Management of sepsis and meningitis in developing countries

Dr Louisa PollockWellcome Trust Liverpool Glasgow Centre for Global Health Research

The scale of the problem... • Global burden of sepsis huge, highest in countries

with least resources• Meningitis– 4% all childhood deaths

• Neonatal sepsis/meningitis– 5% all childhood deaths

• Mortality for both sepsis and meningitis far higher in high-burden countries

• Risk of severe sequelae from bacterial meningitis twice as high in Africa and South-East Asia compared to Europe1

1. Edmond et al 2010

• It is midday, everyone is at lunch except you• Chikondi, a 2 year old girl, has been waiting in the queue with...

– High fever– Fast breathing– A stiff neck– Irritability

• Her malaria test is negative, you are worried she has meningitis...

You are on call at Mulanje District Hospital.....

What is the key to effective treatment?

The key to effective treatment is..

...with the nurse who has gone to lunch

What is the most essential tool for monitoring?

The most essential tool for monitoring is....

....the family

Essentials for the management of meningitis and sepsis

ACCESS TO CARE

HUMAN RESOURCES

Access to care – initial access

• No ambulance service• Poor transport

infrastructure• Distance to health facility• Primary health care

understaffed and under-resourced

• Minimal “out of hours” service

• Costs to family

Access to care - triage• Large numbers of

patients – routine and emergencies

• No formal triage in many settings

• Limited triage capacity• Requirements to

register/ pay before triage in some settings

Access to care - diagnosis

• Limited culture or biochemistry outside teaching hospitals

• Basic microscopy and FBC may be available

• PCV/Hb and malaria screen usually available

• Imaging generally limited to X-ray +/- basic USS

Access to care - drugs

• Drugs ordered centrally from essential drugs list

• Unpredictable and unreliable supply

• Donated drugs often out of date or inappropriate

• Fake/poor quality drugs contribute to resistance

Access to care – supportive care• Limited availability of

oxygen– O2 concentrator limited to

5l/min– Often shared– Electricity dependent

• Bubble CPAP available in some settings

• Monitoring limited– Obs, BP, temp, (O2 sats)

• Nutritional support variable

Access to care – intensive care• No intensive care in most

district hospitals• ITU in teaching hospitals

generally limited to adult surgical care

• Quality of care provided often poor

Human Resources

UK: 500 nurses /50 000 popMalawi: 30 nurses/ 50 000 pop

UK: 135 physicians/ 50 000 popMalawi: 1 physician/ 50 000 pop

•Limited post-graduate training•Limited managerial support and governance•Poorly paid (or unpaid!)•High turnover

Could “Surviving Sepsis” be implemented in developing countries?• 1.2% of surveyed anaesthesia providers in

Sub-Saharan Africa reported capacity to deliver full guideline1

– 72% of recommendations implementable– Likely to be an overestimate

• Modified bundles of care have been proposed according to local resources2

1. Baelani et al 2011 2.Mahavankul 2012

Should “Surviving Sepsis” be implemented in developing countries?• Different causes of sepsis/meningitis• Wider differential diagnosis• Different co-morbidities– HIV, malnutrition

• Different risk:benefit to some interventions– Mechanical ventilation– Invasive monitoring

• Evidence base from high-income countries

ETAT: Emergency Triage, Assessment and Treatment

• WHO Paediatric emergency care guidelines for resource-limited settings

• Training programme and quality improvement strategy

• Designed to fit with IMCI• Uses systematic ABCD

approach to assessment and treatment

• Modified in East Africa to include admission care, malnutrition and neonatal care “ETAT+”

ETAT TRIAGE PROCESS

NO

Impact of ETAT• Improved triage and

emergency care halved in-patient mortality in QECH Malawi

• ETAT+ RCT improved patient outcomes and processes of care in Kenya

• Impact greatest with ongoing monitoring and MoH support

• Ongoing RCPCH supported programme in East Africa

New WHO sepsis guidelines for adults• IMAI (Integrated Management of Adolescent

and Adult Illness) District Clinician Manual• Provide guidelines to care in 1st 2 hours, 2-6

hours, 6-24 hours and post-resuscitation

IMAI sepsis guidelines*

• Emphasise– Early recognition hypotension/ resp distress– Treat infection broadly and early, while seeking source– Fix physiology with judicious oxygen and fluids

• Additional guidance– Pulmonary oedema in severe malaria– Specific fluid management for dengue– Specific antimicrobials for TB, malaria, maternal sepsis

and viral haemorrhagic fevers

*Jacob et al BMC Medicine 2013

Evidence for ETAT/IMAI• Systematic review of evidence

– International Child Health Review Collaboration

– ETAT+• Early monitored sepsis

management in Ugandan adults reduced 30 day mortality by 26%*

• Ongoing study in Malawi assessing impact of clinical care bundle in bacterial meningitis, aiming to reduce mortality (Dr E Wall)

*Jacob et al 2012

• 3141 children in Kenya, Tanzania and Uganda• Malnutrition, severe dehydration, trauma or

severe hypotensive shock excluded• Key finding – 20-40mls/kg bolus over 1 hour

associated with increased mortality vs maintenance fluids only (10.6% vs 7.3%) in children severe febrile illness and signs of reduced tissue perfusion

• Mortality difference highest in children fulfilling ETAT definition of shock (54% vs 20%) but numbers very small (n=65)

The Impact of FEAST on ETAT1. Accept FEAST as best available evidence –change

guideline to a “no bolus” strategyKenyan Paediatric Association (ETAT+)

2. Keep current guideline until further evidence available

WHO (by default)3. Develop a new consensus based conservative fluid

bolus strategy eg boluses 5mls/kg, assess responseETAT Gambia

4. Keep current guideline with caution advised for specific groups

ETAT Gambia

Fluid Guideline 4:Shock due to Severe Infection

Child stable but signs of shock not improving

Child getting worseTHINK

?Fluid overload??Anaemia?

Consider blood or slowing fluid down

Give OxygenGet IV/IO access

Give 20mls/kg bolus normal saline over 20 mins

Closely monitor HR, RR, CRT, BCS

Child improves

Check:Blood Glucose

FBC (priority Hb/PCV)UE (priority Na/ K)

MPS, Blood Cultures

Maintenance FluidsRingers or 0.9%

saline with dextrose

Give 20mls/kg bolus 0.9% saline over 20 mins

(max 3x20mls/kg)If still not improved give blood 20mls/kg over 1 h

• Evidence for paediatric fluid management limited

• Urgent need for trial evidence from high burden, high mortality settings

• Both undertaking research and delivering clinical care challenging in this context

• Improving triage and basic standard of care can dramatically improve mortality

Urgent research gaps...

• Optimal fluid management for septic shock in high burden, high mortality settings

• Efficacy, safety and cost-effectiveness of components of sepsis clinical care bundles in resource-limited settings

• Health systems and operational research to improve access to care and human resources worldwide

The key to management of sepsis and meningitis in developing countries..

• Patience• Resilience• Creativity• Teamwork

Thank you

Useful links - Paediatrics• International Child

Health Review Collaboration– www.ichrc.org

• ETAT+ Kenya– www.idoc-africa.org

Useful links –Adults• IMAI District Clinician Manual• www.who.int/hiv/pub/imai/

imai2011/en/