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Infectious Disease Epidemiology Section Office of Public Health Louisiana Dept of Health & Hospitals

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Clinical Presentation: Lower respiratory Tract Infection

Prodrome ±

 Symptoms of upper respiratory tract
infection: sore throat, rhinorrhea

 Fever, chills
 Nausea, vomiting, diarrhea

 Headache, dizziness

Clinical Presentation: Lower respiratory Tract Infection
 Acute Infection:

   

Fever, chills Back pain, myalgias, arthralgias Headache, malaise, chills Nausea, vomiting

 Chest Infection:

 Cough  Chest pain  Rales, wheezing, noisy chest

 Characteristic changes on chest x-rays  Increasing respiratory distress, may require
mechanical ventilation

Diagnostic etiology of pneumonia
About 40-60% of persons with pneumonia do not have a defined etiology… even after extensive testing for known respiratory pathogens

Community Acquired Pneumonia
Age-specific rates of hospital admission for community-acquired pneumonia caused by S. pneumoniae, M. pneumoniae, C. pneumoniae, or Legionella species

Pneumonia Acute Respiratory Disease & Fever






RICIN toxin Staphylococcal Enterotoxin B


Pneumonia Acute Respiratory Disease & Fever

• They all look alike, sound alike • Not easy to differentiate from other pneumonias
• Bronchoscopy, sputum, bronchial lavage… • Blood culture

• Look for antibodies in serum


Infection type Otitis media Pneumonia Bacteremia Meningitis Deaths Cases Mortality 7,000,000 500,000 5% 50,000 20% 3,000 30% 40,000

 colonizes the upper respiratory tract  cause:
 disseminated invasive infections
- bacteremia
- meningitis

 pneumonia & other lower respiratory tract
infections  upper respiratory tract infections - otitis media
- sinusitis

Risk Factors/ Increased risk for developing pneumococcal infection or experiencing severe disease and complications

 Children < 2 & adults aged > 65 years  Underlying medical conditions
 chronic cardiovascular diseases (CHF/

 chronic pulmonary diseases (COPD or emphysema)  chronic liver diseases (cirrhosis)  Diabetes mellitus with CV or renal dysfunction  Chronic renal failure or nephrotic syndrome  Asthma NO unless with chronic bronchitis…

Risk Factors/ Increased risk for developing pneumococcal infection or experiencing severe disease and complications

 Asplenia Functional or anatomic (SCD or

splenectomy) clearance of encapsulated bacteria from the bloodstream antigens as in immunosuppressive conditions

 decreased responsiveness to polysaccharide
Immunosuppressive conditions:
AIDS, CIDS, leukemia, lymphoma, multiple myeloma, Hodgkins disease, or generalized malignancy, organ or bone marrow transplantation; rx with alkylating agents, antimetabolites, or systemic corticosteroids

Pneumonia in HIV

 Most common bacterial cause of
pneumonia in HIV

 Invasive pneumococcal disease

often first clinical manifestation of children HIV

 AIDS: annual attack rate of

pneumococcal bacteremia ~ 1%

Pneumococcal Vaccine
 Pneumovax-Merck and Pneu-Immune® 23 Lederle
 include 23 purified capsular polysaccharide antigens  serotype-specific antibody develops within 2-3 weeks  in >80% of healthy young adults  responses not consistent among 23 serotypes  immunocompromised patients & children aged < 2
whose immune systems are immature: antibody responses 

Pneumococcal Vaccine
 Effectiveness  against invasive disease: 56% to 81% in case-control
studies  not effective for prevention of common upper respiratory diseases (e.g., sinusitis in children)  efficacy for non-bacteremic pneumonia was not demonstrated in elderly or in persons with chronic medical conditions

 Side effects  mild, local (pain at site, erythema, swelling), < 48 hrs,  systemic reactions (fever, myalgias) severe local
reactions rare


Legionnaires Disease

 58th annual convention of the American Legion’s

Pennsylvania Department at Bellevue Stanford Hotel in Philadelphia, July 21-24 1976

 Starting July 22 - convention attendees and others who
entered hotel became sick: pneumonia

 182 hotel cases + 39 neighborhood cases  34 deaths
 Six months later a small bacterium named Legionella
lung tissues of the cases

pneumophila isolated from guinea pigs inoculated with the

Legionnaires Disease

 Similar agents isolated before but never
before so thoroughly characterized soldier in Fort Bragg, NC scuba diver

 1943 L. micdadei from blood of febrile  in 1959 L.bozemannii from lung tissue of  identified as the causative for Pontiac fever
 retrospectively by serology  outbreak of acute febrile illness, 1968, MI DOH
building in Pontiac


 Legionella  small (0.3  - 0.9 ) bacteria

~ very small Gram neg bacteria

 grows on buffered charcoal yeast extract agar (BCYE)  supplemented by
 antibiotics to prevent overgrowth of Legionella  dye to give Legionella a distinctive color

 grows slowly, 3-5 days to have small colonies


 18 species

 Legionella pneumophila
serogroup 1 is the predominant species in USA
Legionella pneumophila

multiplying inside a cultured human lung fibroblast


 in nature,

 infect free living amebae  as Acanthamoeba, Naegleria and Harmanella  multiply within amebae

 do not colonize respiratory tract  phagocytized by the macrophages, then multiply
within macrophages

 cell surface protein, macrophage infectivity
potentiator (Mip) necessary for invasion of phagocytes and expression of virulence fold

 mutation in the Mip gene increase virulence 80-

Natural Habitat
 Occurs worldwide  preferred habitat: WATER

 preferably WARM WATERS with scale,
sediment, metallic ions and commensal flora

 well adapted to hot water distribution system in

dwellings: colonizes hot water heaters, storage tanks, pipes, shower heads, plumbing materials, faucet aerators, AC cooling towers, evaporative condensers

 found in 1-30% of home hot water

 multiplies in free living amebae:
Acanthamoeba, Naegleria..


 Inhalation of aerosols of water
contaminated with Legionella

 primary mechanism of entry:
aerosols generated by cooling towers, showers, faucets, respiratory therapy equipment and room-air humidifiers

 aspiration of contaminated potable
water also proposed

 NO Person-to-person transmission


 Incubation 2-10 days  80% of reported cases are SPORADIC  Outbreaks in hospitals, cruise ships,
hotels and other large buildings

Clinical: Pneumonia

 Common cause of PNEUMONIA  % community acquired pneumonias due to
Legionella is difficult to estimate

 diagnostic tests for recent Legionella not  retrospective & prospective studies  1%-5%
CAP pneumonias depending on geographic setting immunocompromised or chronically ill individuals

 risk higher among cigarette smokers, elderlies,

 wide range of clinical response  asymptomatic serologic conversion
 self limited febrile illness (Pontiac fever)
 headache, chills  myalgias or progressive

 severe pneumonia (Legionnaire’s
disease) Legionnaire’s disease cannot be distinguished clinically or radiologically from other pneumonias


 Isolation of Legionella from respiratory
secretion cultures

 Visualization of Legionella in respiratory

secretions or tissue by immunofluorescence

 Detection of Legionella serogroup 1 antigen

in the urine by radioimmunoassay, or enzyme immunoassay (EIA)  more sensitive and specific than IF on respiratory
tract secretions  rapid diagnosis  but only detects infection due to this species and serogroup


 Four fold rise in antibody titer to

 rising to above 1:128 in paired sera  Antibodies to Mycoplasma
pneumoniae, Campylobacter jejuni, Pseudomonas aeruginosa and Bacteroides fragilis, may cause falsepositive IFA test results


One elevated antibody titer does NOT confirm case of recent legionellosis
1% - 16% of adults have IFA titers 1:256

Safe Water ”ways”

 grows poorly at < 20 C and > 50 C  killed at temperatures > 60 C
 susceptible to
   
chlorine and bromine disinfectants ozone heavy metal ions UV

 studies performed under lab

conditions not always successful in predicting effectiveness under field conditions

Safe Water ”ways” Cooling towers and evaporative condensers  disinfected by hyperchlorination  safer approaches would be to place
them away from public areas

 to use drift eliminators  to clean from organic matter

 to dose automatically with a biocide

Cooling Tower

Safe Water ”ways”
Whirlpool spas  halogen levels at 4 - 10 mg/L,
monitor frequently

 pH at 7.2 - 7.8  drain and clean system frequently  replace filters regularly

Safe Water”ways”
Hot water system  flushing for >5mn at > 65 C
 hyperchlorination (flushing with water  10 mg/L
free residual chlorine)
• • • • • • •

 may grow back unless
hot water maintained at  50 C cold water at  20 C residual chlorine at  1-2 mg/L of free chlorine risk of scalding users hyperchlorination causes corrosion remove scale and sediments UV, ozone and heavy metals +



 Bordetella pertussis  fastidious Gram neg  Bordet Gengou agar with
15% sheep blood or Regan Lowe

 Swabs to be inoculated
 Delays  isolation  incubated at 35 C, in
moist air

 Growth 5 days

 large droplets  from upper

Humans only

respiratory tract  NOT by droplet nuclei or fomites  Asymptomatic cases exist, role ??

 Without immunity, susceptibility = 100%, no child
escaped pertussis

 Household exposure: attack rate
   

pertussis = 90% to 100%, (in school 50%) mumps = 31% measles=75% chickenpox=61%

Period of Communicability

Incubation 7d (6-25 d)

CATHARRHAL PAROXYSMAL Convales 10-14d 7-14d cence Communicability weeks Onset + 21 d Infected HCW: Onset +21 or Rx+5d
Exposed HCW: ex+6 until +21 or rx+5d

Epidemiology: before Vaccine
 endemic with epidemics

at 3 - 5 years interval in unimmunized population

 majority among children
 40% among infants 
< months 75% among children < 5 years of age

 incidence rate of

whooping cough was about 150 /100,000 /year

 distributed worldwide  outbreaks any time, slightly more during
summer & early fall

Epidemiology After Vaccine

 Immunization or immunity after disease
prevents disease but NOT infection

 US rates down to 0.5 - 1 /100,000/yr  nowadays resurgence
 pertussis = epidemic with 2 - 5 years cycles  immunization  cases but did not change cycles

Epidemiology After Vaccine
 Common among adults

 IgA antibodies only produced after a natural
infection, not after immunization

 Prevalence of IgA antibodies similar among adults
in countries with generalized immunization (USA) or in countries with no systematic pertussis immunization (Germany in the 1970s):  vaccine did not prevent production of IgA  Vaccine did not prevent transmission

 25% of adults with persistent cough have

serologic evidence of recent pertussis infection

Pertussis in the USA

Log scale

Pertussis in the USA

 first week: catarrhal phase:
cough increases

 paroxysmal stage lasts for 3-4

weeks:  starts after 2 weeks  severe spells of coughing  typical whoop: The whoop created by vigorous inspiration through the glottis at end of paroxysm  during paroxysms, the child may turn blue or vomit  fever usually low  subconjunctival, cerebral and nose hemorrhages


 related to age:  50% in young infants
 negligible after 5

 pulmonary complications  Encephalopathy  otitis media, mastoiditis, inanition and
diarrhea are common in developing countries

 permanent neurological

 nasopharyngeal culture  nasopharyngeal mucus
collected on Dacron or calcium alginate swab

a whooping cough syndrome similar to pertussis

 then inoculated on special
culture media  Bordet Gengou agar with sheep’s blood  Regan-Lowe medium
if delay

Bordetella parapertussis, Chlamydia trachomatis


 Stuart’s transport medium  culture + from beginning
of catarrhal stage+ 3 weeks

ImmunoFluorescence Assay (DFA)
not as specific or as

sensitive as culture

Prevention: Early Case Finding

 EARLY DETECTION essential to
institute prevention

 Mild upper respiratory infection 
mild fever + coughing > 1 week duration  SUSPECT PERTUSSIS

Prevention: Contact Investigation
 identify individuals at risk, evaluate immunization

 implement isolation and chemoprophylaxis  monitor for respiratory  for 14 days after contact

 household and other close contacts irrespective of
their immunization status:

 erythromycin po (40 to 50 mg/kg/day in 4 divided

    

doses, maximum 2 g) for 14 days eliminates carriage, may prevent disease if early immune are protected against new disease but not against infection and serve as transmitters compliance poor 5 day azithromycin, or 7 day clarithromycin OK Trimethoprim-Sulfamethoxazole alternate

Prevention: Day Care Centers

 immunization as appropriate

 and chemoprophylaxis: same

doses as the household contacts

 symptomatic children excluded
pending medical evaluation:
may return 5 days after initiation of erythromycin

 children on chemoprophylaxis

Childhood Immunization Schedule
Birth 1m 2m 3m 4m 6m 12m 15m 18m 4-6y 11-12y



DTP Hib Hib Polio
Varicella MMR or MMR Varicella





Pertussis Vaccine

 Whole cell vaccines  Acellular vaccines:
 5 immunogenic components capable individually    
or combined, of producing immunity acellular DPT vaccines initially developed in Japan inactive form of pertussis toxin, filamentous hemagglutinin, agglutinogens, outer membrane protein use of acellular vaccine reduces side effects: fever & irritability USA: acellular vaccines combined with DT recommended

Prevention: Isolation /Exclusion
Isolation of the hospital patient

 Droplet precautions until onset+21d
or rx+7d

 Exclusion from school & day care

Health Care Worker

 1-suspected HCW : removed from patient contact until status
determined  2-infectedHCW: + culture even if asymptomatic) removed from direct patient contact from onset to 21 days or until 7 days after rx start  3-exposed HCW: asymptomatic and neg cultures can continue

Prevention in Health Care Facilities: Triage
 Questions patients with fever and respiratory

 Triage at first points of contact or before performing
history-taking or examinations

Surgical mask on suspect patients early during the triage process

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