SUPPLEMENT ARTICLE
Challenges of Establishing Routine Influenza
Sentinel Surveillance in Ethiopia, 2008–2010
Workenesh Ayele,1 Gelila Demissie,1 Woubayehu Kassa,1 Etsehiwot Zemelak,1 Aklog Afework,1 Berhanu Amare,2
Chad M. Cox,3 and Daddi Jima1
1
Ethiopian Health and Nutrition Research Institute, and 2CDC Ethiopia, Addis Ababa; and 3Influenza Division, Centers for Disease Control and
Prevention, Atlanta, Georgia
Ethiopia launched influenza surveillance in November 2008. By October 2010, 176 patients evaluated at 5 sentinel health facilities in Addis Ababa met case definitions for influenza-like illness or severe acute respiratory
illness (SARI). Most patients (131 [74%]) were children aged 0–4 years. Twelve patients (7%) were positive for
influenza virus. Most patients (109 [93%]) were aged <5 years, of whom only 3 (2.8%) had laboratoryconfirmed influenza. Low awareness of influenza by healthcare workers, misperceptions regarding case definitions, and insufficient human resources at sites could have potentially led to many missed cases, resulting in
suboptimal surveillance.
Influenza is an acute respiratory infection responsible
for an estimated 28 000–111 500 deaths annually
among children aged <5 years, with 99% of these
deaths occurring in developing countries [1]. In
Africa, respiratory infections rank among the leading
causes of morbidity and mortality; however, information on the disease burden of influenza is lacking [2].
The little that is known about influenza in Ethiopia
comes from reports from outbreaks that occurred
during global influenza pandemics of the 20th
century, and two studies of pneumonia patients in the
mid-1990s [3, 4, 5]. In late 2008, Ethiopia launched a
sentinel surveillance program for influenza as part of
pandemic preparedness efforts. In this article, we describe the initiation of an influenza sentinel surveillance program in Ethiopia and summarize findings
from the first 24 months of surveillance findings.
Presented in part: 2010 CDC International Influenza Grantee and Burden of
Disease Meeting, Atlanta, Georgia, 9–11 July 2010; 21st Annual Conference of
the Ethiopian Public Health Association, Mekelle, Ethiopia, 26–28 October 2010
( poster 74); and 2nd Annual Meeting of the African Network of Influenza Surveillance and Epidemiology, Accra, Ghana, 11–12 January 2011 (abstract LAT70003).
Correspondence: Workenesh Ayele, PhD, National Influenza Laboratory, EHNRI,
Arbegnoch St 626, Gullele Subcity, Addis Ababa, Ethiopia (workenesha@ehnri.
gov.et).
The Journal of Infectious Diseases 2012;206(S1):S41–5
© The Author 2012. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
[email protected].
DOI: 10.1093/infdis/jis531
METHODS
Study Design
From November 2008 through October 2010, we conducted year-round, healthcare facility–based sentinel
surveillance in Addis Ababa, Ethiopia, to describe the
prevalence of influenza virus infection among patients
presenting with influenza-like illness (ILI) and severe
acute respiratory illness (SARI).
Setting
Addis Ababa is the capital and largest city of Ethiopia,
with a population of 2.7 million, representing 4% of
the national population of 74 million (2007 official
census data), and has a subtropical highland climate
with year-round moderate temperatures. Surveillance
was limited to Addis Ababa to minimize logistical
constraints of transporting samples to the central laboratory. Participating facilities were chosen on the basis
of predetermined selection criteria, including patient
caseload, staff profile, and existence of the necessary
infrastructure to support surveillance efforts.
The original study design called for the inclusion of
a single ILI surveillance site (Shiromeda Health
Center) selected on the basis of the criteria described
above. This site commenced influenza surveillance activities in November 2008. However, after 20 consecutive months of surveillance, few samples were
collected. Consequently, 2 additional ILI surveillance
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sites (Kolfe and Akaki health centers) were incorporated into
the surveillance program in August 2010, and 3 months of
data from these two sites were included in this analysis. A
combined catchment population of 370 875 is served by the 3
health centers.
SARI surveillance began at 2 sites. One was a general hospital (Yekatit 12) that initiated surveillance in January 2009, and
the other was a hospital (Saint Peter’s Hospital) specializing
mainly in the management of chronic respiratory diseases that
initiated surveillance in June 2009. The catchment population
for Yekatit 12 includes all residents of Addis Ababa. Saint
Peter’s Hospital, as a federal-level referral facility, serves the
entire nation.
Case Selection and Sample Collection
A standardized study protocol was applied across all sites.
Treating physicians at the selected health facilities referred patients fulfilling ILI or SARI case definitions for influenza
testing on site. ILI was defined as a sudden onset of fever
(temperature >38°C), plus either cough or sore throat, in the
absence of other diagnoses. SARI in children aged <5 years
was defined on the basis of the Integrated Management of
Childhood Illness guidelines for pneumonia or severe pneumonia [6]. For individuals aged ≥5 years, SARI was defined as
(1) acute lower respiratory tract infection, with a sudden-onset
fever (temperature >38°C) and cough or sore throat and shortness of breath or difficulty breathing, with or without clinical
or radiographic findings of pneumonia; or (2) death due to an
unexplained respiratory illness.
On the basis of a presurveillance assessment, we anticipated
capturing a minimum of 40 cases weekly from the initially selected ILI site. Collection of oropharyngeal swab specimens
from all of these patients would have overwhelmed our laboratory’s resources and capacity. We therefore instructed trained
healthcare workers to collect an oropharyngeal swab specimen,
using commercially available viral transport medium (VTM;
Becton Dickinson, Sparks, MD), from the first 5 eligible ILI
cases and from all SARI cases who gave their consent on each
working day. Before mid-2009, the period when VTM became
available, specimens were collected in absolute ethanol. Specimens collected in VTM were stored in a refrigerator (temperature, 2°C–8°C) and transported within 1 week of collection
to the National Influenza Laboratory, maintaining the cold
chain.
Information on demographic characteristics and clinical
presentation was captured using a standardized questionnaire
that was administered to all consenting patients by trained
healthcare workers.
Laboratory Methods
Laboratory analysis for the diagnosis of influenza virus infection was performed at the National Influenza Laboratory in
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Addis Ababa. We extracted viral RNA from patient specimens,
using the QIAamp Viral RNA Minikit (Qiagen, Hilden,
Germany) in accordance with the manufacturer’s instructions.
A 1-step reverse-transcription polymerase chain reaction (PCR)
assay was first performed for influenza A and B viruses, followed by further subtyping for influenza A virus–positive
specimens, according to the protocol developed by the World
Health Organization Collaborating Center for influenza at the
Centers for Disease Control and Prevention (CDC; Atlanta,
GA) [7], using an Applied Biosystems 7500 Fast Real-Time
PCR System and sequence detection software (version 1.4)
(Applera, Foster City, CA). A specimen was considered positive for influenza virus if the amplification growth curve
crossed the threshold within 40 cycles. A sample result was
considered indeterminate if the internal control used for the
assay (RNAseP) failed to amplify during PCR cycling.
Statistical Methods
Data from completed questionnaires and laboratory results
were captured using EpiInfo, version 3.5.1 (CDC). Patients
who did not meet either the ILI or SARI case definitions were
excluded from the analysis. We conducted univariate analyses
of demographic variables, using Microsoft Excel 2007. Dichotomous variables were compared using a 1-tailed z-test in Stata
version 11 (StataCorp, College Station, TX). A P value of ≤.05
was considered to be statistically significant.
Ethical Considerations
This surveillance activity was considered to be part of routine
surveillance by the Federal Ministry of Health. The National
Influenza Laboratory is mandated to provide laboratory
support for influenza surveillance. We therefore, did not seek
additional ethical clearance. The rationale for the surveillance
and specimen collection procedures was explained to all participants prior to their enrollment. Each patient (or their
guardian, in the case of minors) was requested to provide
verbal informed consent. Results were reported back to the relevant health facilities as soon as they became available, using
established reporting channels.
RESULTS
From November 2008 through October 2010, we enrolled 368
patients (216 with SARI and 152 with ILI) at the 5 sentinel
health facilities. For 127 patients, specimens were collected
using absolute ethanol, but laboratory testing was delayed for
several months because of a shortage in reagents. During this
period, there was substantial evaporation of the specimens,
leading to insufficient volume for testing. These patients were
excluded from the analysis. We excluded an additional 51
patients who did not meet the SARI case definition and 14
patients with indeterminate laboratory test results. Of the 176
remaining patients, 117 (66%) were from SARI patients, and
the remaining 59 (34%) were from ILI patients (Table 1).
Influenza virus infection was detected in 12 (7%) of the 176
participants. The proportion of patients with influenza virus
detected was higher among those with ILI (7 of 59 [12%]),
compared with those with SARI (5 of 117 [4%]), although this
difference was not statistically significant (P = .06). Fifty-four
percent of patients with ILI and 57% with SARI were male.
Nearly all patients with SARI (109 of 117 [93%]) but just over
one-third of those with ILI (22 of 59 [37%]) were aged 0–4
years. In this age group, the proportion who tested positive for
influenza virus was low (0% among patients with ILI and 3%
among those with SARI). Among all patients with ILI or
SARI, older children and adults (age range, 5–64 years) were
more likely to have an influenza virus–positive sample, compared with children aged <5 years (20% vs 2.3%; P < .01).
Of the 12 patients with confirmed influenza virus infection,
influenza A virus was detected in 11 (92%), and influenza B
virus was detected in 1 (8%). The cases of influenza A virus
infection included 7 patients with seasonal influenza A virus
subtype H3N2, 2 with 2009 pandemic influenza A virus
subtype H1N1, and 2 with viruses that could not be subtyped
because of an insufficient sample volume. Patient enrollment
was highest in May and June 2009 (Figure 1), as was the percentage of specimens that were positive for influenza virus.
October 2010). A critical appraisal of the difficulties encountered during implementation helped us identify factors that
are crucial to the success of the surveillance that were initially
lacking in our case. As the result of our appraisal, we recommend that other resource-constrained countries that are considering initiating or expanding influenza surveillance conduct
the following activities: (1) conduct an assessment of influenza
awareness among healthcare workers and provide ongoing
sensitization, (2) identify appropriate sentinel sites to capture
intended target patient population groups, (3) assess the
ability of participating health facilities to commit sufficient
human resources to influenza surveillance, and (4) use simple,
straightforward case definitions that are easily understood by
healthcare workers. At the same time, there needs to be sufficient political will to ensure program success.
Among participants with ILI and SARI, the percentage of
laboratory-confirmed influenza was 7%, which was lower than
the percent of influenza-positive respiratory specimens reported in studies from other African countries [8, 9]. The low absolute numbers of ILI and SARI cases detected by the
surveillance program limits the generalizability of our findings.
Surveillance relied on healthcare personnel whose multiple
duties may have prevented them from referring patients for
laboratory testing, potentially leading to many missed cases.
Indeed, this seems highly probable because examination of
patient registry logbooks during routine site visits revealed the
documentation of respiratory illness cases that would have
met selection criteria but were never referred for sampling. At
health facilities across Ethiopia, multitasking is not uncommon among healthcare personnel, who are rarely assigned to
follow one surveillance program alone. In many developing
DISCUSSION
This report describes efforts to establish a sentinel surveillance
program for influenza in Addis Ababa and highlights the findings from the program’s first 2 years (November 2008 through
Table 1. Cases of Influenza-Like Illness (ILI), Severe Acute Respiratory Illness (SARI), and Laboratory-Confirmed Influenza Virus
Infection, by Age Group, Sex, and Year—Addis Ababa, Ethiopia, November 2008–October 2010
Distribution of ILI and SARI patients
Characteristic
Distribution of influenza-positive patients
ILI
SARI
Total
ILI
SARI
Total
0–4
5–14
22/59 (37.3)
15/59 (25.4)
109/117 (93.2)
6/117 (5.1)
131/176 (74.4)
21/176 (11.9)
0/22
3/15 (20.0)
3/109 (2.8)
1/6 (16.7)
3/131 (2.3)
4/21 (19.0)
15–64
22/59 (37.3)
2/117 (1.7)
24/176 (13.6)
4/22 (18.2)
1/2 (50.0)
5/24 (20.8)
29/54 (53.7)
65/115 (56.5)
94/169 (55.6)
7/29 (24.1)
2/65 (3.1)
9/94 (9.6)
25/54 (46.3)
50/115 (43.5)
75/169 (44.4)
0/25
3/50 (6.0)
3/75 (4.0)
Age, y
Sexa
Male
Female
Year
2008
4/59 (6.8)
0/117
4/176 (2.3)
0/4
0/0
2009
27/59 (45.8)
49/117 (41.9)
76/176 (43.2)
6/27 (22.2)
3/49 (6.1)
2010
Overall
28/59 (47.5)
59/176 (33.5)
68/117 (58.1)
117/176 (66.5)
96/176 (54.5)
176/176 (100)
1/28 (3.6)
7/59 (11.9)
2/68 (2.9)
5/117 (4.3)
0/4
9/76 (11.8)
3/96 (3.1)
12/176 (6.8)
Abbreviations: ILI, influenza-like illness; SARI, severe acute respiratory illness.
a
Data are missing for 7 suspected cases.
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Figure 1. Distribution of samples tested and positive for influenza virus, by month of sample collection—Addis Ababa, Ethiopia, November 2008–
October 2010.
countries, such a focus is an unaffordable luxury. Long-term
sustainability of programs is best ensured by integrating new
surveillance programs into existing health systems.
Limited awareness about influenza has posed a significant
challenge to the surveillance program. Influenza surveillance is
a relatively new activity in Ethiopia, and few healthcare
workers at sentinel sites have received orientation on the
subject. On-site staff training exercises were conducted at
several of the health facilities, but staff turnover or reassignment of staff to other responsibilities within the same health
facility posed challenges to effectively conducting surveillance.
We found that most healthcare workers were unfamiliar with
the terms “influenza-like illness” or “severe acute respiratory
illness.” Although many of them had no difficulty in identifying pneumonia cases, they did not necessarily consider these
cases as potential SARI cases. Likewise, most healthcare
workers did not associate cases of acute upper respiratory tract
infections with ILI. To address this gap, we requested that
sentinel site staff be vigilant in considering all cases of acute
respiratory illness potential ILI and SARI cases.
Our single-most important challenge may have been related
to perception. Influenza surveillance was launched during a
period when the term “influenza” was considered by patients
and many healthcare workers to be synonymous with “pandemic influenza.” Once the pandemic was over, influenza
became much less of a concern. The Addis Ababa regional
health bureau, which routinely follows the progress of disease
surveillance programs, rarely inquired about influenza surveillance. Much remains to be done to convince stakeholders of
the importance of influenza surveillance.
Compared with children aged <5 years, older children and
adults (age range, 5–64 years) were more likely to have
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influenza. Most participants with SARI were aged 0–4 years,
consistent with findings showing SARI to be a leading cause
of serious illness in young children [11]. We found that 3% of
SARI patients in this age group had influenza. This suggests
that other respiratory pathogens may play a more important
role in the etiology of SARI among young children in our
setting, a finding seen in other studies in Africa [12, 13].
We observed an increase in case enrollment and confirmed
influenza virus infections during May–June 2009. This was
likely due to heightened concerns about pandemic influenza
during this period. The first 2 cases of pandemic influenza A
virus subtype H1N1 were detected in Ethiopia in June 2009 and
involved individuals who recently returned from travel to the
United States, creating a sudden increase in demand for testing;
however, the most frequently identified virus during this period
was seasonal influenza A virus subtype H3N2. These initial
cases did not present through the influenza sentinel surveillance
system but through a separate health facility set up to screen
and quarantine those with suspected pandemic influenza. Influenza sentinel surveillance did not detect a case of pandemic influenza until early 2010. A number of studies conducted in
tropical countries have shown influenza to circulate throughout
the year [14, 15]. However, because of the small numbers of ILI
and SARI cases enrolled and the non-continuous nature of surveillance at some sites, we are unable to draw conclusions about
influenza seasonality in Addis Ababa.
Our study has several limitations. First, the low number of
samples submitted, compounded by the exclusion of nearly
half of the cases because of insufficient sample volume, limits
the generalizability of our findings. Second, our surveillance
was heavily biased toward infants and young children, with
adult SARI cases virtually absent. This finding can likely be
explained by the fact that we included a specialized hospital as
a SARI site. Third, our surveillance was restricted to Addis
Ababa. It is unlikely that these findings are representative of
influenza activity throughout the country, given the huge variation in geography and climate. Finally, our surveillance
system was restricted to public-health sector facilities and may
not represent the overall healthcare system, especially in Addis
Ababa, where the private health sector is significant.
Despite these limitations, we believe that our first two years
of surveillance in Ethiopia provide a limited but helpful initial
description of influenza in the country. Strengthening sentinel
surveillance through ongoing efforts to train healthcare staff
and the gradual inclusion of additional sites across the
country will allow for an improved understanding of influenza
epidemiology in Ethiopia in the future.
Notes
Acknowledgments. We thank the healthcare team members involved
in the surveillance at each of the health facilities; Dr Brett Archer (National
Institute of Communicable Diseases, Johannesburg, South Africa), for his
critical reading of the manuscript and editorial revisions; and Dr Stefano
Tempia (CDC South Africa), for assistance with the statistical analysis. We
also thank the following institutions for their support and respective roles
in implementing the surveillance program: the Ethiopian Federal Ministry
of Health; the Ethiopian Health and Nutrition Research Institute; the
Addis Ababa Regional Health Bureau and the health bureaus of Gulele,
Kolfe-Keranio, and Akaki-Kality subcities, where the sentinel health facilities are located; Yekatit 12 Hospital; Saint Peter’s Hospital; Shiromeda
Health Center; Kolfe Health Center; Akaki Health Center; CDC Ethiopia;
and the World Health Organization country office.
Disclaimer. The contents of this article are solely the responsibility of
the authors and do not necessarily represent the official views of the CDC.
Financial support. This work was supported by the CDC (cooperative
agreement 5U51IP000159-01–5U51IP000159-04), under the federal grant
“Surveillance and Response to Avian and Pandemic Flu by National
Health Authorities Outside the United States” (funding opportunity
number CDC-RFA-IP07-702).
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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