Epidemiological characteristics and hospital outcomes of hospitalized Lassa fever cases during the 2022-2023 outbreak in Liberia

Introduction

Lassa fever (LF) is a viral haemorrhagic fever caused by the Lassa virus (LASV), a member of arenavirus group.^1–3 This LASV would be primarily transmitted to humans through direct or indirect contact with the urine or feces of the infected natal mastomys mice (Mastomys natalensis) during hunting or processing for consumption.^4–6 The mice are the natural reservoir for the LASV. Additionally, the virus may be transmitted from human to human through contact with an infected person's blood, faeces, or other bodily secretions.^7,8 Pregnant women and children have the highest risk of contracting the disease.^3,9 The incubation period for LF ranges from 2-21 days. A systematic review conducted in 2021 reported on clinical data, identified fever, headache, vomiting, abdominal pain, and cough as the most frequently presenting symptoms in individuals suspected of having LF and a retrospective study in 2022 identified fever, fatigue, sore throat, loss of appetite, headache, vomiting, and myalgia as presenting symptoms among confirmed cases. The disease is diagnosed through a real-time polymerase chain reaction (RT-PCR) test and intravenous (IV) ribavirin is a recommended treatment.^10,11 Additionally, oral ribavirin can be used for post-exposure prophylaxis. However, recent studies have reported contradictory results regarding the effectiveness of ribavirin, prompting need for further investigation.¹²

LF is a significant global public health challenge, recognized by the World Health Organization (WHO) as a priority disease for surveillance, research and vaccine development efforts.^1,11 Endemic to various West African countries, including Guinea, Liberia, Nigeria, and Sierra Leone,¹³ the disease is estimated to cause 100,000 to 300,000 new cases and 5,000-10,000 deaths annually.⁶ LF exhibits a seasonal pattern, with most cases reported during the dry season each year.^3,14 The case fatality rate (CFR) among hospitalized patients is estimated to be between 15% and 20% but could be more during epidemics.⁷

In Liberia, LF is a notifiable disease and one laboratory confirmed case constitutes an outbreak. Liberia is experiencing its most protracted LF outbreak, which started in January 2022.¹⁵ In June 2021, the National Integrated Disease Surveillance and Response (IDSR) Technical Guidelines were revised, incorporating an updated Lassa fever case definition. This coincided with efforts to improve case detection through healthcare worker training.¹⁶ Despite these measures, crucial information such as the positivity rate, socio-demographic and clinical characteristics, mode of exposure, CFR, and factors associated with mortality in this outbreak remain largely unknown. Therefore, this study aimed to understand the 2022-2023 LF outbreak in Liberia by investigating characteristics of suspected and confirmed LF cases, mode of exposure, healthcare access (i.e. timelines of admission and treatment), hospital outcomes, and factors associated with mortality among confirmed LF patients.

Methods

Results

Lassa fever diagnosis, ribavirin treatment, and outcome

A total of 439 suspected LF cases were reported between January 2022 and December 2023 ( Figure 1). The median age was 22 (IQR 10-33) years. The majority (66%, 290/439) of the suspected cases were below 30 years. Women (53%, 233/439) of the cases. Occupation data was missing for 174 participants. Among the 265 with recorded occupations, students constituted 32% (141/439) followed by business persons (12%, 51/439). Geographically, Bong County reported 44% (192/439) of the suspected cases, followed by Grand Bassa County (20%, 89/439) and Nimba County (18%, 80/439) ( Table 1).

Figure 1. Lassa fever diagnosis, treatment and hospital outcome, Liberia 2022-2023.

Table 1. Characteristics and positivity rate for Lassa fever diagnosis using reverse transcription-polymerase chain reaction (RT-PCR), Liberia, 2022-2023.

Characteristics	Total suspected*		PT-PCR tested*		Positivity rate¥
	n	%	n	%	n	%
Total	439		416	95	138	33
Age (years)
≤14	143	33	133	32	45	33
15-29	147	33	140	34	50	36
30-39	78	18	73	18	23	31
40-49	46	10	45	11	12	27
≥50	25	6	25	6	8	32
Median age	22 (IQR:10-33) Years
Gender
Male	206	47	206	50	60	29
Female	233	53	233	56	78	33
Occupation
Business	51	11	51	12	15	29
Farmer	33	8	31	7	8	26
Housewife	16	4	16	4	8	50
Student	141	32	137	33	50	36
Tapper	19	4	19	5	11	58
Othersβ	8	2	8	2	3	38
Unknown	171	39	154	37	13	8
Reporting county
Bong	192	44	171	41	60	35
Grand Bassa	89	20	88	21	45	51
Nimba	80	18	80	19	27	34
Montserrado	56	13	56	13	5	9
Othersβ	22	5	21	5	1	5

* Number (and column-proportion) for characteristics and RT-PCR tested.

¥ Number (and row-proportion) positivity rate).

β Others (number of suspected cases): River Gee (n=5), Grand Kru (n=7), Maryland (n=3), Bomi (n=2), Lofa (n=2), Margibi (n=2), Sinoe (n=1).

Ribavirin treatment among Lassa fever cases

Ribavirin treatment was administered to 57% (249/439) of hospitalized suspected LF cases ( Figure 1).

Ribavirin treatment was administered to 83% (115/138) of the confirmed LF cases ( Figure 2).

Figure 2. Geographical distribution of confirmed Lassa fever cases by reporting county, Liberia, 2022-2023.

Epi-curve of confirmed Lassa fever cases by reporting epi week and year

The 2022 calendar year accounted for over half (52%, 72/138) of the confirmed cases. Majority of the confirmed (59%, 81/138) clustered between epi-weeks 1-12 and 40-52, aligning with the dry season (October – March) ( Figure 3).

Figure 3. Epi curve of confirmed Lassa fever cases and deaths by reporting week and year, Liberia, 2022-2023.

Discussion

The study described the epidemiological characteristics and fatality among LF cases hospitalized during the 2022-2023 outbreak in Liberia. Findings showed a substantial burden of LF in Liberia during the outbreak with positivity rates (33%) and CFR (30%), and even higher CFR among the elderly population. Younger age groups were disproportionately affected. Furthermore, the dry season coincided with a surge in confirmed cases. Fever, headache and malaise were the most frequently reported symptoms, and rodent exposure was common among the confirmed cases. Surprisingly, there was death (13%) observed among hospitalized individuals without LF, highlighting challenges in diagnosis and LF management.

Similar to other studies,^6,18 the study found increased positivity with notable concentration of cases in Bong, Grand Bassa, and Nimba Counties. These counties are endemic to LF and adjacent to each other, which likely has potential influence on infected individuals migrating across the borders likely due to intermarriages, farming activities, and in search of jobs. Thus, contributing to the spread of LF in these regions. The positivity could be because LF is one of the immediately reportable priority diseases under surveillance in Liberia and an endemic disease. Additionally, strengthened surveillance systems at all healthcare delivery levels with assigned surveillance officers for the detection and reporting of suspected LF cases, a functional testing national public health reference laboratory and, most importantly, the revised 2021 case definition of LF all contributed to improved detection of LF.¹⁶

The study highlights that younger age groups are disproportionately affected by LF. This vulnerability is likely to be due to increased exposure to rodent reservoirs. Most confirmed cases reported contact with rodents suggesting exposure to rodent droppings or urine during outdoor activities and food handling. Similar to other studies in Liberia^6,18 and Nigeria,¹⁹ majority of the cases were recorded in the dry season (the latter and earlier parts of the two years in the study period: October to March with 2023 accounting for the majority burden. The seasonality of LF cases in West Africa’s dry season is likely due to a combination of factors related to the behavior of the main reservoir, the Mastomys natalensis rodent. During the dry season, with less vegetation and food sources outside, these rodents are likely to seek shelter and food inside homes, increasing their contact with humans. This could lead to frequent interactions between rodents, potentially increasing the spread of the LASV within the rodent population. Less plant cover during the dry season could make rodent burrows and movements noticeable for hunting. A clean environment both in the house and the outside environment might help to reduce the contact between mice and humans. Additionally, effective community infection prevention control programmes in endemic areas by the Ministry of Health and the National Public Health Institute of Liberia might be of help.

Our study identified a high CFR of 33%, more than double the 15% reported by WHO for the region. While this CFR is lower than those reported in Nigeria (60%)²⁰ and Sierra Leone (69%)²¹ and slightly lower than a previous study in Liberia (40%, 41/103), it remains a significant cause for concern. Furthermore, high CFRs were observed in both treated and untreated patients. The short time between symptom onset and hospital admission suggests that healthcare-seeking behaviors alone cannot fully explain the high CFR. Previous studies have raised concerns about the effectiveness of ribavirin treatment and its potential harm.¹² The reliability of the human clinical trial data supporting ribavirin’s use has also been questioned, with pre-clinical studies suggesting that current dosing regimens may not reliably inhibit LASV replication. There was high CFR among middle-aged and older adult population. Although the causes of the high mortality are unknown, it could be likely due to waning immunity among these age groups, making them less effective at fighting off infections like Lassa fever, similar to other studies.¹² However, the reasons for this are unclear, warranting further research in understanding the occurrence. Surprisingly, CFR was higher in Nimba, an endemic LF county, a finding similar to what was reported in a previous study.⁶ The reason for the high CFR in Nimba is unknown considering that Nimba had a median presentation time less than 1 day, pointing out the need for further investigation.

Historical data shows that LF has been misdiagnosed with malaria among patients at treatment facilities in Liberia, which impacts early treatment and patients’ outcome. Suspected LF cases are admitted and begin ribavirin treatment while waiting test results. Some of the LF symptoms (fever and headache) overlap with common diseases like malaria, leading to unnecessary admissions and ribavirin use as well as delays in receiving appropriate treatment. This is concerning, as a 13% death rate was observed among those who did not have LF which may be due to other undiagnosed infections. While the strategy aims to combat LF high CFR, improvements in diagnosis and management are crucial.

These findings have an important implication for the programme’s practice and policy. Addressing the screening and management challenges surrounding LF requires a proactive shift towards preventive measures. Mass vaccination campaigns, although in their developmental stages, offer a promising avenue for mitigating the burden of LF. Initiatives by the WHO and Coalition for Epidemic Preparedness Innovations (CEPI) prioritize LF for vaccine development and enhanced surveillance efforts,²² signaling a step in the right direction. However, given the time frame for vaccine development and implementation, immediate action is warranted. Based on a clearer understanding of seasonal variations within Liberia and across West Africa, public health interventions like vector control programmes and year-round community education campaigns, intensified during the dry season when LF transmission peaks, could significantly enhance community awareness and prevention, thereby reducing mortality rates and easing the burden on healthcare systems. Implementing rodent-proofing measures could likely further reduce exposure risks.

Our findings should be viewed with the following limitations: Firstly, there were incomplete data on duration from onset of symptoms to hospital admission. Exclusion of these records might have affected the estimation of the time from onset of symptoms to hospital admission with respect to socio-demographic characteristics. Secondly, our data was focused on facility-based rather than community-based surveillance, meaning that those who did not seek healthcare were not captured, and we might therefore have underestimated the number of LF cases. Third, we could not explore the effect of ribavirin on mortality due to lack of data. Lastly, our data provides no information on the possible causes of mortality among the suspected cases that were tested negative for LF. Despite these limitations, the study used surveillance data which reflect the program setting, making the findings useful to inform policy and programmes in Liberia and other comparable settings to prevent LF outbreaks.

Conclusions

This study showed a significant burden of Lassa fever in Liberia during the 2022-2023 outbreak, characterized by positivity, CFR, and death among those without the disease, highlighting the urgent need for proactive prevention measures such as vaccination campaigns and intensive public education. Introducing a rapid point-of-care test for LF would help reduce unnecessary admissions, avoid empirical use of ribavirin, and reduce delays in administering the appropriate treatment. Furthermore, the CFR was high among the middle-aged and older adult population, warranting further investigation. Additionally, the incompleteness of some records highlights the need to strengthen data collection practices within healthcare facilities to ensure complete and accurate data for informed outbreak response efforts, and conduct further research to investigate mortality among suspected cases tested negative for LF.

Author contributions

“Conceptualization, E. D, R.W.J, B.I.S, H. T, F.T, P. O, M.B, I.F.K, G.W.G, P. K, D. B. L, L.A.E, P. R, S.H; B.T.V., J.S.M.G; methodology, E. D, H.T, P. O, M.B, C.D.U, R.W.J, B.I.S, F. T, P. A, G.W.G,D.B.L, L.A.E, P. R, S. H, B.T.V, P. K, P.A., I.F.K, J.S.M.G; software; validation, E. D, G.W.G; formal analysis, E. D, H.T, M. B, C.D.U, P.A., GEA; investigation; resources; data curation; writing—original draft preparation, E. D, H.T, M. B, writing—review and editing, E. D, H.T, F. T, P.O, C.D.U, B.T.V, M. B, B.I.S, P. K, P. A, L.A.E, P. R, S. H, I.F.K, GEA; visualization, G.E.A, E.D; supervision; project administration; funding acquisition. All authors have read and agreed to the last version of the manuscript.”

Open access statement

In accordance with WHO’s open-access publication policy for all work funded by WHO or authored/co-authored by WHO staff members, WHO retains the copyright of this publication through a Creative Commons Attribution IGO license (http://creativecommons.org/licenses/by/3.0/igo/legalcode) which permits unrestricted use, distribution and reproduction in any medium provided the original work is properly cited.