M A N AG E M E N T O F S E R I O U S N E W B O R N I N F E C T I O N S

W H E N H O S P I TA L T R E AT M E N T I S N OT

P O S S I B L E

Steve Wall, MD SM MSW FAAP

Saving Newborn Lives/Save the Children

WCPH, Kolkata

February 13, 2015

Questions to be addressed

What is global evidence for community

management of serious newborn infections?

What is additional impact of management of serious

newborn infections at primary level when referral is

not possible?

Can serious newborn infections be treated by

simpler antibiotic regimens?

Figure 2

The Lancet 2015 385, 430-440DOI: (10.1016/S0140-6736(14)61698-6)

Copyright © 2015 Elsevier Ltd Terms and Conditions

Current WHO guidelines

Hospitalization with 10 days of antibiotics

Benzylpenicillin (or ampicillin) + gentamicin

IMNCI – initial antibiotics (ampicillin + gentamicin)

at first level facility, with referral to hospital

If referral not possible, outpatient treatment with

7-10 days of injectable antibiotics (ie, 3 injections

per day)

Hospital treatment is often not possible

Lack of accessible hospitals with newborn care

services

Hospitalization not acceptable to many/most

families

Distance

Cost

Family hardship

Perceived poor quality

Socio-cultural factors

Current evidence: Home-based treatment

Evidence from research studies - community-based

packages included home-based treatment of sepsis

Bang (India): 62% NMR reduction

Baqui (Bangladesh): 34% NMR reduction

ADDITIONAL IMPACT OF

TREATING SERIOUS NEWBORN

INFECTIONS AT PRIMARY LEVEL

Where referral is not possible

COMBINE Study (Ethiopia)

Objective: To evaluate additional benefit on mortality of

management of newborn possible serious bacterial

infections (PSBI) by trained community health workers

Ethiopia’s Health Extension Workers (HEW), linked to

community health volunteers, provided management of PSBI

when referral was not possible

HEWs trained to

Identify signs or newborn PSBI and refer to health center

Treat at health post if referral not possible or not accepted

Gentamicin + amoxicillin for 7 days (7 total injections)

COMBINE Design

Cluster RCT

Comparison: MNH package via antenatal & postnatal home

visits by HEWs and volunteers, with referral of newborn

PSBI to facilities

Intervention: Addition of HEW management of newborn

PSBI (7 days of gent + amox) if referral not accepted

Outcome: Newborn mortality after day one

0

20

40

60

80

100

120

Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2

2011 2012 2013

intervention HP Intervention HC Comparison HP Comparison HC

Trends in care seeking for newborn PSBI

Neonatal Mortality, Days 2-27

Risk ratio 0.70 (0.48, 1.00)

Result. Neonatal deaths after day 1 of life in the

intervention arm were reduced 30% compared to the

comparison arm.

Control Intervention Total

Baseline 13.8 (120) 18.2 (184) 16.2 (304)

Endline 11.2 (100) 9.4 (90) 10.3 (190)

COMBINE Results

Trained community health workers can improve

newborn survival by identifying and treating serious

newborn infections when referral is not possible

Feasible to deliver this intervention effectively

through existing community health platforms

Effective implementation of this intervention requires

programs to ensure supply, create demand, and

continuously monitor to assure coverage & quality

SIMPLER ANTIBIOTIC REGIMENS

FOR SERIOUS NEWBORN

INFECTIONS

In outpatient settings where referral

is not possible

SATT & AFRINEST

SATT – Bangladesh

SATT – Pakistan

AFRINEST

DRC

Kenya

Nigeria

Common study protocol

SATT & AFRINEST Objective

To evaluate if simpler antibiotic regimens are

equivalent to a ‘standard course’ of parenteral

antibiotics for treatment of possible serious

bacterial infections in young infants whose

families do not accept hospitalization.

Treatment regimens

Control arm (reference treatment)

A : IM Gent and Procaine Pen once daily for 7 days 14 injections

Experimental arms

B: IM Gent once daily and oral Amox twice daily for 7 days 7 injections

C: IM Gent and Procaine Pen once daily for 2 days, thereafter oral Amox twice daily for 5 days 4 injections

D: IM Gent once daily and oral Amox twice daily for 2 days, thereafter oral Amox twice daily for 5 days (ARINEST only) 2 injections

Inclusion and Exclusion Criteria

Inclusion Criteria:

Fever (temp ≥380 C)

Hypothermia (temp≤35.5 0 C)

Lethargy (movement only with

stimulus)

Severe chest indrawing

Poor feeding

Hospitalization not accepted

Exclusion Criteria:

Signs of very severe infections

Vomiting or unable to take

oral medication

Weight <1500 grams

Results

Simplified antibiotic regimens were equivalent to the

reference regimen with respect to ‘treatment failure’

rates

Caveat: Evidence for simplest regimen (2 injections of

gent) is available from only one trial (AFRINEST)

Implications

Infants with PSBI should be referred for hospital

treatment – and effective treatment ensured

However, majority of families may not be able to

access hospital treatment at all or in time

Where hospitalization is not possible, these infants can

be treated with simplified antibiotic regimens as

outpatients by trained health providers

Acknowledgements

COMBINE

Investigator Team: Saving Newborn Lives/Save the Children Ethiopia, JSI, LSHTM, JHU,

UNICEF, Ethiopia Pediatric Society,

Funding: BMGF

SATT & AFRINEST

Investigators:

SATT Bangladesh: Projahnmo, JHU, AKU,

AFRINEST PIs from DRC, Kenya, and Nigeria

WHO

LSHTM

Funding: BMGF, USAID

Much progress, but much

to do . . .

- Thanks Photo by Jason Tanner/Save the Children