

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Pneumococcal conjugate vaccines for preventing otitis media

Cited by 83 publications

References 78 publications

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

Acute Otitis Media in Children—Current Treatment and Prevention

Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru

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