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, a member of arenavirus group.^1–3 This zoonotic disease is primarily transmitted to humans through direct or indirect contact with the urine or feces of the infected Mastomys rats (Mastomys natalensis) during hunting or processing for consumption.^4–6 The rats are the natural reservoir for the Lassa fever virus. 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 Lassa fever ranges from 2-21 days. A systematic review conducted in 2021 reported on clinical data, identifying fever (88%), headache (50%), vomiting (49%), abdominal pain (42%), and cough (35%) as the most frequently presenting symptoms in individuals suspected of having Lassa fever. 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

Lassa fever is a significant global public health challenge, recognized by the World Health Organisation (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.^6,14 Lassa fever exhibits a seasonal pattern, with most cases reported during the dry season each year.^3,15 The case fatality rate (CFR) among hospitalized patients is estimated to be between 15% and 20% but can reach 50% during epidemics.⁷

In Liberia, Lassa fever is a notifiable disease and one laboratory confirmed case constitutes an outbreak. Liberia is experiencing its most protracted Lassa fever outbreak, which started in January 2022.¹⁶ 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.¹⁷ Despite these measures, crucial information such as the positivity rate, socio-demographic and clinical characteristics, mode of exposure to rodents, and CFR regarding the current outbreak remains largely unknown. Therefore, this study aimed to understand the 2022-2023 Lassa fever outbreak in Liberia by investigating characteristics of suspected and confirmed Lassa fever cases, mode of exposure, healthcare access (i.e. timelines of admission and treatment) and hospital outcomes.

Methods

Results

Characteristics of the suspected lassa fever cases

A total of 439 suspected Lassa fever 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 There were more women (53%, 233/439) than men. Occupation data was missing for 174 participants. Among the 265 with recorded occupations, students constituted the largest group (32%, 141/439) followed by business persons (12%, 51/439). Geographically, Bong County reported the highest number of suspected cases (44%, 192/439), 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).

Positivity rate of lassa fever cases

Of the 439 individuals suspected of Lassa fever, 437 specimens were collected and majority (95%, 416/439) were tested using RT-PCR test and 138 were Lassa fever positive. The overall positivity rate was 33% (138/416) (Figures 1 & 2; Table 1). Among suspected cases with recorded occupations, tappers had the highest positivity rate (58%, 11/19), followed by housewives (50%, 8/16). Positivity rates were highest in Grand Bassa County (51%, 45/88), followed by Bong (35%, 60/171) and Nimba Counties (34%, 27/80).

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 had more confirmed cases, accounting for over half (52%, 72/138) of the reported cases. More cases (59%, 81/138) clustered between epi-weeks 1-12 and 40-52, aligning with the dry season (October – March) (Figure 3).

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

Discussion

The study described the epidemiological characteristics and case fatality rates among Lassa fever cases hospitalized during the 2022-2023 outbreak in Liberia. Findings showed a substantial burden of Lassa fever in Liberia during the outbreak with high positivity rates (33%) and case fatality rates (30%), with an 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 highest among the confirmed cases. Surprisingly, a high mortality rate (13%) was observed among hospitalized individuals without Lassa fever, highlighting challenges in diagnosis and in Lassa fever management.

Similar to other studies,^6,19 the study found high testing and positivity rates. The high testing and positivity could be because Lassa fever 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 Lassa fever, a functional testing national public health reference laboratory and, most importantly, the revised 2021 case definition of Lassa fever all contributed to improved detection of Lassa fever.¹⁷

The study highlights that younger age groups are disproportionately affected by Lassa fever. This vulnerability is likely to be due to increased exposure to rodent reservoirs. Most confirmed cases reported direct or indirect contact with rodents suggesting exposure to rodent droppings or urine during outdoor activities and food handling. Similar to other studies in Liberia^6,19 and Nigeria,²⁰ most 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 highest burden. The seasonality of Lassa fever 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 more likely to seek shelter and food inside homes, increasing their contact with humans. This could lead to more frequent interactions between rodents, potentially increasing the spread of the Lassa fever virus within the rodent population. Less plant cover during the dry season could make rodent burrows and movements more noticeable for hunting. A better cleaning environment both in the house and the outside environment might help to reduce the contact between rats and humans. Additionally, effective community infection prevention control programmes in endemic areas might be of help.

Our study identified a high CFR of 33%, more than double the 15% reported by the WHO for the region. While this CFR is lower than those reported in Nigeria (60%)²¹ and Sierra Leone (69%)²² and slightly lower than a previous study in Liberia (40%), 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 Lassa fever virus replication.¹² Similar to other studies, the CFR was higher among elderly people. However, the reasons for this are unclear, warranting further research in understanding the occurrence. Surprisingly, CFR was higher in Nimba, an endemic Lassa fever county, a finding similar to what was reported in a previous study.⁶ The high CFR in Nimba could be due to the fact that the county is endemic for Lassa fever, with the majority of cases detected at the health facility rather than through early community detection, which impacts on early treatment. The study highlights challenges in Lassa fever management. Suspected Lassa fever cases are admitted and begin ribavirin while waiting for test results. Some of the Lassa fever symptoms (fever and headache) overlap with common diseases like malaria, leading to unnecessary admissions and ribavirin use as well as delayed appropriate treatment. This is concerning, as a 13% mortality rate was observed among those who did not have Lassa fever which may be due to other undiagnosed infections. While the strategy aims to combat Lassa fever’s 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 Lassa fever requires a proactive shift towards preventive measures. Mass vaccination campaigns, although in their developmental stages, offer a promising avenue for mitigating the burden of Lassa fever. Initiatives by the WHO and Coalition for Epidemic Preparedness Innovations (CEPI) prioritize Lassa fever for vaccine development and enhanced surveillance efforts,²³ 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 Lassa fever transmission peaks, can significantly enhance community awareness and prevention, thereby reducing mortality rates and easing the burden on healthcare systems. Implementing rodent-proofing measures can 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 Lassa fever cases. 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 outbreaks of Lassa fever.

Conclusions

This study showed a significant burden of Lassa fever in Liberia during the 2022-2023 outbreak, characterized by high positivity, high CFR, and a substantial mortality among those without the disease, highlighting the urgent need for proactive prevention measures such as vaccination campaigns and intensive public education. Furthermore, the CFR was high among the elderly 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.

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

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