Speaker: Kathryn Maitland Recorded at: SSAI2017 More from conference: https://scanfoam.org/ssai2017/

1. Sepsis management in resource limited
Africa : challenges and opportunities
Professor Kathryn Maitland
Imperial College, London
Based KEMRI Wellcome Trust Research Programme, Kenya

2. sub-Saharan Africa
Focus of this talk…
• sub-Sarahan Countries
• Paediatric perspective
• Hospitals with limited infrastructure
• …..where there is no access to
ventilation…..

3. Realities in African hospitals:
huge demand and limited resources
Critical care approach to saving
lives – relevance to Africa?

4. The critically sick child: the silent emergency

6. Soroti Hospital, EasternUganda
> 8000 admissions per year

7. Resource-limited emergency room

8. The undifferentiated critically sick child
Severe malaria
Bacterial Sepsis
Sepsis/shock
Severe AnaemiaPneumonia
Meningitis/encephalitis
HIV
Severe malnutrition

9. Fluid
resuscitation
Glycaemic controlTransfusion
Oxygen
Simple treatments: evidence base?
Antibiotics
Antimalarials

10. Most emergency care Treatment Guidelines: ‘strong’ recommendations:
few based on evidence from clinical trials

11. Sepsis?

13. Sepsis definitions

14. Feasibility?
✗
✓x
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✓x
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✓
✓x
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15. Sepsis- the silent emergency
Generic Triage/ emergency section
Vertical/ Syndromic management:
Neonatal /Young infant
The Febrile child (includes malaria**)
Meningo-encephalopathy
Respiratory disease:
oVery Severe Pneumonia
oSevere Pneumonia
oNon-severe Pneumonia
Severe Acute Malnutrition
HIV/AIDS
BUT No mention of ‘sepsis’!!!

16. Africa: Leading causes of under 5y mortality

17. Major challenges for ‘integrated management’ (of sepsis)
• Not specifically mentioned or highlighted as a treatment priority.
• Disproportionate attribution of U5 mortality to ‘pneumonia syndromes’
• Malaria: Endemic area ~ 50% paediatric admissions have malaria
parasites:
 ~10% severe malaria have bacterial co-infection
 Bacterial infection accounts for up one third of all malarial deaths
Most hospitals lack even basic microbiology facilities- so most
antibiotics are usually prescribe ‘blind’

18. WHO pneumonia definitions & treatment recommendations
Give Oxygen
2012 revisions

19. Operational Utility of syndromic management: hypoxia
WHO ‘clinical’ pneumonia definitions and
hypoxaemia (<90%): unselected admission
cohort (n=13183)
4792 (36%) all admissions fulfill severe
pneumonia definitions (SP/VSP)
Only 2168 (16%) had a final diagnosis of
severe pneumonia
Non-specific for pneumonia
High hidden burden of hypoxaemia

20. Hammitt et al Clin Infect Dis. (2012) 54(suppl 2): S190-S199

21. What does this mean for clinical practice?
• The clinical syndrome of severe pneumonia==the critically
sick’ child- hence the VERY high burden of disease
• Burden of hypoxamia in hospital admissions ( as most not
caused by pnuemonia) will remain high – substantial cost
implications for health services
• Recent case control aetiology study (PERCH) – > only 9% -
16%) ‘VSP/SP pneumonia’ ad an identifiable pathogen .

22. Children’s Oxygen Administration
Strategies Trial
!
5 sites 4300 children
2 countries Kenya Uganda
John Fraser, Brisbane
Kathy Rowan

23. Bacterial Aetiology?

24. (Kilifi outside of the ‘Men C’ Epidemic belt in sSA)
Since this publication Haem. Infl B and
Polyvalent Strep Pneumonia vaccines rolled out
Commonest causes of bacteraemia currently- largely gram-neg
pathogens and Staphylococcus
Antimicrobial treatment guidelines often
based on epidemiological data over decade old
Data from Years 2000-2003
Berkley at al NEJM 2005 353 39-47

25. Bacterial co-infection - high proportion of enteric gram-negatives
0%
20%
40%
60%
80%
100%
nts str.pn h.inf
s.typh Other gm neg Other gm pos
Nadjm et al BMJ 2010; 30; 1350-
Case Fatality ~24%
No malaria Recent malaria P. falciparum: increasing parasitaemia

26. Common presenting features: fever, hepatosplenomegaly, respiratory
symptoms. Features of enterocolitis often absent
Main risk factors: HIV (adults) malaria, HIV, malaria and malnutrition (children)

27. Feasey et al Lancet 2012

28. Antibiotic Stewardship?

29. A big problem…that is predicted to rise
• Globally it is estimated that 700,000 people die each year of drug resistance in
illnesses such as bacterial infections, malaria, HIV/Aids or tuberculosis and this
number has been predicted to rise to 10 million people by 2050
• Africa and Asia are predicted to be the most effected

30.  Fluids
Glycaemic control Transfusion
 Oxygen
Simple treatments: evidence base?
Antibiotics
 Antimalarials

31. FEAST trial
MRC funded (n=3215)
NEJM 2011
AQUAMAT trial
Wellcome Trust funded
(n= 5425)
Lancet 2010

32. Does 2.5-3% absolute change in fatality make a
difference?
• ‘if artesunate treatment were widely implemented, the 2.5%
absolute survival advantage over quinine could mean
averting 100,000 deaths of African children every year’
• 3–to-4% worsening of outcome may sound modest, however
this translates into tens of thousands of lives lost whilst
fluid-bolus resuscitation continues to be recommended….

33. Extra slides

34. Transfusion- Issues in Africa

35. Pattern of usage of
blood: demand
UK
Africa
Largely elective-use
Pre-planned and predictable
2/3rd’s blood use: paediatric
transfusions
Largely emergency use
Unpredictable
Highly seasonal

36. Supply: In SSA: < 5 units/1000 population
WHO estimates needs are > 20 units/1000 for current demand

37. WHO needs transfusion?
Brabin et al 2001: Review of evidence:
Haemoglobin and relative risk of death: need for a trial
Meremikwu, M et al 2000
Cochrane review: need for a trial
WHO
Transfusion
thresholds
Stable
‘Complicated’

38. Transfusion questions
• Which children should receive a transfusion?
Current WHO guidelines have not been evaluated in
clinical trials. We don’t know if giving blood to all children
with Hb <6g/dl improves outcome
• How much blood should be given in a transfusion?
A quarter of children receiving transfusions remain
severely anaemic and up to one third get two or more
blood transfusions during a single hospital admission. Will
a larger initial volume reduce re-transfusion and improve
outcome?

39. Factorial design: 3950 children with severe anaemia
FOUR simulataneous Randomisations
• R1 & R2 Transfusion strategies (who and how much
Long-term management
• R3 Micronutrients
• R4 Infection prophylaxis
Blantyre
Malawi
Uganda
TRansfusion and TReatment of severe Anaemia in African Children Trial