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Lassa fever, a deadly infectious disease, is an epidemic threat needing urgent research and development action.
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An outbreak with a high case fatality rate occurring during the Ebola epidemic is described.
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Poor surveillance and response to early cases, a lack of timely specimen collection and transportation and limited treatment options were found.
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Strengthening the Integrated Disease Surveillance and Response system in West Africa is key to aid timely detection and response to outbreaks.
Abstract
Objectives
Lassa fever (LF), a priority emerging pathogen likely to cause major epidemics, is endemic in much of West Africa and is difficult to distinguish from other viral hemorrhagic fevers, including Ebola virus disease (EVD). Definitive diagnosis requires laboratory confirmation, which is not widely available in affected settings. The public health action to contain a LF outbreak and the challenges encountered in an EVD-affected setting are reported herein.
Methods
In February 2016, a rapid response team was deployed in Liberia in response to a cluster of LF cases. Active case finding, case investigation, contact tracing, laboratory testing, environmental investigation, risk communication, and community awareness raising were undertaken.
Results
From January to June 2016, 53 suspected LF cases were reported through the Integrated Disease Surveillance and Response system (IDSR). Fourteen cases (26%) were confirmed for LF, 14 (26%) did not have a sample tested, and 25 (47%) were classified as not a case following laboratory analysis. The case fatality rate in the confirmed cases was 29%. One case of international exportation was reported from Sweden. Difficulties were identified in timely specimen collection, packaging, and transportation (in confirmed cases, the time from sample collection to sample result ranged from 2 to 64 days) and a lack of response interventions for early cases.
Conclusions
The delay in response to this outbreak could have been related to a number of challenges in this EVD-affected setting: a need to strengthen the IDSR system, develop preparedness plans, train rapid response teams, and build laboratory capacity. Prioritizing these actions will aid in the timely response to future outbreaks.
Lassa fever is a rare viral hemorrhagic fever (VHF) listed by the World Health Organization (WHO) as one of the emerging pathogens likely to cause severe outbreaks in the near future with few medical countermeasures (
). There is limited published research on the response to outbreaks of this significant public health threat, essential information to improve preparedness activities.
Liberia is one of the few countries endemic for Lassa fever, the others being found across West Africa where 300 000–500 000 new infections are estimated to occur annually (
). It is transmitted to humans through the excreta of infected rodents, often via contaminated food. Subsequent person-to-person transmission can occur through direct contact with bodily fluids, often due to a lack of appropriate infection prevention and control (IPC) measures whilst receiving care (
). There is some debate over the relative contribution of human-to-human transmission, with a recent study using data from Sierra Leone suggesting just 20% of Lassa fever cases were attributable to this mode of infection (
). Many of those infected will be asymptomatic or have mild infections not requiring clinical treatment. The case fatality rate is estimated at 1–15% (
). Lassa fever is difficult to distinguish from other VHFs such as EVD, as well as other diseases that cause fever, including malaria, shigellosis, typhoid fever, and yellow fever, due to the varied and non-specific symptoms. Laboratory investigation therefore plays an important role in both diagnosis and surveillance of Lassa fever, with a definitive diagnosis requiring testing available only in regional reference laboratories.
Lassa fever is one of Liberia’s 14 immediately notifiable epidemic-prone diseases under the Integrated Disease Surveillance and Response system (IDSR) (
). During the EVD epidemic, surveillance for other IDSR notifiable diseases was compromised and laboratory testing for diseases other than EVD was limited. The epidemic significantly impacted the already weak healthcare system in Liberia (
A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apex.
), including the surveillance system and diagnostic capacity to respond to other public health events.
The outbreak
On February 19, 2016, a cluster of three suspected Lassa fever cases, including one death, was notified to the Liberia Ministry of Health (MOH) from Suakoko District, Bong County. The MOH was requested to assist the County Health Team (CHT) in responding to this outbreak with the support of the WHO Liberia Country Office. Investigations commenced to find additional cases, identify the sources of infection, and control the outbreak.
The public health action taken to contain the outbreak and prevent further cases is reported herein. The challenges encountered when mounting an effective response to a Lassa fever outbreak in an EVD-affected setting were also explored, including the implications for strengthening disease surveillance, response, and prevention activities in Liberia.
Methods
The epidemiological investigations into this outbreak carried out by the response team are described below. These included a retrospective review of surveillance data and health facility-based records, as well as outbreak response activities following guidelines, where available, for the response to a Lassa fever outbreak (
). If a person presents with signs and symptoms consistent with the suspected case definition for Lassa fever (Box 1), the clinician should make a notification to the district surveillance officer (DSO) by the fastest possible means. The patient should be isolated immediately, appropriate IPC precautions taken, and a blood specimen taken for laboratory testing.
Suspected case of Lassa fever: illness with gradual onset with one or more of the following: malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhea, myalgia, chest pain, hearing loss, and a history of contact with excreta of rodents or with a case of Lassa fever.
Confirmed case of Lassa fever: a suspected case that is laboratory-confirmed (positive IgM antibody, PCR or virus isolation).
Source: Liberia IDSR guidelines.
All epidemic-prone diseases have an alert and action threshold, requiring further investigation. Due to its epidemic potential and pathogenicity, the alert threshold for Lassa fever is one suspected case, and a thorough investigation must be undertaken for each case reported. Case investigation is conducted by the district and county health teams, but support can be requested from the national MOH team. The action threshold, and also the definition of a Lassa fever outbreak in Liberia is one confirmed case.
On a weekly basis, summary numbers of all 14 suspected epidemic-prone diseases reported from HCFs in the county are notified from the CHT to the MOH (
). This information is then analyzed and additional information on response actions is requested. The MOH publishes this information for stakeholders in the weekly IDSR bulletin (
During the Ebola epidemic, an embargo was placed on the transportation of samples internationally. Therefore diagnostic capacity was severely compromised, as testing for Lassa fever was not available in-country and referral to the regional Lassa fever laboratory in Kenema, in neighboring Sierra Leone, was not an option.
In the weeks preceding identification of the index case of this outbreak in February 2016, the regional laboratory in Kenema had agreed to lift the embargo and accept specimens from Liberia for Lassa fever testing, although this had not yet occurred in practice.
Outbreak investigation
Following the notification of three suspected cases from the rubber factory community in Suakoko District, Bong County, a rapid response team consisting of representatives from the national MOH disease prevention and control department, the environmental health department, and the WHO, was deployed to Bong County on February 20, 2016. They joined the Bong County surveillance officer (CSO) and Suakoko DSO to conduct further investigations.
Additionally, a team from the MOH supported by the WHO reviewed data on Lassa fever cases previously notified in 2016. An outbreak was suspected in Bong County and an alert was issued to the neighboring counties of Nimba, Gbarpolu, and Lofa, also considered to be endemic for Lassa fever.
Case finding
Following activation of the rapid response team, active case searches were undertaken in HCFs and communities. In- and out-patient registers since the beginning of 2016 were reviewed for any patients who presented with symptoms that fulfilled the suspect case definition from HCFs in the affected district and neighboring districts, where the cluster of cases resided. Active case searches in communities where cases had been reported since the start of the year were undertaken by DSOs together with community health volunteers (CHVs).
Previously notified Lassa fever cases were reviewed to determine the size, location, and timing of the outbreak, previous actions taken, and epidemiological links.
Specimens submitted for Lassa fever testing during the shipping embargo were retrieved from storage at the National Reference Laboratory (NRL) in Margibi County and sent to the regional reference laboratory in Kenema for testing.
Case investigation
All suspected cases at the time were investigated by the outbreak response team. Family members were interviewed if the individual was too sick to be interviewed. Interviews were conducted using a VHF-specific standardized questionnaire administered by the CSO or DSO. Information was collected on patient demographics, history of the disease including clinical signs and symptoms, and possible risk exposures. Whole blood specimens were collected by the HCF laboratory technician or CSO/DSO, for EVD and Lassa fever testing. These were packaged as per international guidelines (
). Unique IDSR identifiers were assigned and applied to the specimen tube and IDSR case investigation form.
Laboratory testing
Specimens taken from suspect cases in the affected areas were transported from the HCF to the NRL. Given that patients with suspected Lassa fever also fulfilled the case definition for EVD, all blood specimens were first tested for EVD by reverse transcriptase polymerase chain reaction (RT-PCR) in Liberia. With WHO facilitation, once specimens tested negative for EVD, an aliquot of each specimen was referred for Lassa fever testing at the regional reference laboratory in Kenema, Sierra Leone.
The diagnostic algorithm used at Kenema Government Hospital involves Lassa antigen detection using a rapid diagnostic test (RDT) and an antigen enzyme-linked immunosorbent assay (ELISA), antibody detection using ELISA for IgM and IgG, and an RT-PCR assay as the confirmatory test to detect viral RNA (Box 2 ). In the laboratory of Kenema Government Hospital, the previously established Trombley RT-PCR assay was used to test specimens from Liberia (
Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and New World hantaviruses.
Contacts were listed as part of case investigation by CSOs and DSOs. For all those residing in the same location as the cluster of three cases and all those with direct contact in the community with known cases, daily temperature screening and monitoring for signs and symptoms commenced. This was undertaken by CHVs with support from the DSO for 21 days since the last known exposure.
Environmental investigation
The locations of current cases were visited to investigate the source of infection or possible sources of contamination and for the implementation of appropriate control measures by the outbreak response team. Assessments were made of sleeping quarters, food preparation and storage areas, sanitary conditions, water supply and drainage, and refuse disposal.
Case management and IPC measures
Case management and IPC measures were reviewed at the referral hospital by the outbreak response team in Bong County with isolation facilities where suspected cases had been managed, to ensure correct procedures were being followed. Stockpiles of ribavirin for treatment and personal protective equipment (PPE) were assessed and the supply chain reviewed. Homes of confirmed cases and their surroundings, as well as the ambulance that transported cases, were decontaminated using chlorine solution.
Risk communication and education
Current risk communication messages were reviewed by the national team for distribution. A community sensitization meeting was held to discuss the Lassa fever situation and preventative measures that should be taken.
Results
Cluster of cases
Of the three reported cases in the rubber factory community cluster, two were confirmed by laboratory testing; one died and one survived. The two confirmed cases shared the same room, worked together, and were interacting socially. Transmission could have occurred person-to-person or could have been from a common exposure to rodent excreta.
Suspect cases were appropriately isolated and received ribavirin and supportive treatment. Ninety contacts were monitored for 21 days and none developed symptoms.
Notification of this cluster led to a wider outbreak investigation.
National outbreak
Prior to this cluster notification, 12 suspected Lassa fever cases including eight deaths had been notified through the IDSR, although not investigated. None were confirmed, therefore the action threshold had not been triggered. Basic epidemiological information had been reported, but no detailed case investigation forms and no reports of investigation activities had been received by the national team.
In total, 53 suspected Lassa fever cases were reported through the IDSR (inclusive of the three in the rubber factory community outbreak) with a date of onset between January 4, 2016 and May 21, 2016 (Figure 1). No cases were reported for the following 6 weeks (two incubation periods). The majority of cases initially presented to a HCF, with 5% (n = 3) identified in the community.
Figure 1Epidemiological classification of Lassa fever cases reported by week of symptom onset—Liberia, weeks 1–20, 2016.
Fourteen cases (26%) were confirmed as having Lassa fever by laboratory testing, 25 (47%) were deemed not a case following laboratory analysis of specimens, and 14 (26%) did not have a specimen tested and therefore remained as suspected cases (Figure 1). Confirmed cases were most commonly female (64%) with a median age of 33 years (range 1–56 years) (Table 1). A wide geographical distribution of suspected cases was seen, with reported cases resident in seven of the 15 counties in Liberia (Figure 2). Confirmed cases were resident in three counties, the majority of which were in Bong County (64%) (Table 1). The incidence rate of Lassa fever for this period was 0.4 per 100 000 nationally, 2.3 per 100 000 in Bong, 0.73 per 100 000 in Nimba, and 0.08 per 100 000 in Montserrado.
Table 1Demographic characteristics of Lassa fever cases reported by epidemiological status—Liberia 2016.
Ribavirin was given to 93% of confirmed cases, 43% of suspected cases, and 64% of those not a case. The case fatality rate (CFR) in confirmed cases was 29%, in suspected cases was 93%, and in those deemed not a case was 9% (Table 1). Suspected cases were more likely to die than confirmed cases (Fisher’s exact test, p = 0.001), although this could not be explained by whether or not ribavirin was received (Fisher’s exact test, p = 0.149) or by a delay in presentation (t-test, p = 0.408), as no information was collected on treatment start date. Twelve of the 14 suspected cases that did not have a sample tested, had a date of onset before the outbreak was recognized by the national team and before the international embargo on the referral of specimens was lifted.
Two of the confirmed cases were friends, as described above, and two other cases were a mother–child pair. The mother and child resided in Sugar Hill community, Suakoko District, a community neighboring the rubber factory where the two friends resided; however, a confirmed epidemiological link was not elucidated between the two pairs. A further two cases were from Sugar Hill, although they developed symptoms 2 months after the mother–child pair, ruling out the possibility of person-to-person transmission. In total, 50% (n = 7) of confirmed cases were from Suakoko District, however no further epidemiological links were identified between the cases.
Laboratory investigations and sample turn-around times
Two of 10 specimens collected before the outbreak was identified were retrieved from storage at the NRL for Lassa fever testing at Kenema. The remaining specimens had tested negative for EVD and been discarded.
Difficulties were reported in timely specimen collection, proper packaging, and transportation, therefore training was undertaken on specimen collection and the referral process at the county level. Close follow-up by telephone and e-mail was ensured to facilitate reporting, however turn-around-times to results were not optimal.
For confirmed cases, the median time between date of onset and date of specimen collection was 6.5 days (range 0–31 days). The median time from sample collection to sample result was 6 days (range 2–64 days). Due to limited resources at the laboratory of Kenema Government Hospital, RT-PCR was not performed on all specimens and only three of the 14 confirmed cases were reported as RT-PCR-positive. Three cases were confirmed by RT-PCR, five by ELISA antigen, and six by ELISA antibody (IgM) (Table 2). No positive IgG results were obtained. All cases were simultaneously tested for EVD and had negative results.
Due to the range of tests performed on each specimen in the rather complicated algorithm, a classification table was developed to assist surveillance officers with case classification.
Once confirmation of the cases was received, the outbreak was notified to the WHO as required under the International Health Regulations (IHR) (
A total of 235 contacts of the confirmed and suspected cases were monitored for 21 days, 90 as a result of the cases from the rubber factory community cluster and the remaining 145 as a result of the cases reported through the IDSR (both suspected and confirmed). None developed symptoms.
Surveillance training emphasizing case detection and early reporting of Lassa fever was undertaken for 314 CHVs, HCF officers-in-charge, IPC focal persons, District Health Teams, and supporting partners from neighboring districts in Bong County. Mentoring on how to undertake detailed case investigation to determine epidemiological links between cases was undertaken with the CSO and DSOs.
Environmental investigations
For the cluster of cases in the rubber factory community, the water supply was via an onsite borehole with water storage facilities. Waste disposal was in an open pit accessible to rodents. Food preparation facilities were adequate. Advice was provided on the removal of rubbish, covering food and storing foods in rodent-proof containers, and preventing access of rodents to food preparation areas by blocking gaps in walls and spaces in floorboards. The homes of suspect cases were disinfected using a chlorine solution.
Risk communication and community education
Health education was provided for families of suspected cases. Simple information, education, and communication materials on Lassa fever were provided to CHVs and HCFs for onward community health education to raise awareness and encourage preventive activities. Messages were also distributed via local radio stations by the CHT to intensify awareness on the prevention and control of Lassa fever. Daily situation reports were prepared by the CSO for distribution to all responders and the national emergency operations centre.
Case management and IPC
Additional ribavirin was required by HCFs in affected counties due to the increase in suspected cases identified. IPC supplies were present in the county and were reported as being used when coming into contact with patients. PPE supplies existed but were not sufficient for an extended outbreak; more were requested and supplied.
International spread
On April 1, 2016, the National IHR Focal Point for Sweden notified the WHO of a 72-year-old female patient with confirmed Lassa fever who had spent 6 weeks undertaking humanitarian work in Liberia during January and February 2016. It was reported that the patient had been exposed to rodents and had been in the same geographic location as the outbreak, unknown to her at the time. The patient was isolated and recovered. Contact tracing in Sweden identified 118 healthcare workers and family members with low-level exposure and no secondary cases were identified (
A summary of the challenges in responding to this outbreak, the immediate interventions taken to address these, and proposed longer term solutions is provided in Table 3.
Table 3Summary of challenges identified during the response to the Lassa fever outbreak, immediate interventions applied, and proposed longer term solutions.
Response pillar
Obstacle to outbreak response
Impact on outbreak
Immediate intervention undertaken
Longer term solution
Surveillance
Late recognition of the outbreak: 12 suspected cases had been notified but not investigated
The delay in confirmation meant that the IDSR action threshold was not reached, which led to a delay in appropriate response interventions and potentially a higher related morbidity and mortality
Active case finding was undertaken in communities and HCFs where suspected cases had been reported, to ensure no additional cases were missed
Refresher training in IDSR requirements for surveillance and the response required
No detailed case investigation forms or reporting templates for investigation activities were in use
Detailed epidemiological data were not available to assess the outbreak and provide appropriate interventions
Surveillance training and follow-up mentoring was undertaken, emphasizing case detection and early reporting of Lassa fever
Lack of historical surveillance data on Lassa fever cases in Liberia
It was difficult to assess areas of potential transmission and determine the possible size and extent of the outbreak
A retrospective review of 2016 IDSR data was undertaken
Strengthening of IDSR reporting, recording, and storage for future reference
Laboratory
No in-country diagnostic capacity The transportation of specimens from healthcare facilities to Kenema, Sierra Leone had ceased during the EVD outbreak
Cases could not be tested for Lassa fever The outbreak was therefore not confirmed in a timely fashion
The system to facilitate transportation of specimens to Kenema, Sierra Leone was re-established and there was subsequent timely feedback of results The WHO provided coordination, transport, and logistical support for the transfer of specimens
Transport and coordination of specimen referral transitioned to MOH In-country diagnostic capacity being developed
Only two of 10 specimens collected before the outbreak could be retrieved from storage at the NRL for Lassa fever testing The remaining specimens had tested negative for EVD and been discarded
A true diagnosis for these eight cases was not possible and the true size of the outbreak was not known
It was ensured that cases were followed up appropriately as if they were true Lassa fever cases
Importance of the differential diagnosis to be emphasized during IDSR training with HCF and laboratory personnel
The complicated diagnostic algorithm caused confusion during case classification by surveillance personnel
Cases were wrongly classified as not a case and the true size of the outbreak was not apparent
A review of case classification was undertaken by laboratory and epidemiology experts supporting the MOH
Classification algorithm developed to assist surveillance officers with case classification
The time taken from date of sample collection to sample result varied widely
It was not known whether suspected cases were true cases or not, increasing the burden on HCFs in terms of the isolation and treatment of patients using appropriate precautions
Close follow-up by telephone and e-mail was ensured to facilitate reporting; however turn-around-times to results were not optimal
The MOH with support from international partners is working towards the implementation of RT-PCR assays appropriate for the detection of Liberian strains at the NRL
Case management
Ribavirin was given to those not a case
This led to a shortage of ribavirin at HCFs with cases and a potential unnecessary impact of side effects on those without the disease
Faster follow-up and relay of sample results to treating clinicians
A system for timely feedback on laboratory results to HCFs is to be developed and monitored for effectiveness
Lack of ribavirin due to an increase in number of cases
Potential delays in cases receiving appropriate treatment
Additional ribavirin was requested from the national MOH and received
An annual review of usage and stock levels is to be undertaken as part of preparedness activities, based on expected case numbers deduced from surveillance data
Infection prevention and control
PPE supplies were not sufficient for an extended outbreak
This led to potential exposure of healthcare facility staff and nosocomial transmission
PPE supplies were requested and obtained from the national MOH
Adequate PPE supplies to be maintained at the national level and requests for an increase in supplies to be addressed promptly
Environmental investigations
Poor waste disposal in an open pit accessible to rodents, food not stored in appropriate containers in homes, and homes accessible to rodents
This led to further transmission
Advice was provided on the removal of rubbish, covering food and storing foods in rodent-proof containers, and preventing access of rodents to food preparation areas by blocking gaps in walls and spaces in floorboards Homes of suspect cases were disinfected using a chlorine solution
At the start of the annual Lassa fever season, community health workers and CHVs should visit areas where cases have previously been reported to provide this information as part of community awareness raising
Risk communication
Lack of knowledge in the community on Lassa fever and how to prevent infection
There was a potential increase in the number of cases due to a lack of prevention activities in areas of ongoing transmission Additionally, a lack of recognition of symptoms led to late presentation at healthcare facilities and poorer outcomes
Information, education and communication materials were provided to CHVs and HCFs for onward transmission to communities Public health awareness raising messages were distributed via local radio stations
Lassa fever prevention materials and messages should be shared with the community at the start of the annual Lassa fever season
CHV, community health volunteer; EVD, Ebola virus disease; HCF, healthcare facility; IDSR, Integrated Disease Surveillance and Response system; MOH, Ministry of Health; NRL, National Reference Laboratory; PPE, personal protective equipment; RT-PCR, reverse transcriptase polymerase chain reaction.
Fifty-three cases of Lassa fever were reported in Liberia in the first half of 2016, 14 of which were confirmed. Although a small number against the backdrop of the EVD epidemic, the CFR of 29% emphasizes the importance of prioritizing efforts to minimize transmission during the annual Lassa fever season. Comparison with the previous year’s figures is difficult, as the same period in 2015 coincided with the Ebola crisis when surveillance, reporting, and laboratory confirmation of diseases other than EVD was limited. Patients presenting with symptoms of Lassa fever in 2015 would likely also have fulfilled the case definition of a suspected case of EVD due to the comparable symptoms (
). It is unlikely that any differential diagnosis would have been pursued once a patient tested negative for EVD, both due to the lack of confirmatory testing available and the severe strain on HCFs at the time.
The reported cluster of three Lassa fever cases in February 2016 led to the identification and response to a wider ongoing outbreak. The delay in response could be related to a number of challenges in the post-EVD setting: a poor healthcare system further weakened by the impact of the world’s largest ever EVD outbreak, a need to test all specimens for EVD prior to other testing, a lack of in-country confirmatory capacity, a delay in receipt of laboratory results due to the time taken to transport samples out of the country, and a lack of investigation of early cases. Some of these were compounded by a relatively inexperienced cadre of surveillance personnel requiring further training in field epidemiology and the IDSR.
The importance of dedicated training on surveillance to strengthen the ability to detect and respond to outbreaks with epidemic potential is widely recognized (
). Efforts to strengthen the IDSR system, as a result of the Ebola epidemic, started in mid-2015 following the height of the crisis, to enhance the timely recognition of any future epidemics. This outbreak demonstrated that by February the system was partially functioning, since weekly notification of suspected Lassa fever cases had occurred from HCFs to the county health team and the national MOH. However no immediate case-reporting occurred, an essential component to ensure timely outbreak detection and response. In the wake of the EVD epidemic, interventions were established by the MOH together with partners to increase the number of healthcare personnel undertaking dedicated surveillance and response training. This included short courses on the IDSR, a frontline field epidemiology training program (
), and specimen collection training. The increased capacity and capability of public health personnel should lead to improved detection, prevention, and response to communicable diseases in Liberia.
The late response to this outbreak may have resulted in avoidable deaths. It is, however, unknown whether the 14 early cases (including at least 13 deaths) retrospectively identified during the outbreak investigation were true cases, due to the lack of confirmatory laboratory testing. An embargo instituted during the EVD outbreak meant that biological specimens were not being referred into or out of affected countries. This had a significant impact on public health systems in Liberia during the EVD outbreak, as well as the early recovery period, as diagnostics for other diseases of epidemic potential ceased. This is a key policy issue for discussion at a global level in ensuring preparedness for future epidemics.
Although the significantly higher CFR in suspect cases did not appear to be related to a lack of receipt of ribavirin or a delay in admission, the data were collected retrospectively and therefore should be treated with caution due to problems with recall bias and a lack of completeness of data. The 29% CFR in confirmed cases is similar to those reported in the published literature for cases that are hospitalized (
). A further limitation of this investigation was that data were not collected on either co-morbidities or alternative diagnoses following a negative test for Lassa fever. It is recommended that in future outbreaks this information is recorded to gain a greater understanding of co-morbidities and differential diagnoses for those presenting with Lassa fever-like symptoms.
One of the challenges faced by those responding to the outbreak was the delay in receipt of laboratory results at the HCF. The median time from sample collection to a result was 6 days, although this varied considerably in range. This could be attributed to poor road conditions, delays in communicating results, a delay in recognition of the outbreak, and the time taken to re-establish a referral system for samples to be tested in Sierra Leone. This outbreak investigation highlighted the urgent need to develop diagnostic capacity for Lassa fever virus within Liberia. Therefore, the MOH, with support from international partners, are working towards the implementation of RT-PCR assays appropriate for the detection of Liberian strains at the NRL.
Accurate and rapid diagnosis of Lassa fever is challenging due to the non-specific clinical presentation, the high degree of Lassa virus genetic diversity observed in West Africa, and biosafety concerns. While there are many diagnostic assays for Lassa virus, there is currently no validated pan-Lassa virus assay available to both provide a diagnosis at any time point during the clinical course of illness and capture the diversity among viral strains (
). Therefore a range of tests are employed to provide a final confirmation, which can complicate interpretation by national surveillance officers. ReLASV, a lateral flow rapid diagnostic test, has now been commercialized (Corgenix I: ReLASV antigen rapid test package insert-IVD; Corgenix, Inc., St. Ingbert, Germany) and could be used for point-of-care testing, although this test currently has research use only status. In one study from Kenema Government Hospital in Sierra Leone, the use of ReLASV identified 95% of acute Lassa fever cases (defined as RT-PCR-positive, increasing IgM titers, or IgM-positive with IgG seroconversion), while missed cases were associated with resolving disease or mild disease with low levels of viremia (
). This test kit enables the rapid diagnosis of Lassa fever virus within 15 min and has the potential to change the way Lassa fever is detected and treated if available to be deployed with outbreak investigation teams in the field.
A positive legacy of the EVD epidemic is the skill-specific training of healthcare personnel, which aided the response. Once the response was initiated, CHVs conducted contact tracing, IPC professionals disinfected homes of cases, and burial teams performed safe and dignified burials of individuals with this highly infectious disease. Continued mentorship and refresher training will be required to maintain these learnt skills.
). Healthcare providers need a high index of suspicion for those returning from endemic regions.
In countries where Lassa fever is endemic, including Liberia, preparedness is key, and this outbreak underscores the need to encourage annual preparative work before the traditional Lassa fever season commences in November/December. This will involve raising awareness of signs and symptoms of Lassa fever in communities and the distribution of information on keeping homes rodent-free, as well as reminding HCFs of the case definition and ensuring prepositioning of ribavirin and adequate PPE.
In conclusion, this outbreak demonstrates the importance of strengthening the IDSR system, improving medical countermeasures for Lassa fever, developing preparedness plans, training rapid response teams, and building laboratory capacity to test for infectious diseases in-country. Recommendations were made to the national MOH incident management system in Liberia and a number of these activities, as described above, have now been implemented. Prioritizing these actions will aid the timely response to future outbreaks.
Conflicts of interest
All contributing authors declare no conflicts of interest.
Funding
No additional funding was provided for this work.
Acknowledgements
We would like to thank all of those who participated in the response team, particularly members from Bong CHT, treating clinicians who provided detailed information, and personnel from the reference laboratory in Kenema, Sierra Leone.
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