Non-classical pneumococcal infections
(endocarditis, peritonitis, conjunctivitis,
sinusitis, neonatal sepsis)
Zsofia Meszner MD PhD
‘Heim Pál’ National Institute of Child Health
‘Szent László’ Hospital for Infectious
Diseases
Budapest, Hungary
2
Pneumococcal disease: it all starts with
nasopharyngeal carriage (NPC)
Acute Otitis
Media (AOM)
Pneumonia
Bacteraemia
Antibiotic resistance
Spread to other individuals
Meningitis
ECDC. Pneumococcal infection – Factsheet for health professionals. October 2011.
Non-classical pneumocococal infections
Common characteristics:
• Rare, difficult to find correct data as to incidence, prevalence in
childhood
• Diagnosis depends upon awareness, culturing practice, possibilities
and intention
IPD – non-IPD
• Pneumococcal endocarditis, peritonitis, neonatal sepsis are
IPD syndromes, as opposed to pneumococcal conjunctivitis and
sinusitis
Pneumococcal endocarditis*
*www.hindawi.com/journals/crim/2010/982521/fig1/
Pneumococcal endocarditis
• Incidence of infective endocarditis/IE in adults (USA) has
been reported to be 1.5-6.0 per 100,000 patient years*
• IE incidence in children in general population is
approximately three times lower2**
• Pneumococcal endocariditis is responsible for <2% of all
IE***
*Pasquali SK et al : Trends in endocarditis hospitalizations at US children’s hospitals: impact of the 2007
American Heart Association Antibiotic Prophylaxis Guidelines. Am Heart J. 2012, 163:894-899.
** Ravindranath Waikar et al. Cureus, 2019, 11(3):
*** Perier A, Int J Cardiol. 2019 Aug 1;288:102-106
Method:
• This multicentric observational retrospective study included adult patients
presenting with definite S. pneumoniae IE according to modified Dukes
criteria from four French university hospitals between 2000-2015.
• Survival rate at 90 days and 2 years after diagnosis, appropriateness of
antibiotherapy, and pneumococcal vaccination status were determined.
• Risk factors for mortality were studied by univariate analysis.
Results:
• 50/3886 (1,3% of all) IE had pneumococcal IE
• Mostly males - with a mean age of 60 ± 14 years.
• Predisposing conditions for IE or for invasive pneumococcal disease
(IPD) involved 24% and 78% of the cases, respectively.
• Only 2 patients were vaccinated against pneumococcus before IE and
13 (26%) after IE.
• Antimicrobial strategy was in accordance with the 2015 ESC Guidelines
in 28%.
• Cardiac surgery was performed in 56%, and was associated with better
survival (p = 0.012).
• In the 40/50 patients followed until 2 years, the survival rate was 67%,
deaths occurring mostly before 90 days.
• Age ≥ 65 was a risk factor for mortality (p = 0.011).
Conclusion:
• Pneumococcal IE remains rare but with a poor prognosis.
• Resort to surgery is yet to be determined, improves survival.
• Predisposing conditions for IPD are the main factors leading to
pneumococcal IE.
• They could be prevented by vaccine coverage improvement !!
• The Austrian syndrome* is a pathology caused by disseminated Streptococcus
pneumoniae infection and characterized for the triad of pneumonia,
endocarditis and meningitis.
• It has an estimated incidence of 0.9-7.8 cases per ten millions people each
year, and a mortality of 32%.
• Alcohol abuse, as the main risk factor, appears only in four out of ten patients.
• 14% of patients do not have any risk factor.
• Two out of three patients are males and it occurs in the middle aged of life.
• It is more frequently on native valve, aortic valve is injured in the half of the
cases. Severe regurgitation occurs in two per three patients.
• Appropriate antimicrobial treatment and early endocarditis surgery decrease
mortality.
• It is possible that Austrian syndrome epidemiology is changing by the
introduction of 13-valent pneumococcal conjugated vaccine in the
children´s calendar.* Described by Osler in 1881.
Anamnesis:
• a 3-week history of productive cough, rhinorrhea, non-bloody non-bilious emesis
• intermittent fevers with a maximum temperature of 102 °F
• treated for pneumonia twice in the past six months + recurrent ear infections
• was diagnosed to have moderate persistent asthma a year ago
• uncomplicated birth history
• no history of any structural heart disease or any other congenital defects
• the child was up to date with vaccines including four doses of pneumococcal
conjugate vaccine (PCV)13
• there was no family history of recurrent infections, immunodeficiency,
consanguinity, or cardiac problems
Diagnosis:
• Chest X-ray: opacification in the right lower lobe
• Cardiac echocardiography: 3-mm vegetation on the anterior mitral valve leaflet
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Primary blood culture:
• Streptococcus pneumoniae, serotype 3N sensitive to penicillin G and ceftriaxone
Outcome:
• Recovery after 4-w of AB treatment, Follow up echocardiogram one month:
resolution of vegetation
Discussion/literature:
• Mayo clinic* – between 1950-2011
– 97 IE, one case of pneumococcal endocarditis
• 5-year long study/Japan**
– 2/170 cases of pneumococcal endocarditis, both with no risk factors
• US Pediatric Multicenter Pneumococcal Surveillance Group*** prospective study,
eight major centers with invasive disease due to S.pneumoniae – between 1993-2003.
– 11 cases/3065 – only one child had no history of structural heart disease!
*Johnson JA et al: Infective endocarditis in the pediatric patient: a 60-year single-institution review. Mayo Clin Proc. 2012, 87:629-635.
**Ishiwada N et al: Pneumococcal endocarditis in children: a nationwide survey in Japan. Int J Cardiol. 2008, 123:298-301
***Givner LB et al: Pneumococcal endocarditis in children . Clin Infect Dis. 2004, 38:1273-1278
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Risk factors for Pneumococcal disease and
complications*
• Immunocompetent children– Chronic heart disease
– Chronic lung disease
– Diabetes mellitus
– CSF leaks
– Cochlear implants
• Children with functional or anatomic asplenia– Sickle cell disease and other hemoglobinopathias
– Congenital or aquired asplenia or splenic dysfunction
• Children with immunocompromised conditions– HIV infection
– Chronic renal failure and nephrotic syndrome
– Disease associated with treatment with immunosuppressive drugs or radiation therapy, or
solid organ transplantation
– Congenital immunodeficiency
*CDC MMWR Recomm Rep 2010;59(RR-11):1-18.
Summing up pneumococcal endocarditis
• rare condition, but may occur in any age
• majority of cases above 65ys
• in children extremely rare
• majority with risk factors/underlying heart conditions
• PCVs in pediatric immunization programs have an
impact on incidence
Note:
• there are occasional cases in immunocompetent,
otherwise healty children too
Pneumococcal peritonitis*
*IDCases, Volume 15, 2019, e00489
Pneumococcal peritonitis
• Tis a form of primary peritonitis(PP), what is a diffuse infective inflammation of the
peritoneal cavity in the absence of a localized source – mainly caused by Gram
negative bacteria, extremly rarely by pneumococcus
• ..is a rare occurrence and represents a clinical challenge because of its subtle and
non-specific clinical findings.
• ..in current literature generally „case reports” can be found
• ..in adults, the so called „primary peritonitis” without an identifiable intra-abdominal
source is extremely rare in healthy individuals;
• T PP is commonly seen in cases of nephrotic syndrome, cirrhosis and end-stage
liver disease, ascites, immunosuppression, and inflamed peritoneum due to pre-
existing autoimmune and oncological conditions
PP due to S. pneumoniae in children
• Pediatric cases are known for nearly a hundred years*
• PP due to pneumococcus occurs almost always in females
• S.pneumoniae may reach the peritoneal cavity by migration via the female genital
tract
• The symptoms usually mimick acute appendicitis
• PP is a rare complication of idiopathic nephrotic syndrome (INS) in children- may lead
to end-stage disease!
• Immunisation with the 13-valent pneumococcal conjugte vaccine is of great
importance!!
*Armitage TG, Williamson RCN. Primary peritonitis in children and adults. Postgrad
Med J 59: 21–4, 1983,.
Dugi DD 3rd, Musher DM, Clarridge JE 3rd, Kimbrough R. Intraabdominal infection
due to Streptococcus pneumoniae. Medicine (Baltimore). 2001;80:236–44
Neonatal sepsis due to pneumocaccal
infection:
„early onset”* vs. „late onset”
*https://parenting.firstcry.com/articles/neonatal-sepsis-causes-symptoms-treatment/
Burden of Pneumococcal Disease in Children
Adapted from CDC. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/pneumo.pdf.
Accessed September 10, 2008.
otitis media
pneumonia
Severity of
disease
No
nin
vasiv
eIn
vasiv
e
Each case of meningitis:
>x 1,000
>x 100
x 10
Incidence
Real “burden of disease” is underestimated because specific diagnosis of
pneumonia and otitis media is difficult; blood cultures, chest-x-ray, and
punctures are not routinely performed
meningitis
bacteremia/
sepsis
• Textremly rare, with high (approx. 60-70%) mortality
• Tis usually acquired intrapartum, from the colonization of the maternal
genital tract
• Tearly-onset presentation of symptoms, usually within the first 48 hours
after birth
• T the virulence seems to be higher for S.pneumoniae, which has in
addition a higher infant invasion/ maternal colonization ratio than
Streptococcus Agalactiae.
• Pneumococcal vaccination has not resulted in a significant decline of
neonatal cases.
• Strategies to prevent early- onset neonatal S.pneu sepsis (NSPS) are
evolving
• Some interventions worth considering for prevention:
– treatment for all pregnant women with a positive vaginal culture to
S.pneumoniae,
– clinicians’ increased awareness of SPNS and prompt aggressive
antibiotic treatment of affected neonates
– further surveillance studies
– assessment of risk factors for SPNS,
– as well as evaluation of other strategies such as vaccination during
pregnancy, aiming to protect these infants are needed.
Pneumococcal conjunctivitis*
* AAP Gateway
Pneumococcal conjunctivitis
• Symptoms
– redness; gray or yellow discharge; itching, burning, pain, or dryness; and crusting
in the morning.
• Diagnosis
– generally uncapsulated S.pneumoniae
• Unusal, though sometimes may cause outbreaks
– schools, college campuses
• Risk factors significantly associated with conjunctivitis*
– having close contact with someone with conjunctivitis
– attending a party
– living in a fraternity or sorority house
– wearing contact lenses, sleeping with them
– being a first-year student
*N Engl J Med 2003; 348:1112-1121
• 1,3% of all conjunctivitis cases are caused by bacteria– S.aureus > H,influensae > S.pneumoniae > M.catarrhalis
• Apart from the well-known „classical” pneumococcal syndromes,
S.pneumoniae– is also one of the top pathogens contributing to bacterial keratitis and conjunctivitis
– has several virulence factors that wreak havoc on the conjunctiva, cornea, and intraocular
system.
• Virulence factors playing a role– Pneumolysin (PLY) is a cholesterol-dependent cytolysin that acts as pore-forming toxin
– Neuraminidases assist in adherence and colonization by exposing cell surface receptors to
the pneumococcus
– Zinc metalloproteinases contribute to evasion of the immune system and disease severity.
• Outcome– Conjunctivitis – good; keratitis – possible scaring; endophtalmitis – visual loss!!
Pneumococcal sinusitis*
*www.medicinenet.com/sinusitis/article.htm
Rhinosinusitis - basic facts
• Tis not rare:
– affects many pediatric patients as well as 1 in 6 adults in any given year,
resulting in ambulatory care, pediatric, and emergency department visits.
• Tuncomplicated rhinosinusitis
– requires no imaging or testing and does not require antibiotic treatment.
• Tusing strict clinical diagnostic criteria
– may minimize unnecessary antibiotics.
• Twhen indicated
– amoxicillin with or without clavulanate for 5 to 10 days remains the first-line
antibiotic, despite increasing incidence of staphylococcal sinusitis in the post-
pneumococcal conjugate vaccine era.
• Temergency providers also need to recognize
– atypical cases in which uncommon but serious complications of sinusitis cause
both morbidity and mortality
Clinical manifestations
• acute catarrhale sinusitis – as part of any URTI
• acute purulent rhinosinusitis (ABRS)• bacterial – S.pneumoniae
• fungal
• dentogen
• chronic sinusitis• risk factors
• irritation
• alien bodies, etc.
The role of risk factors in rhinosinusitis
• Risk factors– „host” faktorok
• age
– infants – immunological/anatomical immaturity
– elderly – immunologically senile („senile” T ly)
• underlying diseases
– mucoviscidosis, diabetes mellitus, mucociliary defectT
– immunosuppressivev treatment, malignant disease
– anatomical defect – septum deviation, atresia
– polyp, tumor
– „environmental” – indirect „host” factors• environmental
– smog, smoke, swimming poolsT
• alien bodies, trauma, iatrogen (tooth extraction)
Acute bacterial rhinosinusitis - ABRS
• Antibacterial treatment is necessary only in selected
cases:
– non specific signs and symptoms of URTI (rhinorrhoea, cough,
mainly) persisting for the minimum of 10 days without
improvement
– acute sinusitis creates diagnostic difficulty due to the lack of
sensitive and specific tests to discriminate viral from bacterial
etiologies in primary care settings.
– the diagnosis of acute bacterial sinusitis is usually based on
clinical criteria, and it is uncommon in patients who have been ill
for less than 10-14 days. Sinus inflammation is common with a
viral URI, but these symptoms resolve after 7-10 days. Patients
who continue to have symptoms without improvement for 10-14
days may have a bacterial infection.
Acute bacterial rhinosinusisits - ABRS
• In rare cases, patients may present with more severe signs of acute
bacterial sinusitis. These often include fever, facial swelling, facial pain,
and maxillary tooth pain.
• Most cases of sinusitis are self-limited, but antibiotic treatment confers a
modest benefit. In uncomplicated cases, use a narrow spectrum drug such
as amoxicillin for initial treatment. Strains of pneumococci with
intermediate penicillin resistance can still be effectively treated with
amoxicillin.
• deteriorating general condition (e.g. high grade fever 39ºC, facial swelling
and pain, maxillary pain after 5-7 days)
• need to treat at once, if serious complications occur (ethmoiditis,
celullitis orbitae)
13-PCVs in NIPS have reduced the pneumococcal sinusitis burden
considerably
mészner
• Aims:
– All children 0 to <18 years old hospitalized for sinusitis, pneumonia, or
empyema in Stockholm County, Sweden, from 2003 to 2012 were
included in a population-based study of hospital registry data on
hospitalizations due to sinusitis, pneumonia, or empyema.
• Results:
– Hospitalizations for sinusitis decreased significantly in children
aged 0 to <2 years, from 70 to 24 cases per 100 000 population (RR =
0.34, P < .001)
• Conclusions:
– PCV7 and PCV13 vaccination led to a 66% lower risk of
hospitalization for sinusitis
Take home messages
• Non-classical pneumococal infection
– may generally be uncommon - though might lead to life threatening courses and
complications
• Pneumococcal endocarditis
– usually occurs with underlying conditions and risk factors
– unique cases may occur in otherwise healthy and immunocompetent children
• Pneumococcal peritonitis
– may mimick appendicitis in competent hosts
– nephrosis sy poses risk for it
– more often occurs in females
• Pneumococcal neonatal sepsis
– ‚early onset’ has an acceptable high mortality
– needs new strategies for prevention and treatment
• Pneumococcal conjunctivitis
– may have outbreaks
• Pneumococcal sinusitis– PCV childhood immunisation programs greatly reduced the burden
mészner