Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 22  |  Issue : 2  |  Page : 122-126

An insight into Ribavirin post-exposure prophylaxis for Lassa fever infection prevention amongst health-care workers in a specialist hospital in North-Central Nigeria


1 Department of Obstetrics and Gynaecology, Dalhatu Araf Specialist Hospital (DASH), Lafia, Nigeria
2 Department of Internal Medicine, Dalhatu Araf Specialist Hospital (DASH), Lafia, Nigeria
3 Department of Surgery, Dalhatu Araf Specialist Hospital (DASH), Lafia, Nigeria
4 Department of Pharmacy, Dalhatu Araf Specialist Hospital (DASH), Lafia, Nigeria
5 Department of Community Medicine, Dalhatu Araf Specialist Hospital (DASH), Lafia, Nigeria

Date of Submission20-Mar-2020
Date of Decision13-May-2020
Date of Acceptance15-Jun-2020
Date of Web Publication11-Sep-2020

Correspondence Address:
Dr. Chidiebere Nwakamma Ononuju
Department of Obstetrics and Gynaecology, Dalhatu Araf Specialist Hospital (DASH), Lafia
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomt.jomt_8_20

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  Abstract 


Background: Oral ribavirin is used as standard post-exposure prophylaxis (PEP) in preventing the nosocomial spread of Lassa fever (LF) in outbreaks. This study sought to have an insight into the incidence and case fatality rate of Lassa fever infections, assess the biosocial data and outcome of the healthcare workers who received ribavirin PEP and determine the adverse effects associated with ribavirin PEP therapy at the Dalhatu Araf Specialist Hospital Lafia Nasarawa State Nigeria. Methods: This was a prospective study done between January 2017 to December 2018. Data on biosocial, details of exposure to the Lassa virus, the dosage of ribavirin therapy, adverse effects and outcomes were obtained. Results: The incidence of LF infection was 16% of all suspected cases, with a case fatality rate of 57.1%. General body weakness 30 (44.8%) and loss of appetite 25(37.2%) were the common adverse drug effects reported. The majority of the healthcare workers, 66 (98.5%) remained asymptomatic for secondary LF infection after completion of their oral ribavirin PEP, only, 1 (1.5%) became symptomatic for secondary LF infection, and expired on the sixth-day post-needlestick exposure. Conclusion: Lassa fever infection is common in Nasarawa State, and it is associated with a high case fatality rate. Healthcare workers on duty are at risk of being exposed when adherence to infection prevention and control is inadequate. Oral ribavirin PEP therapy was found to have a low adverse effect profile and efficacious in the prevention of symptomatic secondary LF infection.

Keywords: Lassa fever, outbreaks, ribavirin PEP, secondary infection


How to cite this article:
Ononuju CN, Changkat LL, Adiukwu CV, Okwaraoha OB, Chinaka UE, Ashuku YA, Chinaka SU, Ezeaku EC, Ikrama HI. An insight into Ribavirin post-exposure prophylaxis for Lassa fever infection prevention amongst health-care workers in a specialist hospital in North-Central Nigeria. J Med Trop 2020;22:122-6

How to cite this URL:
Ononuju CN, Changkat LL, Adiukwu CV, Okwaraoha OB, Chinaka UE, Ashuku YA, Chinaka SU, Ezeaku EC, Ikrama HI. An insight into Ribavirin post-exposure prophylaxis for Lassa fever infection prevention amongst health-care workers in a specialist hospital in North-Central Nigeria. J Med Trop [serial online] 2020 [cited 2020 Sep 20];22:122-6. Available from: http://www.jmedtropics.org/text.asp?2020/22/2/122/294824




  Introduction Top


Lassa fever is a zoonotic disease associated with acute and frequently fatal haemorrhagic events caused by the Lassa virus,[1] endemic in Nigeria and other West African Countries.[2],[3] Lately, there has been increasing outbreaks of Lassa fever cases in Nigeria, making it a public health catastrophe.[2],[3] In early 2019, 554 laboratory-confirmed Lassa fever cases and 124 deaths were reported in Nigeria by the Nigerian Center for Disease Control, with a case fatality rate of 22%, the number of healthcare workers affected were 18.[3]

Worldwide, there is no known vaccine available against the Lassa fever virus in humans. Ribavirin has become a recommended standard treatment for Lassa fever cases and for post-exposure prophylaxis to prevent secondary infection. Its efficacy is enhanced by early administration, especially when the drug is administered within the first 6 days of the onset of clinical symptoms.[2],[4] Despite growing concerns regarding toxicity, efficacy, and lack of specificity associated with Ribavirin, there is a growing body of evidence suggesting that ribavirin antiviral therapy is effective against Lassa fever virus infections in humans especially when used in combination with an experimental antiviral drug like with Favipiravir.[5],[6]

Ribavirin is a guanosine analogue that is active against a broad spectrum of DNA and RNA.[1.5]

It significantly inhibits the Lassa virus replication in vitro medium but exhibits a diminished effect on viremia in vivo.[5] The main mechanism of action of Ribavirin is largely unknown, however, several hypotheses have been postulated. Popular among them is the Mutagenic hypothesis in which ribavirin acts as a mutagen to reduce the infectivity of the new virion. Other hypotheses include inhibition of viral replication, regulation of cellular destruction, and enhancement of antiviral immunity.[5],[7],[8]

Many healthcare workers (HCW’s) who care for patients with Lassa fever are at risk of being exposed to the disease largely when infection prevention control measures are insufficiently implemented.[4],[9] In Nigeria, healthcare workers who have been categorized as high-risk exposure to Lassa fever cases are generally counseled and receive oral ribavirin PEP. Therefore the study sought to gain insight into Ribavirin post-exposure prophylaxis for Lassa fever infection prevention amongst health-care workers at the Dalhatu Araf Specialist Hospital (DASH) Lafia Nasarawa State Nigeria.


  Materials and methods Top


Approval was sought from the Health Research Ethics Committee of Dalhatu Araf Specialist Hospital, P.M.B. 007, Lafia Nasarawa State, Nigeria, and was obtained on the 20th of September 2016, DASH/ADM/88/S.9/C/16 before the commencement of this study.

This was a prospective study in which consecutive healthcare workers who had direct contact with confirmed Lassa fever cases and were categorized as high-risk exposure (category 3)[4] at the Dalhatu Araf Specialist Hospital Lafia Nasarawa State Nigeria between January 2017 to December 2018 were counseled and enrolled for the study.

Biosocial information like age, sex, profession, Unit of the hospital was the exposure occurred and details of the exposure to the Lassa virus, medical history, dosage and duration of ribavirin administered, and the use of concomitant medications was obtained and computed into an electronic worksheet. The respondents were followed-up by phone calls and personal visits to study their adherence and adverse effects. All of them monitored their axillary temperature in the mornings and evenings for 21 days from the last day of exposure and they were to report fever (≥38.0°C) for further evaluation. Statistical analysis was performed using SPSS (version 19, Chicago, IL, USA). The incidence of Lassa fever infection was calculated and the age of the respondents expressed as means ± standard deviations.

Categorization of contacts and dosage of Ribavirin

A contact for the purpose of this study is defined as a person who has been exposed to an infected person or to an infected person’s body fluids, or tissues within three weeks of contact with a confirmed or probable case of Lassa fever. At DASH Lafia, in line with the Nigeria Centre for Disease Control guideline for Lassa fever case management, Category 3- (high-risk contacts) are those health workers who had unprotected exposure of their broken skin to infectious body fluids, had unprotected handling of clinical or laboratory specimens, mucosal exposure to splashes and penetration of their skin by a contaminated sharp instrument.[4] Healthcare workers working in emergency units and those with lengthy (i.e. for hours) contact in an enclosed space without proper use of personal protective equipment were also categorized as high risk.[4]

Post-exposure prophylaxis with Ribavirin was commenced for high-risk contacts of confirmed cases, in whom ribavirin was not contra-indicated. All the respondents received a prophylactic regimen of Ribavirin 600mg by mouth every 6 hours for 7 days after counseling. These health workers were monitored closely and RT-PCR for the Lassa virus was to be done for them if they developed signs and symptoms of Lassa fever.

Drug adherence for the purpose of this study is defined as the degree to which the respondents were committed to using oral Ribavirin PEP therapy dosage and duration. It was determined by phone calls and physical visits to the respondents.


  Results Top


Incidence and case fatality of Lassa fever infection in DASH

Over the period of this study, between January 2017 and December 2018, there were 89 suspected cases of LF at DASH. Fourteen of these patients were confirmed positive with LV-specific reverse-transcriptase polymerase chain reaction test, the incidence of LF was 16% of suspected cases. Eight (57.1%) of these patients died while on admission, while 6 (42.9%) survived and were discharged home alive. The case fatality rate was 57.1%. This is shown in [Table 1].
Table 1: Incidence/case fatality of Lassa fever infection, biosocial of exposed HCWs and their outcome after ribavirin PEP therapy at DASH

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Biosocial data of the HCWs exposed to confirmed LF infection

Seventy-two health care workers were identified as primary contacts of 14 confirmed Lassa fever cases, among them only 67 (93.1%) were categorized as high risk, and all of them received ribavirin PEP and were enrolled for this study. Amongst the healthcare workers who were exposed to LF patients, 26 (39.0%) were nurses, 20 (30.0%) were ward attendants, 15 (22.3%) were medical doctors, while 6 (9.0%) worked in the laboratory. Their mean age was 38 years ±12.4. Also, 37 (55.2%) of these health workers were females while 30 (44.8%) were males. All the health workers were exposed to Lassa virus in the hospital during work hours at their work units, 25 (37.0%) worked at the accident and emergency unit, 20 (29.7%) in the Gynaecology/Obstetrics emergency units, 10 (15.0%) at the Internal medicine department, 8 (12.0%) at the theatre, 3 (4.5%) in the surgery department and only 5 (7.5%) in the laboratory

(Haematology and Microbiology). Twenty (29.9%) of the respondents had pre-existing medical conditions, these conditions were, Hypertension n = 10 (14.9%), Diabetes mellitus n = 4 (6.0%), Glaucoma n = 3 (4.5%), Peptic ulcer disease n = 2 (3.0%), and chronic hepatitis C infection n = 1 (1.5%). All of the respondents continued their regular medications whilst on ribavirin PEP. These medications included Metformin, Glyburide, Amlodipine, Chlorothiazide, Paracetamol, Multivitamins, Timolol eye drop, Antacids, Antimalarial drugs, and Antimicrobial drugs. This is shown in [Table 1].

The outcome of the HCWs after ribavirin PEP therapy

The majority of the HCW’s, 66 (98.5%) were asymptomatic of secondary LF infection after completion of their PEP, however, 1 (1.5%) of the respondent became symptomatic for secondary LF infection, and tested positive for the LV-specific reverse-transcriptase polymerase chain reaction test. He died from complications of septicemia on the sixth-day post needlestick-exposure. The expired HCW was a male nurse who worked at the accident and emergency unit, he tested positive to both hepatitis C virus and Lassa virus. There was no history of Lassa fever infection amongst his household or close associates in his community. This is shown in [Table 1].

The adverse effects associated with oral ribavirin PEP

All the respondents had begun taking oral ribavirin within 2 days post-exposure. All of them (100%) reported complete adherence to the 7 days therapy. Forty-two (62.7%) of the respondents reported adverse effects: general body weakness 30 (44.8%), loss of appetite 25 (37.2%), and dizziness 15 (22.4%). These symptoms were not life-threatening and resolved on their own without any clinical intervention. Only one of them developed a fever on the third-day post-exposure (with a recorded temperature above 38 degrees), and were admitted into the hospital. This is shown in [Table 2].
Table 2: Adverse effects and outcome associated with ribavirin PEP against Lassa fever infection

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  Discussion Top


The incidence of Lassa fever infection reported in this study was 16% of all suspected cases. This finding is similar to the 16.7% previously reported in Nasarawa State Nigeria but slightly lower than the 42% reported in Irrua-Edo State Nigeria.[9],[10] This shows that LF infection is common in Lafia and other parts of Nasarawa State Nigeria. The case fatality rate of 57.1% observed among patients with confirmed Lassa virus infection treated in DASH was high, although this observation is lower than 62.15% previously reported in the State, [9] however, it is higher than the average national rates of 26% recorded in 2018, and the 22% reported in the first quarter of 2019.[3] This observation may be attributed to late presentation, delays in making a diagnosis, and commencement of treatment, this is important considering that early intervention with the administration of ribavirin has been shown to improve outcomes of the patients.[4] The virulence of the Lassa virus sprain prevalent in the Nasarawa state should also be subjected to genomic evaluation to understand their peculiarity. Efforts should be channeled to continuous upgrade of intervention strategies, improvement of diagnostic facilities and training of health care providers.

The study identified 67 (93.0%) of the healthcare workers who were high-risk contacts and all of them were exposed while caring for patients without adequate provision and use of personal protective equipment at the emergency outlets of the hospital. This staggering number of high-risk exposure underscores the need to urgently review the infection prevention and control protocols at DASH Lafia. Similar findings have been reported previously in Nigeria[3] and in Sierra Leone.[2] In the first quarter of 2019, 18 healthcare workers were infected with Lassa virus in Nigeria,[3] and in most of these cases, adherence to infection prevention control was poor.[11] The provision of the full set of personal protective equipment is recommended for all healthcare workers who provide direct care to patients with Lassa fever, however, the optimal implementation of this recommendation is still plagued by inadequate resources to ensure its attainability in Lafia and other parts of Nigeria.

Although secondary Lassa fever infection was not observed in the majority 66 (98.5%) of the healthcare workers after the completion of their ribavirin therapy, however, 1 (1.5%) of them developed secondary infection whilst on ribavirin PEP, and died on the sixth-day post-needle stick exposure, giving a case fatality rate of 1.5%. These findings are slightly different from reports from Jos Nigeria,[12] Sierra Leone[2] and Germany[1] in which all the HCW’s who received ribavirin PEP did not develop secondary LF infection. The mortality recorded in this study was not on any known medical treatment for hepatitis C virus infection co-morbidity and the possibility of underlying liver disease was not ruled out. These may have contributed to his early clinical deterioration and death. Regrettably, no autopsy was done on him.

High nosocomial secondary LF attack rates amongst healthcare workers have been reported in other health facilities in Nigeria,[13] in the first quarter of 2018. Ten out of the seventy-seven confirmed cases reported in four states of Nigeria were health-care workers, 4 of them died despite receiving ribavirin,[13] also 18 healthcare workers developed secondary LF infection in the first quarter of 2019,[3] in Ebonyi state Nigeria a case fatality of 31% was reported amongst healthcare worker following secondary Lassa virus infection.[14] Ribavirin PEP failed to stop the secondary transmission of Lassa virus infection in some healthcare workers in Nigeria. This brings to light the various arguments for and against the efficacy of oral Ribavirin PEP.[1] However, the consensus is that the use of oral ribavirin PEP should not replace the consistent application of basic infection control measures and isolation of cases which are traditional consistent keys known in the prevention of secondary transmission of Lassa virus infection.[15]Forty-two (62.7%) of the respondents in this study reported adverse effects. These adverse effects were general body weakness 30 (44.8%), loss of appetite 25 (37.2%), and dizziness 15 (22.4%). These adverse effects were not life-threatening and resolved on their own without any clinical intervention. Similar findings have been reported in Jos Nigeria and Sierra Leone.[2],[12]

Lassa fever infection is common in Nasarawa State Nigeria, it is associated with a high case fatality rate, and healthcare workers are at risk of being exposed to infection from Lassa fever patients when adherence to infection prevention control is inadequate. Oral ribavirin PEP therapy has a low adverse effect profile, and efficacious in the prevention of symptomatic secondary Lassa virus infection in most of the high risk exposed healthcare workers. However, the use of oral Ribavirin PEP should not diminish the consistent application of basic infection control measures, isolation of cases, and adequate provision/use of personal protective equipment at the hospital emergency units to prevent the nosocomial spread of Lassa virus infections.


  Conclusion Top


Immunoassay for Lassa virus IgM or IgG antibodies was not done for the healthcare workers exposed to confirmed Lassa fever cases due to the cost and non-availability of the test in our health facility. Therefore this limited the study in determining the occurrence of asymptomatic secondary infection among the respondents. This highlights the need to establish an immunology laboratory at the Dalhatu Araf Specialist Hospital and subsiding the cost of this test. The implementation of this will go a long way in enhancing the management of patients with infectious diseases in a resource-limited setting like ours and equally aid future research engagements.

Furthermore, the study was also limited by our inability to carry out a viral genomic investigation of viral isolates from the expired healthcare worker and the patient with Lassa fever infection who was the primary source of the Lassa fever infection. This would have gone a long way in confirming secondary transmission in the index case, but regrettably, we were hindered by logistics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Eberhardt KA, Mischlinger J, Jordan S et al. Ribavirin for the treatment of Lassa fever: A systematic review and meta-analysis. Int J of Infect Dis 2019;87:15-20.  Back to cited text no. 1
    
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Dan-Nwafor CC, Furuse Y, Ilori EA et al. Measures to control protracted large Lassa fever outbreak in Nigeria. Euro Surveill J 2019;24:1560-7917.  Back to cited text no. 3
    
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National guidelines for Lassa fever case management: Nigeria Centre for Disease Control (NCDC), November 2018. www.ncdc.gov.ng. Last assessed on March 30th, 2020.  Back to cited text no. 4
    
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Carrillo-Bustamante P, Nguyen THT, Oesterreich L et al. Determining Ribavirin’s mechanism of action against Lassa virus infection. Sci Rep 2017;15;7:11693.  Back to cited text no. 5
    
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Westover JB et al. Low-dose ribavirin potentiates the antiviral activity of Favipiravir against hemorrhagic fever viruses. Antiviral Res 2016;126:62-68.  Back to cited text no. 6
    
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Lau JYN, Tam RC, Liang TJ, Hong Z. Mechanism of action of ribavirin in thecombination treatment of chronic HCV infection. Hepatology 2002;35:1002-9  Back to cited text no. 7
    
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Feld JJ, Hoofnagle JH. Mechanism of action of interferon and ribavirin in the treatment of hepatitis C. Nature 2005;436:967-72  Back to cited text no. 8
    
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Solomonaudu E, Adiukwu C, Surajudeen B et al. Lassa Fever burden among Suspected Cases Presenting In Health Facilities in Nasarawa State, North Central Nigeria. IOSR-JDMS 2019;18:25-29.  Back to cited text no. 9
    
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Ehichioya DU, Asogun DA, Ehimuan J et al. Hospital-based surveillance of Lassa Fever in Edo State, Nigeria; 2005-2008. Trop Med Int Health 2012;17:1001-4.  Back to cited text no. 10
    
11.
Richmond JK, Baglole DJ. Lassa fever: Epidemiology, clinical features,and social consequences. BMJ 2003;327:1271-5.  Back to cited text no. 11
    
12.
Isa SE, Okwute A, Iraoyah KO et al. Postexposure prophylaxis for Lassa fever: Experience from a recent outbreak in Nigeria. Niger Med J 2016;57:246-50.  Back to cited text no. 12
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13.
Nigeria Centre for Disease Control and Prevention. National Centre for Emerging and Zoonotic Infectious Diseases. Division of High-Consequence Pathogens and Pathology. Archived 31 January 2018. Last Assessed on March 22nd, 2020.  Back to cited text no. 13
    
14.
Agboeze J, Onoh R, Eze J, Nwali M, Ukaegbe C. Clinical Profile of Lassa Fever Patients in Abakaliki, Southeastern Nigeria, January − March 2018. Ann Med Health Sci Res 2019;9:598-602.  Back to cited text no. 14
    
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Choi MJI, Worku S2, Knust B3 et al. A case of Lassa fever diagnosed at a community hospital—Minnesota 2014. Open Forum Infect Dis 2018;5:1-5.  Back to cited text no. 15
    



 
 
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