DISEASE BACKGROUND AND OUTBREAK CHARACTERISTICS

1. The Nipah Virus (NiV) is an RNA virus that belongs to the genus Henipavirus of the Paramyxovirus family. Its natural reservoir hosts are fruit bats (Pteropus spp.) and possibly other species of bats. Pigs may serve as intermediate amplifying hosts for outbreaks in humans. Animal-to-human transmission may occur by: (i) direct contact with infected animals, such as bats and pigs, or their body fluids or excretions; and (ii) consumption of raw date palm sap or fruits contaminated by saliva or urine of infected bats. Limited human-to-human transmission of NiV among family, caregivers, community contacts, and healthcare providers of infected NiV patients through close contact with their secretions and excretions has been documented.
 

2. NiV was first identified in an outbreak of acute encephalitis among pig farmers in Malaysia in 1998-1999, which saw 265 cases of acute encephalitis (brain infection), accounting for 105 deaths. As part of this outbreak, Singapore saw 11 cases in March 1999, with one fatality. A high incidence of cases during the Malaysia-Singapore outbreak presented with encephalitis or had neurological symptoms, with no occurrence of human-to-human transmission. In subsequent outbreaks in Bangdalesh and India, a higher incidence of respiratory involvement were reported with limited human-to-human transmission.
 

3. NiV infection can cause severe neurological symptoms and/or encephalitis and pneurmonia. It is a highly fatal illness, with a case fatality ratio (CFR) estimated between 40 to 75% in past outbreaks depending on local capabilities for epidemiological surveillance and clinical management (CFR ~ 40% for outbreaks in Malaysia and Singapore; CFR >70% for outbreaks in Bangladesh). At present, there are no licensed vaccines or therapeutics available for the prevention and treatment of NiV infection.

CURRENT OUTBREAK SITUATION IN KERALA (2023)

4. On 12 September 2023, the Kerala State Health Department of India confirmed an outbreak of NiV in Kozhikode district, Kerala State. As of 29 September, six laboratory-confirmed human cases of NiV infection, including two deaths (CFR: 33%), were reported in this outbreak. The index case succumbed to the infection on 30 August and residual samples collected from the case subsequently tested positive for NiV on 15 September.The remaining five confirmed cases, including one health worker, had known exposure history to the index case. Nosocomial transmission may have been implicated in three cases.
 

5. At least three of the cases in this current outbreak presented to hospital with pneumonia and/or respiratory distress. The outbreak virus had been identified as an Indian Genotype or I-Genotype strain, similar to the strain found in Bangladesh which is associated with a higher likelihood of atypical pneumonia and severe respiratory problems, including acute respiratory distress.
 

6. Public health measures including closure of public institutions, quarantine, contact tracing, strengthening surveillance and infection control activities at health facilities, and risk communications to the community had been imposed to mitigate the spread of NiV infection in Kerala. As of 29 September, 865 contacts remain under observation. At the time of publication, most public health measures have been lifted, although the public was advised to exercise caution till 26 October, which marks the 42nd day after the last reported case on 15 September. The source of the outbreak remains under investigation. More information on the current outbreak in Kerala can be found at https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON490.

RISK ASSESSMENT

7. This is the sixth outbreak in India since 2001 when the first outbreak was reported in Siliguri town, West Bengal. Another five outbreaks had been reported since – in 2018 from Nadia district, West Bengal (5 cases, CFR:100%) and Kozhikode and Malappuram, Kerala (23 cases including probable cases, CFR:91%); in 2019 from Ernakulum, Kerala (1 case who survived); and in 2021 from Kozhikode, Kerala (1 case, CFR: 100%). Fruit-eating bats were identified as the primary source of infection in the 2018 outbreak in Kerala, with all subsequent cases occurring by person-to-person transmission through close contact with NiV cases.

8. The current outbreak in Kerala is not unexpected, given the three previous outbreaks in the state, coupled with the known presence of infected animal hosts in Kerala state and throughout India. Fruit bats from the area near the index case’s native village in Kozhikode district had previously tested positive for NiV during the 2018 outbreak. There have been no details regarding Personal Protective Equipment (PPE) use and infection control lapses contributing to nosocomial transmission in this outbreak.

9. The necessary surveillance and control measures have been put in place to mitigate the spread of NiV. Current cases are clustered and epidemiologically linked to the first case, and cases remained localized to Kozhikode district. No further transmission has been detected as of 29 September. Additional cases may be detected as the source of infection remains unidentified. The Kerala state government had expressed confidence in controlling the situation. Importation of a case into Singapore is possible, however, at present the risk is low given that there is no ongoingcommunity transmission involved in the outbreak. Nonetheless, alongside limited human-to-human transmissibility of NiV, the presence of well-established infection control practices would mitigate the risk of a serious public health impact in the event of an imported case in Singapore.
 

SIGNS AND SYMPTOMS

10. The incubation period of the NiV in humans is between 4 to 45 days, with >90% of symptoms developing between 4 and 14 days after exposure. Asymptomatic and mild infections have been reported, but only a minority of infected persons (<10%) were found to be truly asymptomatic. Human-to-human transmission has been reported. Duration of infectious period is unknown, but it likely begins during the incubation period and continues until the patient stops shedding the virus.
 

11. As the signs and symptoms for NiV are non-specific, doctors should be alert to any traveller from NiV-affected regions with these presentations. In addition, doctors should always ask for travel history in patients presenting with signs and symptoms of encephalitis or respiratory distress, as they can be the result of many severe travel-related illnesses.
 

12. Doctors should suspect NiV infection in patients who present with:
• Acute encephalitis picture with initial symptoms of fever, headache, myalgia, vomiting, sore throat, followed by dizziness, drowsiness, altered consciousness, seizures and coma; OR
• Atypical pneumonia, and acute respiratory distress; OR
• Relapse encephalitis and late-onset encephalitis in those with initial non-encephalitic or asymptomatic diseases reported

AND

• Within the last 14 days prior to onset of symptoms,
o Travel from NiV affected countries or regions (currently Kerala, India) with an ongoing NiV outbreak; OR
o Exposure to bats or bat-contaminated food or pigs; OR
o Exposure to a confirmed NiV case; OR
o Consumed sap or other products from palm trees

DIAGNOSIS

13. Diagnosis in acute infection is primarily by detection of NiV by PCR in blood samples. The following samples can be sent to the National Public Health Laboratory (NPHL) for diagnosis of acute NiV infection:

• Plain blood (3-5 mL in a red top tube), throat/nasal swabs, CSF (~2 mL) and/or urine (~2 mL), (depending on clinical presentation) can be sent for NiV PCR (together with Submission Form for VHF Testing and Nipah Virus PCR, Annex A). Where in doubt, the laboratory should contact NPHL for further assistance (see Annex A). There should be proper instruction and training in packaging before transport of sample between laboratories (see Annex B).
• For patients with high clinical suspicion for NiV infection, upon MOH request, additional plain blood sample (3-5 mL in a red top tube) should be sent during the acute phase, and a second sample (i.e., convalescent sample) sent 10-14 days after symptom onset. NPHL may forward the paired samples to a reference laboratory.

CLINICAL MANAGEMENT

14. The initial clinical manifestations of NiV infection are non-specific and are similar to other diseases such as viral encephalitis, bacterial meningoencephalitis and pneumonia. It is important to evaluate and manage (as applicable) suspect cases for more common causes of encephalitis (including Japanese encephalitis virus and rickettsial infections) or acute respiratory distress according to local guidelines until the diagnosis of NiV infection is confirmed.

15. Patients with NiV infection generally present with fever, headache, dizziness and vomiting. Central nervous system (CNS) involvement occurs in the vast majority of symptomatic cases. A broad spectrum of neurological presentations has been reported, including aseptic meningitis, focal brainstem involvement, and diffuse encephalitis. Seizures and myoclonic jerks may occur in 20% of patients, while cerebellar signs are reportedly common. The disease is rapidly progressive for a majority of patients, with clinical deterioration leading to brainstem dysfunction and coma in 5-7 days. In survivors, relapsing and late-onset encephalitis (up to 11 years in the longest known case) are distinguishing features, occurring in up to 20% of cases. MRI brain in patients with CNS involvement typically demonstrates multiple small, discrete, hyper-intense lesions in the cerebral cortex, subcortical and deep white matter. Disseminated multifocal and confluent lesions in both cortex and white matter were also observed. CSF is abnormal in the majority of patients, showing lymphocytic pleocytosis and elevated protein.

16. Respiratory involvement occurs in up to 69% of cases, with the majority presenting with cough and dyspnoea. Chest X-ray changes of pneumonia and acute respiratory distress have been described.

17. Clinical management is supportive, and the respective specialists (neurologists, respiratory physicians, infectious diseases physicians, etc.) can be consulted according to clinical needs. Ribavirin has been used to treat NiV infections, but there are no rigorous studies on its actual efficacy. There are monoclonal antibody therapies that are currently under development and evaluation for treatment of NiV infections, and one monoclonal antibody from Australia, m102.4, has completed phase 1 clinical trials and has been used on a compassionate use basis. In addition, the antiviral treatment remdesivir has been effective in nonhuman primates when given as post-exposure prophylaxis, and may be complementary to immunotherapeutic treatments, although human data are lacking . Late remdesivir treatment (3 days post infection) has been reported to partially protect African green monkeys from lethal Nipah virus infection.The drug ribavirin was used to treat a small number of patients in the initial Malaysian NiV outbreak, but its efficacy in people is unclear. Confirmed cases can be transferred to NCID for further management at the discretion of the primary physician/hospital.
 

INFECTION PREVENTION AND CONTROL

18. Patients who are under investigation or confirmed to have NiV infection should ideally be isolated in an airborne infection isolation room (AIIR) and be placed on strict contact, droplet and airborne precautions – healthcare staff directly involved in patient care should don PPE1 comprising gowns, gloves, N95 masks and eye protection (face shield/ eye goggles) when attending to these patients. Risk to healthcare staff can be mitigated with good infection prevention and control practices. Visitors should not be allowed.
 

19. All waste generated during the care of NiV suspect and confirmed patients should be handled as biohazard waste, according to institutional policy.
 

20. Linen and laundry from suspects and confirmed cases should be managed as infectious linen and laundry. Institutions may consider the use of disposable linen.
 

21. Rooms occupied by suspect or confirmed cases of NiV should be terminally cleaned with bleach-based disinfectants after discharge. Enhancement of terminal cleaning with either UV-C disinfection system or hydrogen peroxide vaporization is recommended.
 

22. On the management of deceased bodies of suspect or confirmed cases of NiV, the handling of the body should be kept a minimum . The ward/hospital staff should ensure the following:
• All orifices must be plugged in with 10,000 ppm sodium hypochlorite.
• The body is double-bagged in sealed and leak-proof heavy-duty plastic cadaveric body bags, before the body is taken out of the isolation room.
• The surface of each body bag is wiped down with a suitable disinfectant (e.g. bleach), sealed and affixed with a ‘biohazard’ label.
• The body should not be sprayed, washed or embalmed.

MANAGEMENT OF CONTACTS
 

23. Caregivers to cases are at highest risk. Close contacts of persons with confirmed NiV infection should be advised to monitor for the development of fever for the duration of the incubation period (up to 45 days), and to seek medical attention early if this occurs. Healthcare staff who are close contacts (but protected with adequate PPE) should be monitored by their respective hospital
1 Personal protective equipment (PPE) posture will be reviewed from time to time as more data about the outbreak is available.
epidemiology units while community close contacts will be monitored by MOH and placed under quarantine, if necessary.
 

OTHER LABORATORY TESTING

24. For laboratory tests including non-microbiology tests which do not include virus propagation, specimens may be handled in a BSL-2 laboratory with additional precautions based on the laboratory's risk assessment. The laboratory should adhere to their standard procedures for handling samples potentially containing dangerous pathogens.

NOTIFICATION TO MOH

25. NiV infection is a notifiable disease under the Infectious Diseases Act (IDA). Any patient suspected of being infected with NiV infection should be reported immediately to MOH’s Communicable Diseases Group. Please call the Surveillance Duty Officer of the Communicable Diseases Group at 9817 1463 (available 24 hours), followed by submission of the MD131 Notification of Infectious Diseases Form through the Communicable Diseases Live & Enhanced Surveillance (CDLENS) system at http://www.cdlens.moh.gov.sg, or by fax to 6221-5528/5538/5567.
 

26. Please disseminate this alert to the relevant staff for their attention.

Prepared by:
Communicable Diseases Group
Ministry of Health, Singapore
National Centre for Infectious Diseases

BACKGROUND

1. Lassa Fever (LF) is an acute viral haemorrhagic fever (VHF) caused by the Lassa virus, which is known to be endemic in Benin, Ghana, Guinea, Liberia, Mali, Nigeria and Sierra Leone, but likely exists in other West African countries as well (Figure 1). Lassa virus is an arenavirus and its natural reservoir is the Mastomys natalensis multi-mammate rat (not native outside Africa) and contact with infected rodents or their excreta remains the key route of human infection.
 

2. Human-to-human transmission can occur through direct exposure to blood or other bodily fluids from an infected person. The incubation period of the disease ranges from 2 to 21 days (average 10 days). The overall case-fatality rate (CFR) for LF is around 1 to 2% in Africa but can reach up to 20% in severe hospitalised cases.
 

3. In the endemic countries, LF cases typically peak during the dry season from November to May. However, transmission also occurs all year round with sporadic cases being reported, but below epidemic thresholds. About 100,000-300,000 cases occur per year in West Africa, with an estimated 5,000 deaths/year. With continued circulation of the Lassa virus in endemic countries, sporadic exportation events to non-endemic countries have been reported. From 2010 to February 2022, a total of 12 cases of LF were imported into non-endemic countries by travellers from West Africa. The most recent cases were reported in the UK on 9 February 2022 involving an imported index case from Mali and two secondary cases within his household. Prior to these cases, two imported cases from Sierra Leone were reported by the Netherlands in November 2019. While no additional known cases of exportation have been reported since the cases in the UK, the occurrence of exported cases from endemic countries, which may increase during peak seasons, highlights the need for continued vigilance on the LF situation. Please refer to Annex A for an update on the current LF situation in the UK and West Africa.

Figure 1. Geographical distribution of LF in West African Affected Countries, 1969-2018
Source: WHO fact sheet on Lassa Fever (https://www.who.int/health-topics/lassa-fever#tab=tab_1

 

RISK ASSESSMENT
 

4. The risk of importation of a LF case into Singapore is considered very low due to the very low travel volume between the affected countries in West Africa and Singapore.

5. The likelihood of exposure to LF during travel may increase during seasonal flare-ups in affected countries, but largely limited to visitors to rural areas, where living conditions are basic and the likelihood of entering into contact with infected rodents or their excreta is high. This risk of infection can be significantly reduced if travellers are informed and aware of the risks, particularly in areas with ongoing transmission.

6. In the event of an importation, prompt recognition of suspected cases and meticulous infection control practices in healthcare institutions will mitigate the risks and prevent onward transmission.

PATIENTS TO IDENTIFY FOR INVESTIGATION

7. Infection is mild in 80% of cases (low grade fever, malaise, headache). In 20% of patients, more prominent symptoms and severe disease may develop. These include pharyngitis, respiratory and gastrointestinal symptoms, conjunctivitis, abdominal/chest/back pain, and in severe cases facial swelling, bleeding, shock, encephalitis, pulmonary oedema, multi-organ failure (See Annex B). Incubation period of the disease ranges from 2 to 21 days (average 10 days).

8. As the signs and symptoms for LF are varied and non-specific, doctors should be alert to any traveller from LF-affected regions with a febrile illness and should always ask for a travel history.

9. Some patients (~17% in the Nigerian outbreak of 2018) may recall a history of contact with rodents (including preparing rodents for cooking or consumption), rodent droppings or contact with person with suspected/confirmed LF.

10. All suspected cases meeting the case definition below should be identified for LF investigation:

Persons with fever and/or viral syndrome (e.g., headache, vomiting, fatigue or cough)
 

AND

Onset of symptoms within 21 days of
i. travel history to an endemic area (West Africa, mainly in Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, and Nigeria); OR
ii. travel history to an area with an ongoing LF outbreak, OR
iii. contact with a patient with suspect or confirmed LF.
11. Suspect cases should immediately be notified to the MOH Surveillance Duty Officer (See section ‘Notification to MOH’).

NOTIFICATION TO MOH

12. All suspected cases of LF should be reported to MOH immediately and instructions will be provided on further management of these cases. Please call the Surveillance Duty Officer of the Communicable Disease Division at 9817 1463, followed by submission of the MD131 Notification of Infectious Diseases Form through the Communicable Disease Live & Enhanced Surveillance (CDLENS) system at http://www.cdlens.moh.gov.sg/, or by fax to 6221 5528/38.

13. MOH will arrange for transfer of suspected cases to the National Centre for Infectious Diseases (NCID) on a case-by-case basis. All confirmed LF cases will be managed at the High-Level Isolation Unit (HLIU) in NCID.

DIAGNOSTIC TESTING

14. Diagnosis in acute infection is primarily by detection of Lassa Virus by PCR in blood specimens and/or virus isolation from throat swab or urine specimen. The level of viremia generally declines after the sixth day of illness, but in severe cases may persist till mortality.
 

15. Diagnostic tests should be performed only after discussion with the MOH Surveillance Duty Officer and the National Public Health Laboratory (NPHL). The following samples can be sent to NPHL for diagnosis of Lassa virus infection:
- Plain blood (3-5 mL in a purple EDTA top tube) for Lassa Virus PCR (together with Submission Form for VHF Testing, Annex C).
- In addition to blood sample, if the diagnostic suspicion is high, a throat swab in Universal Transport Media (UTM) and urine specimen should be submitted for PCR and virus isolation.
 

16. The hospital laboratory should contact NPHL for further assistance (see Annex C). There should be proper instruction and training in packaging before transport of sample between laboratories (see Annex D).

CLINICAL MANAGEMENT

17. The initial clinical manifestations of LF are non-specific and may be similar to other diseases such as the other VHFs, (e.g., Yellow Fever, Dengue, Ebola/Marburg virus), malaria, rickettsial infections, enteric fever (typhoid and paratyphoid fever) and influenza. Pending diagnostic evaluation for LF and other VHFs, and diagnostic evaluation for other similar illness, empiric treatment (e.g., for malaria, enteric fever, rickettsial disease) should be considered, according to local guidelines.

18. Patients with confirmed LF will be transferred for further management at the High-Level Isolation Unit (HLIU) in NCID. Treatment of LF is supportive care and with ribavirin. Consider early initiation of ribavirin for confirmed cases. Intravenous ribavirin is preferred over oral ribavirin, if available. Please refer to Annex E for dosing regimens.
 

19. Ribavirin is teratogenic and careful counselling about side effects and impact on conception plans for six months must be discussed with patients. Females of reproductive age should be screened for pregnancy prior to its use and should be advised to avoid pregnancy for six months after treatment with ribavirin. Pregnancy should be avoided for six months in women partners of males who are treated with ribavirin. Because of the high morbidity and mortality in pregnant patients with LF, ribavirin should be considered and may be used after careful counselling.

20. A checklist for the management of patients with LF is found in Annex F.
 

INFECTION CONTROL

21. Patients who are under investigation for LF, pending transfer to the HLIU in NCID, should be isolated in a single-bedded isolation room, and be placed on strict contact and respiratory precautions. There is no epidemiological evidence supporting airborne spread of the virus between humans, although blood and body fluids are considered highly infectious. The personal protective equipment (PPE) for healthcare workers is thus be aligned to that for preventing the transmission of Ebola virus disease (EVD).
 

22. All staff who come into direct contact with a suspect or confirmed LF case or their body fluids, including (but not limited to) healthcare workers, persons responsible for transporting patients (e.g., ambulance staff), and cleaners should wear enhanced PPE1 as for EVD, consisting of:
- Disposable fluid-resistant hood to cover the head and neck areas (staff with long hair may wish to use head cover prior to wearing hood);
- Eye protection gear (e.g., disposable downward face shields secured at forehead or goggles);
- Fluid-repellent N95 mask;
- Inner and outer disposable fluid-resistant (AAMI 4) gown (should extend to below knee);
- 12- inch double nitrile or latex gloves certified for healthcare use (extended cuffs should reach up to mid forearm); and
- Disposable fluid resistant boot covers (should extend up to knee-height).
 

23. Restrict the entry of non-essential staff to the patient’s room; visitors should not be allowed. Maintain a register of all staff who enter patient’s room.
 

24. Waste generated from suspect patients should be double bagged, sealed and disposed of by a licensed waste-contractor, as for waste for suspect EVD patients. Please refer to MOH Circular 35/2019, which contains detailed guidance on PPE use, waste management and the handling of dead bodies (with suspected or confirmed EVD).
 

25. Contacts of persons with LF or healthcare workers with unprotected exposure to an infected patient or their body fluids are at risk of acquiring disease. Such exposures include exposure of mucous membranes or broken skin to blood/body fluids (including respiratory secretions), without the proper PPE, or needle stick injury.
 

26. HCWs (including those with protected exposure) in contact with a confirmed case or their body fluids should be closely monitored (twice daily temperature monitoring) by their respective hospital epidemiology units for the duration of the incubation period of LF (i.e. 21 days) from the last known contact with the patient or their body fluids. In addition, HCWs with unprotected exposure before the case was isolated would be contact traced by MOH and appropriately followed up (e.g., quarantine). In the case of accidental exposure to the patient,

1 Enhanced PPE is designated for those with direct patient care/contact. Many hospital staff will thus not need to follow the enhanced PPE recommendation. In such cases, hospitals’ own protocol should be followed.

patient’s body fluids or a breach in technique occurs while removing contaminated PPE, exposed persons should immediately decontaminate themselves, report the exposure to their supervisor, seek advice from an ID physician and report the exposure to MOH.
 

27. Community close contacts will be contact traced by MOH and followed up for 21 days from the last known contact with the patient as appropriate (e.g., quarantine, phone surveillance or self-monitoring). Contacts may be referred to NCID for assessment and post-exposure prophylaxis with oral ribavirin.

OTHER LABORATORY TESTING
 

28. For laboratory tests including non-microbiology tests for persons under investigation for LF, which do not include virus propagation, specimens may be handled in a BSL-2 laboratory with additional precautions based on the laboratory’s risk assessment. Clinicians need to alert their respective laboratories and discuss prior to hand-dispatching of specimens (pneumatic tubes should not be used). The measures may include the following:
- The laboratory should have restricted personnel access and the specimens should be handled in an area segregated from the rest of the laboratory and can be decontaminated.
- PPE should include disposable gloves (double layers), particulate filter respirator mask with fluid shield protection, impermeable gowns and protective eye wear.
- Screw-capped buckets for centrifuges. Loading and unloading of samples should be carried out inside a Class II biosafety cabinet.
- Tests should be performed in a way that does not generate aerosols. Closed automated systems and instruments based on dry chemistry should be used.
- Class II biosafety cabinet must be used when there is a potential for generating aerosols.
- All work surface and equipment should be decontaminated appropriately.
- Staff involved in handling laboratory specimens must be kept to a minimum. Staff handling the tests should be trained and certified in the handling of high-risk pathogens, and competent.

Prepared by: Public Health Group National Centre for Infectious Diseases
Ministry of Health,
Singapore
Date: 26 March 2022 Version 2.0

 

ANNEX A

CURRENT SITUATION

1. On 9 February 2022, WHO was notified of three cases (including one death) of LF in the United Kingdom (UK). The index case had travel history to southern Mali near Guinea border prior to illness onset. The source of infection in Mali remains unknown. The second and third cases involved the wife and new-born of the index, respectively, both of whom had no travel history to Mali. At the time of reporting, the second case remained hospitalized while the third case deteriorated 10 days after birth and died on 10 February. As of 4 March 2022, UK authorities confirmed that the monitoring period for contacts in association with the three cases had ended with no further cases being identified. These were the first cases of LF reported from the UK since 2009 and represented the second known case of secondary LF transmission in Europe. A total of 11 cases of LF had been detected in the UK since 1980.
 

2. In Nigeria, LF outbreaks of various magnitude had been reported almost every year since the discovery of Lassa virus in 1969. Of concern, the country reportedly experienced an upsurge of LF cases in year 2022. Between January 2022 and 13 March 2022, a total of 630 confirmed cases including 112 deaths (CFR: 17.8%) had been reported from 23 of 36 states across Nigeria. In contrast, the number of LF cases were reported during the same period in 2021 was lower [191 confirmed cases, including 42 deaths (CFR: 22%)] and more limited in geographical distribution (from 12 states). Based on the latest risk assessment from WHO dated 4 February 2022, the risk of LF in Nigeria was assessed to be high due to an increase in the number of cases compared to previous epidemic seasons, gaps in surveillance and response capacity, as well as suboptimal infection prevention and control procedures.
 

3. No cases had been formally documented in Benin, Ghana, Guinea, Liberia, Mali and Sierra Leone in the recent months, although this was likely due to lack of surveillance and under-reporting of LF in these countries. Given their endemicity, the occurrence of cases, especially during the epidemic season (from November to April) is expected.
 

4. In addition, isolated cases, periodic isolation of LF virus, or serological evidence of LF virus circulation had have also been reported previously in Cote d’Ivoire, Burkina Faso and Togo.

ANNEX B

Clinical Features and Clinical Management of Lassa Fever

1. Symptoms and Signs of Lassa Fever
Day of Illnesses Signs/Symptoms
1-3

General weakness, malaise, chills, fever
4-7

Sore throat with or without oral ulcerations, headache (frontal > occipital), chest pain, back pain, joint pain, nausea, vomiting, diarrhoea, cough, proteinuria.

After 7 days
Severe abdominal pain, intractable vomiting, conjunctiva oedema and injection, facial and neck edema, cervical lymphadenopathy, tinnitus, maculopapular rash, haemorrhage, deafness (1/3 of cases, not severity dependent), pulmonary oedema

Most common signs/symptoms (all cases)
Sign/symptom %
Fever
96%
Headache
59%
Abdominal pain, Vomiting, Fatigue
40-49%
Cough, Sore throat, Chest pain, Anorexia, Diarrhoea
21-33%
Myalgia, Arthralgia, Haemorrhage, Dyspnoea
15-19%
Disorientation, Conjunctivitis, Photophobia, Rash, Jaundice, Hiccups
2-5%
2. Laboratory Findings
 Lymphopenia (maximally depressed at 11 days after illness onset)
 Thrombocytopenia and platelet dysfunction
 Proteinuria
 Elevated liver enzymes (AST > ALT)
 Usually normal PT and APTT, even in patients who develop bleeding
 Renal dysfunction (elevated urea, creatinine)
3. Disease Progression in Survivors versus Non-survivors
Survivors Non-survivors
Fevers resolve with occasional spikes in temperature
Develop hypotension, shock, agitation, lethargy/obtundation
Mean duration of illness 14 days (range: 11-21 days)
Mean duration of illness 12 days (range: 12-15 days)
*Mortality rate: 15-20% of hospitalised patients, ~1% overall (all cases)
 

4. Pregnancy and LF
- High maternal / foetal mortality
- Higher levels of viremia in pregnancy, virus also present in placental tissue
- Vertical transmission (mother to child) has been documented
- May lead to spontaneous abortion
- Risk of death highest in 3rd trimester (30%) (1st Trimester 18%, 2nd Trimester 5%; overall in pregnancy 21%)
- Evacuation of uterus (by spontaneous abortion, evacuation of retained products of conception or normal delivery) has been shown to improve mother’s chance of survival (10% vs 38% mortality, P= 0.0016)
- Overall foetal death is estimated to be 92% (1st/2nd trimester) and 75% (3rd Trimester)
 

5. Paediatric patients and LF
- Similar presentation as adults, except sore throat and pharyngitis less frequently reported (27% vs 70%)
- Overall case fatality rate 12%
- The “swollen baby syndrome” (anasarca with normal creatinine and albumin, abdominal distension, bleeding) is a distinctive presentation and highly diagnostic of LF in children. It is seen in the neonatal period, infancy and childhood, and has a poor prognosis
 

References:
1. “Lassa Fever: Epidemiology and Clinical Presentation information for healthcare workers” , Dr Aaron Kofman, US CDC, Viral Special Pathogens Branch
2. Iiori EA et al, Epidemiologic and Clinical Features of LF Outbreak in Nigeria January 1- May 6, 2018; Emerging Infectious Diseases, Volume 25, No. 6, June 2019