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ISSN 2413-2640 December 2016, Volume XII, Number 2
Ethiopian Pediatrics Society
Tele: +251-114667346/0114166879 Email: [email protected]
Website: www.epseth.org P.O.Box. 14205
Addis Ababa, Ethiopia
Original articles Improving Neonatal Health Outcomes in Ethiopia through an Innovative and Sustainable Healthcare
Model……………………………………………………..……………………………………….…...…1
Bogale Worku , Lillian Kidane , Kelemua Abera , Anand Kumar , Pinar Egeli , Yohanne Kidolezi
Trends in health service utilization of ICCM and IMNCI in four regions of Ethiopia,
from 2011 to 2015…………………………………………………………...….………………….……13
Efrem Teferi, Zergu Tafesse, Ismael Ali
Pattern and outcomes of childhood malignancies at University of Gondar Hospital, Ethiopia :
Nonconsecutive case series……...……………………………………………………………………….21
Mulugeta Ayalew , Mahlet Abayneh , David M.Gordon
Factors influencing coverage and key challenges to achieving targets of routine immunization
in africa: a systematic review……………..………………………..………...……...……………….…..31
Efrem Teferi
Case Report
Crigler Najjar syndrome type I, a rare but severe cause of
Unconjugated Hyperbilirubinemia in children……………………………….………………….…..…...43
Abebe Habtamu
Instruction to Authors………………………………………………………....…………….…….….…. 46
Ethiopian Journal of Pediatrics and Child Health
The official organ of Ethiopian Pediatric Society
Tel-251-01-466-73-46/011-416-68-79
E-mail : [email protected] Website : www.epseth.org
Addis Ababa Ethiopia
The Ethiopian Journal of Pediatrics and Child Health aims to contribute towards the improvement of
child health in developing countries, particularly in Ethiopia. The journal publishes original articles,
reviews, case reports pertaining to health problems of children.
Editorial board
Damte Shimelis, Editor-in-chief
Mulugeta Betre , Associate Editor-in-chief
Etsegenet Gedlu
Nigussie Deyessa
Birkneh Tilahun
Tsinuel Girma
Tigist Bacha
Advisory board members: Dereje Kebede, Getachew Teshome, Amha Mekasha, Demissie Habte,
Lulu Muhie, Ruth Nduatithe, Tigist Ketsela
Rebecca Zewdie, Secretary
Table of contents Improving Neonatal Health Outcomes in Ethiopia through an Innovative and Sustainable
Healthcare Model……………………………………………………..…………………….…….…1
Bogale Worku , Lillian Kidane , Kelemua Abera , Anand Kumar , Pinar Egeli , Yohanne Kidolezi
Trends in health service utilization of ICCM and IMNCI in four regions of Ethiopia,
from 2011 to 2015……………………………………………………...….………………….……13
Efrem Teferi, Zergu Tafesse, Ismael Ali
Pattern and outcomes of childhood malignancies at University of Gondar Hospital, Ethiopia :
Nonconsecutive case series……...………………………………………………………………….21
Mulugeta Ayalew , Mahlet Abayneh , David M.Gordon
Factors influencing coverage and key challenges to achieving targets of routine immunization
in africa: a systematic review……………..………………………..………...……...……………...31
Efrem Teferi
Case Report
Crigler Najjar syndrome type I, a rare but severe cause of
Unconjugated Hyperbilirubinemia in children……………………………….……………………..43
Abebe Habtamu
Instruction to Authors………………………………………………………....…………….……... 46
Bogale Worku. Ethiop J. Pediatr. Child Health, 2016, Vol. XII, No. 2
ORIGINAL ARTICLE
IMPROVING NEONATAL HEALTH OUTCOMES IN ETHIOPIA THROUGH AN INNOVATIVE AND
SUSTAINABLE HEALTHCARE MODEL
Bogale Worku 1 , Lillian Kidane 2,Kelemua Abera 3, Anand Kumar 3, Pinar Egeli 3, Yohanne Kidolezi3
ABSTRACT
Introduction : Neonatal mortality continues to be a critical challenge in developing countries like Ethiopia. It is
established that well-equipped healthcare facilities and skilled healthcare workers are vital for reducing neonatal
mortality and improving health outcomes.
Approach : A hypothesis was proposed to improve neonatal health outcomes through an innovative model. It in-
volved collaboration between, local and non-profit organizations, technology partners, skill development partners,
and sustenance Monitoring & Evaluation (M&E) partners which were managed by GE Healthcare, under the ac-
tive guidance of the Ethiopian Federal Ministry of Health (FMOH).
The model included setting up advanced technology within the Neonatal Intensive Care Units (NICUs), training
the healthcare staff about the technology, and good clinical practices in new-born care (NICU solution). This hy-
pothesis was evaluated using a pilot outcomes study, which covered four district level hospitals in Ethiopia for
duration of six months.
Results: The pilot analysis demonstrated that the intervention resulted in significant improvement of clinical and
skill outcomes. For example, neonatal mortality declined by 24% and overall neonatal health outcomes, at dis-
charge, improved by 3.3%. There was an increase in throughput with the units handling more than double the
number of new-borns, and, the number of new-borns referred to other hospitals decreased by half. The skills and
competencies of the NICU staff improved following the initial training and periodic refreshment trainings during
the pilot.
Conclusion: This partnership model had a positive impact on neonatal health outcomes. Such strategic partner-
ships focusing on improving neonatal health outcomes can be replicated and sustainably scaled up.
1 Ethiopian Pediatric Society, Addis Ababa, Ethiopia Corresponding author: Bogale Worku [email protected] 2 GE Global Operations 3 GE Health Care
INTRODUCTION
Background: As the world transitions from
Millennium Development Goals (MDGs) to
Sustainable Development Goals (SDGs), ne-
onatal mortality remains a global challenge.1
Even after the commendable reduction in
Infant Mortality Rate (IMR) by more than
half (from 89 to 44 deaths per 1000 live
births) between 1990 and 2015, Neonatal
Mortality Rate (NMR) has decreased by only
37% over the same period.2 2015 statistics
show that almost one million neonates
(~36% of all neonatal deaths) die on the day
of birth and another one million die within
the next six days after birth.3,4 The neonatal
death projection for 2016 to 2030 is expected
to be 50% of 69 million child deaths. This
underscores the need for focus and care
1
during the neonatal period (first 28 days of
life) and calls for comprehensive and innova-
tive action plans by all countries to attain the
SDG target of reducing NMR to 12 per 1000
live births by 2030.5
Ethiopia has demonstrated its commitment
in improving maternal and new-born health
outcomes by implementing the National
Newborn and Child Survival strategy.6 This
policy helped the country achieve the MDG
4-IMR target, two years ahead of the 2015
deadline.7 In 2015, Ethiopia had a NMR of
27.7, which is comparatively better than
many other African nations; however, it is
still quite far from the SDG targets. To meet
the challenge of achieving the SDG targets,
Ethiopia is also trying to increase access to
effective coverage of life-saving, high-
impact neonatal and child health interven-
tions through national-level plans such as
Growth and Transformation Plan (GTP) and
Health Sector Development Plans (HSDPs)
IV. These plans focus on achieving the 2035
goal of reducing NMR to less than 10 per
1000 live births.8
Need for New Partnership Model for Im-
proving Neonatal Health Outcome
Limited resources in health facilities lack of
timely access to end-to-end neonatal care and
lack of consistent neonatal care delivery
practices are some of the key challenges ex-
isting in neonatal care within emerging mar-
kets.9 Moreover, environments with limited
resources often lack appropriate technology
for essential new-born care.10 Additionally,
pre-term and complicated deliveries require
expert and timely intervention to save the
lives of both neonates and mothers, which is
missing. It has also been established that
most neonatal complications resulting in
mortality are preventable with simple but
timely interventions.11
Most of the large-scale programs to reduce
neonatal mortality in limited resource envi-
ronments have faced scalability and sustaina-
bility challenges.12 Invariably, misalignment
of priorities and objectives among key stake-
holders has led to long-term program imple-
mentation challenges. Such challenges un-
derscore the need for new collaborative ap-
proaches to develop effective, sustainable,
and scalable neonatal care programs.
To address the above, this project introduced
a collaborative framework of strategic part-
ners and stakeholders that included the Gov-
ernment, funding agencies, and national
groups of healthcare professionals, NICU
equipment suppliers, and local implementing
partners. This innovative model involved a
strategic collaboration between multi-
disciplinary partners including local and non-
profit organizations, technology partners,
skill development partners, and sustenance
M&E partners, which were managed by GE
Healthcare, with the active guidance of the
Ethiopian Federal Ministry of Health
(FMOH). A schematic of this model is de-
picted below (Figure 1).
2
The model involved three partners with ex-
pertise in three key specific areas: technolo-
gy, healthcare staff skills development and
sustenance (medical technology manage-
ment). The model was further supported by
non-profit funding partners such as United
States Agency for International Develop-
ment (USAID), and approved by the Ethiopi-
an FMOH. It was governed by a Program
Manager to ensure seamless collaboration
among the various partners. Each partner was
an expert in its domain, accountable for a
specific primary outcome, and all partners
were jointly accountable for the success of
the overall project.
This model translated into the pilot project
with a common goal - to deliver improved
neonatal health outcomes and enhance the
clinical skills of healthcare providers. More-
over, the pilot would serve as evidence to the
Ethiopian FMOH for implementation of a
sustainable neonatal health program, which
could later be scaled to address gaps in ac-
cess to quality neonatal health services
across Ethiopia.
The pilot project was developed and imple-
mented with Ethiopian Paediatrics Society
(EPS) as the skills development, measure-
ment and evaluation partner, GE Healthcare
as the technology partner, and Infinity Ad-
vanced Technologies Solutions Plc. as the
sustenance partner.
GE Healthcare was responsible for identify-
ing and providing high quality, impactful and
appropriate technology to cover the resource
limitations. This included both GE and non-
GE technologies.
Figure 1.Innovative model for sustainable neonatal health outcomes
3
Ethiopian Paediatrics Society owned the de-
sign of the clinical content and training struc-
ture. It was responsible for implementing
these trainings through an integrated end-
user training program for NICU staff. Ethio-
pian Paediatrics Society adapted the clinical
training tools to the local Ethiopian context,
trained the selected site staff, provided
monthly refresher sessions, conducted evalu-
ations, and collected data from the pilot sites.
GE Healthcare also supported EPS in the da-
ta analysis and technology related compo-
nents of the initial and monthly refresher
trainings.
Infinity Advanced Technologies Solutions
Plc. was responsible for the procurement,
logistics, installation and provision of on-
going comprehensive service / maintenance
of all the medical technology used for the
pilot.
Funding was provided by USAID Health En-
terprise Fund. This funding was part of
Strengthening Health Outcomes through the
Private Sector (SHOPS) project, led by Abt
Associates.13 GE Ethiopia II, the legal entity
of GE in Ethiopia, matched the funding by
providing project management and execution
resources. GE Ethiopia II, the grantee of the
USAID grant was responsible for allocating
and disbursing funds to each of the assigned
partners in the pilot. The funds were allocat-
ed to each partner as per their operating cost
structure.
Pilot Methodology
The objective of the pilot was to evaluate the
viability of a multi-disciplinary partnership
model aligned with the common goal of im-
proving neonatal health outcomes. Neonatal
health outcomes were assessed along key
indicators, which included: changes in neo-
natal mortality and referrals, utilization of the
NICU services, and effects on NICU staff
skills.
The Ethiopian FMOH was approached to
identify the sites for deploying the partner-
ship model. As per the FMOH recommenda-
tion, four Ethiopian district level hospitals
located in rural areas outside Addis Ababa
were identified. These hospitals were at a
distance of at least 100 kilometres from the
nearest paediatric referral hospital. Two hos-
pitals were located in Oromia region (Assela
Hospital in Assela, and Adama Hospital
Medical College in Adama), and two were
located in SNNR region (Nigist Eleni Mo-
hammed Memorial General Hospital in Ho-
saena, and Hawassa University College of
Health Sciences and Referral Hospital in Ha-
wassa). The total number of neonates ob-
served during the pre- and post-NICU inter-
vention period was 1156 and 2402, respec-
tively, and this data were collected in real
time for one year (6-month before and 6-
month data after the NICU intervention).
This data were then retrospectively analysed
to quantify the neonatal outcomes.
4
Pilot Feasibility Assessment and NICU
Technology Solution
GE and EPS teams conducted two rounds of
site assessments at each site. The assess-
ments included identification of clinical
needs, level of infrastructure, and NICU clin-
ical practices base lining. Additional infor-
mation assessed included statistics on NICU
admissions, number of births, deaths, and
birth complications. The additional technolo-
gy to be deployed in the pilot was chosen to
augment the existing NICU technology at
these sites in consultation with EPS and Ethi-
opian FMOH.
The NICU technology solution at each pilot
site included two radiant warmers (GE lulla-
by warmer, GE lullaby warmer prime), a
bubble Continuous Positive Airway Pressure
(CPAP) device, two high performance14 pho-
totherapy devices (GE lullaby Light Emitting
Diode (LED) phototherapy), neonatal moni-
tor (GE Carescape V100), resuscitation sup-
port laryngoscope, and thermal support to
transfer neonates from the Labour and Deliv-
ery Section to the NICU.
A continuous training program was designed
to align with the HSDP IV15 which focused
on scaling up the training of community and
mid-level healthcare professionals. While
EPS team developed a comprehensive neona-
tal care curriculum, GE Healthcare provided
inputs to refine relevant aspects of the neona-
tal clinical sessions for seamless integration
with the NICU technology being deployed as
part of the pilot. Ethiopian Paediatrics Socie-
ty and GE co-developed the NICU staff skills
assessment templates and questionnaires for
assessing pre- and post-training skill levels
pertaining to clinical information, equipment
functionality and knowledge demonstration.
An initial three-day clinical and equipment
training workshop was planned and conduct-
ed at Adama Hospital Medical College.
Nineteen NICU staff from all the four pilot
sites attended the session. The topics covered
in the training program included risks of pre-
term delivery (i.e., gestational age <37
weeks), risk factors, clinical management,
role of nutrition, and breast feeding manage-
ment. The workshop also included sessions
on essential neo-natal care and its standardi-
sation, diagnosis and management of perina-
tal asphyxia, neonatal jaundice, neonatal ap-
noea, and hyaline membrane disease.
In addition, a detailed hands-on session was
conducted for using the NICU solution
equipment. A few examples of the topics
covered were: how to operate the equipment,
manage alarms, and clinically correlate the
equipment indicators with the new-born con-
ditions. Ethiopian Paediatrics Society and
GE team members conducted monthly visits
to all the sites for six months to monitor, as-
sess, re-train, and suggest improvements in
clinical practice and equipment usage. After
six months, a final skill assessment of both-
clinical and equipment knowledge was
conducted through a theoretical exam and
5
equipment knowledge was conducted
through a theoretical exam and a practical
demonstration by the NICU staff at each of
the pilot sites.
Data Collection and Analysis
A list of key measurable outcomes were de-
fined and validated with stakeholders, which
included EPS and GEHC, prior to initiating
the pilot. The key measurable outcomes that
were agreed upon were - clinical indicators
on neonatal mortality, overall new-born out-
comes, improvement in the overall health,
and decrease in complications of the neo-
nates.
Data were extracted from completed data
collection templates and encoded by skilled
data entry clerks. Ethiopian Paediatrics Soci-
ety and GE Healthcare teams collected daily
and monthly data on the use of the equip-
ment and neonatal health indicators. Ethiopi-
an Paediatrics Society was responsible for
organising the infield collection and coding
of the data. Additional data were taken from
manual log register entries, individual in-
patient records, and skill assessment reports.
Following the cleansing, editing, and check-
ing the data for overall consistency, data
were entered, integrated, and analysed by GE
Healthcare in collaboration with EPS.
Certain variables such as weight of neonates
(birth weight and discharge weight) were
converted into single data (grams) units. Cat-
egorical variables such as gestational age,
antenatal care (ANC) visits, and gravida
were converted into standardised numerical
coded variables. Birth date, discharge date,
and date of admission based on the Ethiopian
calendar were converted into Gregorian cal-
endar dates.
Neonatal birth weight data were the prime
criteria used for data validation purpose. The
following data were excluded from the anal-
ysis: exceptionally low or exceptionally high
birth weight (considered as outliers), length
of stay (LOS) outlier data, null data
(captured as blanks) and missing values for
more than five variables.
Datasets were first de-identified to remove
patient names and gender related bias. Inde-
pendent sample t-test was used to compare
pre-versus-post time frames. The paired sam-
ple t-test was used to compare the pre- and
post-training skill assessment data.
In most of the NICU cases, antibiotics (due
to prevalence of sepsis), was the main inter-
vention. Hence, the analysis was performed
for potential outcomes and benefits in two
scenarios - excluding and including antibiot-
ics. The data were analysed in Microsoft Ex-
cel version 2010 using Statistical Analysis
for Excel pack. This data were validated and
approved by EPS.
Results
Post NICU intervention, a significant in-
crease of 108% (from 1156 to 2402 new-
borns) was observed in NICU throughput
across the four pilot sites. Three of the four
sites showed more than 80% increase in
6
NICU admissions (Table 1). While a greater
number of neonates were treated during the
post intervention period, the number of neo-
nates referred to other hospitals decreased by
50%. The increase in overall throughput and
the reduction in referrals can be attributed to
the efficiency of the intervention.
Post NICU intervention, the timely availabil-
ity and usage of advanced technology led to
an overall 3.3% (from 85.3% to 88.1%) im-
provement in health status of neonates at the
time of hospital discharge. In addition, neo-
natal mortality decreased by 24% (from
8.2% to 6.2%) of NICU admitted neonates
(Table 1).
Table 1: Patient inflow, neonatal mortality and improvement in neonatal health across pilot sites
Pilot sites Neonatal Inflow (n) Neonates with “Improved”
health status (%)
Neonatal deaths (%)
NICU scenario Pre Post Pre Post Pre Post
All sites 1156 2402 85.3 88.1 8.2 6.2
Adama 439 1184 90 91 5 4
Assela 266 487 80 87 10 8
Hawassa 188 408 83 86 14 11
Hosaena 263 323 84 84 8 8
Total sample size across sites: Adama - 1623, Assela - 753, Hawassa - 596, Hosaena - 586, and Overall – 3558
Post NICU intervention, the overall average
LOS shortened significantly by more than a
day (from 8.3 days to 7.2 days) indicating
faster recovery. The average LOS shortened
regardless of the need for antibiotics, alt-
hough, 90% of neonates still received antibi-
otics. The shortening of LOS can be attribut-
ed to the impactful technology in conjunction
with the appropriate clinical education.
Further, in-depth analysis of NICU effective-
ness as per neonatal complications (singular
cases: one complication only) revealed a sig-
nificant reduction in LOS by three days
amongneonates diagnosed specifically with
only jaundice cases. GE Lullaby LED
Phototherapy improved clinical performance
through faster degradation of bilirubin com-
pared to other phototherapy devices at the
sites.
The reduction in mortality rate and improve-
ment in neonatal health status seemed corre-
lated to the improved skills and knowledge of
NICU staff. The average skill assessment
scores of NICU staff improved from 69% to
77% after a three-day end-user training pro-
gram. After the six monthly monitoring vis-
its, the average skill assessment score further
improved to 79%. This improvement in the
average skill assessment score was consistent
across the four sites (Figure 2).
7
The NICU staff evaluation of the training
program demonstrated high effectiveness of
the program. 79% of the NICU staff found
the training program “effective” or “very ef-
fective” in enhancing their technical skills.
Eighty-nine percentages of the NICU staff
was “likely” or “very likely” to recommend
this training program to their colleagues, or
other healthcare workers. Additional analysis
revealed that there was an overall increase of
6% points in ANC visits during the NICU
intervention post-period. This increase can
be attributed to the promotional activities
conducted by Ethiopian FMOH. In concur-
rence with the NICU solution intervention,
we see more institutional practice and better
documentation with greater record keeping
compliance for capturing ANC visits.
Overall, the pilot benefits measured by the
reduction in neonatal mortality and improved
health outcomes were consistent across the
four sites.
Discussion and Conclusion
Governments of many developing nations are
facing the challenge of providing access to
comprehensive quality neonatal care for the
susceptible neonatal population. Results from
this pilot indicate that there is an emergent
need to conceptualise, innovate, implement,
and extend such neonatal healthcare interven-
tions to achieve improved neonatal health
outcomes.
The post-NICU intervention results indicate
that an innovative and sustainable healthcare
model that leverages appropriate technology,
trainings, and stakeholder partnership in mul-
tiple sectors, can be highly successful in ful-
filling the objective of improving neonatal
health outcomes. The pilot results showed a
significant reduction in neonatal mortality.
Moreover, a significant reduction in LOS of
neonates in NICU and improved neonatal
health conditions at the time of discharge
was observed. The NICU solution seemed
Figure 2: Percentage improvement in average skill score of clinical staff across four hospitals
8
instrumental in increasing admissions while
reducing the number of referrals to other
hospitals due to neonatal complications. The
improved outcomes can also be attributed to
the availability of appropriate technology
and skilled clinical staff. The equipment
provided in the pilot was designed to reduce
neonatal complications in a limited-resource
environment. The pilot also underscored the
need for end-to-end and continuous NICU
staff training programs as a critical compo-
nent to enable overall improvement of neo-
natal health outcomes. The technology and
continuous training program increased the
confidence of physicians, and other
healthcare staff in managing neonatal com-
plications.
In limited resource settings, such as Ethio-
pia, most neonates have low and dispropor-
tionate coverage of comprehensive and
skilled clinical interventions. As of 2011,
89.7% births in Ethiopia took place in home
settings, 8.7% in public hospitals, and 1.2%
in private hospitals. Critically, Ethiopia has
only 8% coverage of NICU infrastructure in
public hospitals, which is insufficient to
manage around 2.34 million neonatal popu-
lation susceptible to complications.16
These multiple limiting factors to neonatal
care access require a systematic approach
for achieving scalable national-level neona-
tal care programs.
Ethiopian FMOH has demonstrated focus by
outlining the “National Newborn and Child
Survival Strategy” with a NMR goal of
11/1000 by 2020. The strategy focuses on
covering gaps with equitable coverage and
development of neonatal care across regions.
This strategy acknowledges the need to scale
up existing high impact interventions such as
early postnatal care and skilled birth attend-
ance. The implementation of this strategy has
boosted the child survival efforts in the coun-
try through improved coordination, partner-
ship, resource mobilization and scaling up of
high impact interventions. In 2015, FMOH
came up with a five-year plan aimed at en-
hancing and channelizing human and finan-
cial resources to build a robust healthcare
infrastructure and improve accessibility of
related services to communities (Health Sec-
tor Transformation Plan 2020).17, The devel-
opment and implementation of innovative
and sustainable partnership models, as
demonstrated by this pilot, is vital for the
sustainable success of such plans. In this
context, comprehensive and national-level
neonatal care intervention programs require a
strong partnership between federal or local
governments or Ministries of Health, local
healthcare professional organizations, the
private sector, and non-profit organizations.
Sustainable partnerships of this kind seem to
create a win-win situation for the achieve-
ment of program goals. The key components
of this approach, such as comprehensive-
ness, governance, funding, project and quali-
ty management, integrated training, and
9
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Limitations of the Study
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tations are limited laboratory infrastructure
to perform regularly routine bilirubin meas-
urements (to assess and compare the rate of
bilirubin reduction), omission of NICU ad-
setup while pre- and post-NICU data were
collected across the entire NICU. This could
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sole technology within the NICU. Nonethe-
less, the results of this pilot not only sup-
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10
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[Internet]. 2013 [cited 2016 Oct 19].
http://www.who.int/maternal_child_adolescent/epidemiology/profiles/maternal/eth.pdf
17. The Federal Democratic Republic of Ethiopia Ministry of Health. Health Sector Transfor
mation Plan [Internet]. 2015 Oct [cited 2016 Nov 09].
http://www.moh.gov.et/documents/26765/0/Health+Sector+Transformation+Plan/5542a23-
9bc7-46a2-8c1f-8b32c2603208?version=1.0
12
Ephrem Teferi. Ethiop J. Pediatr. Child Health, 2016, Vol. XII, No. 2
ORIGINAL ARTICLE
TRENDS IN HEALTH SERVICE UTILIZATION OF ICCM AND IMNCI IN FOUR
REGIONS OF ETHIOPIA, from 2011 to 2015
Efrem Teferi, Zergu Tafesse, Ismael Ali
ABSTRACT
Background: Integrated Management of Newborn and Child hood Illness (IMNCI), Integrated Community Case
Management (ICCM),and Community Based Newborn Care (CBNC) are proven strategies used in Ethiopia to
reduce child mortality, by treating major killer diseases of newborns and children, utilization of which can contrib-
ute to reduction of under five mortality.
Methodology: We conducted cross sectional household surveys every year from January to March 2011-2015 to
monitor outcomes of health interventions in Integrated Family Health Program (IFHP) target areas. Data were
collected using checklists for household containing selected questions for each area of focus. The data were en-
tered and analyzed using SPSS16.0 version.
Results: In the last four years (2011 -2015), children 0-23 months who had illness with diarrhea/fever and cough,
within two weeks of the survey declined significantly, from 32.5 to 29%, and health seeking behavior raised from
56.6 to 67.6% (p value 0.0391 and 0.0001 respectively). The number of children treated in Health Post (HP) was
13-17 per month, but decreased in Health Centers (HCs) from 112 to 80 per month, which is significant (p value
0.00). Proportion of children who sought advice or treatment for the illness, in HCs was 57.7% and HPs 30.8%.
Mothers or caretakers were asked why they did not seek treatment or HPs, 37.9% said that HPs were not always
open and, 29.2% do not know about treatment in HPs.
Conclusion: The significant drop in incidence of disease and increase in health seeking behavior showed that pre-
ventive interventions have brought change in Ethiopia which may be due to strengthening of Health Extension Pro-
gram (HEP) and ICCM/CBNC scale up to treat sick children. Many mothers are still taking their children HCs for
treatment which are far from HPs. There is a need to keep HPs open daily and conduct social mobilization about
treatment given in HPs, which will increase utilization.
1 Integrated Family Health Program, Addis Ababa, Ethiopia * Corresponding author: Efrem Teferi [email protected]
INTRODUCTION
INTRODUCTION
IMNCI and ICCM are strategies used to re-
duce under five mortality in Ethiopia.IMNCI
training package was adapted in 1997,to
build health workers skills at health centers
to treat pneumonia,diarrhea,malnutrition and
measles, which are the major causes of under
-five mortality(1).ICCM was started in
2010,which aims to improve access to treat-
ments by providing free treatments to the ru-
ral population to improve under five mortali-
ty outcomes, factors such as affordability,
accessibility and availability were challenges
mentioned by care givers (2).The terms ac-
cess, utilization, availability and coverage are
used interchangeably to reflect whether peo-
ple are receiving the services they need (3).
13
The Millennium Development Goal (MDG
4) aimed to reduce under-five mortality by
two-thirds between 1990 and 2015, Ethiopia
has achieved MDG 4 (under-five mortality),
three years earlier (4). Diarrhea, pneumonia,
and malaria, are responsible for 52% of child
deaths worldwide. Child deaths could be re-
duced by 63% worldwide if coverage rates of
effective prevention and treatment interven-
tions were to increase to 99% (5).Lack of
access to and utilization of health services for
delivery are the main reasons for high mater-
nal and neonatal mortality (6).Utilization of
health care system may depend on socio- de-
mographic, social structure, level of educa-
tion of mothers, cultural beliefs and practic-
es,gender,,economic ,political sys-
tem ,disease pattern and health system
(6,7,8,9). In rural areas, the distances to
health care facilities and the poor condition
of roads, time, effort and cost required to ar-
rive at the point of delivery can be substan-
tial.(5).The better off are more likely to seek
care for a child when sick (10,11). In Kenya
IMNCI utilization was only 14%, lack of
training of HWs and follow up were men-
tioned as reasons for low utilization (12).
In Ethiopia health service utilization in Jim-
ma zone was found to be 46%, household
income, socioeconomic status, presence of
disabling health problem, presence of illness
episode, transport cost, perceived treatment
cost and distance to health center were pre-
dictors (12).In other studies utilization was
62%, shortage of money was the major, fol-
lowed by distance, poor quality of service
and self-medication (12).
The objective of this paper is to show trends
in health service utilization of IMNCI and
ICCM identify the challenges and suggest
solutions.
Checklist used as questioner; to mother or
care taker with a child less than 24 months
I. Has (name had an illness with diarrhea/
fever/cough at any time in the last two
weeks? Go to the next question if answered
yes,
II.Did you seek advice to treatment for the
illness from a health worker? If yes go to
next question
III.Where did you take the child? 1. HP
2.HC, 3.hospital, 4.clinic 5.Other (specify)
IV.Why did you not take the child to the
health post?
1.I do not know about treatment in HP 2.HP
is not always open 3.Drugs were not availa-
ble in HP 4.I do not trust HEWs 5.HP is far
6.Others specify
V.At any time during illness did (name) giv-
en any drug by health worker for illness
(diarrhea/fever/cough)?
Methodology
We conducted cross sectional household sur-
veys every year from January to March 2011
-2015 to monitor outcomes of health inter-
ventions in IFHP target areas. The surveys
include interviewing mothers and household
14
heads with children under two years old
about the childhood immunization, nutrition-
al status, ITN utilization, household sanita-
tion, and family planning status.
Sample Selection Procedures
We determined that 2,560 households (640 in
Amhara, 960 in Oromia, 480 in Tigray, and
480 in SNNP) would allow for detection of a
12% change in coverage, assuming an initial
prevalence of 50%, a design effect of 1.5,
and a non-response rate of 10%.
IFHP is supporting 300 woredas in the coun-
try, through 16 implementation clusters or
zones (groups of woredas): four in Amhara,
six in Oromia, three in Tigray, and three in
SNNPR. Zonal cluster offices prepared sam-
pling frames, from which we randomly se-
lected woreda health offices, health centers
(HC), health posts (HP), and households
(HH), applying the following ratios in the
field: five HH/HP, two HP/HC, and two HC/
woreda health offices. Interviewers selected
HHs using a random walk technique (in ran-
domly selected kebeles, and gots spinball
technique used to identify the direction, and
every fifth HH interviewed. Each cluster pro-
vided 160 households (2560 total house-
holds/16 total clusters).
Data collection methods and processes
Data were collected using checklists for
household containing selected questions for
each area of focus for recording purposes.
Each interviewer observed and verified
whether key behaviours were in place in se-
lected HHs. The checklists included standard
questions that are used to calculate key indi-
cators in household surveys. Data collectors
were IFHP cluster office and regional pro-
gramme office staff. All attended a 2 days
training on completing the checklist, eligible
household selection and other data collection
procedures.
Data quality control
During data entry, a random sample of
checklists (10% of the checklists at each lev-
el) was double-entered with to verify the
quality of data entry, and the matching report
showed excellent agreement (99.0%). Coun-
try office and regional program office moni-
toring and evaluation officers supervised
quality of data collection and data in the
field.
Data processing and analysis
All completed checklists from the structured
interviews were submitted to the IFHP coun-
try office. A team of data entry clerks well
versed with the basics of the checklists per-
formed the data entry. Their roles included
office editing, coding of open-ended ques-
tions, data entry, and random verification of
entered data. Data encoding, entry and pro-
cessing were managed by the country office
monitoring and evaluation team. The data
were entered and analyzed using SPSS16.0
version. Basic analysis tools such as univari-
ate tables, percentage analysis and graphs
were produced.
15
We reported key coverage indicators in
both ICCM and non-ICCM areas using X2
testing to determine whether there were any
statistical differences
Ethical aspects Consensus was reached
with RHBs, zonal and woreda health offic-
es to conduct the follow up and verbal con-
sent was obtained from households before
collecting in formation.
Results
In the last four years (2011 -2015), children
0-23 months who had illness with diarrhea/
fever and cough in the last two weeks of the
survey (incidence of illness) declined from
32.5 to 29%, and those who sought
treatment from HWs (health seeking behav-
ior) raised from 56.6 to 67.6% (fig.1) .The
proportion of children who sought advice
or treatment for the illness in health centers
was 57.7%, health posts 30.8% (fig.2). The
average number of children treated in
health was 13 - 17 per HP /month, but de-
creased in health center per week decreased
from 112 in 2012 to 80 per HC/month (fig
3).When mothers or caretakers were asked
why they did not seek advice in HPs 37.9%
said that health posts were not always open,
and 29.2 % do not know about treatment
service in health posts (fig 4).
Figure 1.Incidence of illness and health seeking behavior
16
Figure 3.Majour reasons for not seeking not seeking treatment from HP
Figure 4.Trends in health service utilization of HCs and HPs
Figure 2, Places where parents sought treatment
17
Discussion
Incidence of illness has dropped from 32 in
2012 to 29 % in 2015 (p value 0.0391).
Health seeking behavior has increased signif-
icantly from 56.6 in 2011 to 67.6% (p value
0.0001). Those who received any kind of
treatment varied from 96 to 90%. Alive and
Thrive survey also showed done in same
area showed decrease in incidence of illness
in 2010 to 2014, in under five children (fever
26-16%,cough 31.9-21.6%,diarrhea 15.9-
11.4%, p<0.001) (15).A study in L10KE are-
as also showed decrease in incidence of ill-
ness (ARI 10-6%, diarrhea 23-13%,fever 23-
10%) and increase in treatment (ARI 35-
69%,diarrhea 44-51%, fever 41-
66%,p<0.05),in 12-23 months children (2008
-2014) (16).IFHP end line survey done in
2013 did not show much increase in diarrhea
and ARI treatment from 2008 to 2013 (32.5-
34.6%, 46.8%-36.5% respectively)
(17).There is seasonal variation in incidence
of illness, and it is difficult to compare re-
sults of different surveys. The study done in
India showed, prevalence of diarrhea, fever
and cough was 9.1%, 14.8% and 17.7% re-
spectively. The proportion of children, who
did not receive any type of medical treatment
during an episode of diarrhea and fever/
cough, was 36.9% and 28.9% respectively
(10). Incidence of illness is lower, but more
children received treatment in our country.
The utilization in health posts was low, the
average number of children treated in health
post was 13- 17 cases per HP/month, increas-
ing slowly, other studies also showed in-
creasing trend The results are higher than
study done in SC areas 6-10 cases /month
(18), but similar with findings in West Ha-
rargie and Jimma ,16/HP/month (19).The
average number of children treated in per
health center per month decreased signifi-
cantly from 112 in 2012 to 80 per HC/month,
(p value-0), which is different from findings
from previous study, before and after intro-
duction of ICCM, in which there was in-
creasing trend two years after introduction of
ICCM (20).The major reasons for not using
HPs was that they closed 37.9% (similar to
finding in study done Jimma and West Ha-
rargie ( 21), and 29.2% of mothers do not
know about treatment of child illness in the
health posts. The Ugandan survey on accept-
ability and utilization of showed 27-57% of
caregivers took their febrile children to Com-
munity Health Workers (CHW) for treat-
ment, those located 1-3 km.utilized more
than others (22,23).
Conclusion
The drop in incidence of illness and increase
in health seeking behavior show that preven-
tive methods being promoted are bringing
change in the community. This is also re-
flected in the data that cases in HCs are de-
creasing, and increasing in HPs. There are
many sick children who are not taken to
health facilities for treatment. The utilization
in health posts where treatment is free is still
low and mothers are taking their children to
health centers, The need for daily opening of
HPs and conducting social mobilization us-
ing HDA is crucial.
18
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20
Mulugeta Ayalew. Ethiop J. Pediatr. Child Health, 2016, Vol. XII, No. 2
ORIGINAL ARTICLE
PATTERN AND OUTCOMES OF CHILDHOOD MALIGNANCIES AT UNIVERSITY OF GONDAR
HOSPITAL, ETHIOPIA : NONCONSECUTIVE CASE SERIES
Mulugeta Ayalew 1, Mahlet Abayneh 1, David M.Gordon 1
ABSTRACT
Background : Childhood malignancy is an increasingly significant problem in low income countries. Despite the
burden of the disease, little is known about patterns and outcomes of childhood malignancies in Ethiopia..
Objective : To describe the pattern and outcome of childhood malignancies at a teaching hospital in Northwest
Ethiopia
Methods: A nonconsecutive case series of children aged ≤14 years admitted with the diagnosis of any malignant
cancer to University of Methods: A nonconsecutive case series of children aged ≤14 years admitted with the diag-
nosis of any malignant cancer to University of Gondar Hospital from September 2011 to September 2014. Univer-
sity of Gondar Hospital is a tertiary care teaching and referral hospital in northwest Ethiopia.
Results: The total number of admissions to the Pediatrics ward during the study period was 4,400. Medical rec-
ords of 142 cases were reviewed and 110 (2.5%) cases were selected for the study. 67.3 % of them were male. Pa-
tient age ranged from 5 months to 14 years (median 6.5 years, IQR 3.2-12.0 years). The peak age at diagnosis was
10 -14 years. Acute lymphoblastic leukemia was the commonest type of malignancy, comprising 30% of cases. Fi-
nal diagnosis was made by fine needle aspiration for forty-six cases (41.8%). Thirty-nine percent abandoned treat-
ment and 11% died. Multi-organ failure secondary to severe sepsis was the immediate cause of death in 33% of
deaths.
Conclusion and recommendation: Malignancies represent a significant proportion of admissions. Acute lympho-
blastic leukemia is the commonest type of malignancy. Further research is required to determine best practices for
the management of pediatric malignancies.
1 Department of Pediatrics and Child Health, University of Gondar, Gondar, Ethiopia Corresponding author: Mulugeta Ayalew: [email protected]
1. Background
An estimated 80-85% of pediatric cancer cas-
es occur in the global south, where the 5-year
survival can be less than 10% (1). Despite
the tremendous burden that these diseases
place on health care systems, relatively little
is known about pediatric malignancies and
the manner of presentation in Ethiopia. Afri-
ca bears a great burden of childhood cancer.
Cancer is now curable in developed countries
as survival rates approach 80%, but in Afri-
ca,>80% of children still die without access
to adequate treatment(2) .The costs of treat-
ment, diagnostic investigations, meals and
hospital stay are borne by patients and their
families. Because no coordinated cancer reg-
istry exists in Ethiopia, few studies have ex-
plored the incidence of pediatric malignan-
cies and to our knowledge none have report-
ed outcomes from our region. This study
21
aimed to describe baseline characteristics for
patients with childhood malignancies diag-
nosed at University of Gondar Hospital
(UGH) in Northwest Ethiopia. UGH is a ter-
tiary care government-funded referral hospi-
tal with a catchment area of 5 million people
(3). The department of pediatrics and child
health is the only site treating children with
malignancies in northwestern Ethiopia. Chil-
dren with malignancy receive chemotherapy
based on protocols for treatment of malig-
nancies in our country. In addition, surgery
will also be done for non-advanced cases of
solid tumor. Different types of supportive
cares are also given.
2. Methods
A nonconsecutive case series was performed
on medical records of one hundred ten cases.
One physician retrieved the admission regis-
tration book for children aged ≤ 14 years
with diagnosis of malignancy admitted to
UGH between September 2011 and Septem-
ber 2014. Cases for whom a medical record
was available and either a histopathologic or
radiographic diagnoses of malignancy was
made were included in the study. Cases who
had presented with a relapse or for a follow-
up visit were excluded from analysis. Data
was collected using a pretested data extrac-
tion form. Hand-written data was checked for
completeness and accuracy and transcribed
into a computer database. Means and stand-
ard deviation or medians and inter-quartile
ranges were calculated for continuous varia-
bles. Frequency percentages were calculated
for categorical variables. All statistics were
generated using Epi-info version 7.0. Ethical
approval for this study was obtained from the
UGH internal review board.
3. Results
155 patients with malignancies were identi-
fied from the pediatric ward’s admission-
discharge log books.142 cases had medical
records available; the remaining 13 charts had
been lost. 32 cases did not fulfill the inclusion
criteria 110 cases were selected for analysis.
Figure 1. Study Flow
Of 110 cases, 74 (67.3%) were males (Figure
2). Patient age at diagnosis ranged from 5
months to 14 years, 36.4% of cases presented
between 10-14 years, 30% presented between
1-4 years, 29% between 5-9 years and 4.5%
presented <1 year. The median age was 6.5
years (IQR: 3.25-12).
List of 115 patients were selected from
Medical records of 13
patients were unavailable
Medical records of 142 patients were available
110 patients were selected for analysis
32 incompletes records
were excluded
22
Female patients were younger at diagnosis,
with median age of 5.0 years (IQR: 2.0-11.5)
versus 7.0 years (IQR: 4.0-12.0) for males.
Most patients came from rural areas (56.4%).
26% of patients presented with severe acute
malnutrition (weight for height less than
70%, mid upper arm circumference less than
11 cm or edema of both feet) 22% had mod-
erate acute malnutrition (weight for height
between 80-70%, MUAC 11-12.5) and 20%
were under weight (weight for age less than
5th centile) (Figure 3). 71% presented with
duration of illness of more than 30 days be-
fore diagnosis. Patients from rural areas pre-
sented with a mean duration of illness of
3.3±4.2 months while the duration of illness
for patients from urban area was 2.7 ±4.3
months.
Figure 2: Gender distribution by age group among children with childhood malignancies at University of Gondar,
September 2011-september 2014
Figure 3: Nutritional Status of children diagnosed with childhood malignancy at University of Gondar,
September 2011-September 2014
23
Among clinically diagnosed malignancies,
acute lymphoblastic leukemia (ALL) ac-
counted for the majority (37%), followed by
Hodgkin lymphoma (HL) and rhabdomyo-
sarcoma (RMS) (10% each) of the cases.
Acute myelogenous leukemia (AML) and
malignant bone tumors were not considered
clinically (Table 1).
Table 1: Demographic characteristics of patients with malignancies among children age ≤ 14 years admit-ted to Gondar University Hospital, September 2011-September 2014 Age ( years )
Sex < 1 1-4 5-9 10-14 Total
Male
2(1.8%)
20(18%)
22(20%)
29(26%)
73(66%)
Female
3(2.7%)
13(12%)
10(9%)
11(10%)
37(34%)
Total
5(4.5%)
33(30%)
32(29%)
40(36%)
110(100%)
Final diagnosis was made by fine needle as-
piration(FNAC) for 46 cases (42%), Bone
marrow aspiration (BMAC) for 39 cases
(35.4%), tissue biopsy for 11 cases (10%)
and imaging modalities for 27 cases
(24.55%). A combination of FNAC and im-
aging were used in 20 cases (18.18%),
whereas biopsy and Imaging were used for 2
cases (1.82%). 7 cases (6.4%) were diag-
nosed after combining imaging results and
clinical considerations (Table 2).
24
Table 2: Modalities used to diagnose childhood malignancy at Gondar University Hospital, September 2011-September 2014
Type Method of diagnosis (%)
BMAC FNAC Biopsy Imaging Clinical
ALL 30 (90) 2 -- -- 41(37)
AML 7(100) -- -- -- --
BL -- 10 (83) -- -- --
HL -- 9 (75) -- -- 12(11)
NHL -- 2 (50) 1 (25) -- 9(8)
ES -- 1 (50) 1 (50) -- --
OS -- 2 (100) -- -- 2(1)
NB -- 8 (89) 1 (11) -- 9(8)
RMS -- 3 (38) 4 (50) 1 (12.5) 11(10)
WT -- 3 (60) 1 (20) 1 (20) 7(6)
HEP -- 4 (100) -- -- 3(2)
RB -- -- 3 (100) -- 3(2)
CNST -- -- -- 3 (100) 3(2)
PTC -- 2 (100) -- -- 1(0.9)
MISC 1 (25) 1 (25) -- -- 9(8)
Total 38 47 11 5 110(100)
ALL=acute lymphoblastic leukemia; AML=acute myelogenous leukemia; BL=Burkitt's lymphoma;
BMAC=bone marrow aspiration cytology;FNAC=fine needle aspiration cytology;NHL=non-Hodgkin's lympho-
ma; HL= Hodgkin's lymphoma; OS=osteosarcoma; ES=Ewing's sarcoma; NB=neuroblastoma;
RMS=rhabdomyosarcoma; WT=Wilm's tumor; HEP=hepatoblastoma; RB=retinoblastoma; CNST=central nerv-
ous system tumor; PTC=papillary thyroid carcinoma
Plain X-ray was the most frequently used
imaging method, in 98 cases (89.09%) of ra-
diographically-confirmed cases.
Among pathologically diagnosed malignan-
cies, leukemias, accounted for 33 cases
(30%). Among the leukemias, ALL was
more prevalent than AML (30% vs 6.4%).
Lymphomas were the second most prevalent
malignancies, accounting for 28 cases
(25.4%). Burkitt Lymphoma and Hodgkin
Lymphoma were the most common type of
lymphomas, each accounting for 11% of the
malignancies, followed by Non-Hodgkin
Lymphoma 3.6%.
From the total of 110 patients 104 (94.5%)
were offered treatment in the hospital and 5
(4.5%) were referred to higher treatment cen-
ter. Of those who started treatment in the
hospital 21 (20%) patients were discharges
against medical advice, 18(20%) patients ab-
sconded before being formally discharged,
26(25%) patients did not appear for the
scheduled follow up care and treatment. Only
2(1.8%) patients were declared cured and
25
discharged from care. Until the time of com-
pletion of data collection 19(18%) patients
were on treatment. 12(11%) patients died
during their hospital stay. Multi-organ failure
secondary to severe sepsis was considered
the immediate cause in 4(33%) cases, and
respiratory failure due to brain metastasis
was considered for 3(25%) cases.
4. Discussion
In this study malignancies accounted for
2.5% of all admissions to the pediatric ward
this figure has increased from a previous re-
port in 1992 (0.66%,(4) ) and is consistent
with a similar report in 2010 (2.8%, (5)). The
figure is comparable to that for other Ethiopi-
an hospitals (3.1%,(6) ) and a hospital in
Ghana(1.6%). Malignancies in our study dis-
proportionately affected males in 2:1 ratio.
This finding agrees with other studies from
the global south (4, 6-9). This gender dispari-
ty is believed to reflect cultural and econom-
ic factor elsewhere (10). This ratio was found
to be lower(1.14:1) in developed countries
(11).
In our study, more than half of the patients
were from rural areas. This agrees with find-
ings from other studies in Africa (6, 12) and
may reflect the underlying population distri-
bution; in northwest Ethiopia, 85% of the
population lives in a rural area.
On average, patients in our study were sick 3
months prior to diagnosis of malignancy, and
that delay ranged as high as 2 years. Almost
three quarters presented with duration of ill-
ness of more than a month before diagnosis,
and a longer wait time was observed among
rural patients. This may be due to lack of
transportation, lack of money to get transpor-
tation and delay in early referral of patients
from rural areas. The time to diagnosis in our
study was lower than that reported in other
Ethiopian hospitals (23 weeks (6)). In our
study, the highest number of malignancies
was detected among children age 10-14
years. This differs from studies in Ethiopia,
Nigeria, India and Australia, in which peak
incidence occurs from 0-4 years (4, 6, 11,
13). This may be due to the difference in the
cancer types among different countries.
In our study almost half of patients had mod-
erate or severe wasting and this high rate of
wasting might contribute to poor outcome in
children with malignancies. Cases with mal-
nutrition have lower survival rates than well -
nourished patients(14).Nutritional status may
have a role in the carcinogenesis by causing
immune deficiency, also by inadequate in-
take of antioxidants(15).
In our study 87% of patients had cytopatho-
logic or histopathologic confirmation of ma-
lignancy. The relatively high proportion may
be because our center is a teaching and refer-
ral hospital where relatively pathological ser-
vice is better than other centers in the coun-
try. In a Namibian study a rate of 91% were
recorded (16). Australian study showed that
95.4% of childhood cancers were histologi-
cally verified (11). Studies have shown that
26
CT scan have affected the management of
about 30% of patients with cancer. Most of
the children with cancer living in developing
countries could not profit from those ad-
vanced diagnostic facilities because of the
cost (10). In our study only 10% of the pa-
tients had CT scan. This low rate of imaging
among cancer patients is mainly due to eco-
nomical reason.
In our study, leukemias accounted for 30%
of malignancies. This finding differs from
other studies in Ethiopia, which reported
lymphomas and Wilms tumor as most preva-
lent malignancies (4) (6). Lymphomas, and
in particular Burkitts lymphoma, are the most
commonly encountered malignancies else-
where in Africa (8, 17, 18). This finding is
consistent with findings from developed
countries (11, 19, 20).
The second most common observed malig-
nancy was lymphoma (25.4%), in agreement
with reports from Latin America and Asian
countries(13, 21) and in contrast to devel-
oped countries, where CNS tumors were re-
ported to be more common than lymphomas
(22, 23) .Burritt and Hodgkin Lymphoma
were the most commonly encountered lym-
phomas, followed by other Non Hodgkin
Lymphoma. This dominance of Burkitt’s
lymphoma among childhood lymphomas
parallels other findings from Africa (8, 17,
18). In the third place of frequency neuro-
blastomas were more common than African
countries (6, 17). The third most common
childhood cancers reported from Sudan and
Nigeria were Nephroblastomas (17, 18),
whereas in developed countries, lymphomas
were in the third place (13, 22, 23) . The
prevalence of Wilms tumor and retinoblasto-
ma as evident in our study is in accord with
the pattern from other studies from Africa
and USA, (18, 22). This shows that these tu-
mors are prevalent in children less than 5
years of age. Besides a two year study (2005-
2006) at Black Lion Hospital, Addis Ababa
showed the common malignant cancers in
children in descending order of frequency
were Wilm’s tumor, leukemias, lymphomas
and rhabdomyosarcoma (6).
There were only 3 cases (2.73%) of CNS tu-
mors; all of them were diagnosed clinically
and using CT scan finding. This low frequen-
cy of CNS tumors is mainly because our cen-
ter did not have the neuroimaging and neuro-
surgery facilities required for diagnosis. This
finding is in agreement with other findings
from resource-poor countries (18, 24).
In our study, 11% of patients died during ad-
mission. ALL, RMS, and retinoblastoma in
aggregate accounted for three-quarter of in-
patient death. Multi-organ failure secondary
to severe sepsis, respiratory failure secondary
to CNS metastasis, and status epilepticus
were described as the proximate causes of
death in three-quarters of cases. The study
under-estimates overall mortality, since al-
most 65% of patients left the hospital before
treatment was complete or were lost to
27
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30
Ephrem Teferi. Ethiop J. Pediatr. Child Health, 2016, Vol. XII, No. 2
ORIGINAL ARTICLE
FACTORS INFLUENCING COVERAGE AND KEY CHALLENGES TO ACHIEVING
TARGETS OF ROUTINE IMMUNIZATION IN AFRICA: A SYSTEMATIC REVIEW
Efrem Teferi
ABSTRACT
Background: Immunization is one of the most important cost effective public health interventions available for
prevention of childhood illnesses and death. Complete vaccination status rates according to the World Health Or-
ganization (WHO) vaccination schedule is low. Coverage (average) for the 3rd dose of DPT (Diphtheria, Pertus-
sis, and Tetanus) in Africa in 2013 was 75%.
Objective: To identify the factors contributing to low coverage and the challenges to routine immunization in Afri-
ca.
Methods: review of published journal articles from Pub med and Google search
Results: Current literature has identified several barriers to immunization, including lower parental education,
younger maternal age, lower income, being a female child, and larger family size. Low access to services and in-
adequate awareness about vaccination were also barriers to complete vaccination series. Children were more like-
ly to be vaccinated if their mother received antenatal care during pregnancy and delivered in health facility.
Health facility factors, such as long waiting times, missed opportunities and high dropout rates were associated
with lower rates of vaccination. Availability of vaccines was not a major problem, but there was problem of distri-
bution according to the need of health facilities.
Conclusion: There is a need to give health education on immunization to raise awareness of parents. Improving
litracy of women, participation in household decision making also improved immunization coverage. Development
and use of micro-plans, maps, and monitoring charts in health facilities improved the use of data for action. EPI
training of health workers helped to provide good quality immunization service.
Parent reminder and recall systems and mass media interventions have the potential to increase immunization
coverage. Verbal, video, or provider delivered communication tools may also increase parents’ understanding.
Key words; Child survival, EPI, routine immunization, coverage/access
* Corresponding author: Efrem Teferi [email protected]
INTRODUCTION
Immunization is one of the most important and cost
effective public health interventions available for pre-
vention of childhood illnesses and death. Routine im-
munization is a regularly scheduled service that reach-
es new cohort of children. The expanded program on
immunization (EPI) was launched in 1974 by the
World Health Organization (WHO). Less than 5% of
the world’s children were vaccinated during the first
year of life against six killer diseases, Polio, Diphthe-
ria, Tuberculosis, Pertussis (whopping cough), Mea-
sles and Tetanus, later new vaccines such as hepatitis
B (HepB B),Haemophilus influenza type b (Hib),
Pneumococcal Conjugate Vaccine (PCV) and Rota
were included . Strategies were introduced in different
countries as part of immunization activities, including
decision to eradicate of poliomyelitis, and the emer-
gence of national immunization days (NID) and sup-
plementary immunization Activities (SIA) to control
of measles (1, 2).
31
Children received these lifesaving vaccina-
tions and increasing numbers are also pro-
tected by new and underused vaccines, More
than 100 million infants are immunized each
year saving more than 3 million lives annual-
ly (3). Global mortality attributed to measles
declined by 92 % from an estimated 733,000
deaths in 2000, to 134,200 in 2016 (WHO
2016).The prevalence of Polio has declined
dramatically since 1990: the number of polio
cases worldwide as of 2009 was 1604, and as
of August 2015 just 74 (WHO 2015). DPT3
coverage in Africa in 2013 it reached 75%
(4).
Globally 21.8 million eligible children were
unimmunized (did not complete 3 dose series
of DPT), and 1.5 million died from vaccine
preventable diseases (VPD).Out of the un-
vaccinated, 6.6 million were in Africa (2, 4).
There is a disparity in access to most of the
lifesaving EPI vaccines by children in the
world today and access by children in devel-
oping countries still remains a challenge.
Vaccines need to be transported at correct
temperature to prevent them from either
freezing or being exposed to too much heat
(3). This systematic review was conducted to
identify key challenges in achieving targets
in Africa, focusing on assessing factors con-
tributing to low immunization coverage, and
their solution.
MATERIALS AND METHODS
The peer reviewed journal articles in Pub
Med were the main source of data. A Google
search was used for more general searches,
Inclusion criteria were: journals that dis-
cussed on immunization in Africa focusing
on low immunization coverage and challeng-
es in immunization services (English 1999-
2014), and exclusion criteria were: Journals
that were not peer reviewed or not focusing
on Africa.
The methodology of data collection and anal-
ysis used by the journals reviewed in this
study were Demographic and Health Surveys
(DHS), WHO, UNICEF immunization cov-
erage estimate, administrative coverage of
routine vaccination, Census of households to
identify those with children aged 0±2 years.
WHO and UNICEF derive national coverage
estimates through annual country by country
review of all available data, including admin-
istrative and survey based coverage. Results
of structured interviews with mothers relat-
ing to vaccination were also included.
Searches were made with the following
terms: routine immunization, coverage, de-
faulter rate, defaulter tracing, polio campaign
and SIA.
The search identified 27 peer reviewed stud-
ies and a concept centered approach was
used to review the articles.
RESULTS
Until 1990 less than one-half of children in
developing countries completed routine vac-
cination programs. According to coverage
data from WHO/UNICEF administrative re-
ports, African region have shown continuing
32
progress, Average Coverage of DPT3 in
Africa in 2011 was 71% compared to 52%
in 2000.The coverage was stagnating start-
ing from 2006, Figure 1 shows that WHO/
UNICEF estimate of DPT 3coverage at re-
gional level was ten points lower than the
reported administrative data. Considerable
disparities observed between and within
countries, some decreased others showed
modest increase. The region as a whole
showed faltering coverage, and in 2013
reached 75% (2, 4, 5).
Current literature has identified several bar-
riers to immunization, including lower pa-
rental education, younger maternal age, and
lower income. Child’s gender (being a fe-
male), large family size, low access to
health services, and inadequate awareness
about roles of vaccines were found to be
barriers to completion of the required vac-
cinations. Children from poorest households
were more likely remain unimmunized. In
studies from Ethiopia and other low and
middle income countries, low access to ser-
vices and inadequate awareness of the roles
of vaccines were found to be barriers. In
other studies urban children were more
than two times as likely as rural children to
have all basic vaccinations (6-9).
Country specific examples have found that
health facility factors, such as long waiting
times at facilities, and shortage of vaccines
were associated with low rates of vaccina-
tion. Children delivered in public and pri-
vate institutions were more likely to have
complete vaccinations in several countries.
Recent studies suggest over reporting of
individual vaccines coverage across low-
33
and middle-income countries (LMIC) due to
inconsistent data sources (2-7).
Children were 1.35 times more likely to be
fully vaccinated if their mothers participated
in all household decisions than if they did
not. Children with mothers who had complet-
ed secondary education were 1.77 times
more likely to be fully immunized compared
with children whose mothers had no formal
education, which is also true for Ethiopia.
Children were 2.27 times more likely to be
fully vaccinated if their mother had four or
more antenatal care visits than those whose
mothers had no antenatal visits. Missed op-
portunities, and high dropout rates were ma-
jor factors contributing to low immunization
coverage as shown by studies done in
Mozambique, India and Bangladesh (9).
Proximity to health facility, measured by the
time taken to reach to the nearest health facil-
ity, was associated with full vaccination.
Children from households living within a 60-
minute walking distance from a health facili-
ty were more likely to complete vaccination
schedules than those located farther than a 60
-minute walking distance (10).
According to the 2011 Ethiopian Demo-
graphic and Health Survey (EDHS), DPT-
Hep-Hib-3 coverage was 36.5% among chil-
dren 12-23 months of age. National EPI cov-
erage survey conducted in 2012 showed a
higher coverage; DPT-Hep-Hib3 coverage
was 65.7%, DPT-Hep-Hib 1 coverage was
80%, this shows that there is good access,
but high dropout rate. The 2011 EDHS also
showed that urban children were more than
two times as likely as rural children to have
all basic vaccinations. The difference be-
tween 2011 DHS and 2012 surveys may be
due to in methodology or EPI activities two
years after 2011 DHS (11, 12).
The commonest reason given for missing a
child's vaccine in Western Cape, South Afri-
ca, was clinic factors, 47%, followed by a
lack of information, 27%. Common clinic
factors were missed opportunities, not being
told by nurses to return, and being given in-
correct return dates by clinic staff. The over-
all drop-out rate of fully immunized children
between 9 and 18 months of age was 24.5%
(11.8% between DPT1 and DPT3), higher in
Ethiopia 26.6% among 12-23 months (DPT1
and DPT3). The results indicate that the
Western Cape is at risk for an outbreak of
preventable childhood diseases and it is like-
ly that this is also the case for other provinc-
es of South Africa and Ethiopia. Late first
vaccinations in urban areas herald later gen-
eral defaulting (11- 15).
In study done in Malawi, mothers observed
lack of skill of some vaccinators, who did not
know how to inject properly, because blood
oozed from the injection site. Health workers
seldom had time to provide vaccination in-
formation during vaccinations sessions. In
the study from Ethiopia, mothers stressed
34
that health workers were not interested in
teaching mothers about immunization during
the vaccination sessions. The absence of
proper birth registration data can lead to in-
accuracies in reported coverage. No country
in Africa had efficient system for tracking
and motivating the parents of dropouts and
no acceptors. Findings in Bangladesh, Ethio-
pia, and India showed that, there was usually
no list of dropouts. In Malawi, mothers were
informed if the vaccination status of their
children was inadequate when they attended
for curative services. There were various rea-
sons why women did not present their chil-
dren for vaccination. Heavy work-loads, ill-
ness, attendance at funerals, flooding of
roads, and excessively hot weather were
some of the reasons mentioned by women
who could not attend vaccination sessions. In
some studies, noncompliance with the im-
munization schedule was related to parents’
lack of time (40.3%), forgetting to return
(33.2%), losing the immunization card
(10.3%), travels (7.7%), and lack of money
(1.1%) (9, 16).Table 1 and 2 summarize bar-
riers to immunization
Lower parental education
Younger maternal age
Female gender of child
Larger family size
Poverty
Heavy workload of the mother
Poor community participation and ownership
Mother’s not participating in decision making
Forgetting when to return
Proximity to health facility
Home delivery
Table 1: Barriers to Immunization (Parental factors)
35
Irregular vaccine delivery
Poor health worker skill
Lack of monitoring
Rude service providers
Missed opportunities
Absence of birth registration
Poor community participation and ownership
Long waiting time at health facilities
Failure to pass immunization message by health
worker
Table 2: Barriers to Immunization (health facility factors)
Discussion
Immunization is one of the important and
effective child survival strategies. Vaccine
Preventable Diseases (VPD) contributes 16-
29% of child mortality in resource limited
settings (7, 24, 25). Complete vaccination
status rates in Africa, according to the World
Health Organization (WHO) vaccination
schedule is low. Coverage (average) for the
3rd dose of DPT in Africa in 2013 it reached
75%, compared to 96% in Western Pacific
and European region. Reaching everyone
with health services has always been hard,
and reaching the last 20% is harder still. And
those who need the services most-the “hard-
to-reach” tend to be the ones who receive
them least (2-4).
Strong health system is necessary for deliv-
ery, barriers identified urban settings were,
lack of financing, human resources and vac-
cines and supplies. Lack of vaccines has
been reported to affect service utilization
negatively. Assessment by Global Alliance
for Vaccines and Immunization (GAVI) re-
vealed that availability of vaccines is not the
major problem, what is needed is a function-
al delivery system, a trained workforce to
deliver the vaccines and increased communi-
ty participation. The health sector should
provide mothers with information regarding
access to vaccinations education on their im-
portance prior to delivery. Association be-
tween women’s decision making autonomy
and vaccination highlights the need for initia-
tives that improve their autonomy in order to
attain gender equality. The use of ANC dur-
ing pregnancy and institutional delivery en-
courages the use of health services including
immunization (6, 8, 9,).
36
The combined effect of distant facilities and
few service providers resulted long waiting
times before receipt of services at public fa-
cilities. Safety concerns for the child, rude
service providers, and unqualified workers
were major concerns for consumers. Service
provision was further hindered by the lack of
transport. Health worker motivation in urban
areas is often low because of the high cost of
living, may be increased by involving them
in evaluations and providing them with ver-
bal and written feedback. High vaccination
Coverage citywide may conceal pockets of
low coverage that act as foci for continuing
transmission of target diseases, and many
defaulters. It is necessary to increase commu-
nity motivation and to ensure that children
complete the immunization series.In Mozam-
bique, health staff and community represent-
atives conduct house to house visits to identi-
fy eligible children and refer them to the
nearest health center or outreach session. Im-
proving disease surveillance data can identify
high-risk populations and provide infor-
mation about the effectiveness of EPI (7, 26).
The presence of health extension workers at
the lowest administrative level in Ethiopia is
an excellent opportunity to reach every child
and to mobilize every family for routine im-
munization and for SIAs. (4, 8, 17).
Childhood immunization programmes in sub
-Saharan Africa show that parent reminder
and recall systems and mass media interven-
tions have the potential to increase immun-
ization coverage. Verbal, video, or provider
delivered communication tools may also in-
crease parents’ understanding, especially if
the tools are structured, tailored and interac-
tive. Increased political and financial com-
mitment from governments by all immuniza-
tion stakeholders are needed to maintain
achievements and make additional progress
in EPI. As part of routine immunization
Child Health Days (CHD),which include vit-
amin A supplementation, deworming and
ITN distribution, and Immunization Plus
Days (IPD) are carried out have been con-
ducted in some African countries and found
to be cost effective (2, 5,18).
The quality of immunization data in many
African countries is questionable. Various
external evaluations have identified many
inconsistencies in reported data suggesting
that immunization data monitoring remains
weak in most African countries. Recent stud-
ies suggest substantial over reporting of indi-
vidual vaccines coverage across low- and
middle-income countries (LMIC) due to in-
consistent data sources, therefore population-
based surveys are often the best available
means to estimate vaccination coverage at
both local and national levels. (1, 19, 20, 21)
The Reaching Every District (RED), now
renamed as reaching every child (REC) initi-
ative strategy involves prioritizing low-
performing districts by strengthening five
important immunization functions at the dis-
trict level. These functions are planning and
37
management of resources, capacity-building
through training and supportive supervision,
sustainable outreach links between commu-
nities and health facilities, active monitoring
and use of data for decision-making. The de-
velopment and use of micro plans, maps, re-
view meetings and wall monitoring charts
facilitated the use of data for action. Health
facilities can improve stock management
through estimation of vaccine needs, thus
reducing the risk of having to cancel sessions
due to inadequate stock and reaching every
child (1, 2, 5, 19, 21).
Measles kills more children than any other
EPI target diseases. The large number of
confirmed measles outbreaks and cases that
occurred among unvaccinated children aged
<5 years indicates the likely cause of the out-
breaks was an accumulation of susceptible
individuals who were not reached by routine
vaccination services or during measles SIAs
(2, 17).
The required level of immunity in popula-
tions to prevent epidemics of infectious dis-
eases has been estimated at about 95% and
85% for measles and polio, respectively,
achieving and maintaining ≥90% MCV1
coverage nationally and ≥80% in each dis-
trict is recommended (14, 21, 25, 27).
Supplementary immunisation activities im-
proved in measles and routine immunization
coverage in later infancy and reduction in
inequalities .New vaccine delivery strategies
have also helped to reach the hardest to reach
children in Ethiopia and other parts of sub-
Saharan Africa (14, 17, 22)
Findings from district level case studies in
three African countries (Ethiopia, Cameroon
and Ghana) on coverage and trends showed
four direct drivers of routine immunization;
cadre of community centered health workers,
health system and community partnership,
regular review of programme and health
workers performance, and Immunization ser-
vice tailored to community needs. The ena-
bling factors were political and social com-
mitment and the actions of development part-
ners, which created supportive conditions.
Each was present in some way in better per-
forming districts and was either absent or
where coverage was weak (23).Table 3 ex-
plores some of activities for raising immun-
ization coverage.
38
Limitation of the review
The review demonstrates immunization in
Africa and challenges focusing on assessing
factors contributing to low immunization
coverage. The situation in different countries
is different, factors contributing to problems
may differ, but there are also common fac-
tors which apply for many African countries.
It would have been good to asses those con-
tributing to Ethiopia, but it was difficult to
find enough published evidence
In some studies conservative estimate that
complete vaccination status had to have a
health card with time documentation. Alt-
hough this allows for the potential of under-
estimating vaccination coverage by not in-
cluding vaccinations that had missing health
cards.
Some of the analysis of coverage and disease
incidence trends were carried out with data
submitted by countries through the WHO/
UNICEF joint reporting form and were not
independently validated or cross-checked.
Conclusion and Recommendation;
Many concerns related to health system is-
sues such as stock outs and long wait times,
should be addressed as part of a wider ap-
proach to improve health systems. Access to,
and timeliness of vaccinations, quality of ser-
vice delivery need to be improved, poor in-
frastructure, and immunization monitoring
are among the many challenges faced by
most African countries, all requiring evi-
dence-based interventions.
Association between women's decision mak-
ing autonomy and vaccination shows the
need to attain gender equality, and provide
information and education on benefits of
childhood vaccination is important.
Table 3.Activities to raise immunization coverage
Sustained outreach link between community and health facilities
Use cadres of community health workers
Immunization services tailored to community needs
Capacity building and supportive supervision
Active monitoring and use of data for decision making
Prioritizing low performing districts
Planning
Management of resources
Health workers monitoring
Regular program review
Political and social commitment
Action of development partners
39
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in Africa: Looking beyond 2015, 2013,doi: 10.1371/journal.pmed.1001405
2. Nashimarimana D, Mihigo R and Clements C, Routine immunization services in Africa: back to
basics, 2013 J vaccines Immun, 1(1):6-12, http://dx.doi4312/2053-1273:2013-2
3. Progress towards immunization, September 2009, the living proof project, online
www.livingproof.org
4. Harris JB, Dubo MG, Eggers R, Brown DW,Sodha SV,Global routine vaccination coverage, 2013,
morbidity and mortality weekly report (MMWR),online https://www.cdc.gov
5. Tarantola D, Hacen M, Lwanga S, Clements CJ, Is immunization coverage in Africa slipping? An
evaluation of regional progress to 2013, SciMedcentral, Annals of vaccination 1(2):1007, December
2013
6. Wiysonge C, Olalekan A, Peter M, Ndumbe P, and Hussey G, Individual and Contextual Factors
Associated with Low Childhood Immunization Coverage in Sub-Saharan Africa: A Multilevel Anal-
ysis, 2012, DOI: 10.1371/journal.pone.0037905
7. Babirye J, Engebretsen I, Rutebemberwa E, Kiguli J. and Nuwaha F. Urban settings do not ensure
access to services: findings from the immunization programme in Kampala Uganda, 2014,
2014BMC Health Services Research, 14:111 doi:10.1186/1472-6963-14-111,online at: http:// www.
biomed central. com/ 1472-6963/14/111
8. Wado Y, Afework M, and Hindin Childhood vaccination in rural southwestern Ethiopia: the nexus
with demographic factors and women's autonomy, 2014 Pan Afr Med J.; 17(Suppl 1): online Jan 18,
2014. doi: 10.11694/pamj.supp.2014.17.1.3135,PMCID: PMC3946289
9. Canavan M, L. Sipsma H, M. Kassie G, and H. Bradley E, Correlates of Complete Childhood Vac-
cination in East African Countries, 2014,PLoS One.; 9(4): e95709,online Apr 21, 2014.
Doi: 10.1371/journal.pone.0095709, PMCID: PMC3994083
10. Okwaraji Y, Mulholland K, Schellenberg J, Andarge G, Admassu M, and Edmond K, The associa-
tion between travel time to health facilities and childhood vaccine coverage in rural Ethiopia, com-
munity based cross sectional study, 2012 BMC Public Health. 12: 476. Online Jun 22, 2012.
doi: 10.1186/1471-2458-12-476,PMCID: PMC3439329
Antenatal care is a good opportunity to pro-
vide mothers with information about vac-
cination.
Mass campaigns for measles and polio
should be continued until coverage is sus-
tained above 90%. Identifying and reaching
low coverage neighbourhoods. Improving
disease surveillance can identify high risk
populations and provide information about
the effectiveness of EPI.
40
11. Ethiopian Demographic Health Survey (EDHS), July 2014
12. Ethiopian National Coverage Survey, FMOH, Ethiopian Health and Nutrition Research Institute,
2012
13. Corrigall J, Coetzee D, Cameron N, Is the Western Cape at risk of an outbreak of preventable child-
hood diseases? Lessons from an evaluation of routine immunization coverage. S Afr Med J. 2008;
98(1):41-5.
14. Cassell J,Leach M.,Fairhead M.,Small K.The social shaping of childhood vaccination practice in
rural and urban Gambia ,2006, ,Health Policy and Planning, Volume 21, Issue 5,Pp. 373-391
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vaccinations in Africa and Asia, 1999, World Health Organization Bulletin of the World Health Or-
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10.1186/1471-2458-14-193
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childhood immunizations in Cameroon, 2004,Bulletin of the World Health Organization September,
82 (9), WHO unpublished document EPI/GAG/89/WP.2.412 WHO Bulletin OMS.Vol 691991.
23. Fond A, Kangat N, Stainglass R, et al., Drivers of routine immunization coverage improvement in
Africa: Findings from district level case studies, Health policy and planning 2014,1-11,doi:10.1093/
heapol/czu011.
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12–23 months in Ambo Woreda, Central Ethiopia, 2012,BMC Public Health.; 12: 566.online Jul 28,
2012. Doi: 10.1186/1471-2458-12-566 PMCID: PMC3508824
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42
Abebe Habtamu . Ethiop J. Pediatr. Child Health, 2016, Vol. XII, No. 2
CASE REPORT
CRIGLER NAJJAR SYNDROME TYPE I, A RARE BUT SEVERE CAUSE OF UNCONJUGATED HY-
PERBILIRUBINEMIA IN CHILDREN
Abebe Habtamu
ABSTRACT
Crigler Najjar Syndrome Type I is a rare and severe autosomal recessive disorder of bilirubin metabolism. It has
been associated with consanguinity in some patients. Infants without any evidence of hemolysis, develop severe,
permanent, unconjugated hyperbilirubinemia within the first few days of life resulting in chronic kernicterus.
Department of Pediatrics and Child Health, Tikur Anbessa Specialized Teaching Hospital , Addis Ababa, Ethiopia Corresponding author: Abebe Habtamu: [email protected]
INTRODUCTION
This rare and severe autosomal recessive
disorder of bilirubin metabolism occurs with
an incidence of 0.6–1.0 per million live
births. Occurs in all races and has been
associated with consanguinity in some
patients (1).It is characterized by non-
hemolytic unconjugated hyperbilirubinemia.
According to serum total bilirubin concentra-
tion (STBC), Crigler Najjar Syndromes
(CNS) is classified into two types: type I
(CNS-I), in which the STBC is more than 25
times that of the normal level ranging from
342 to 684 μmol/L, and type II (CNS-II), in
which it is 6-25 times with a range of STBC
within 103-342 μmol/L [2,3].
In 2002, Al Shurafa et al. analyzed the out-
come of six children with Crigler-Najjar
Syndrome type I & reported. The first three
had living-related liver transplants in Saudi
Arabia and the Middle East. Two developed
acute hepatocellular rejection, (treated with
methylprednisolone pulse therapy) & one
had a biliary leak (surgically repaired). Post-
op bilirubin levels returned to normal in all
three and no further phototherapy was re-
quired (4).
Few hundred cases reported since the first
report in 1952 by Crigler and Najjar in six
infants in three families. All six infants devel-
oped severe, permanent, unconjugated hyper-
bilirubinemia within the first few days of life,
without any evidence of hemolysis. Five of
the six infants died of kernicterus by the age
of 15 months (1).
The sixth infant was free of neurologic dis-
ease until 15 years of age, when kernicterus
suddenly developed in adolescent and died
six months later (1).
CASE REPORT
A 2-year and 4 months old female presented
with jaundice noticed since 10th day of life
and presented to Tikur Anbessa Specialized
Teaching Hospital. Pregnancy and delivery
history was unremarkable. Physical examina-
tion showed no dysmorphic features, stable
43
vital signs, and anthropometric measure-
ments were normal for her age, had deep ic-
teric sclera and skin, no pallor had hepato-
megally of 4cms below the right costal mar-
gin with total liver span of 10cms but no
splenomegally. She was assessed with a
modified Glasgow Coma Scale and it was
3/5, muscle tone was normal.
INVESTIGATIONS
Total serum Bilirubin 34, direct 22 (almost
all the time) T3, T4, TSH- Normal, VDRL,
Nonreactive, DNA PCR negative, CMV, tox-
oplasmosis all were non revealing, liver en-
zymes and liver function tests were normal,
hepatitis viral markers ( HBSAg, anti HCV
antibody and HAV antibody) were negative.
U/S- Normal, no evidences of biliary atresia,
and choledochal cyst.
She was on follow up at the pediatrics gas-
troenterology/ hepatology clinic and periodic
phototherapy was given. While on follow-up,
she developed altered mentation and abnor-
mal body movement since 1 yr and 8 months
of age. At which time patient was referred
and went to America for genetic analysis.
Genetic analysis showed UGT1A1 mutations
deserted in association with CN I have in-
cluded nonsense, frame shift and missence
mutations which is indicator of homozyosity.
Crigler Najjar Type II patients typically have
2 missence mutations, but may also be com-
pound heterozygous for one missence and
one nonsense frame shift mutation. The find-
ing fits best for CN( Crigler Najjar type I)
DICUSSION
CNS I should always be suspected in infants
who developed persistent jaundice due to
unconjugated bilirubin within the first few
days after birth. These children have normal
liver function test, may have neurologic
symptoms due to kernicterus. Occasionally,
late onset kernicterus in adolescence may be
possible.
The hallmark of CNS I is pure unconjugated
hyperbilirubinemia, ≈ 20 to 25 mg/dl but can
be as high as 50 mg/dL. Stool color is nor-
mal, but fecal urobilinogen excretion is di-
minished due to the marked reduction in the
conjugation of bilirubin and rate of bilirubin
production, bone marrow morphology, and
RBC morphology and survival are normal.
Prenatal diagnosis and genetic counseling
are recommended because of the high fre-
quency of consanguinity. Inhibitors of heme-
oxygenase, such as tin-protoporphyrin or tin-
mesoporphyrin, results in marked inhibition
of the enzyme activity in various organs. A
single dose of tin-mesoporphyrin adminis-
tered in neonates, shortly after birth, resulted
in an average of 76% reduction of bilirubin
and abolished need for phototherapy (5).
Histopathology findings are nonspecific on
light and electron microscopy. Exclusion of
other persistent unconjugated hyperbiliru-
binemia conditions in infancy is necessary.
In our case, 2 years and 4 months old female
child who had no response for phototherapy
and early phenobarbitone, genetic analysis
44
revealed Crigler Najjar syndrome type I.
A liver transplant is the only definitive treat-
ment for Crigler-Najjar syndrome type I. It
rapidly normalizes bilirubin levels. Despite
its risks, some advocate prophylactic liver
transplantation to avoid the risk of kernicter-
us which may not be fully reversible once it
is established. Hepatocyte transplantation is
a promising alternative (6)
CONCLUSION
Definitive diagnosis can be made by in vitro
expression of mutant DNA from patients but
this method is too elaborative and expensive
for routine use. UGT1A1 mutations deserted
in association with CNS I has included non-
sense, frame shift and missence mutations.
Patients with type II CN, typically have 2
missence mutations, but may also be com-
pound heterozygous for one missence and
one nonsense frame shift mutation.
Taking the poor response for medical treat-
ment (medical history) and genetic analysis,
this patient is a real case of Crigler Najjar
syndrome type I.
REFERENCE
1. Hong Y.S, Jin J.Y, Ryoung Lee W.R. A case of Gilbert’s syndrome in a neonate with severe
hyperbilirubinemia. J Korean Soc Neonatol 2010; 17:266-9c Ne
2. Canu G, Minucci A, Zuppi C, Capoluongo E: Gilbert and Crigler Najjar syndromes: an up-
date of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood
Cells Mol Dis 2013, 50(4):273-280.
3. Strassburg CP: Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Du-
bin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol 2010, 24(5):555-71.
4. Center for Arab Genomic Studies A division of Sheikh Hamadan Award for Medical Sci-
ences. The catalogue for Transmission Genetics in Arabs CTGA Database
5. Aloulou H, Thabet A.B, Khanfir S, Mansour L.B, Chabchoub I, Labrune P, et. al. La Mala-
die De Crigler Najjar De Type I En Tunisie : Etude De 30 observations. La tunisie Medicale
- 2010 ; 88:10 : 707-09
6. Galbraith R.A, Drummond G.S and Kappas A. Suppression of bilirubin production in the
Crigler Najjar Type I Syndrome: Studies with the Hemi Oxygenase inhibitor Tin-
Mesoporphyrin. Pediatrics 1992; 89:175.
45
46
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