This presentation by Luke C. Mullany of Johns Hopkins University, "Neonatal Infections: Global and Regional Burden and Interventions" was part of a dynamic panel moderated by JSI's Dr. Penny Dawson on February 13, 2015 at the 14th World Congress on Public Health in Kolkata, India. Four speakers summarized evidence for interventions proven to reduce newborn mortality (e.g., chlorhexidine) and shared important policy and programmatic experiences in prevention and treatment of neonatal infections. JSI's Leela Khanal and Dr. Nosa Orobaton spoke about experiences from Nepal and Nigeria in scaling up chlorhexidine use in those countries. Another speaker shared results from the COMBINE trial in Ethiopia, implemented primarily by JSI with support from SAVE/SNL, which evaluated the impact on neonatal mortality of health extension worker-led management of bacterial infections.

1. Neonatal infections: global
and regional burden and
interventions
Luke C. Mullany,PhD, MHS
Associate Professor, Johns HopkinsUniversity
(lmullany@jhu.edu)
Kolkata, February 2015

2. Global Neonatal Mortality
• Almost 3 million neonatal deaths / yr
– Now at least 44% of child mortality
– Older infant and child mortality reductions out-
pacing those in newborns
• Sub Saharan African and South Asia
have highest rates and burden
• India almost 25% of all neonatal deaths
Source: Liu et al, Lancet, 2014

3. Up to 50%
of neonatal
deaths are in
the first 24 hours
75% of neonatal
deaths are in
the first week
Source: Lancet 2005;365:891-900
When do neonatal deaths occur?

4. Overall and infection-specific causes
• Top three causes:
– Complications of preterm
– Intra-partum related events
– Infections
• ~800,000 infection related deaths
– Sepsis, pneumonia, tetanus, meningitis,
omphalitis, diarrhea, etc

5. Etiology
• Overall, etiology not well characterized
in settings with highest risk
• Relative contribution of vertical vs.
environmental acquisition uncertain
• Bacterial vs viral etiologies not well
distinguished
• Most large community-based datasets
resort to “PSI”, “PSBI”

6. pSBI – Global Estimates
• Overall
incidence
– 7.6%
• Case-
fatality
– 9.8%
Source: Seale et al, Lancet Inf Dis, 2014

7. Causes/Risk Factors for Infections
• Baby factors
– Underdeveloped immunity, preterm/LBW, sex
• Maternal/Caretaker factors
– Maternal infection, under-nutrition
– Unhygienic labor/delivery practices
– Delayed recognition and care-seeking
• Health system factors
– Low access, human resource gap, poor quality
• Environmental/Social factors
– Decision making autonomy, cost, etc

8. Preventative Interventions
• Improved nutrition during pregnancy
• Identification and treatment of infections
in mother
• Clean and hygienic practices during
labor, delivery and postpartum
• Improved newborn care practices
(breastfeeding, cord care, thermal care)
• Extra care and attention for preterm/LBW

9. Ex 1: Early Initiation of Breastfeeding
• Recent studies show early initiation
(<24 hours) can reduce neonatal death
• Both a nutritional and thermal care
intervention
• Helps establish good feeding pattern
(i.e. establish exclusivity and duration)
• Numerous studies have shown
population based change is possible
Source: Debes, Kohli, Walker, Edmond, Mullany, BMC Public Health, 2013

10. Ex 2: Kangaroo Mother Care
1. Skin to skin contact with mother or other
caretaker
2. Support for early breastfeeding
3. Rapid identification and support
• Established as a preventative intervention
for hospitalized, preterm, stabilized
infants
• Lack of strong evidence for community-
wide scale up to all babies
Source: Lawn et al , 2014

11. Ex 3: Chlorhexidine Cord Care
• Accelerating use of chlorhexidine cord
cleansing in high-mortality settings
• Safe, readily available, broad spectrum
topical antiseptic
• Randomized trials in South Asia
demonstrate reduced death and
omphalitis

12. • Sarlahi District, Nepal: 2002-2006
– Mullany, Darmstadt et al, Lancet 2006
• Sylhet District, Bangladesh: 2007-2009
– Arifeen, Mullany et al, Lancet 2012
• Sindh Province, Pakistan: 2008-2009
– Soofi, Bhutta et al, Lancet 2012
S Asia CHX Cord Cleansing Trials

13. Pooled Analysis
MORTALITY: Any CHX vs. No CHX
Study
Overall 0.77 (0.63, 0.94)
RR (95% CI)RR (95% CI)
1.5 .75 1.2
Nepal 0.76 (0.58, 1.00)
Bangladesh 0.88 (0.74, 1.04)
Pakistan 0.62 (0.45, 0.85)
MORTALITY: Any CHX vs. No CHX
23% reduction in mortality among
those receiving intervention
Source: Imdad, Mullany, Baqui, et al, BMC Public Health, 2013

14. Impact on Cord Infection
In all studies…
Multiple CHX reduced cord infection
• Nepal: 33% – 75% reduction
• Bangladesh: 15% – 45% reduction
• Pakistan: 40% – 50% reduction

15. Summary of Mode of Action
0Day 7 14
Prevent continued
exposure with
repeat applications
Colonization
of the patent
vessels
Sepsis Death
Visible
infection
Sepsis Death
Early applications
protect during
patent period
CHX Application
Mortality Risk HIGH MEDIUM LOWER
Primary benefit of
early CHX
cleansings
Additional benefit
of multiple
cleansing
Slide courtesy of Segre J September 2011

16. Updated WHO Cord Care Guidelines
• All trials done in settings with NMR>30
and very high proportion of home
births
• WHO Guidelines now recommend CHX
for use in these high risk settings
• Lower level facility-births may also
benefit
• Pending African trials in lower mortality
settings with lots of facility births

17. “We won’t benefit from chlorhexidine
because harmful practices are no longer
common”
– Not necessarily true. The cord stump is still
exposed to pathogens through routine home
and facility practices
– Among babies where caretakers followed
suggested “cleaned cord practices”,
chlorhexidine still reduced infection and
mortality
Common Questions / Thoughts

18. “This intervention would only help babies
born at home”
– Facility born babies in the Bangladesh and Nepal
trials receiving CHX:
• Lower mortality, fewer cord infection, reduced
colonization, and same relationship between cord
separation time and cord care, as seen in home births
– facilities also struggle to achieve hygienic
practices
– babies are discharged into same environment as
home-born babies
Common Questions / Thoughts

19. “Promotion of chlorhexidine is
inconsistent with our previous
messages..”
– Messages can be shaped to fit consistently
with promotion of clean cord care
– Topical chlorhexidine can be promoted as a
“tool to help caretakers achieve a clean cord”
Common Questions / Thoughts

20. How to interpret the WHO guidelines?
• WHO recs (home, >30 NMR) reflect study
settings
• Impacts of interventions vary with context
• As systems and quality improve, benefits
realized will also vary over time
• Common sense required, recognizing
variable risks within country, across
health system levels, across season, etc

21. Treatment Interventions
• How do we achieve rapid and accurate
identification and treatment of infection?
– Improve recognition and decision making by
caretakers
– Appropriate and feasible scheduling of PNC
through outreach (i.e. CHW) or in-facilities
– Additional targeting of those at highest risk
– Increase access to care at all levels of health
system
– Improve quality of care in facilities

22. Simplified Antibiotic Trials
• Antibiotics in communities or lower level
facilities challenged by:
– Non-specificity of algorithm(s) to identify sick
babies
– Adherence to regimens is poor/difficult
– Unknown or ill-characterized antibiotic resistance
• Series of community/facility non-
inferiority trials to identify simplified
regimens
• Study designs released in PIDJ
supplement (2013), results pending (2015)

23. Etiology of Infection
• Aetiology of Neonatal Infections in
South Asia (ANISA)
– 3 country (Ind, Pak, Bang), 5-site cohort study
• CHWs visit babies over 0-59 days, refer
“sick” babies to physician assessment
• Collect NP and blood from cases and
controls
• Aim is to estimate etiologic distribution
of infections in the region

24. Conclusions
• Despite progress, challenges remain
• Needs are clear:
– Improved routine and targeted preventative care
across the pre-pregnancy, pregnancy, delivery,
and post-partum continuum
– Improved recognition and care-seeking for
infections
– Improved diagnostics at community and facility
levels
– Better data on etiology and antibiotic resistance