Epidemiology and Infection
cambridge.org/hyg
Short Paper
Cite this article: Heitzinger K et al (2019).
Using evidence to inform response to the 2017
plague outbreak in Madagascar: a view from
the WHO African Regional Office. Epidemiology
and Infection 147, e3, 1–5. https://doi.org/
10.1017/S0950268818001875
Received: 8 January 2018
Revised: 20 April 2018
Accepted: 12 June 2018
Key words:
Epidemics; infectious disease control; plague
Author for correspondence:
K. Heitzinger, E-mail: heitzk@uw.edu
© The Authors and World Health Organization
2018. WHO has granted permission to
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Using evidence to inform response to the 2017
plague outbreak in Madagascar: a view from
the WHO African Regional Office
K. Heitzinger1, B. Impouma1, B. L. Farham1, E. L. Hamblion1, C. Lukoya1,
C. Machingaidze1, L. A. Rakotonjanabelo2, M. Yao1, B. Diallo2, M. H. Djingarey1,
N. Nsenga1, C. F. Ndiaye2 and I. S. Fall1
1
2
Health Emergencies Programme, World Health Organization Regional Office for Africa, Brazzaville, Congo and
World Health Organization Country Office for Madagascar, Antananarivo, Madagascar
Abstract
The 2017 plague outbreak in Madagascar was unprecedented in the African region, resulting
in 2417 cases (498 confirmed, 793 probable and 1126 suspected) and 209 deaths by the end of
the acute urban pneumonic phase of the outbreak. The Health Emergencies Programme of the
WHO Regional Office for Africa together with the WHO Country Office and WHO
Headquarters assisted the Ministry of Public Health of Madagascar in the rapid implementation of plague prevention and control measures while collecting and analysing quantitative
and qualitative data to inform immediate interventions. We document the key findings of
the evidence available to date and actions taken as a result. Based on the four goals of operational research – effective dissemination of results, peer-reviewed publication, changes to policy and practice and improvements in programme performance and health – we evaluate the
use of evidence to inform response to the outbreak and describe lessons learned for future
outbreak responses in the WHO African region. This article may not be reprinted or reused
in any way in order to promote any commercial products or services.
The 2017 outbreak of plague in Madagascar was unprecedented in the African region, resulting
in 2417 cases (498 confirmed, 793 probable and 1126 suspected) and 209 deaths by the end of
the acute urban pneumonic phase of the outbreak [1, 2]. Plague is endemic in the plateau of
Madagascar and approximately 400 cases (mostly, the bubonic form of the disease) are reported
annually, most of them from September to April [2, 3]. The 2017 outbreak began on 1 August
2017, occurred primarily in urban, non-endemic areas and was predominantly (77% of cases) of
the rapidly fatal, pneumonic form of the disease [2]. A concerted national and international
response led by the Ministry of Public Health of Madagascar with support from WHO and
other partners was mounted and the outbreak was contained within 3 months (Fig. 1) [1].
The Health Emergencies Programme of the WHO Regional Office for Africa (WHE),
together with the WHO Country Office and WHO Headquarters assisted the Ministry of
Public Health of Madagascar in the rapid implementation of plague prevention and control
measures while collecting and analysing quantitative and qualitative data to inform immediate
interventions. WHO recommends 15 strategies for plague prevention and control [2], which
reflect WHO guidance on the topic [4–6]. We supported data collection relevant to eight of
those strategies including enhanced surveillance; contact identification, prophylactic antibiotic
administration and follow up; laboratory confirmation; infection prevention and control; case
management; social mobilisation and community engagement; risk communication; and safe
and dignified burials. We document the key findings of the evidence available to date and
actions taken as a result. We evaluate the use of evidence to inform response based on the measures of success of operational research: dissemination of results, peer-reviewed publication,
changes to policy and practice, and improvements in programme performance and health.
Based on this evaluation, we summarise lessons learned for future outbreak response in the
WHO African region.
Enhancement and use of surveillance data
Plague surveillance was passive prior to this outbreak, with case reporting to the Ministry of
Public Health of Madagascar by healthcare facilities. However, active surveillance was established following detection of a larger than expected number of pneumonic plague cases via
field investigations and confirmation of cases by rapid diagnostic testing at Institute Pasteur
de Madagascar (IPM); over 4400 community health workers and 340 supervisors were trained
to conduct community-based active surveillance, contact tracing and follow up activities across
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K. Heitzinger et al.
Fig. 1. Epidemic curve of suspected, probable, and confirmed outbreak-associated plague cases in Madagascar and key response actions, 1 August-26 November
2017 (adapted from [2])
the country. On 1 October 2017, the Ministry of Public Health
and WHO deployed rapid response teams to investigate cases
detected through surveillance and identify potential exposures
and epidemiological links. Case investigations continued throughout the outbreak to inform control measures. The Ministry of
Public Health compiled and shared epidemiological surveillance
data with IPM and WHO through daily response coordination
committee meetings, which included all actors in the response.
Contact identification, prophylactic antibiotic administration
and follow up
Contact tracing data were managed by a team hired by the Ministry of
Public Health with financial support from WHO and the
International Federation of the Red Cross and Red Crescent
Societies. Contacts were traced using specially developed Excel
tools that facilitated the collection of demographic information for
the source case and contacts, type of exposure, last date of contact
with the source case and daily follow-up information. Monitoring
of contacts was done using VOOZANOO (EpiConcept, Paris,
France), a software program implemented during the Ebola outbreak
in Guinea in 2014. This facilitated data standardisation across
regions. Regional field coordinators entered aggregate contact tracing
data into VOOZANOO daily and access was shared with the
Ministry of Public Health, making near real-time contact tracing
data available for decision making. Field workers followed up
contacts to provide post-exposure prophylaxis and treatment with
doxycycline or co-trimoxazole. As of 30 November 2017, 7494
contacts were identified and all received prophylaxis and completed
the 7-day follow up period.
Laboratory confirmation of cases and relevant challenges
IPM played a critical role in laboratory confirmation, diagnosis and
dissemination of information about plague cases during the outbreak. Cases were confirmed by culture, serologic testing, or
RDTs, depending on available laboratory capacity. From the start
of the outbreak on 1 August to 7 October 2017, samples from
endemic and non-endemic areas had different testing protocols,
with only samples testing positive by RDT at other laboratories
and field sites being sent to the National Plague Control
Laboratory (housed within and supervised by IPM) for further testing. Starting on 7 October, following the official declaration of the
outbreak, all samples were tested by RDT in the field or by RDT
and polymerase chain reacation (PCR) at reference laboratories.
Any RDT-positive samples were subsequently cultured for
Yersinia pestis at the National Plague Control Laboratory. As of 2
November, to enhance diagnostic capacity, samples were additionally sent to IPM for differential culture. On 3 November, qPCR
replaced conventional PCR as a routine testing method, as qPCR
was faster and more specific. It was not always feasible to send samples to IPM in a timely manner because of the cost of shipment to
the sending facilities. However, IPM confirmed plague infection in
the first reported case and provided diagnostic capacity for the
Ministry of Public Health throughout the outbreak. IPM shared
results regularly with the sending facilities, the Ministry of Public
Health, WHO and partners and also provided more than 2000
RDTs to Toamasina, the Centres Hospitaliers d’Antananarivo
and the Plague Department of the Ministry of Public Health,
thus increasing the regional availability of laboratory testing capacity in the country. The laboratory cultured isolates of Yersinia
pestis, testing isolate sensitivity to the antibiotics recommended
by the National Plague Control Programme. Thirty-three isolates
of Yersinia pestis were identified and all demonstrated sensitivity
to the recommended antibiotics, thus informing the current plague
treatment protocol in the country.
WHO and partners addressed two key challenges to laboratory
confirmation during the course of the outbreak, a delay between
sample collection and reporting results and a need for rapid
implementation of infection prevention and control (IPC) measures in healthcare facilities. First, to reduce the 5–7-day lag
between sample collection and IPM providing results to clinicians,
a new sample transport system was implemented on 10 November
2017, enabling twice daily sample collection from plague treatment reference hospitals, with transport to IPM for testing.
Staff was trained to ensure samples were always collected with
their associated minimum clinical and epidemiological data to
ease interpretation and a call line was established for clinicians
to contact IPM if documents were missing, thus facilitating identification of suspected case samples. This system reduced the
amount of time from sample collection to communication of
results to approximately 48 h and will be maintained until the
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Epidemiology and Infection
end of plague season. The second challenge to plague surveillance
was the absence of an effective feedback mechanism to alert IPM
of RDT shortages at facilities. Some facilities, therefore, experienced shortages of RDTs despite having an ample supply in the
region. The regional health directorate requested that healthcare
facilities send negative RDTs to IPM, which would indicate to
IPM when additional RDTs are needed and enable IPM to distribute RDTs in advance of facility shortages.
Infection prevention and control
To facilitate rapid implementation of IPC measures, WHO and
partners developed a tool for rapid assessment of IPC in healthcare facilities. IPC experts deployed by WHO used this tool to
conduct rapid IPC assessments from 9 to 15 October 2017 in
four of five priority healthcare facilities in Antananarivo. These
experts continued to assess facility IPC measures throughout
the outbreak and supported capacity building of healthcare workers and rapid implementation of IPC measures to avoid
healthcare-associated infections among healthcare workers. The
main finding of the initial rapid assessments was that IPC measures were not being implemented to standard in most plague triage and treatment centres (PTTCs), with several key deficiencies
contributing to the overall inadequacy of IPC. First, healthcare
workers had very limited IPC knowledge and training. To address
this, Médecins du Monde, Médecins Sans Frontières and other
partners provided mentorship and support to PTTC staff in
order to increase adherence to IPC standards. WHO IPC experts
also conducted short training workshops in areas directly affected
by plague (Fianarantsoa, Antsirabe and Tamatave) and trained
IPC trainers nationally. However, in spite of training, on-the-job
application of IPC knowledge remained poor and the WHO IPC
sub-committee recommended the appointment of regional IPC
focal points to lead regional management teams in providing additional support to facilities in the implementation of improved
IPC measures. As of 1 December 2017, five regional IPC focal
points had been selected and recruitment is ongoing in other
regions to implement this plan.
A second deficiency identified by the IPC assessments was
inadequate supply chain management, resulting in inappropriate
re-use and shortages of materials. WHO and partners identified
supply needs and implemented an official supply chain management system that included a central storage site managed by the
Ministry of Public Health from which supplies were distributed
to regions and facilities. The WHO IPC/case management subcommittee recommended a daily inventory of consumables by
healthcare workers so that logisticians could monitor stocks and
request additional orders when needed. A third key finding of
the IPC assessments was the limited number and poor quality
of sanitation and facilities for bathing at PTTCs. Response coordination committee partners including Action Contre la Faim,
Médecins Sans Frontières and UNICEF established genderspecific sanitation and bathing facilities in PTTCs and other priority facilities. A fourth key finding of the IPC assessments was
the inappropriate management of healthcare waste in PTTCs.
This was addressed by UNICEF through the construction of
waste volume reducers for safe storage and waste incineration,
as well as a glass destroyer and facilities for organic waste disposal.
Finally, the IPC assessments found that the protocol for patient
flow through triage and isolation areas was not clearly defined,
leading to suspected cases coming into contact with and potentially infecting others at the hospitals. WHO IPC/case
management teams advised healthcare facility managers to clearly
demarcate and monitor patient flow with the assistance of a hospital security guard. The standard operating procedures for triage
and patient flow were revised based on this experience and are
pending validation and finalisation.
Case management
To support the urgent need for case management during the outbreak, WHO and Global Outbreak Alert and Response Network
partners deployed international experts in plague case management to evaluate the current plague case management protocol
in Madagascar. This evaluation found difficulties in implementation of the protocol, notably the need to provide injectable antibiotics to patients every 3 h post-admission, which carried a
significant risk of a missed injection. WHO case management
experts decided to revise the treatment protocol to include the
administration of levofloxacin; it was piloted in two hospitals
and is pending review for feasibility and sustainability.
Social mobilisation, community engagement and risk
communication
A risk communication and community engagement technical committee led by the Ministry of Public Health was established to
implement plague communication activities during the outbreak.
This committee used the pre-existing national plague communication plan to develop regional communication plans to increase
community knowledge about the plague and also encouraged community engagement and prompt care seeking by suspected cases.
Focus groups of community members and healthcare workers
were conducted to assess plague-related knowledge, attitudes and
practices in the eight districts initially affected by the outbreak.
They noted a generalised fear of plague, misinformation from
plague-related rumours and a desire for plague-related information, particularly from community leaders and healthcare workers,
along with key messages to be transmitted via posters, TV or radio
messaging (Malala Ranarison, written communication). On 10
November 2017, a multi-sectoral communication meeting was
held in Toamasina, led by the regional government with participation by WHO and partners, to discuss the need to strengthen
community engagement and mobilisation activities and preparation of a polio vaccination campaign integrating plague prevention
messages. WHO developed an operational action plan to
strengthen community engagement regarding plague prevention
during the period from November 2017 to January 2018. A review
of risk communication and community engagement and mobilisation activities was held on 30 November and an expanded review of
lessons learned was planned.
Safe and dignified burials
In Madagascar, people are traditionally buried in family burial
vaults and the corpses are periodically ritually exhumed, a practice known as Famadihana [7]. The onset of plague symptoms
has been reported during these exhumations, thus the Ministry
of Public Health of Madagascar recommends a 7-year period
between death and exhumation of a plague case to reduce the possibility of disease [7]. There is a national burial protocol for plague cases, dating to 1932, which allows the government to bury
plague victims in a mass grave. However, it is controversial and
difficult to implement. WHO and UNICEF jointly conducted
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focus groups to determine the acceptability of changes to increase
the safety of burial practices. A key finding was that any change
would only be acceptable if definitive proof of plague infection
of the deceased could be provided (Malala Ranarison, written
communication). However, focus group participants expressed
willingness to change certain aspects of traditional burial practices, including shortening or discontinuing wakes, allowing
others to prepare the body for burial or families wearing personal
protective equipment to prepare the body themselves, using body
bags for plague victims and burying adjacent to the family vault
instead of inside it. WHO and UNICEF developed a revised
safe and dignified burial protocol based on these findings and pretested it in Antananarivo and Tamatave; 90% of the population
consulted was in favour of the measures proposed in the protocol
[2]. WHO engaged the Malagasy Red Cross to take responsibility
for the revised safe and dignified burial protocol and submitted
the protocol for approval by the government of Madagascar.
Training of trainers for the burial teams was conducted to facilitate implementation of the protocol during future plague seasons
or outbreaks in the country.
Evaluation of WHO’s use of evidence to inform response
measures
The success of WHO’s use of data and information to inform outbreak response can be determined by assessing progress toward the
four goals of operational research [8]. In all cases, the findings of
data collection activities were communicated back to teams and
partners in the field to facilitate evidence-based action, thus meeting the first goal of operational research activities. The response
coordination mechanism, directed by a high-level working group
chaired by the prime minister and involving health sector response
coordination led by the Ministry of Public Health with support by
WHO, non-health response coordination led by the National Risk
and Disaster Management Office of Madagascar and health sector
partners coordination, was critical to facilitating this communication. Future plague outbreak responses would likely benefit from
similar high-level interdisciplinary coordination mechanisms to
ensure engagement and cooperation of all relevant partners. The
second goal, peer-reviewed publication of the research, has not
yet been achieved, however, WHE aims to publish their research
during the coming months and support colleagues from partner
organisations in doing the same. The important qualitative
research conducted regarding community mobilisation and
engagement, risk communication and safe and dignified burial
practices represents an ideal opportunity for peer-reviewed publication; dissemination of this information via the peer-reviewed literature could be used as evidence to advocate for policy change and
inform future plague outbreak response. Despite the fact that all
papers resulting from this work are in preparation, WHE has
already advocated for important changes to practice and policy,
the third goal of operational research. The approval and implementation of revised case management and safe and dignified burial protocols represent an important opportunity to improve the
future plague prevention and treatment in the country.
The fourth and most important measure of success in operational research is whether implementation of evidence-based
actions results in improvements in response and in human health.
Anecdotal evidence suggests that WHE’s actions increased the
speed of laboratory confirmation, IPC capacity of healthcare
workers, IPC supply availability, case management and community plague knowledge, but data were not systematically collected
K. Heitzinger et al.
to confirm these observations. Data collection to evaluate those
aspects of response at this stage could nevertheless be valuable
to inform interventions during the remainder of the plague season
and during future outbreaks in Madagascar. WHE collected data
regarding eight of the 15 strategies for plague control and prevention; although not all of the remaining seven strategies are readily
evaluated using data, one strategy, vector control, could have been
better informed by data. WHE did not implement vector control
activities or collect data to assess their effectiveness during the
outbreak due to an absence of available technical expertise.
Future plague outbreak responses in the WHO African region
would benefit from the early recruitment of staff with that expertise and the integration of vector-related data collection activities
into outbreak response. During this outbreak, data collection
was managed by a data management team that comprised
WHE, Ministry of Public Health and IPM staff, strategy-specific
response committees and a qualitative researcher jointly hired
by WHO and UNICEF. To implement systematic data collection
in the context of future WHE outbreak responses, there is a need
for greater institutionalisation of operational research as part of
the WHE Programme. The infectious hazards management
unit, whose mandate includes knowledge generation to inform
control of all hazards, should lead this effort, with participation
from other programme areas.
Although WHE was successful in collecting data to inform
action during the 2017 plague outbreak in Madagascar and evidence was suggestive that those actions improved the effectiveness
of response strategies and human health, increased implementation
of operational research activities into outbreak response and publication of this research in the peer-reviewed literature are needed to
improve scientific understanding of the effectiveness of outbreak
response activities and improve plague outbreak prevention and
control measures at the national, regional and global levels.
Acknowledgements. We thank Julienne Anoko, Freddy Banza-Mutoka,
Fanny Chereau, Margarita Ghiselli, Konate Issiaga, Gilbert Kayoko, Jean Paul
Ngandu Mbanga, Samuel Mesfin, Malala Ranarison, José Rovira-Vilaplana
and Annika Wendland for providing their insights and detailed information
regarding each aspect of the response to the 2017 Madagascar plague outbreak.
This research received no specific grant from any funding agency, commercial or
not-for-profit sectors. However, the response and relevant collection of evidence
were supported by WHO Contingency Funds for Emergencies, the Norwegian
Agency for Development Cooperation, the Italian Ministry of Foreign Affairs,
the Korean government, the Bank of Africa Madagascar Foundation, the
United Nations Children’s Fund (UNICEF), the United Nations Development
Programme (UNDP) and the United Nations Population Fund (UNFPA).
Conflict of interest. None.
Disclaimer. The authors alone are responsible for the views expressed in this
article and they do not necessarily represent the decisions, policies, or views of
the World Health Organization.
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