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?