important diseases in disasters · neisseria meningitidis • can cause severe brain damage • cfr...
TRANSCRIPT
Important diseases in disasters:Respiratory tract transmission
Dr Tim HealingMSc, PhD, FSB, CBIOL, Dip.Clin.Micro, DMCC
Course Director,
Course in Conflict and Catastrophe Medicine
Worshipful Society of Apothecaries of London
Faculty of Conflict and Catastrophe Medicine
TB
Meningococcal disease
Measles
Diphtheria
TB
• Caused by bacteria of the genus Mycobacterium– (Also known as Acid Fast Bacilli - AFB)
• Most human cases are due to M.tuberculosis
• A small proportion are caused by M.bovis
• The other major mycobacterial pathogen is M.leprae
• Many other Mycobacteria can infect humans. Most are rare opportunists affecting those with damaged immune systems (e.g. with HIV)
Among 3,570 culture
confirmed TB cases notified
in UK in 2016:
M.tb 96.2% (3,434)
M.bovis 1.0% (34)
M.africanum 1.4% (51)
M.microti 0.1% (3)
M.tb complex 1.3% (48)
TB
• TB is one of the three
primary diseases of
poverty (together with
AIDS and malaria).
• It remains as one of
the top 10 causes of
deaths worldwide
• 95% of active TB
infections occur in
developing countries
Worldwide TB statistics • The proportion of people
with TB slowly falling (Incidence falling about 2%/year)
• Total number of new cases still increasing (due to population growth)
• In 2016– 6.6 million cases of TB
notified
– 1.0 million children <15Y
– TB deaths • 1.3 million in HIV-negative
people
• 0.4 million in HIV-positive people
• 250,000 children
TB statistics• 30% of world’s population carry TB
• Top 7 countries (64% of cases) India, Indonesia, China,
Phillippines, Pakistan, Nigeria, South Africa
• 1% of world’s popn infected each year
• Most carry it inactively (may activate if immune system
weakened)
• TB carriers
– 5-10% of HIV-ve become sick/infectious during their lifetime
– 5-10% HIV+ve become sick/infectious per year
• Each untreated active TB case will infect ca. 10 -15
people/year.
• Possible that only about 35% of paediatric TB cases are
detected in some high-burden countries*
(*Dodd et al, Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.
Lancet Global Health, Early Online Publication, 9th July 2014)
TB incidence rates worldwide in 2016 (WHO)
5664 cases were notified in the UK in 2016, an incidence of 10.2/100,000 population.
TB & HIV
Estimated TB deaths (excluding HIV +ve individuals)
2016
Problems for TB control
• Poverty
• Poor medical care
• Emergence of drug
resistance
• Interaction with HIV
• Population increase
• Poor surveillance
• Difficulties of lab diagnosis
& drug resistance testing
Problems for TB
control
• Diagnosis
• Difficult on S&S
(especially in children)
• CXR and multiple
sputum samples
• Slow culture: 2-6
weeks
TB• Fever
• Chills
• Night sweats
• Loss of appetite
• Fatigue
• Weight loss
• Cough with blood stained sputum
Anti TB drugsFirst line drugs– Ethambutol (E)
– Isoniazid (H)
– Pyrazinamide (Z)
– Rifampicin (R)
[In the UK it costs about
£5000 to treat a patient on
first line drug therapy
Treatment duration 6/12]
Second line drugs– Aminoglycosides
(Amikacin)
– Polypeptides
(Capreomycin)
– Fluoroquinolones
(Ciprofloxacin)
– Thioamides
(Ethionamide)
– Cycloserine
– Terizidone
[In the UK it costs £50,000
to £70,000 to treat a
patient on second line
drug therapy
Treatment duration 20 –
24 months]
Third line drugs– Rifabutin
– Macrolides
(Clarithromycin)
– Linezolid
– Thioacetazone
– Thioridazine
– Arginine
New drugs- Bedaquiline
- Delamanid
Vitamin D
Treatment regimen for new patients
[isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z)]
May be written as: 2HREZ/4HR3
• Intensive phase drugs daily for two months,
• Continuation phase drugs given three times a week
• Multiple drugs avoid resistance
• Problems with compliance
Intensive phase Continuation phase
2 months of HRZE 4 months of HR
Drug resistance in TB• Caused by inconsistent or partial treatment
• Multidrug-resistant TB (MDR/RR-TB)
– MDR: resistance to at least Isoniazid and Rifampicin,
– RR: resistant to Rifampicin
• WHO estimates that there were 600,000 new cases with resistance to rifampicin in 2016 of which 490,000 had MDR-TB
• MDR-TB rates are high in some countries (e.g. India, China, the Russian Federation – ca 50% of cases).
• Requires extensive and expensive chemotherapy (up to two years of treatment) with second-line anti-TB drugs
• Extensively drug-resistant TB (XDR-TB) has recently emerged
– MDR-TB + resistance to a fluoroquinolone + at least one second-line injectable agent
– A serious threat to TB control, (particularly where many TB patients are also infected with HIV)
• Worldwide, only 54% of MDR-TB patients and 30% of XDR-TB are currently successfully treated
% new &
previously treated
TB cases with
MDR TB (2016)
XDR TB
WHO Stop TB Strategy
(2006)
• Achieve universal access to high-quality care for all people with TB
• Reduce the human suffering and socioeconomic burden associated
with TB
• Protect vulnerable populations from TB, TB/HIV and multidrug-
resistant TB
• Support development of new tools and enable their timely and
effective use
• Protect and promote human rights in TB prevention, care and
control
WHO DOTS Strategy
DOTS (Directly Observed Therapy, Short Course) - 5 elements
1. Political commitment at all levels accompanied by sustained, increased financing, and a centralized and prioritized system of TB monitoring, recording and training.
2. Improved case detection through quality assured bacteriology (at least sputum smear microscopy)
3. Standardized treatment regimen of 6-8 months with supervision and patient support by a healthcare worker or community health worker for at least the first 2 months
4. Effective drug supply and management system.
5. A standardized recording and reporting system allowing assessment of treatment results and programme impact.
Green Light Committee
• Subgroup of Stop TB Partnership’s Working
Group on MDR-TB
– Advisory body for WHO & the Stop TB Partnership
– Co-ordinated by GLC secretariat at WHO
• Objectives are:
– Increase access to preferentially priced, quality
assured 2nd line drugs by well performing TB control
programmes
– Ensuring proper use of 2nd line drugs to prevent
resistance
– Advisory body for development of policies &
procedures for managing drug resistant TB
Costs of treating TB (TB Report 2017)
The median cost per patient
treated in 2016 was:
• US$ 1253 for drug-
susceptible TB
• US$ 9529 for MDR-TB.
• (New shortened regimens
of 9–12 months cost about
US$ 1000 per person*).
* For those with MDR TB sensitive to the second line drugs
TB in disasters
• Not an acute problem in the short term
• Potential long term problem– Risks of transmission due to
overcrowding, poor conditions, malnutrition
– Risks to aid workers
• Difficult to treat in mobile (e.g. refugee/IDP) populations– Incomplete treatment
• development of resistance
• cases remain infectious
• Primarily a host government problem – need to develop policy to deal with this in conjunction with WHO
Meningococcal
disease
• Caused by the Gm –ve bacterium Neisseria meningitidis
• Can cause severe brain damage
• CFR for meningitis 9-14% even with treatment
• Severe form is meningococcal septicaemia – high risk of DIC.
(CFR ca. 40%)
• Organism carried in throat by between 10% & 20% of the population
• Rates highest in children & young adults & higher in males than females in some countries Photo: Dr Brodsky
Serogroups of N.meningitidis
• 12 serogroups identified
• 5 can cause epidemics– A, B, C, W135, X
• Geographic & epidemic potential varies from group to group– Gps A, B & C: >90% of cases
– Gp A: ca. 80-85% of cases in African meningitis belt
– Gps B & C: most common in Europe & many Latin American countries
Geographical distribution
• The majority of cases in tropical and sub-tropical regions
• Meningitis belt of sub-Saharan Africa, (Senegal in the west to Ethiopia in the east) has the highest rates– 21 countries & 300 million people at
risk
• The most affected countries in the region are Burkina Faso, Chad, Ethiopia, and Niger (>65% of cases in meningitis belt)
Numbers of cases• Ca. 1.2 million cases/yr worldwide
• Average attack rate:– Industrialized nations 1-3 / 100,000
– Major African epidemics 100 – 800/ 100,000 (up to1% locally)
• Meningitis belt– Epidemics every 7-14 years
– Trend currently downward
– 2009 epidemic season:• 14 countries reporting
• 88,199 suspected cases
• 5,352 deaths (CFR 6.1%)
– 2014• 19 countries reporting
• 11,908 suspected cases
• 1146 deaths (CFR 9.6%)
– Major vaccination programme started 2010
Seasonality
• Highest incidence
– Winter and Spring in Europe and North America
– Dry season in sub-Saharan Africa• Damage to nasopharyngeal mucosa – increased
risk of infection– Dust
– Cold winds
– URTI
• Overcrowded housing
• Population displacement – pilgrimages, markets
Transmission
• From person to person in droplets of
respiratory or throat secretions
• Close and prolonged contact required
– Kissing
– Sneezing
– Coughing
– Living at close quarters (e.g. in a dormitory)
– Sharing eating or drinking utensils (risk of
transmission of respiratory secretions)
Symptoms
• Meningitis:– Stiff neck
– Fever
– Sensitivity to light /photophobia
– Confusion
– Headache
– Altered or loss of consciousness
– Convulsions / seizures
(Severe risk of neurological sequelae)
• Septicaemia– Haemorrhagic / petechial rash / purpura
– Gangrene/peripheral ischaemia
– Septic shock/Circulatory Collapse• Fever
• Low blood pressure
• Tachycardia
• Tachypnea
(High mortality but less risk of neurological sequelae)
Diagnosis• Clinical examination
• Lumbar puncture showing
purulent spinal fluid
• Meningococci / Gm –ve
diplococci in CSF
• CSF:
– raised WBC count (neutrophils
predominant)
– raised protein
– low/absent glucose
• Agglutination tests
• Various RDTs
• Blood culture
• PCR
Treatment
• Start immediately. Do not delay for lab investigations.– Immediate IM benzylpenicillin
– Immediate hospitalisation
• Further treatment involves:– IV antibiotics
• broad spectrum 3rd generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime)
• or benzylpenicillin/ampicillin/amoxycillin
• or chloramphenicol
– IV fluids
– Oxygen
– Inotropic support
– Management of raised intracranial pressure
– [Steroids may help some patients (unlikely to affect long term outcomes) – see NICE treatment guidelines].
WHO first-line treatment for meningitis in
low-income countries in epidemics
• Based on a single injection of a cheap, long acting drug
• Two drugs used– Oily chloramphenicol
– Ceftriaxone
• Oily chloramphenicol– A long-acting oil based preparation of chloramphenicol
– Dose: 100 mg/kg (maximum dose 3g) as a single IM injection. (repeated if there is no clinical response after 48 hours).
– not available in USA or Europe
• Ceftriaxone– usually given daily for five days
– a single dose is equivalent to one dose of oily chloramphenicol
– cheaper than chloramphenicol
– (100 mg/kg (max. 4 g) IM)
Complications
• Complications – Early:
• Raised intracranial pressure
• DIC
• Seizures
• Circulatory collapse
• Organ failure
– Late• Deafness
• Blindness
• Lasting neurological deficits
• Reduced IQ
• Gangrene leading to amputations
Vaccines• Polysaccharide vaccines - used during a response to outbreaks, mainly in
Africa:
– Either bivalent (serogroups A and C), trivalent (A, C & W), or tetravalent (A, C, Y &
W).
– Not effective before 2 years of age
– Offer a 3-year protection but do not prevent carriage and therefore do not induce herd
immunity
• Conjugate vaccines are used in prevention (routine immunization schedules &
preventive campaigns) & outbreak response:
– Confer longer-lasting immunity (5 years and more), prevent carriage and induce herd
immunity.
– Can be used as soon as of one year of age.
– Available vaccines include:
• Monovalent C
• Monovalent A
• Tetravalent (serogroups A, C, Y, W).
• Protein based vaccine against N. meningitidis B (e.g. Bexsero, Trumenba). Can
be used for routine immunization and in outbreak response.
Prevention & Control• Vaccination:
– Populations in high prevalence areas
– Those travelling to or working in high prevalence areas
– Vaccination of contacts of sporadic cases not recommended.
– Protective levels of antibodies are not achieved until 7–14 days after vaccination - cannot prevent early onset disease in these contacts
• Avoid overcrowding, close and prolonged contact, sharing utensils
• Chemoprophylaxis.– Antibiotic prophylaxis for close contacts, when given promptly,
decreases transmission risk.• Outside the African meningitis belt, chemoprophylaxis is recommended for
close contacts within the household
• In the meningitis belt, chemoprophylaxis for close contacts is recommended in non-epidemic situations
– Ciprofloxacin is the antibiotic of choice, ceftriaxone an alternative.
• (Avoid using Rifampicin – risk of TB resistance)
Disaster implications
Movement of populations, added to
crowding in camps, poor urban areas etc.
can increase rates of transmission and lead
to outbreaks
Measles(rubeola, morbilli)
• Caused by a paramyxovirus – (enveloped, single-stranded, negative-sense RNA virus)
• Potentially lethal disease
• Estimated to have killed ca 200 million people worldwide in the last 150 years
• Estimated - more than 20,000,000 cases each year
• Mortality:– in developed countries is ca 1/1000
– in sub-Saharan Africa ca 10%
– in cases with complications, the rate may rise to 20-30%
• Common in crowded emergency settings, large population displacements and high levels of malnutrition
Measles surveillance 2017
• 273,552 cases of measles were reported to WHO of which 145,356
were laboratory confirmed
• In general, the number of reported cases reflects a small proportion
of the true number of cases occurring in the community. Many cases
do not seek health care or, if diagnosed, are not reported.
• Despite this under-reporting, timely measles surveillance is critical to
disease control
• Identifying and confirming suspected cases allows:
• early detection of outbreaks
• analysis of on-going transmission in order to mount more effective
vaccination measures
• estimation of the underlying true incidence based on the patterns in
reported data
Measles – WHO data
• One of the leading causes of death
among young children even though a
safe and cost-effective vaccine is
available.
• Measles vaccination resulted in a 84%
drop in measles deaths between 2000
& 2016 worldwide.
• In 2016, ca. 85% of the world's
children received one dose of measles
vaccine by their first birthday through
routine health services – up from 72%
in 2000.
• During 2000-2016, measles
vaccination prevented an estimated
20.4 million deaths
• In 2016, there were 89,780 measles
deaths globally – the first year
reported measles deaths fell below
100,000/year
Measles
• Spread via respiratory tract (respiratory tract secretions: direct contact / aerosol transmission)
• Very transmissable - 90% of non-immunes living with an infected person will catch it.
• Virus remains active and contagious in the air or on infected surfaces for up to 2 hours.
• Incubation period 9-12 days
• Infective from 2 - 4 days before, until 2 - 5 days after onset of rash (i.e. 4 - 9 days infectivity)
Symptoms
• The three Cs– cough
– coryza
– conjunctivitis
• Fever ca. 4 days – up to 40oC (104oF).
• Koplik’s spots inside mouth (pathognomonic but transient - may be missed )
• A generalized maculopapular erythematous rash appears 2 - 4 days after initial symptoms. Lasts ca. 8 days.– said to "stain“ - changes colour from red to
dark brown, before disappearing
– may not be easily visible in patients with coloured skin
• SPHERE field definition
Complications
• Relatively common & include– Diarrhoea
– Pneumonia
– Otitis media
– Acute encephalitis (and rarely subacute sclerosing panencephalitis)
– Corneal ulceration leading to scarring
• More likely in children <5Y or adults >20Y.
• Causes loss of vitamin A:– potentially blinding eye lesions in young children
– risk of infection
– severe growth faltering
• CFR– in UK in 2016 there were 531 confirmed cases and 1 death (CFR
0.19%)
– In immunocompromised patients CFR is ca. 30%
– In underdeveloped countries with malnutrition and poor health care CFR can approach 30%
Treatment• No specific treatment
– Paracetamol, Ibuprofen etc. to reduce fever and pain
– If required, a fast-acting bronchodilator for cough
– Avoid aspirin for children (Reye’s syndrome risk?)
• WHO - severe complications from measles can be avoided though supportive care
– good nutrition
– adequate fluid intake
– treatment of dehydration with ORS
– complications such as otitis media, pneumonia and bronchitis, eye infections require appropriate antimicrobial and other treatment
• No specific treatment for measles encephalitis (mortality rate of ca. 15%)
• Vitamin A supplement:
– all children in developing countries with measles should receive 2 doses of vitamin A supplements, given 24 hours apart (oral dose of 200,000 IU or 100,000 IU in infants)
– reduces mortality (up to 50%) in children aged under two years
– reduces risks of eye damage and blindness
Control
• Mass measles vaccination campaigns
(EPI) 6/12 -15Y.
– Routine immunisation for children
– Can use measles or MMR vaccines
• If vaccination coverage for a population is
unknown, assume it is inadequate and
vaccinate!
Measles outbreaks in the USA,
• The USA experiences several
outbreaks of measles each
year.
• These are often associated
with travel to endemic areas
• Many children in the USA are
at risk due to failure to
vaccinate
• 2014: 23 measles outbreaks,
including one large outbreak of
383 cases, occurring primarily
among unvaccinated Amish
communities in Ohio.
• 2015: a large, multi-state
outbreak linked to an
amusement park in California.
• .
Implications for disasters
• Especially deadly in countries experiencing or recovering from natural disasters or conflicts– Damage to health services
– Interrupted immunisation programmes
– Overcrowding in camps
• The worst single killer of children in refugee situations in some instances
• Vaccinate children as routine in refugee situations (unless known to be of good vaccination status)
• Give Vitamin A to children with measles– 2 doses 24 hours apart
– Helps prevent eye damage and blindness
– Reduces deaths from measles by 50%
• Good care reduces risk of complications– ORS for dehydration
– Good nutrition
– Antibiotics for eye & ear infections and pneumonia
Diphtheria
• URTI caused by Corynebacterium diphtheriae(Gm +ve)
• Spread by respiratory droplets from throat (coughing, sneezing)
• Affects tonsils, pharynx, larynx and (occasionally) the skin
• Symptoms include– sore throat,
– low fever
– adherent membrane (a pseudomembrane) on the tonsils, pharynx and/or nasal cavity
• Complications include:– Myocarditis (ca 20% of cases)
– Peripheral neuropathy (ca 10% of cases)
– Renal damage
• Mortality in treated patients is 5% - 10%
• Untreated mortality can reach 20% in children <5Y
Other complications
• Intubation or a tracheotomy may be needed if
breathing and swallowing are affected because:
– pseudomembrane becomes extensive
– lymph nodes in the neck swell
• Abnormal cardiac rhythms can occur early in the
course of the illness or weeks later, and can lead
to heart failure
• Diphtheria can also cause paralysis in the eye,
neck, throat, or respiratory muscles.
Treatment• Severe cases may need admission to ICU.
• Antitoxin– Give immediately if diphtheria is suspected
– Do not wait for lab confirmation before giving antitoxin
– Does not neutralize toxin bound to tissues - delayed administration associated with increased mortality risk.
• Antibiotics are used in patients or carriers to eradicate the organism and prevent its transmission – Metronidazole
– Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d)
– Procaine penicillin G, IM for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg).
– Patients allergic to erythromycin or penicillin G can be given clindamycin or rifampicin
Vaccination
• DPT vaccine is recommended for all
school-age children.
• Boosters recommended for:
– adults (the effects of the vaccine decrease
with age without constant re-exposure)
– those travelling to areas where the disease
has not been eradicated
Control
• Mass vaccination for epidemics
• Treat contacts with antibiotics
• Effective treatment of cases:
– Reduces death rate
– Reduces risk of transmission
Disaster implications
• Especially common in
Former Soviet Union and
Asia
• Outbreaks can occur with
overcrowding of susceptible
groups (esp. infants,
children)
• Can therefore occur with
population displacement
• Consider vaccination
programme
Diphtheria in Yemen
As of 14/04/2018
• 1,584 suspected cases & 85 deaths (CFR 5.4%) since Oct 2017
• Children <5Y – 20% of cases & 38 % of deaths
• Most affected age group: 5-15Y (44% of cases)
• 6,842 contacts traced & given prophylactic antibiotics
• WHO, UNICEF, and partners recently vaccinated 2.7 million children 6W – 15Y
• Problems of importing vaccines and antibiotics due to port closures/blockade
(Data from Reliefweb)
Any
Questions?