ISSN 2413-2640 December 2016, Volume XII, Number 2

Ethiopian Pediatrics Society

Tele: +251-114667346/0114166879 Email: eps_2011@yahoo.ca

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 : eps_2011@yahoo.ca 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 bogaleworku@gmail.com 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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bilirubin reduction), omission of NICU ad-

setup while pre- and post-NICU data were

collected across the entire NICU. This could

attenuate the real impact, had this been the

sole technology within the NICU. Nonethe-

less, the results of this pilot not only sup-

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also demonstrated that a blend of appropri-

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10

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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 eteferi@ifhp-et.org

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: mulugetaayalew27@yahoo.com

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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height have prognostic significance in children with acute lymphoblastic leukemia? The

American journal of pediatric hematology/oncology. 1994;16(3):225-30.

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macology. 1992;14(3):361-6.

16. Wessels G, Hesseling PB. Incidence and frequency rates of childhood cancer in Namibia.

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19. Kebudi R. Pediatric oncology in Turkey. Journal of pediatric hematology/oncology.

2012;34 Suppl 1:S12-4.

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and adolescents in the United States, 2001–2003. Pediatrics. 2008;121(6):e1470-e7.

21. de Camargo B, de Oliveira Santos M, Rebelo MS, de Souza Reis R, Ferman S, Noronha CP,

et al. Cancer incidence among children and adolescents in Brazil: First report of 14 popula-

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epidemiology research program. Cancer Epidemiology Biomarkers & Prevention. 2004;13

(10):1552-4.

23. Michel G, Von Der Weid N, Zwahlen M, Redmond S, Strippoli MP, Kuehni C. Incidence

of childhood cancer in Switzerland: the Swiss childhood cancer registry. Pediatric blood &

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Nigerian Journal of Paediatrics. 2013;40(2):175-8.

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 eteferi@ifhp-et.org

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

REFERENCES

1. Machingaidze S, Wiysonge C, Hussey G, Strengthening the Expanded Programme on Immunization

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

15. Streefland P, Chowdhury A,& Jimenez P, Quality of vaccination services and social demand for

vaccinations in Africa and Asia, 1999, World Health Organization Bulletin of the World Health Or-

ganization,77(8)

16. Ndiaye N, Ndiaye P., Diédhiou A., Guèye A.Sante T. , Factors related to failure to complete im-

munization of children aged 10-23 months in Ndoulo (Senegal)]. 2009,Sante. Jan-Mar; 19(1):9-13.

Doi: 10.1684/san.2009.0139.

17. Metiku Tesfaye T, Masresha B., Kegne W, et al. Progress in Measles Mortality Reduction in Ethio-

pia, 2002–2009, 2011,J.infDis;204 Suppl.1:3232-8, doi: 10:3201/ eid1902.120301

18. Vijayaraghavan M, Wallace A, Mirza I,Kamadjeu R, Robin Nandy R, Economic Evaluation of a

Child Health Days Strategy to Deliver Multiple Maternal and Child Health Interventions in Soma-

lia,2012, The journal of infectious diseases, Volume,Pp. S134-S140.

19. Ryman T., Macaulay R., Nashimarimana D., et al. reaching every district (RED) approach to

strengthen routine immunization services: evaluation in the African region, The 2005 WHO–

UNICEF 22, Journal of public health, by guest on May 25, 2014 http://

jpubhealth.oxfordjournals.org/

20. Grout L., Conan N, Giner A., et al. Local discrepancies in measles vaccination opportunities: results

of population-based surveys in Sub-Saharan Africa, 2014, BMC Public Health, 14:193 doi:

10.1186/1471-2458-14-193

21. Arevshatian L, Clements C, Lwanga S, AO Misore A, P Ndumbe P, et al. An evaluation of infant

immunization in Africa: is a transformation in progress? WHO volume 85, volume 6, June 2007:449

-457

22. Waters H, Dougherty S,Tegang S.,Tran N,Wiysonge C, Long K.,Nathan D. Coverage and costs of

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.

41

24. Etana B. and Deressa W, Factors associated with complete immunization coverage in children aged

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

25. Vasishtha VM, Bijnor SC, Status of immunization and need for intensification of routine immuniza-

tion in India, Indian Paediatrics 357 volume 49, May 2012

26. Cutts F, Strategies to improve immunization Services in urban Africa WHO Bulletin OMS. 1991;

69:408

27. Balcha G. Masresha B,Fall A, et al. Measles Mortality Reduction and Pre-Elimination in the African

Region, 2011,The Journal of Infectious Diseases 2001–2009.

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: abebehab@gmail.com

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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