Neonatal infections: global

and regional burden and

interventions

Luke C. Mullany, PhD, MHS

Associate Professor, Johns Hopkins University

(lmullany@jhu.edu)

Kolkata, February 2015

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

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?

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

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”

pSBI – Global Estimates

• Overall

incidence

– 7.6%

• Case-

fatality

– 9.8%

Source: Seale et al, Lancet Inf Dis, 2014

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

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

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

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

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

• 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

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

Impact on Cord Infection

In all studies…

Multiple CHX reduced cord infection

• Nepal: 33% – 75% reduction

• Bangladesh: 15% – 45% reduction

• Pakistan: 40% – 50% reduction

Summary of Mode of Action

0 Day 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

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

“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

“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

“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

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

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

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)

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

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