High fatality of Lassa fever outbreak in Kenema District- Sierra Leone, January 2023

Binta Bah^1,2,&, Umaru Nyallay³, Philp Gevao^3,4, Joel Mansaray^2,3, Paul Mansary¹, Umaru Sesay^3,5, Anna Jammeh^3,5, Solomon Aiah Sogbeh^2,3, Amara Alhaji Sheriff^2,3, Joseph Sam Kanu^2,4, James Sylvester Squire^2,4, Adel Hussein Elduma^3,5, Mohamed Alex Vandi², Monique Aaro Foster⁶, Gebrekrstos Negash Gebru³

 

¹National Public Health Agency, ²Sierra Leone Field Epidemiology Training Program, ³Ministry of Health, Sierra Leone, ⁴College of Medicine and Allied Health Sciences, University of Sierra Leone, ⁵African Field Epidemiology Network, ⁶Division of Global Health Protection, United States Center's for Disease Control and Prevention

 

 

^&Corresponding author
Binta Bah, Sierra Leone Field Epidemiology Program, National Public Health Agency, Wilkinson Road, Freetown, Sierra Leone.

 

 

 

 

Lassa fever is an acute viral zoonotic hemorrhagic fever disease caused by the Lassa virus, a member of the arenavirus family. Lassa fever is spread by the Mastomys natalensis rat, and its incubation period ranges from 2 to 21 days. Most cases of Lassa fever (about 80%) are either asymptomatic or present with mild symptoms [1]. However, those with symptoms are usually gradual and begin with fever, general weakness, and malaise, followed by headache, sore throat, muscle pain, chest pain, nausea, vomiting, diarrhea, cough, and abdominal pain. When the disease is advanced, patients may present with facial swelling, fluid in the lung cavity, bleeding, and low blood pressure. The Case Fatality Rate (CFR) of Lassa fever is 1% among the general population but can rise up to 15% among hospitalized patients [1].Among pregnant women, the CFR ranges from 7% to 30% in early pregnancy and late pregnancy respectively [2] . Lassa Fever is endemic in parts of West African countries including Sierra Leone, Liberia, Guinea, and Nigeria [1]. Every year, an estimated 500,000 people are infected with Lassa fever causing 5,000 deaths with the majority of cases and deaths occurring in the West African region [3].

 

In Sierra Leone, Lassa fever has been in circulation since the 1950s, and the infection has caused many outbreaks resulting in thousands of infections and fatalities [4] For instance, a space-time trend analysis revealed that, between 2012 and 2019, it was reported that 3,277 people were suspected for Lassa fever with 428 hospitalized in Sierra Leone [5] . Although the true magnitude of the disease is unknown, the Eastern region of Sierra Leone, where Kenema is located, has been identified as endemic for Lassa fever accounting for the highest incidence of Lassa fever [5] .

 

In 2022, 10 cases were confirmed of Lassa fever between February and October with a 60% case fatality rate. To mitigate the persistent occurrence of Lassa fever, the Government of Sierra Leone introduced several interventions, including the construction of Lassa fever ward in Kenema district to manage Lassa fever cases [6] and incorporated Lassa fever as Acute Hemorrhagic Fever Syndrome (AHFS) into the Integrated Disease Surveillance and Response (IDSR) system, as an immediately reportable disease [7].

 

On 16 January 2023, the Kenema district surveillance unit received notification about suspected cases of Lassa fever from the Kenema Government Hospital (KGH) and the Medicine San Frontier (MSF) hospital. On receipt of notification, a rapid response team was established to investigate the suspected cases. The rapid response team was comprised of the Kenema district rapid response team members and a trainee from the Frontline level Sierra Leone Field Epidemiology Training Program-. The investigation aimed to confirm the diagnosis, identify the source of infection, and search for additional cases.

 

 

Study setting

 

Kenema district is one of the 16 districts of Sierra Leone and is located in the Eastern Province. The district has a population of about 772,472 and 132 peripheral health units, six private hospitals, and two Government hospitals [8] . Kenema district is known to be endemic for Lassa fever [5] . The Kenema Government Hospital (KGH) is the main referral hospital in the Eastern province, which has an isolation and the only treatment facility for Lassa fever since 1976 [5] . The hospital has the capacity to perform enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) tests on human and animal samples for Lassa fever and other hemorrhagic fever viruses.

 

Case definition

 

We developed a working case definition based on the surveillance case definition of the Sierra Leone Ministry of Health (MoH) for Lassa fever. A suspected case was defined as any person residing in the Kenema District with a fever above 38°C and not responding to appropriate anti-malaria and antibiotic treatment within 72 hours with no localized infection from 18 December 2022 to 31 January, 2023. A confirmed case was any suspected case with laboratory confirmation (positive ELISA or RT-PCR test) for Lassa fever virus.

 

Data collection

 

We used the viral hemorrhagic fever case investigation form to collect data from the suspected cases. Through interviews of cases and record reviews from December 2022 to February 2023, clinical, demographic and travel history were gathered. We also searched for cases at the communities and health facilities to understand the extent of the infection.

 

Laboratory diagnosis

 

Blood samples were collected from cases and sent to the Viral Hemorrhagic Fever Reference Laboratory in Kenema district for testing. In the field, a rapid diagnostic test was conducted on rodents trapped to screen for Lassa fever virus infection. At the reference laboratory in Kenema District, RT-PCR and ELISA tests were conducted to confirm the diagnosis.

 

Contact tracing

 

We defined a contact as any person who had direct or indirect contact with a case or surfaces contaminated by body secretions of cases within Kenema district from 1 - 31 January 2023. A total of 58 contacts (20 households and 38 healthcare worker) were monitored and followed up for 21 days.

 

Environmental assessment

 

We assessed case-patients´ household structure, and general hygiene and searched for evidence of rodents´ infestation. We used the H.B Sharman trapping technique to trap rodents in the houses of the case-patients and neighboring houses. Residents' most-eaten foods such as dry fish, groundnuts, and rice, were used as baits to catch rodents. Samples were collected from the rodents for both rapid diagnostic tests and confirmation was done by the Polymearse Chain Reaction (PCR) at the Kenema reference laboratory.

 

Data analysis

 

Descriptive analysis was followed to present the Lassa fever cases frequency and proportion.

 

Ethical considerations

 

This investigation was part of a routine investigation of outbreaks or epidemic prone diseases and diseases of national and international concern. Therefore, it did not require an ethical clearance from the Sierra Leone Ethic and Scientific Review Committee. We however obtained permission from the Directorate of Health Security and Emergencies (DHSE) to conduct this study. We obtained verbal consent from case patients and their families to conduct the investigation. Personal identifiable information of cases and contacts were not disclosed and were only accessed by the study investigators.

 

 

Four cases of Lassa fever were confirmed in the Kenema district. Two cases were from Lower Bambara chiefdom and two from Nongoma chiefdom (Figure 1). Three of the cases were females (3/4: 75%). All cases were notified by healthcare workers from the Kenema Government Hospital and Medicine San Frontier Hospital. Two of the case-patients died (Table 1). All the cases were detected late and it took the cases an average of 10 days from onset of fever to the clinician´s suspicion of Lassa fever.

 

Cases presentation

 

Case-patient one: On 23 December 2022, a 25-year-old woman from Kenema City traveled to Weima village for the Christmas holiday. On 8 January 2023, in Weima village, she developed a high fever (>38°C), headache, and joint pains lasting for 6 days. On 14 January 2023, her family members purchased pain relief tablets including Novalgin from a local drug vendor and gave her to treat her illness. The next day, 15 January 2023, she was taken to Weima Community Health Center for further medical examinations and treatment. The nurses on duty referred her immediately to the Kenema Government Hospital (KGH) because of the severity of her illness.

 

On arrival at the KGH, the patient presented with additional symptoms, including abdominal pain, vomiting, and difficulty breathing. The nurse at the triage centre immediately triaged her, diagnosed her with severe pneumonia, and transferred her to the female medical ward. On the same day, the attending clinician, a medical doctor, reviewed the patient and prescribed the following medications: dextrose normal saline, IV paracetamol, and IV ceftriaxone. On 16 January 2023, the attending clinician reviewed the patient´s charts and discovered that she had a temperature of above 40.5°C. Because of the high temperature and prevailing symptoms, the attending clinician suspected Lassa fever and immediately transferred the patient to the isolation centre. On the same day, blood samples were collected, and laboratory analysis was conducted. On 17 January 2023, laboratory results confirmed positive for Lassa fever and the case was transferred to the Lassa fever ward for management. At the Lassa fever ward, IV ribavirin proctor, IV ceftriaxone, tab paracetamol, mirakof, folic acid, and azithromycin were administered, and the patient responded to the treatment. On 28 January 2023, the case recovered and was discharged.

 

Case-patient two: On 9 January 2023, a 22-year-old woman with 34 weeks´ pregnancy from Kamboma village in Lower Bambara chiefdom, developed fever, side or flank and breast pain. Two days later, the case-patient developed excessive bleeding, vomiting, and generalized body pain, and was taken to the Kamboma Community Health Post (CHP) for medical care. On arrival at the Kamboma CHP, she was screened for malaria (through rapid diagnostic test), but the result was negative. The case-patient was treated with paracetamol and ibuprofen and sent back home. At home, the case-patient was treated with amoxicillin and ibuprofen by her husband, who is a community health worker, but she could not respond. On 18 January 2023, she was taken to the Kamboma health facility and presented with generalized body pain, restlessness and respiratory distress. Then, she was referred to MSF hospital in Kenema on the same day. At the MSF hospital, the clinician suspected Lassa fever and notified the surveillance unit for investigation. A blood sample was collected and sent to the KGH for Lassa fever testing. On 19 January 2023, the case-patient died and the sample tested positive for Lassa fever on 20 January 2023.

 

Case-patient three: On 24 December 2022, a 21-year-old lactating mother from Kenema City travelled to Bongor village within Kenema District for the Christmas holiday. Two weeks later, on 6 January 2023, whilst in Bongor village, she developed fever. She returned to Kenema City and was taken to the KGH for medical care. On arrival at KGH, she presented with a high fever, cough, and joint pain. The medical doctor suspected tuberculosis and recommended laboratory tests. The laboratory test result came out positive for Mycobacterium tuberculosis on the same day. Anti-tuberculosis medications were prescribed.

 

The symptoms of high fever, cough, and headache persisted, and the case-patient was taken to the MSF hospital on 14 January 2023. The case-patient was within 42 days of post-partum period. The clinician at the MSF hospital referred the case-patient to the KGH. On arrival at KGH, she was triaged at the maternity ward where she presented with additional symptoms including difficulty breathing, muscle pain, joint pain, and restlessness. The clinician at the KGH admitted the case-patient at the maternity ward for observation. On admission, oxygen was initiated, and later dextrose normal saline, normal saline, and ceftriaxone were administered.

 

On 22 January 2023, after 8 days of treatment in the hospital without improvement, the clinician suspected Lassa fever and notified the district surveillance team for investigation. On the same day of notification, a blood sample was collected, and the result came out positive for Lassa fever on the next day, on 23 January 2023. The case-patient was transferred to the Lassa fever ward and treated with IV ribavirin, IV ceftriaxone, and azithromycin for five days. On 28 January 2023, the case-patient died.

 

Case-patient four: On 15 January 2023, a 2-year-old boy from Largo village, Nongowa chiefdom presented with three days of onset of fever at Largo Community Health Center (CHC). On arrival, the case-patient was diagnosed with malaria, treated with anti-malaria drugs, and discharged. On 18 January 2023, as symptoms persisted, the case-patient was taken to the Largo Community Health Centre for further medical care. On 19 January 2023, the clinician at the Largo CHC referred the case-patient to MSF Hospital. On arrival at MSF, the case-patient was suspected of having Lassa fever. The patient was isolated, and blood samples were collected and sent to KGH for testing. Results came out positive for Lassa fever on the 20 of January 2023. The case was then taken to the Lassa fever ward and treated with ribavirin, IV ceftiazole, and paracetamol. He recovered after a few days and was discharged on 30 January 2023.

 

Epidemiological findings

 

There was no epidemiological link between the reported cases. Additionally, the case-patients had not reported contact with people who had been diagnosed with or had signs and symptoms suggestive of Lassa fever within 21 days before the onset of the signs and symptoms. None of the case-patients traveled out of Kenema District; however, only two of the cases travelled from Kenema town to the village.

 

Record reviews (registers, case-based forms, and rumor logbooks) and active case searches in the communities of case-patients showed no additional cases with signs and symptoms of Lassa fever. All the cases were recorded in the health facility registers at the facilities where they were suspected of Lassa fever. A total of 58 contacts (20 at households of cases and 38 health care workers in health facilities) were identified, line listed, and monitored daily for 21 days following the last contact with the confirmed cases. None of the contacts developed signs and symptoms of Lassa fever.

 

Environmental assessment including rodent trappings

 

The case-patients lived in mud houses with unpaved floors. The houses were poorly constructed and had poor toilet facilities, with some using communal toilets. Some of the houses were constructed in a wetland, and the houses were crowded. Rodent droppings and boreholes were observed in the homes of case-patients. We set 15 rodent traps in the community of cases and captured three rats. Using the Lassa fever RDT kit, samples from two rats tested positive for Lassa fever. However, on the confirmatory RT-PCR and ELISA tests, only one was positive, one negative, and the other was indeterminate (Table 2).

 

 

In this study, we confirmed four cases of Lassa fever with two deaths, a case fatality rate of 50 percent (CFR: 50%), in Kenema District, Sierra Leone. Majority of the case were female. Two of the four cases died, including a pregnant woman and a lactating mother. There was no epidemiological link between the reported cases. Tests on the three trapped rodents revealed inconsistent results between the rapid diagnostic screening test and confirmatory RT-PCR and ELISA, with the RDT showing two of the three samples positive for Lassa fever while the confirmatory RT-PCR and ELISA test revealed only one positive which implies the low specificity of the (RDT) screening test.

 

All the Lassa fever cases in this study visited health facilities at some point during the course of their illness. However, none of these cases was suspected of having Lassa fever infection by the healthcare workers when they first sought treatment. Low suspicion of Lassa fever by healthcare workers may lead to late detection of Lassa fever, which can worsen the prognosis [6] hermore, the delay in clinical suspicion of Lassa fever may be due to the similarities of clinical manifestations to other infectious diseases such as malaria and other acute viral hemorrhagic fever diseases [9]. The cases were initially diagnosed and treated for malaria or pneumonia which are common conditions seen at health facilities in countries endemic with these diseases. This low index of suspicion of Lassa fever by clinicians might partly explain the high case fatality rate, where half of the cases died before or during treatment [5] . Contrary to our finding, the Lassa fever case fatality rate is generally 1% among none hospitalized and up to 15% among hospitalized in other countries in the region [10], [11] .

 

Another reason for the high case fatality rate in this study could be attributed to the late seeking of healthcare services by infected patients. A study conducted in Nigeria showed that suspected cases of Lassa fever who live in rural areas were identified as one of the factors for late presentation [12] . Early diagnosis and treatment of Lassa fever cases is crucial to increase the chance of survival. Lassa fever cases exhibit a wide range of case fatality rates. Some studies have reported a higher case fatality rate than what we found in this study [13], [14]. Conversely, other studies have reported a lower case fatality rate [15, 16, 17]. Additionally, a study conducted in Nigeria found similar results to our current study [18]

 

However, other studies have reported findings that are similar to what we found in the current study. For instance, M. Buba and colleagues reported a Lassa fever CFR close to 60% [18] . The inconsistencies in the outcomes of Lassa fever cases might partly be due to varying patients´ treatment-seeking and the type of care patients receive. Patients seeking early treatments and receiving prompt and correct treatments usually have positive outcomes [19].

 

Lassa fever has increased disease severity among pregnant women as the virus has high affinity to placental and fetus tissues. Lassa fever in the first trimester has a higher chance of abortion and death [6]. The chances of death among pregnant women increase with the advancement of the pregnancy [20]. Evidence indicates that pregnant women are more likely to be infected with Lassa fever than non-pregnant women [21] . A study conducted in Nigeria suggested that 50% of pregnant women were at risk of Lassa fever infection [22] .

 

In this study, it was found that one of the two cases who died because of Lassa fever infection was a pregnant woman. Lassa fever infection is a high risk of fatality during the pregnancy period, and the mother in the third trimester has a high chance of abortion and death [23] . Evidence indicates that pregnant women are more likely to be infected with Lassa fever than non-pregnant women [21] . A study conducted in Nigeria suggested that 50% of pregnant women were at risk of Lassa fever infection [22] Our findings revealed that one of the Lassa fever cases that resulted in death was a lactating mother. This could be due to the Lassa fever infection occurring during late pregnancy as the disease is not common among lactating mother. In this study, three out of the four Lassa fever cases were females. This could be due to the daily home activities practiced by females, which expose them to the droppings of infected rats. However, study conducted in Nigeria showed that there was no significant difference between males and females regarding Lassa fever infection [24].

 

The presence of rodents (rats) and their droppings in the households of case-patients in addition to confirmation of Lassa fever in rodents indicates that rodents could be the source of the infection. These findings are similar to the results reported in a study conducted in Southern Nigeria, where confirmed Lassa fever cases were linked with rodents that were positive for Lassa fever and could be the source of the infection [25] The inconsistent results between the rapid diagnostic screening test and confirmatory RT-PCR and ELISA tests among rodents have several implications. First, despite the weakness of the RDT in being less specific and reliable, it has some advantages. It is mostly cheap, readily available and easily to use in the field.

 

Limitations

 

Late presentation and diagnosis of these Lassa fever cases did not allow the investigation team to conduct a thorough contact tracing which is a limitation for this study.

 

 

A Lassa fever outbreak was confirmed in the Kenema District of Sierra Leone. Rodents were likely to be the possible source of infection. We sensitized the community on early health care seeking and improved environmental sanitation. We recommend increasing the suspicion index of clinicians for Lassa fever infection and also including Lassa fever as one of the differential diagnoses of malaria.

 

 

The authors declare no competing interests.

 

 

Conceptualization and design: BB, UN. Data Collection: UN, BB. Analysis, and Interpretation: BB, PPG. Drafting and Review of Manuscript: BB, UN, PPG, JFM, PSM, AHE, US, AJ, JSK, JSS, MAV, GNG. The final approval was made by all authors.

 

 

We thank the Kenema District Health Management Team, MoH, DHSE, SLFETP frontline program, mentors and colleagues, US CDC, and AFENET and all those who facilitated the successful completion of this study.

 

 

Table 1: Characteristics of Lassa fever cases, Kenema District, Sierra Leone 2023

Table 2: Rodents characteristics trapped during Lassa fever investigation, Kenema District, Sierra Leone, 2023

Figure 1: Lassa fever affected Chiefdom in Kenema district, Sierra Leone, January 2023

 

 

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