The first imported case of Lassa fever in China: a case description

Introduction

Lassa fever (LF), caused by the Lassa virus (LASV), is a contagious and febrile disease. The initial discovery of the disease traces back to 1969 when it was first documented in Nigeria, and it has since become endemic in the West African region (1). According to the Centers for Disease Control and Prevention (CDC), the prevalence of LF in West Africa is a significant public health concern, with an estimated annual incidence ranging from 100,000 to 300,000 cases. Tragically, this infectious disease claims the lives of approximately 5,000 individuals each year (2). However, it is important to note that these estimates are not precise due to uneven surveillance of cases. In specific regions of Sierra Leone and Liberia, it is indicated that annually, 10–16% of hospital admissions can be attributed to LF. LASV can be contracted by humans through indirect exposure to surfaces or items tainted with the excreta of rodents carrying the virus. This includes contaminated food or household objects (2,3). In rare cases, person-to-person transmission can occur (2,4,5). The disease manifests in a wide range of symptoms, ranging from mild to severe, and can be potentially fatal. Cases of LF are rarely reported in non-endemic areas of the world, with the reported cases primarily being sporadic, imported from West Africa (6). Here, we present a detailed report on the first diagnosed case of LF in China.

Case presentation

The 49-year-old female patient had experienced high fever (temperature above 39 ℃), accompanied by severe headache, fatigue, and loss of appetite while working in Guinea, Africa, 19 days before admission to our hospital (Public Health Clinical Center of Chengdu). The local hospital in Africa diagnosed her with “malaria” and treated her with artemisinin and levofloxacin. The patient’s condition improved, and she returned to China. Approximately one week after returning, the patient developed back pain, abdominal pain, frequent urination, urgency, nausea, and vomiting. Subsequently, she also experienced symptoms such as slow reaction, and hearing loss. The blood smear for malaria parasites at the local hospital was negative, and she was treated with antibiotics and anti-inflammatory drugs, but her fever persisted without improvement. Due to the worsening hearing loss, it was suspected to be LF, and she was admitted to our hospital for isolation treatment.

Upon admission, the patient had a body temperature of 37 ℃, pulse rate of 78 beats per minute, respiratory rate of 18 breaths per minute, blood pressure of 106/70 mmHg, and oxygen saturation level of 98% (FiO₂ 33%). The patient was lethargic and exhibited decreased hearing. Multiple laboratory test results and trend charts during hospitalization are shown in Figure 1. Malaria parasite testing was negative. A full blood specimen was collected for LASV serum fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) detection, which resulted in a Ct value of 31.45 (a Ct value ≤35 is considered positive for the presence of LF virus nucleic acid; 35< Ct value ≤40 is classified as a suspicious sample; a Ct value of “undetected”, it indicates a negative result). The immunoglobulin G (IgG) antibody test yielded a positive result. Imaging studies (Figure 2) upon admission showed a small amount of pericardial effusion, bilateral pleural effusion, compression and inflammation of the lower lungs, peritonitis, abdominal effusion, reduced size of the left kidney, dilation of the left renal pelvis and ureter, and swelling of the left perirenal fascia. A diagnosis of LF was confirmed.

Figure 1 Laboratory test results and trend charts. The chart reflects the changes in some abnormal laboratory indicators of the patient throughout the entire hospitalization period. Following active treatment, the clinical indicators of the patient showed significant improvement before discharge. ALT, alanine aminotransferase; AST, aspartate aminotransferase; LPS, lipase; AMY, serum amylase; CR, creatinine.

Figure 2 Plain chest and abdominal CT images at admission. (A) Showed compression and inflammation of the lower lungs (white arrow). (B) Showed pericardial effusion (white arrow) and bilateral pleural effusion (yellow arrows). (C) Showed a small amount of abdominal effusion (white arrow) and the swelling of the left perirenal fascia (yellow arrow). (D) Showed the dilation of the left ureter (white arrow). (C,D) Showed the reduced size of the left kidney. CT, computed tomography.

The patient was placed under isolation treatment and administered ribavirin 500 mg intravenously every 6 hours to inhibit viral replication. After two weeks of active treatment, the patient’s clinical symptoms improved significantly. Follow-up computed tomography (CT) scans (Figure 3) revealed significant absorption of the effusions, and the hydroureteronephrosis and peritonitis also improved. However, the patient’s hearing level gradually declined and remained unrecovered, and she was diagnosed with bilateral severe sensorineural hearing loss (SNHL) according to a comprehensive hearing test (including pure tone audiometry, tympanogram, and otoacoustic emissions). The timeline diagram in Figure 4 depicts the entire course of disease onset, manifestation, treatment, and prognosis for this patient.

Figure 3 Plain chest and abdominal CT image before discharge. (A,B) Revealed a reduction in pericardial effusion and bilateral pleural effusion, along with a re-expansion of the previously compressed lung tissue and a decrease in inflammatory changes. (C) Demonstrated an improvement in the swelling of the left renal fascia (yellow arrow). (D) Indicated an improvement in the dilatation of the left ureter (white arrow). CT, computed tomography.

Figure 4 The timeline of the patient’s disease progression. This diagram depicted the entire course of disease onset, manifestation, treatment, and prognosis for this patient. LASV, Lassa virus; qRT-PCR, quantitative real-time polymerase chain reaction; IgG, immunoglobulin G.

All procedures performed in this study were in accordance with the ethical standards of the relevant institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

LF is an infective disease caused by the zoonotic pathogen Lassa virus (LASV). It is endemic throughout western Africa, with the Mastomys natalensis rodent serving as the major reservoir host (7,8). In the context of human infection, transmission most commonly occurs when individuals come into contact with contaminated rodent excreta, either through direct inhalation or ingestion. Furthermore, direct contact with the bodily fluids of LF patients also poses a significant risk (9). According to estimates provided by the CDC, the prevalence of LF cases in West Africa is alarmingly high, with an annual incidence ranging from 100,000 to 300,000, leading to a significant number of fatalities, approximately 5,000. However, other researches (10) suggest that the figures may be higher, ranging from 300,000 to 500,000 cases per year. It is important to note that these estimates are approximate due to the lack of consistent surveillance for cases across the region. The human-to-human transmission of LF virus is not commonly observed, but there have been sporadic reports. For instance, Fisher-Hoch et al.’s review of two hospital outbreaks of LF in southern central Nigeria recorded nine healthcare workers and one patient’s relative experiencing secondary infections (5). According to a research conducted by Haas and colleagues, of which the objective was to evaluate the risk of secondary transmission following the introduction of LF into Europe, the study identified a group of 232 individuals who had been exposed to a LF case imported into Germany. Notably, no symptomatic secondary infections were observed among the exposed individuals. However, it is worth noting that LASV-specific IgG antibodies were detected in a serum sample collected from a physician who examined the index patient on the ninth day of illness (4). In non-endemic countries particularly outside Africa, most cases are imported (11). A retrospective review conducted by Kofman et al. investigated the clinical and epidemiological characteristics of all imported LF cases worldwide from 1969 to 2016 (12). This study involved the analysis of 74 publications and a total of 33 patients who traveled from 7 West African countries to 9 other countries by searching PubMed. After gathering and evaluating data on case demographics, distinct clinical manifestations indicative of LF, the duration from a patient seeking medical attention to the clinical suspicion of LF, and the extent of contact tracing, the study revealed a comparable array of obstacles with regard to the prompt diagnosis, timely treatment, especially when medical professionals are not familiar with this disease.

LF can manifest in various ways, and due to the diverse and nonspecific nature of signs and symptoms, clinical diagnosis can be challenging. Approximately 80% of cases demonstrate either no symptoms or exhibit mild symptoms such as fever, malaise, headache, and chest pain. A study (13) conducted in Sierra Leone revealed that all 441 admitted patients with LF exhibited fever. This patient initially presented with a high fever (temperature above 39 ℃), and the recurrent fever was also present during hospitalization. However, it is important to note that fever may not be continuous, meaning that the absence of fever upon presentation does not eliminate the possibility of LF. Mucosal bleeding can be present in up to 20% of patients (6), while the patient in this case report did not show. The patient exhibited a unique attribute of hearing loss, and after undergoing a hearing test, the diagnosis revealed bilateral severe SNHL. According to previous literature (14), approximately one-third of survivors experience SNHL, and it is detected either 10 to 15 days following the initial symptoms in cases of LF, or during the subsequent recovery phase. Our patient developed hearing loss approximately 7 days after the onset of the disease, which is earlier than what is mentioned in the literature, and there was no observable progression towards hearing recovery thus far. Cummins et al.’s study (15) provided a comprehensive review of multiple reports regarding hearing loss in patients with LF, and indicated that the incidence of sudden-onset SNHL in cases of LF surpasses that of any other postnatally acquired infection. Additionally, complete recovery is only achieved by a minority of affected individuals. A prospective case-control study (16) of LF patients between July 2007 and April 2009 in the southern part of Nigeria even concluded that conservative treatment was ineffective in managing acute severe SNHL that occurred after LF. Furthermore, the diminished ability to discern speech observed in these patients suggested that the use of hearing aids would not provide any notable improvement in their hearing. The exact mechanism of LASV-induced hearing loss is unknown but appears to be immune-mediated (14). Further studies are required to comprehend LASV-induced hearing loss, which will contribute to the development of a potent and secure LASV vaccine and therapeutics. We will also continue to follow up on the patient’s hearing condition after discharge. This patient also experienced effusions, peritonitis, as well as hepatic and renal dysfunction, which is in line with previous studies (17,18). Furthermore, this patient developed reactive hyperamylasemia, which has been infrequently reported before. According to the patient’s imaging comparison, there was evidence that the effusions largely absorbed and also improvement of hydroureteronephrosis and peritonitis after active treatment. This indicated a strong potential correlation between the imaging manifestations in the chest and abdomen and the acute changes caused by LF. The imaging findings, although not highly specific, can still serve as clinical indicators for suspected LF. It is noteworthy that the reduced size of the left kidney in our patient is contrary to previous reports (18), which have suggested an increase in renal volume.

Currently, there are no Food and Drug Administration (FDA)-approved vaccines against LASV for human use (19), and while a few vaccine candidates have shown promise, none have yet proven to be efficacious in animal models, preventing their progression to phase I human studies (2). Off-label use of ribavirin has shown some effectiveness in reducing mortality, while side effects may encompass hemolytic anemia and infusion-related reactions, including rigors (8). There are also emerging treatments such as monoclonal antibodies and favipiravir. Monoclonal antibodies have been studied extensively for their efficacy in combating the Lassa virus by targeting the viral glycoprotein. In preclinical animal models, these antibodies have shown promising results. In addition to the antibodies, a combination of favipiravir and ribavirin has displayed synergistic activity against the Lassa virus, as demonstrated in vitro studies. This combination therapy has also exhibited improved survival rates in mouse models. However, all of this remains at the stage of animal experimentation and has not yet been approved for clinical use. Out of safety concerns, we adopted ribavirin to combat the LASV, combined with other symptomatic treatment methods, and this treatment method seemed to be effective for this patient. When LF was suspected, this patient was immediately admitted to the isolation ward of our hospital, and there was no secondary transmission. The isolation of patients with LF and the use of personal protective equipment by healthcare staff are critically important.

In conclusion, we reported the first case of LF in China. Prompt diagnosis, treatment, early isolation, and vaccine research are of paramount importance, given the contagious nature of this disease, its diverse symptoms, and the potential long-term consequences such as hearing loss. More research efforts need to be devoted to address future challenges posed by similar infectious diseases.

Acknowledgments

We wish to express our sincere thanks to Liang Huang for his professional help and constructive suggestions for this article.

Funding: None.

Footnote

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1784/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the relevant institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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