Abstract:
The World Health Organization recommends inpatient hospital treatment of young infants
up to two months old with any sign of possible serious infection. However, each sign may
have a different risk of death. The current study aims to calculate the case fatality ratio for
infants with individual or combined signs of possible serious infection, stratified by inpatient
or outpatient treatment.
Methods
We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick
infants as pneumonia (fast breathing in 7–59 days old), severe pneumonia (fast breathing in
0–6 days old), clinical severe infection [severe chest in drawing, high (> = 38˚C) or low body
temperature (<35.5˚C), stopped feeding well, or movement only when stimulated] or critical
illness (convulsions, not able to feed at all, or no movement at all), and referred them to a
hospital for inpatient treatment. Infants whose caregivers refused referral received outpa tient treatment. The case fatality ratio by day 15 was calculated for individual and combined
clinical signs and stratified by place of treatment. An infant with signs of clinical severe infec tion or severe pneumonia was recategorised as having low- (case fatality ratio �2%) or
moderate- (case fatality ratio >2%) mortality risk.
Results
Of 7129 young infants with a possible serious infection, fast breathing (in 7–59 days old)
was the most prevalent sign (26%), followed by high body temperature (20%) and severe
chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness
(16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for indi vidual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for
outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe
infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We categorized infants into low-mortality risk signs (case fatality ratio �2%) of clinical severe
infection (high body temperature, or severe chest in drawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only
when stimulated, low body temperature or multiple signs of clinical severe infection). We
found that both categories had four times lower case fatality ratio when treated as outpatient
than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001),
respectively. In contrast, infants with signs of critical illness had nearly two times higher
case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%,
p = 0.097).
Conclusions
The mortality risk differs with clinical signs. Young infants with a possible serious infection
can be grouped into those with low-mortality risk signs (high body temperature, or severe
chest in drawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well,
movement only when stimulated, low body temperature or multiple signs of clinical severe
infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that
consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings.