LASSA FEVER

Background

Lassa fever (LF) is an acute viral illness and a viral haemorrhagic fever (VHF). The causative agent is a single-stranded RNA virus in the family Arenaviridae, the Lassa virus. This zoonotic disease is associated with high morbidity and mortality, and it has both economic and health security consequences. The illness was first reported in Lassa community in Borno State, Nigeria, when two missionary nurses died from an unusual febrile illness. Since then cases and outbreaks continue to be reported in Nigeria and the diseases is increasingly recognised to be endemic in many parts of West Africa, including Nigeria, Benin, Ghana, Mali and the Mano River region (Sierra Leone, Liberia and Guinea), with the disease probably existing in other West African countries as well. An estimated 300,000-500,000 cases and 5,000 related deaths occur annually in West Africa. In 2018, NCDC reported the largest ever number of cases in Nigeria, with over 600 confirmed cases and over 170 deaths. The increase is not thought to be due to any new virus strains, and may at least be partially explained by increasing surveillance capacity.

Lassa fever (LF) is an epidemic prone disease for immediate notification on the IDSR platform in Nigeria. The actual incidence rate in Nigeria is unknown, but case fatality rates range from 3% to 42% (and over the last two years has remained between 20% and 25%). Historically, outbreaks occur during the dry season (November to April), however, in recent years, cases have also occurred during the rainy season. Lassa fever importation into non-endemic countries has occurred in the UK, USA, and Germany, amongst others.

Transmission

The Lassa virus is transmitted to man by infected multi-mammate rats, the mastomys natalensis species complex which is the reservoir host. Humans become infected from direct contact with the urine and faeces of the rat which contains the virus, through touching soiled objects, eating contaminated food, or exposure to open cuts or sores. Secondary transmission from person to person can occur following exposure to the virus in the blood, tissue, urine, faeces or other bodily secretions of an infected individual. Hospital-acquired (nosocomial) transmission from person to person are not uncommon, and importantly can occur if appropriate Personal Protective Equipment (PPE) is not worn when managing suspected cases.

Symptoms

Lassa fever presents with symptoms and signs similar to those of many febrile illnesses, thus making it difficult to diagnose clinically. The incubation period is between 6-21 days. It causes a syndrome characterised by fever, muscle aches, sore throat, nausea, vomiting, chest and abdominal pain. Although fever is not a constant presenting symptom, Lassa fever should be suspected in patients with fever (≥380C) not responding adequately to regular antimalarials and antibiotics. It should also be suspected in any outbreak setting with patients presenting with a compatible syndrome. It also likely has a wide spectrum of disease presentation, from relatively mild illness to severe haemorrhagic manifestations. Case definitions can guide diagnosis

Diagnosis/Testing

A high index of suspicion aids diagnosis, especially in endemic areas like Nigeria, or in patients returning from other endemic areas in West Africa. Diagnosis is based on clinical features (guided by case definitions above) and laboratory confirmation. Laboratory diagnosis is by viral amplification from blood samples using Reverse-Transcription Polymerase Chain Reaction (RT-PCR).

Case Definitions

The Technical Guidelines for Integrated Disease Surveillance and Response (IDSR) in Nigeria gives the following standard case definitions:

Suspected case of Lassa Fever:

Illness with gradual onset with one or more of the following: malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhoea, myalgia, chest pain hearing loss and a history of contact with excreta of rodents or with a case of Lassa Fever

Confirmed case of Lassa Fever:

A suspected case that is laboratory confirmed (positive IgM antibody, PCR or virus isolation) or epidemiologically linked to a laboratory confirmed case.

There are also additional case definitions for clinical decision making to guide management of Lassa fever cases in health facilities, developed by NCDC in November 2018. These include:

Alert case

Any person who has an unexplained fever (i.e. malaria and other common causes of fever have been ruled out), with or without bleeding OR Any person who died after an unexplained severe illness with fever and bleeding.

Suspected case

Patient with fever for 3-21 days with a measured temperature of 38OC or more with one or more of the following: vomiting, diarrhoea, sore throat, myalgia (muscle pain), generalised body weakness, abnormal bleeding, abdominal pain OR in Neonates: Maternal Lassa fever +/- signs and symptoms.

Any of the following scenarios should raise the index of suspicion:

a. Patient has not responded to standard anti-malaria treatment and treatment for other common infectious causes of fever within 48-72 hours.

b. History of recent contact with a probable or confirmed case of Lassa fever within 21 days of onset of fever.

c. Patient with history of fever and history of travel to high risk/burden area of Lassa fever.

d. Contact with body fluids or tissues of a dead patient with a febrile illness, symptoms and signs highly suggestive of Lassa fever leading to death.

Probable case

A suspected case who has one or more of the following complications:

a. Hearing loss

b. Facial or neck swelling

c. Seizures

d. Restlessness

e. Confusion

f. Hypotension (SBP< 90mmHg in adults and

Treatment

Treatment should be carried out in designated isolation centres by trained staff. Standard infection prevention and control (IPC) measures for LF must be in place. The drug of choice is Ribavirin, an antiviral agent, administered orally or parenterally. Prognosis is best if this treatment is commenced early, usually within six days of onset of symptoms. High quality supportive treatment should also be instituted based on clinical assessment of patients, which improves patient outcomes.

Infection Prevention and Control (IPC)

Prompt diagnosis of Lassa fever is key. There is currently no vaccine that protects against Lassa fever. The collaboration of government agencies working with development partners has increased the recognition of Lassa Fever and the need for deployment of enhanced IPC measures. Other prevention and control measures include:

• Continued advocacy and sensitisation of communities, States, their leaders and other stakeholders.

• Strengthening of the surveillance system for early detection, isolation and confirmation of cases.

• Promoting good environmental and personal hygiene. This is to discourage rodents from entering homes and having access to food stuff. Effective measures include storing grain and other foodstuff in rodent-proof containers, disposing of garbage far from the home, and maintaining clean households.

• Reminding care givers to be careful and maintain standard precautions to avoid contact with blood and body fluids while taking care of an infected person.

• Avoiding nosocomial transmission of infections in health-care settings, with health care workers observing all necessary IPC precautions when caring for patients, regardless of their presumed diagnosis.

• Ensuring staff in Lassa fever treatment centres apply extra infection control measures to prevent contact with the patient’s blood and body fluids and contaminated surfaces or materials.

• Following safe injection practices at every stage.

• Training health care workers in the laboratories in appropriate specimen receipt and handling, and ensuring all patient samples are properly labelled on collection with appropriate details included such as haemorrhagic manifestations.

• Ensuring safe burial practices are adhered to for anybody that died (or is suspected to have died) of Lassa fever.

Nigeria References

Ajayi NA, Nwigwe CG, Azuogu BN, Onyire BN, Nwonwu EU, Ogbonnaya LU, et al. Containing a Lassa fever epidemic in a resource-limited setting: outbreak description and lessons learned from Abakaliki, Nigeria (January–March 2012). Int J Infect Dis 2013;17(11):e1011–6.

Ilori EA, Frank C, Dan-Nwafor CC, et al. Increase in Lassa Fever Cases in Nigeria, January-March 2018. Emerg Infect Dis 2019;25(5):epub (doi:10.3201/eid2505.181247).

Siddle KJ, Eromon P, Barnes KG, et al. Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018. N Engl J Med 2018;379(18):1745-1753

Tambo E, Adetunde OT, Olalubi OA. Re-emerging Lassa fever outbreaks in Nigeria: Re-enforcing “One Health” community surveillance and emergency response practice. Infect Dis Poverty 2018;7(1):37.

Further Reading

NCDC: www.ncdc.gov.ng/themes/common/docs/protocols/92_1547068532.pdf

CDC: www.cdc.gov/vhf/lassa

WHO: www.who.int/csr/disease/lassafever/en

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