Incidence and etiology of omphalitis in Pakistan: A community-based cohort study

Abstract

Although omphalitis (umbilical infections) among newborns is common and a major cause of neonatal deaths in developing countries, information on its burden and etiology from community settings is lacking. This study aimed to determine the incidence and etiology of omphalitis in newborns in high neonatal mortality settings in Karachi, Pakistan.
Trained community health workers surveyed all new births in three low-income areas from September 2004 to August 2007. Pus samples from the umbilical stumps were obtained from babies with pre-defined signs of illness and subjected to culture and antimicrobial susceptibility testing.
Among 6904 births, 1501 (21.7%) newborns were diagnosed with omphalitis. Of these, 325 (21.6%) were classified as mild, 1042 (69.4%) as moderate, and 134 (8.9%) as severe; 141 (9.3%) were associated with clinical signs of sepsis. The incidence of omphalitis was 217.4/1000 live births; moderate-severe omphalitis 170.3 per 1000 live births; and associated with sepsis 20.4 per 1000 live births. Of 853 infants with purulent umbilical discharge, 64% yielded 583 isolates. The most common pathogens were Staphylococcus aureus, of which 291 (95.7%) were methicillin-susceptible Staphylococcus aureus (MSSA) and 13 (4.2%) methicillin-resistant S. aureus (MRSA); Streptococcus pyogenes 105 (18%); Group B beta-hemolytic streptococci 59 (10 %); Pseudomonas spp., 52 (8.9 %); Aeromonas spp. 19 (3.2%); and Klebsiella spp. 12 (2%).
A high burden of omphalitis can be associated with sepsis among newborns in low-income communities in Pakistan. S. aureus is the most common pathogen isolated from umbilical pus. Appropriate low-cost prevention strategies need to be implemented.

Full text

Review Article
Incidence and etiology of omphalitis in Pakistan: a community-based cohort
study
Fatima Mir1, Shiyam Sundar Tikmani1, Sadia Shakoor2, Haider Javed Warraich1, Shazia
Sultana1, Syed Asad Ali1, Anita K M Zaidi1,2
1Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
2Division of Microbiology, Department of Pathology, Aga Khan University, Karachi, Pakistan
Abstract
Introduction: Although omphalitis (umbilical infections) among newborns is common and a major cause of neonatal deaths in developing
countries, information on its burden and etiology from community settings is lacking. This study aimed to determine the incidence and
etiology of omphalitis in newborns in high neonatal mortality settings in Karachi, Pakistan.
Methodology: Trained community health workers surveyed all new births in three low-income areas from September 2004 to August 2007.
Pus samples from the umbilical stumps were obtained from babies with pre-defined signs of illness and subjected to culture and antimicrobial
susceptibility testing.
Results: Among 6904 births, 1501 (21.7%) newborns were diagnosed with omphalitis. Of these, 325 (21.6%) were classified as mild, 1042
(69.4%) as moderate, and 134 (8.9%) as severe; 141 (9.3%) were associated with clinical signs of sepsis. The incidence of omphalitis was
217.4/1000 live births; moderate-severe omphalitis 170.3 per 1000 live births; and associated with sepsis 20.4 per 1000 live births. Of 853
infants with purulent umbilical discharge, 64% yielded 583 isolates. The most common pathogens were Staphylococcus aureus, of which 291
(95.7%) were methicillin-susceptible Staphylococcus aureus (MSSA) and 13 (4.2%) methicillin-resistant S. aureus (MRSA); Streptococcus
pyogenes 105 (18%); Group B beta-hemolytic streptococci 59 (10 %); Pseudomonas spp., 52 (8.9 %); Aeromonas spp. 19 (3.2%); and
Klebsiella spp. 12 (2%).
Conclusions: A high burden of omphalitis can be associated with sepsis among newborns in low-income communities in Pakistan. S. aureus
is the most common pathogen isolated from umbilical pus. Appropriate low-cost prevention strategies need to be implemented.
Key words: incidence; etiology; omphalitis; community acquired; umbilical infection; Staphylococcus aureus; MRSA; newborn;
antimicrobial susceptibility
J Infect Dev Ctries 2011; 5(12):828-833.
(Received 24 May 2010 – Accepted 21 April 2011)
Copyright © 2011 Mir et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction
Neonatal infections account for 12% of global
child mortality [1]. In developing countries such as
Pakistan, inadequate attention to skilled birth
attendance has led to half of all child deaths
occurring in the neonatal period, with sepsis as one of
the major causes of death [1]. Umbilical infections
(omphalitis) are common among newborns in
developing countries and may predispose to life-
threatening neonatal sepsis [2-4]. Incidence rates in
newborns in nurseries from developing countries
range from 2 per 1000 to 54 per 1000, with figures
from Turkey as high as 77 per 1000 live births. Case
fatality rates range from 0-15% in these hospitalized.
Very few population-based studies on rates of
umbilical infection have been reported [5-8].
Predictably, community-based rates for omphalitis
are much higher (105 per 1000 live births in Nepal)
due to the co-existence of many risk factors such as
the following the high proportion of babies born at
home; low rates of peri-partum skilled birth
attendants; sub-optimal use of infection control
practices during and after birth (hand washing,
disinfection of delivery surface and instruments,
sterile cord cutting and tie methods); cultural
practices involving application of unsafe substances
such as cow dung to the cord; and delayed health-
care seeking behavior among families [5]. These sub-
optimal peri-partum practices are prevalent in South
Asia and may predispose to as high if not higher
incidence rates of omphalitis in countries such as
Pakistan [9,10].
The objective of this study was to determine the
incidence and etiology of non-tetanus omphalitis in
low-income community settings of Karachi, where
neonatal mortality is high and home births

Mir et al. - Omphalitis in Pakistan J Infect Dev Ctries 2011; 5(12):828-833.
829
predominate. We identified the most common
causative organisms and their antimicrobial
susceptibility patterns in a community cohort, with a
secondary objective to observe association between
omphalitis and sepsis and establish appropriate
management strategies for omphalitis.
Methodology
Study setting
Pakistan is a large developing country with an
estimated population of 180 million. The neonatal
mortality rate in Pakistan is 54 per 1000 live births,
with two-thirds of all births occurring at home [7].
Karachi is Pakistan’s largest city with about 18
million people. This study was conducted in three
low-income (two peri-urban and one urban)
communities in Karachi where newborn and young
infant surveillance and care systems were established
to conduct studies on clinical signs predictive of
serious illness in young infants [8]. The primary
source of income in the two peri-urban coastal areas
is derived from fishing while in urban areas manual
labor and employment in small factories prevail.
Family earnings range from minimum wage to lower-
middle income, with the majority averaging less than
$1.25 per day (World Bank definition of extreme
poverty). Baseline demographic data (from
demographic surveillance conducted by the
Department of Pediatrics and Child Health, Aga
Khan University, in study sites) shows that neonatal
mortality in the three study sites is 45 per 1000. Most
deliveries are conducted at home by traditional
(unskilled) birth attendants (TBAs) who have no
formal certification or licensure. The TBAs are local
women, often illiterate, who provide pregnancy and
child birth care based primarily on experience and
knowledge acquired informally through the traditions
and practices of the communities. In addition, the use
of sterile delivery kits (as an indicator of effective
infection control practices) in home deliveries is low
(32%) [6,7,9].
Each community’s primary health-care needs for
children are provided by Aga Khan University
(AKU) Department of Pediatrics and run by the
Primary Health Care (PHC) center, which is staffed
with physicians and community health workers.
The appropriate approval was obtained from the
Aga Khan University’s Ethical Review Committee.
Study design
Community health workers (CHWs) were trained
to detect clinical signs of serious illness in enrolled
pregnant women and newborns through periodic
household surveillance in the three sites. Newborn
visits by CHWs were conducted within 48 hours of
birth and after one week, two weeks, and one month
of birth. Over 70% of newborns born at home were
seen within 48 hours of birth because of strong links
established with local TBAs. Newborns with
omphalitis or other illnesses were referred to the PHC
center where they were evaluated by study
physicians.
For CHW training purposes, a standard picture
set was developed by the principal investigator that
showed various clinical presentations of omphalitis.
The diagnosis of omphalitis was made following the
criteria indicated in Tables 1 and 2. If redness
extending to the base of the umbilical stump or
surrounding abdominal wall was present, and/or
purulent discharge from the umbilical stump was
noted, the patient was diagnosed with omphalitis.
These infections were categorized as mild, moderate,
or severe according to definitions based on clinical
algorithms from prior community-based work (Table
1) [10]. In addition, babies were also examined for
systemic signs of sepsis (Table 2).
Mild
 Redness extending to umbilical base but < 2 cm of abdominal wall around umbilical stump involved
 No associated purulent discharge
Moderate
 Redness around umbilical stump < 2 cm with associated purulent discharge, or purulent discharge alone
without any redness
Severe
 Redness around umbilical stump with > 2cm extension to abdominal wall, and/or swelling around
umbilicus
 With or without purulent discharge
Table 1. Grading of omphalitis on the basis of severity

Mir et al. - Omphalitis in Pakistan J Infect Dev Ctries 2011; 5(12):828-833.
830
Sample collection and specimen processing
Swabs in Amie’s medium (Medical Wire and
Equipment, Wiltshire, UK) used to culture babies
with umbilical purulent discharge were transported to
the Aga Khan University Hospital (AKUH) Clinical
Microbiology Laboratory within five hours of
collection. Swabs were plated directly to locally
prepared 5% sheep blood agar, chocolate agar and
MacConkey agar plates. After aerobic incubation of
MacConkey plates (35+ 2°C, air) and chocolate and
sheep blood agars (5-10% CO2) for 24 and 48 hours,
the results were reported semi-quantitatively as few
colonies, moderate growth, or heavy growth of the
recovered organism. Gram-negative bacteria were
identified by API 20E and API 20NE kits
(bioMérieux, Marcy l'Etoile, France) and S. aureus
was identified by the tube coagulase test. Lancefield
groups of streptococci were determined by latex
agglutination with appropriate anti-sera using the
PathoDx kit (Remel Inc., Thermo Fisher Scientific
USA).
All antimicrobial susceptibilities were performed
by the Kirby-Bauer disk diffusion method following
the guidelines established by the Clinical Laboratory
Standards Institute [11]. The D-test to detect the
macrolide-lincosamide-streptogramin-B inducible
(MLSBi) phenotype was determined for isolates of S.
aureus, S. pyogenes, and S. agalactiae.
Blood cultures were collected from 56 of 141
(39.7%) infants with suspected sepsis and omphalitis
whose parents provided consent. After skin
disinfection with 70% alcohol swabs, blood was
collected in a BACTEC Peds Plus/F bottle (Becton
Dickinson, Franklin Lakes, NJ, USA) and transported
to the Aga Khan University Clinical Microbiology
Laboratory for detection in the automated BACTEC
9240 instrument (Becton Dickinson, Franklin Lakes,
NJ, USA). When flagged positive by the instrument,
the bottles were examined by Gram stain and bacteria
were identified by tests mentioned previously for
umbilical cultures [12].
Data analysis
Data was analyzed by the Data Management
Unit, Department of Pediatrics, Aga Khan University.
Incidence rates and confidence intervals were
calculated using SPSS16.0 (SPSS, Chicago, IL,
USA). The primary outcomes of omphalitis
determined from predominantly home-delivered
babies in the community were incidence, etiology,
and antimicrobial susceptibilities of the common
pathogens causing infections.
Results
Incidence
During the study period of September 2004 to
August 2007, there were a total of 6904 births in the
three surveillance areas, 65% of which were
delivered by TBAs. Among the birth cohort, 1501
(21.7%) were diagnosed with omphalitis by the
CHWs. Of these, physicians categorized 325 (21.6%)
as mild, 1042 (69.4%) as moderate, and 134 (8.9%)
Any three of the following:
1
Respiratory Rate > 60/minute
2
Feeding difficulty/weak suck
3
Fever > 37.5° C (axillary)
4
Temperature < 36.0°C (axillary) and not increasing on warming
5
Lethargic or < normal movement
6
Excessive crying or irritability
7
Weak, abnormal or absent cry
8
Persistent vomiting (last 3 feeds)
9
Abdominal distension
10
Hypoglycemia – blood glucose < 40 mg/dl
11
Presence of skin, eye, or local umbilical infection
Table 2. Clinical Definition of Sepsis

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as severe infections. The incidence of omphalitis was
217.4/1000 live births (95% CI = 207.8-227.3);
moderate to severe omphalitis, 170.3/1000 live births
(95% CI = 160.8-180.3) and the incidence of
omphalitis with sepsis was 20.4/1000 live births
(141/ 6904) (95% CI = 17.3- 24). With home or
clinic-based antimicrobial therapy, case fatality rate
for omphalitis alone was 0.15% (2/1360) and for
omphalitis with sepsis, it was 0.7% by day 7 (1/141).
The overall case fatality observed in this cohort of
infants with omphalitis was 3/1501 (0.2 %).
Etiology
Cultures were collected and processed in 675
(79%) from a total of 853 babies with umbilical
purulent secretions. Of 675 specimens cultured, 432
(64%) yielded 583 pathogens; 299 (69%) were pure
cultures and 133 (30.7%) were polymicrobial.
Among the 141 babies with omphalitis and sepsis, 56
(40%) received parental consent to have blood
cultures drawn. However, only one blood culture
grew S. aureus and one was polymicrobial
(Klebsiella pneumoniae, E. coli, and Enterobacter
spp).
Bacteria isolated from the umbilical exudate in
descending order of frequency were as follows: S.
aureus (52%); Streptococcus pyogenes (Group A
beta-hemolytic streptococci) (18%); Streptococcus
agalactiae (Group B beta-hemolytic streptococci)
(10%); Pseudomonas spp. (9%); Aeromonas spp.
(3.2%); and Klebsiella spp. (2%). Umbilical cultures
obtained from 54 of 141 babies (38%) with
omphalitis and sepsis grew pure cultures in 19 and
polymicrobial cultures from 13 cases. Gram-negative
bacteria were isolated from 17.8% (8/45) of umbilical
cultures obtained from patients with omphalitis and
sepsis and 17% (99/583) from those with moderate-
severe omphalitis irrespective of sepsis.
Antimicrobial susceptibility patterns
Among 304 S. aureus isolates, 13 (4.3%) were
methicillin-resistant (MRSA), 291 (95.7 %) were
methicillin-susceptible (MSSA), 240 (78.9%) were
erythromycin- susceptible, 287 (94.4%) were
clindamycin-susceptible, and 204 (67.1%) were
cotrimoxazole-susceptible. Two percent of all S.
aureus were D-test positive. From 164 beta-
hemolytic streptococci (Group A = 105, Group B =
59), 121 (73.7%) were erythromycin-susceptible
(Group A = 77, Group B = 44), and 142 (86.5%)
were clindamycin-susceptible (Group A = 91, Group
B = 51). Fifty percent of S. pyogenes was D-test
positive and all S. agalactiae were D-test negative.
Results for commonly isolated Gram-negative
bacteria showed 100% susceptibility to gentamicin
and amikacin with Pseudomonas spp. (n = 52),
Aeromonas spp. (n = 19), and E. coli (n = 9); and
92% with Klebsiella spp. (n = 12). Ciprofloxacin
susceptibility was 100%, 98%, 91.6% and 89% with
Aeromonas spp., Pseudomonas spp., Klebsiella spp.
and E. coli, respectively. Susceptibility to ceftriaxone
was 91.6% with Klebsiella spp. and 89% with E.coli.
Discussion
The burden of omphalitis in our population was
determined to be 217.4/1000 live births, a rate
comparable to that of Gadchiroli, rural Maharashtra,
India (197/1000 live births) [13]. We provide
additional information regarding the etiology and
antimicrobial susceptibility patterns of pathogens
causing omphalitis in the study patients.
The umbilical cultures obtained from our patients
grew predominantly Gram-positive bacteria, in
contrast to one hospital-based study from India where
Gram-negative bacteria predominated [14]. This may
reflect higher colonization rates with Gram-negative
bacteria in babies born in hospitals compared to those
born at home. Results demonstrated that S. aureus
and beta-hemolytic streptococci accounted for 80%
of all pathogens causing community-acquired
omphalitis. The predominance of S. aureus suggests
the inclusion of an anti-staphylococcal agent (e.g.,
cloxacillin) in treatment regimens for infants with
omphalitis either with or without sepsis. Although an
overall low incidence of MRSA (umbilical cultures)
from the community was observed, most of the cases
were recovered in the latter half of the study period,
which may be indicative of a rise in community-
acquired MRSA infections.
It is noteworthy that Group B streptococci (GBS)
were isolated from 10% of umbilical exudates but
none from blood cultures. The low positivity rate of
GBS in blood cultures has also been reported in other
developing areas (range of 0.22% in East
Asia/Pacific to 15% in Africa). A culture positivity
rate of 7% in South Asia stems from community
surveillance in Karachi, Pakistan, and tertiary center
data in Sevagram and Karnataka, India [15]. GBS
neonatal sepsis may be under-detected in South Asia
due to the inability to obtain blood cultures within the
first 48 hours of life when these bloodstream
infections most commonly occur. Newborns
delivered at home who develop sepsis do not usually

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832
present to medical facilities to obtain blood cultures
and hospital-born babies are often treated with
antimicrobial agents before obtaining cultures [16].
Among GBS and S. pyogenes isolates, resistance to
macrolides (approximately 25%) was higher while
that to clindamycin (approximately 13%) was similar
to hospital cohort data from India (17.6% S.
pyogenes; 14.3% GBS) [29-30]. Since macrolides are
commonly used to treat respiratory infections in
Pakistan, the drug resistance may be a consequence
of the availability of antibiotics over the counter
without the need of a doctor’s prescription.
Reassuringly, antimicrobial resistance in enteric
Gram-negative bacteria and Pseudomonas spp. was
found to be quite low. This is in contrast to the high
number of extended spectrum beta-lactamase (ESBL)
producing E.coli and other enteric pathogens reported
from urinary tract infections in developing countries
[17-24]. Of interest, Aeromonas spp., a known
enteropathogen causing diarrhoea, was shown to
colonize and possibly infect newborn babies in our
study. The clinical consequences of this are
unknown.
One limitation of this study was the difficulty in
distinguishing the routine physiological inflammatory
response and redness associated with cord separation
from infected umbilical stumps in cases where
discharge is not present. Thus some of the 325 cases
(22%) classified as mild omphalitis (redness without
discharge) may have represented physiological
redness only. Thus we may have over-estimated the
true burden of omphalitis in this population.
However, even if these cases are excluded, the
estimated incidence of omphalitis would be 170 cases
per 1000 live births. It is highly recommended that
standardized and validated diagnostic criteria
defining omphalitis should be developed by the
World Health Organization to enable accurate
recognition and treatment.
This study did not evaluate possible risk factors
contributing to the high incidence of omphalitis in the
study population, notably low birth weight and
inadequate birth attendant and maternal education. As
previously reported, omphalitis could result from the
practice of applying non sterile products to the
umbilical stump, such as mustard or coconut oil,
surma (antimony or lead containing compound used
to line eyelids), soil or ghee (home-made unclarified
butter), or animal dung. In addition, unsanitary
delivery practices, including poor hand washing,
unclean delivery surfaces, and unsterile cord cutting
and tying are other contributory factors to developing
omphalitis [3,5,25]. Simple, cost-effective
interventions can be implemented to reduce risks
associated with omphalitis [4,5,9]. Although
untreated omphalitis is a high mortality condition [2],
the overall case fatality rate of omphalitis in our
study was low (0.2%, 3/1501). This was most likely a
consequence of early recognition through active
surveillance and institution of appropriate
antimicrobial therapy in a research setting. Reported
case fatality rates in hospital cohorts have ranged
from 13-19% [14,26]. In a community-based cohort
in rural Nepal, the risk of mortality was found to be
46% higher (95% CI: 8-98%) among infants with
omphalitis compared with those without [2]. Use of
chlorhexidene antiseptic on the umbilical stump for
prevention of omphalitis in this trial reduced neonatal
mortality by 24% (RR 0.76, 95% CI 0.55-1.04)
compared to dry cord care [4]. Implementation of
preventive strategies, as well as early and accurate
diagnosis, and appropriate therapeutic management
for newborns with omphalitis with and without sepsis
are urgently needed for developing countries
[25,27,28].
Acknowledgements
The authors would like to thank Ms Aatekah Owais and Dr Farah
Naz Qamar for help with data analysis. Editorial help provided
by Shamsa Panjwani is also gratefully acknowledged.
Dr. Fatima Mir and Dr. Shiyam Sunder received research training
support from the National Institute of Health’s Fogarty
International Center (1 D43 TW007585-01). The parent studies
during which these data were collected were supported by the
Saving Newborn Lives Initiative at Save the Children, USA,
funded by the Bill and Melinda Gates Foundation.
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Corresponding author
Dr Anita K. M. Zaidi
Professor, Department of Pediatrics and Child Health
Aga Khan University
Stadium Road PO Box 3500
Karachi 74800, Pakistan
Fax: (92 21) 493-4294, 493-2095
Telephone: (92 21) 4930051 Ext 4955, Direct: 486-4955
Email: anita.zaidi@aku.edu
Conflict of interests: No conflict of interests is declared.