Management of Severe Measles Infection and Pneumonia
Christopher J. Gregory, MD, MPH
International Emerging Infections Program
US CDC Southeast Asia Regional Office
June 2, 2016
Center for Global Health
Division of Global Health Protection
Major Challenges in Measles Management
 Highly contagious
• Large outbreaks
• Nosocomial transmission
• Historically a leading cause of childhood mortality
 Serious complications
• Diarrhea
• Pneumonia
 Secondary infections
 Increased mortality in certain vulnerable groups
• Neonates
• Immunocompromised
 Underrecognized disease burden
• Usually delayed presentation of deaths
 Loss of clinical and parental recognition and experience
90% Reduction in Estimated Measles Deaths,
1985–2012
1,200
Estimated Deaths (1000s)
1,000
800
600
400
200
0
Source: WHO/IVB estimates, February 2014
During 2000–2012
• 77% decrease in incidence
• 78% decline in deaths
•
13.8 million deaths averted
Measles virus
• RNA virus
•Humans are the only reservoir
• Multiplies in the respiratory tract
• Transmitted via respiratory secretions
or aerosols
•Most infectious human pathogen
• R0 around 20
Measles disease
- An acute disease
• Highly infectious: almost everyone exposed
gets the disease if not immune
• Mortality highest in children <2 years,
immunocompromised people (including
malnutrition), and those with high level of
exposure (dose effect)
Measles disease:
Classic manifestations
• Fever
• Maculopapular rash
• The 3Cs:
 Cough
 Coryza (runny nose)
 Conjunctivitis (red eyes)
Photo courtesy of Professor Samuel Katz,
Duke University Medical Center.
Clinical course of measles
- Incubation period: 14 days (range, 7 – 18 days)
- Prodrome: begins 10 – 14 days after exposure (or 2- 4 days prior to
rash)
– High fever, cough, coryza, conjunctivitis
– Period of greatest infectiousness (virus shedding)
- Rash begins: 2 – 4 days after prodrome starts
- Complications: occur mostly in 2nd and 3rd weeks
– Any disease or death not clearly due to another cause (e.g., trauma) during the
30 days following rash onset
- Case Fatality Ratio (CFR) 0.1 – 10 %
– Up to 30% in humanitarian emergencies
Measles complications
Corneal scarring
causing blindness
Vitamin A deficiency
Encephalitis
Older children, adults
≈ 0.1% of cases
Chronic disability
Pneumonia &
diarrhea
Diarrhea common in developing countries
Pneumonia ~ 5-10% of cases, usually bacterial
desquamation
Measles mortality
Key papers on measles management
Measles and Pneumonia
- Pneumonia is seen in up to 80% of hospitalized measles cases
- Responsible for:
- 25-100% of measles-associated deaths
- 8-50% of pneumonia deaths in developing countries with endemic
measles
- Pneumonia early in phase of measles infection typically due
to direct infection with measles virus
- Later episodes of pneumonia typically associated with
secondary infections
Measles and Pneumonia
- Measles can predispose to mycobacterium tuberculosis
reactivation
- Hospitalized patients with measles more likely to acquire
nosocomial infections than other patients
- Case-control study from South Africa demonstrated 6-fold increase in
bacteremia rate
- Reports of measles infection leading to bronchiectasis and
recurrent chest infections
- Increased mortality among children with measles infection for
at least a year afterwards
- Attributed to immune suppression and associated vitamin A deficiency
- Malnutrition a risk factor for both pneumonia and death for
pneumonia in measles
Management of measles pneumonia
- Vitamin A supplementation shown in multiple clinical trials to
reduce morbidity and mortality from measles
- Effect most prominent in younger children and those with pneumonia
- Meta-analysis of four hospital-based trials showed 67%
reduction in mortality
- Also reduced hospital length of stay and patients receiving
vitamin A resolved pneumonia more quickly
- All severe (hospitalized) measles patients should receive 2 daily
doses of vitamin A
- <6 months old: 50,000 IU/day
- 6-11 months old: 100,000 IU/day
- ≥ 12 months old: 200,000 IU/day
Antibiotics and measles
•
•
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Little evidence of benefit of prophylactic antibiotics
Antibiotics should be given to severe pneumonia patients
Given findings in previous studies, would be wise to ensure
good coverage for S. pneumo and S. Aureus
 Potential treatment regimens: IV amoxicillin-clavulante,
cefuroxime, or oxacillin + chloramphenicol or 3rd generation
cephalosporin
 If concern over resistant S. pneumo or S. Aureus, consider
Vancomycin + Clindamycin
Pneumonia and respiratory support
•
•
•
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No evidence for specific treatment for measles-associated
pneumonia apart from Vitamin A
Most important factors are to avoid and treat hypoxia,
maintain nutritional status and avoid complications
Common complications for hospitalized pneumonia patients
include nosocomial infections (including ventilatorassociated pneumonia, urinary tract infections, blood stream
infections), malnutrition, secondary lung damage from
ventilator injury or oxygen toxicity, oversedation
Goal is to maintain homeostatic balance while primary injury
resolves
Basic requirements for high dependency units
Gentle lung approach
•
•
•
•
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Goal is to provide minimum amount of oxygen to maintain
adequate oxygenation (Sp02 >90%) and perfusion
Large tidal volumes or high distending pressures can result in
secondary lung trauma (volutrauma or barotrauma)
Inadequate humidification can predispose to atelectasis and
airway obstruction
Excess oxygen beyond needed to maintain O2 saturation can
lead to additional lung damage from oxidative stress
High oxygen saturations, low CO2 levels and/or excess
sedation can reduce ventilatory drive
Adjunct measures
•
•
Steroids not shown to have benefit for pneumonia and can
increase immunosuppression
Early enteral nutrition should be goal
 Reduce infection, fluid overload and optimizes nutritional status
•
Avoid sedation as much as possible
 Decreases cough and ventilatory drive; can produce delirium
and interfere with maintaining normal sleep patterns
Non-invasive ventilation
•
•
•
In recent years, increasing use of non-invasive ventilation
Effective in most cases of moderate respiratory distress
Most common provided via CPAP (continuous positive
airway pressure)
 Similar to PEEP on ventilator
 Improves oxygenation by maintaining lungs “open” and close to
functional reserve capacity
 Allows continued spontaneous respirations
 Can also augment CO2 removal to limited extent by alveolar
collapse and ventilation-perfusion mismatch
 Gentler on lungs than invasive ventilation and less complications
• Fewer nosocomial infections, less need for sedation etc
 Requires less equipment and technical expertise
Continuous Positive Airway Pressure
•
Case-fatality rate in many countries for hypoxaemic
pneumonia despite oxygen, antibiotics is 5-10%
 Up to 20% in neonates
•
•
Additional means of respiratory support needed in these
children
Continuous positive airway pressure (CPAP) is one option
 Relatively low-cost and simple
 Especially beneficial in neonatal population
 Demonstrated beneficial effect in many countries for decreasing
mortality and reducing need for high levels of oxygen
CPAP: General Principles
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•
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CPAP is indicated in infants or older children with severe
respiratory distress or apnea despite oxygen therapy
Maintains lung volume during expiration, decreases
atelectasis (alveolar and lung segmental collapse), improves
oxygenation and reduces respiratory fatigue
Can be delivered with or without ventilator
 Options also include high-flow nasal cannula and bubble CPAP
CPAP options
Bubble CPAP
Monitoring patients on CPAP
Summary of severe measles management
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Early administration of vitamin A
Reduce opportunities for in-hospital exposure of patients,
family and staff
Antibiotics covering Streptococcus pneumoniae and
Staphylococcus Aureus in complicated/worsening patients
Oxygen
CPAP
Ventilator
Avoid complications during hospital stay
 Secondary infection, immunosuppression, worsened nutrition