Postgraduate Seminar by

Dr. D.C Briggs

LASSA FEVER

OUTLINE

• Introduction

• Overview of epidemiology and virus characteristics

• Recent Lassa Fever Outbreaks in Nigeria

• Pathogenesis

• Clinical Features and Case Management of Lassa Fever

• SOP for managing Lassa Fever in UPTH

• Prevention

• The Nigerian response so far

• Conclusion

Introduction

•Viral Haemorrhagic Fevers (VHF) are a clinical syndrome characterized by fever, bleeding tendency and shock.

•VHFs are endemic in parts of Africa, South America, the Middle East and Eastern Europe.

Introduction continued

VHFs are of particular public health importance because they:• Spread within a hospital setting

• Have a high case-fatality rate

• Are difficult to recognize and detect rapidly

• Have no effective treatment

• Have a potential usage for bioterrorism

• Drain the healthcare system following an outbreak

Introduction continued

• Lassa fever is an acute viral hemorrhagic fever caused by the Lassa virus.

• Lassa virus has an unusual potential for human-to-human spread and has resulted in many small epidemics in Nigeria, Sierra Leone, and Liberia.

• Medical workers in Africa and the United States have also contracted the disease.

• Patients with acute Lassa fever have been transported by international aircraft, necessitating extensive surveillance among passengers and crews.

Introduction condition

• Environmental conditions in Nigeria support the natural reservoirs of Lassa fever virus and cases of person to person transmission is presently been reported.

Overview of Epidemiology & Characteristics of virus.

Lassa Fever Virus

Pictures taken from Google images on free access online web pages.

Overview of the epidemiology of Lassa Fever

Disease Genus, Family Reservoir Vector Distribution Clinical cases/year

Lethality

Lassa Fever Arenavirus Rodent(lives in a persistent asymptomatic state)

Rodent West Africa 300,000 2 – 20%

VHF ofImportance

Virus Characteristics Vector Infectivity period

Mode of Transmission

Lassa fever virus

Enveloped , round, pleomorphic virus50-300nm(diameter)SS genome with 2RNA segments

Mastomysnatalensis

Urine: up to 32 daysSemen: 3 months

Contact with rodent and their excreta; aerosolized,ingested

Virus Characteristics

Transmission of Lassa FeverRodent –to – human transmission Human –to – human transmission

Inhalation of aerosolized virus Direct contact with blood, tissues, secretions or excretions of infected humans

Ingestion of food or materials contaminated by infected rodent excreta

Needle stick or cut

Catching and preparing Mastomys as a food source

Inhalation of aerosolized virus

Mastomys natalensis

• Reservoir of the Lassa virus

• Has a chain of breasts made up of 10 – 12 nipples

• Tails longer than the body

Epidemiology – Lassa Fever

• Discovered in Nigeria, 1969

• Endemic in parts of West Africa; Liberia, Nigeria, Sierra Leone and Guinea.

• Seasonal clustering: late rainy season and early dry season

• Affects all age groups

• Overall mortality is estimated to be about 1% but is around 15-20% for hospitalized patients.

• However, during epidemics, mortality may be up to 50%.

Epidemiology – Lassa fever

• Lassa virus also causes high foetal mortality and high mortality in pregnant women. • The mortality rate is 92% for foetuses in early pregnancy

• 75% for foetuses in the third trimester

• 100% in the neonatal period for full-term babies

• The mortality rate for gravid women is 7% in the first two trimesters, 30% in the last trimester, and 50% for pregnant women who delivered within one month.

Epidemiology

• The Lassa virus is transmitted to humans via at least 2 vector species; M. huberti and M. erythroleucus. (State Deparment, 2003).

• These rodents reproduce at very high rates and like to live in very close proximity to humans, especially where food is kept.

• There are 4 strains: Josiah (the most studied strain from Sierra Leone), Nigeria, LP and AV.

Recent Outbreaks of Lassa Fever in Nigeria

Outbreak - Lassa fever in Nigeria

• First outbreak 1969 , 2 Nuns died in Bornu state.

• In March 2012 , the Fed MOH notified WHO – LF Outbreak. 623 suspected cases, including 70 deaths (CFR 11.2%) involving 19 of the 36 States.

• 108 had been laboratory confirmed.

• 3 doctors and 4 nurses were reported to be among the fatalities.

Edo,ondo,Oyo,Lagos,Anambra,Ebonyi,Abia,Rivers,Taraba,Nasarawa, Kaduna, Kano, Adamawa, Yobe, Borno, FCT, Plateau, Gombe

Outbreak – Lassa fever

• In 2013: 1195/39 CFR: 3.26%

• In 2014: 989/36 CFR: 3.64%

• As of 16/01/2015 : 6 cases, no deaths

• Most recent outbreak started December 2015 till date.

Spot map showing cases of Lassa fever by state and LGA from Week 35 2015 – Week 2 2016

LASSA FEVER OUTBREAK IN NIGERIA Daily Situation Report No. 11: 19 January, 2016 Nigeria Centre for Disease Control (NCDC)

Lassa fever in Children

• 2.9-10% of admissions in Liberia.

• ? 3% of admissions in Nigeria.

• 20% of children in a village with an epidemic were sero-positive although none was ill.

• Akpede et al. (2012) reported 5 cases of Lassa fever in children who presented at the hospital.

Pathogenesis of Lassa Fever

• Although different pathophysiologic processes occur in different VHFs, the following are common:

1. Vascular damage

2. Disorders of coagulation

3. Immunological impairment

4. End organ damage

Pathogenesis of Lassa Fever

Clinical Features & Management of Lassa Fever

Clinical Features

• A spectrum from asymptomatic (80%) to severe disease, characterized by loss of plasma from small vessels (capillary leakage) and bleeding.

• Liver involvement is common, including jaundice.

• Clinically, these infections can be confused with other causes of febrile illness and a high index of suspicion is needful.

Symptoms of Lassa Fever• Incubation Period

• Lassa Fever 10 (3 – 21) days

• Common symptoms: • Fever, malaise, fatigue and body aches.

• Nausea; vomiting; diarrhoea; headache

• Diarrhoea; productive cough; proteinuria; low BP anaemia.

• Facial edema; convulsions; mucosal bleeding (mouth, nose, eyes);

• internal bleeding; confusion; disorientation; coma and death.

Case Definition for a suspected Lassa Fever

• Fever >380C for < 3weeks AND

• Absence of signs of local inflammation (ie. the sickness is systemic) AND

• Absence of a clinical response after 48hr of anti-malaria treatment &/OR a broad spectrum antibiotic AND

• Two major or one major and two minor signs described below:

Case definition for suspected case continued

MAJOR SIGNS

• Bleeding

• Swollen neck or face

• Conjunctivitis or subconjunctival haemorrhage

• Spontaneous abortion

• Petechial or haemorrhagic rash

• New onset tinnitus or altered hearing

• Persistent hypotension

• Raised transaminases esp. AST>ALT

• Known exposure to a Lassa fever case

MINOR SIGNS• Headache

• Sore throat

• Vomiting

• Diffuse abdominal pain/ tenderness

• Chest/ retrosternal pain

• Cough

• Diarrhea

• Generalized myalgia or arthralgia

• Profuse weakness

• Proteinuria

• Leucopenia < 4000/L

Clinical Stages of severe Lassa Fever (adapted from McCarthy 2002)

STAGE SYMPTOMS

1(days 1-3)

General weakness and malaise.High fever, >39OC, constant with peaks of 40-41oC

2(days 4-7)

Sore throat (with exudative patches) very commonHeadache , back, chest, side or abdominal painConjunctivitisNausea and vomitingDiarrhea Productive coughProteinuriaLow blood pressure (systolic <100 mmHg)Anaemia

3(after 7 days)

Oedema of the face and neckConvulsionsMucosal bleeding (mouth, nose, eyes)Internal bleedingEncephalopathy with confusion or disorientation

4(after 14 days)

ComaDeath

LSHTM Jan- Feb 2015 online course materials on Ebola in context: understanding transmission, response and control.

Differential Diagnoses• Severe Malaria

• Typhoid fever

• Shigellosis

• Leptospirosis

• Rickettsial diseases

• Viral hepatitis

• Cholera

• Meningococcaemia and Gram negative sepsis

• Other VHFs (Ebola/ Marburg , Rift Valley Fever, Chikungunya, O’nyong-nyong, WNV, Zika)

Complications of Lassa Fever• Deafness (1/3 of cases), permanent

• Spontaneous abortion

• Hypovolemic shock

• Respiratory distress resulting from airway obstruction, pleural effusion, or congestive heart failure may occur.

• 10–20% of patients experience late neurologic involvement characterized by intention tremor of the tongue and associated speech abnormalities. In severe cases, there may be intention tremors of the extremities, seizures, and delirium. The cerebrospinal fluid is normal.

• Anuria

• Death

Laboratory investigations• CBC:-mild Leucopaenia and Lymphopaenia / Mild thrombocytopaenia

• Urinalysis: Proteinuria

• Serum: High BUN

• High liver transaminases (AST>150 U/L)

• Definitive Tests:• IgM ELISA, IgG ** (** occurs late)• Lassa Virus Antigen• RT-PCR (3

rdday)

• Viral culture (7- 10 days)• Post mortem – Immunohistochemistry on tissue specimens

Case Management of Lassa Fever

• Isolation

• Infection control – barrier nursing

• Ribavirin : shown to reduce mortality 5-10 fold if given intravenously within 6 days of the clinical illness.

• Loading dose: IV 30mg/kg (max. 2g), followed by 15mg/kg 6hrly for 4 days (max. 1g), then 7.5mg/kg (max. 500mg) 8 hrly for 6 days

• Dilute Ribavirin in 150mls of 0.9%NS and infuse slowly.

• no convincing evidence that oral rivabirin delays or prevents Lassa fever

SOP in UPTH for Managing Lassa Fever

SOP in UPTH for Management of Lassa Fever

If Healthcare staff sees any patient with features that meet the case definition for suspected Lassa Fever in UPTH, the worker should do the following:

Ensure use of Personal Protective Equipment (PPE)

Use the diagnostic criteria to ascertain the patient meets the case definition

If patient meets the case definition, Notify the CMAC and the Infection Control VHF Team, send the patient to Isolation Unit in A&E;

SOP in UPTH for Management of Lassa Fever

Collect a blood specimen ensuring adequate infection control precaution for VHF Testing and case confirmation in EDTA Bottle (4mls);

Test for Malaria, Widal, FBC, E/U/Cr and LFT;

Set up intravenous line with Normal Saline;

Recommend Oral Rehydration solution;

SOP in UPTH for Management of Lassa Fever

Treat for malaria;

Commence broad spectrum antibiotics – ceftriaxone 1gm daily and Metronidazole 500mg 8 hourly;

If patient meets case definition for suspected VHF Lassa also commence IV Ribavirin loading dose in line with outlined Protocol for Ribavirin; and

Review management further based on screening results.

Lassa Fever Isolation Ward – Management Guidelines

• Strict barrier nursing with PPE

• Set up IV line

• Collect 10mls of whole blood from all patients into EDTA Bottle

• IV Fluids

• Analgesics

• Monitor vital signs

• If fever + conjunctivitis + petechial stat Ribavirin until test result is out.

• No visitors into the ward

• Obey strict movement guidelines in ISW

• Record all contacts

PPE – All Close Contacts

• Wear protective clothing always

• Wear mask and gloves always

• Stat prophylaxis with Ribavirin (400mg bd for 10days)

• All clothing used must be treated with 10% Bleach (Sodium hypo chloride)

• Monitor temperature for 21 days, if > 380C, Report immediately for blood test and prophylaxis.

Flow chat for reporting VHF outbreaks in Rivers state

Donning and Doffing a Personal Protective Equipment

• Training of all health care workers in the use of PPE is vital.

• CDC recommends facilities use a powered air-purifying respirator (PAPR) or an N95 or higher respirator in the event of an unexpected aerosol generating procedure.

Recommended PPE

• PAPR or N95 Respirator

• Fluid resistant or impermeable gown that extends to at least mid calf or coverall without integrated hood

• Nitrile examination gloves with extended cuffs (2 pairs)

• Fluid resistant or impermeable boot covers that extend to at least mid calf or shoe covers

• Fluid resistant or impermeable apron that cover torso to level of mid-calf

• Face shield/ eye goggles/ surgical hood

Donning

• Remove personal clothing and items

• Inspect PPE prior to Donning

• Perform Hand hygiene

• Put on inner gloves

• Put on boot or shoe covers

• Put on gown or coverall

• Put on outer gloves

• Put on respirator**

• Put on outer apron (if used)

• Disinfect outer gloves

• Verify***

Doffing• Inspect for visible contamination

• Disinfect outer gloves

• Remove apron

• Inspect PPE for stains, cuts, tears

• Disinfect outer gloves

• Remove boot or shoe cover

• Disinfect and remove outer gloves

• Inspect & disinfect inner gloves

• Remove respirator/ face shield

• Disinfect inner gloves

• Remove surgical hood

• Disinfect inner gloves

• Remove gown or coverall

• Disinfect inner gloves

• Disinfect washable shoes

• Disinfect & remove inner gloves

• Perform hand hygiene

• Inspect

• showers and Scrub

** put on N95 respirator and surgical hood over it before apron and then outer gloves and lastly face shield*** integrity of ensemble is verified by a trained observer

Prevention of Lassa Fever

General Health Promotion

• Clean environment

• Good health seeking behavior

• Proper Hand Washing

• Health education via media, pamphlets, religious & social gatherings, etc

• Proper nutrition

Specific Health Protection

• Fumigation – Rodents

• Proper storage of farm produce

• Avoidance of Bush burning practices

• Putting food away in rodent-proof containers

• Barriers preventing rodents from entering into houses

• Routinely clean and disinfect commonly touched surfaces like bathroom surfaces, since some germs can stay infectious for hours or days and lead to transmission.

• Early self referral

Specific Health Protection

•Regular hand washing with soap & water,

hand sanitizers

•Avoid contact with body fluid/secretions of infected or

dead persons

•Proper cooking/ avoidance of bush meat

•Report any suspected case to local authorities

Specific Health Protection

• Proper disposal of sharps & clothing of sick individuals (Incineration)

• Proper burial of corpse.

• Enact border laws to curb spread

• Avoid attending or hosting public gatherings/events unless strictly

indicated (in case of an outbreak).

Specific Health Protection

• Condom distribution for survivors

• Oral ribavirin for high risk / close contacts

• Training of health care staff

• Enhancement of disease surveillance

Specific Health Protection

• Avoid blood donation

• Standard precautions – (PPE – mask, gloves, gowns, goggles)and Infection control measures – complete equipment sterilization and isolating infected persons

• Barrier nursing

-Use of personal protective equipment (PPE)

-Infection control measures such as handwashing, handling and disposal

of sharps, reprocessing of reusable equipment and instruments, cough

etiquette, aseptic technique, waste management and handling of linen.

Transmission- based precautions• Includes any or a combination of the following:

• Allocating a single room with closing door to patient with a suspected or confirmed infection (isolation)

• Placing patients colonized or infected with the same infectious agent and antibiogram in a room together (cohorting)

• Wearing a specific PPE

• Providing patient-dedicated equipment

• Using disinfectants with label claims specifying its effectiveness against specific infectious organisms.

• Using specific air-handling techniques

• Restricting movement both of patients and healthcare workers.

Early Diagnosis & Prompt Treatment• High index of suspicion

• Prompt dissemination of case definition

• Screening/ triaging / risk assessment

• Isolate/Quarantine

Early diagnosis & Prompt treatment

• Readily available & accessible diagnostic

• Provision of ribavirin

Early Diagnosis & prompt Treatment

• Prompt resuscitation & Supportive treatment: correct fluid &

electrolyte deficit, blood or blood component transfusion, antipyretics,

analgesics, intranasal oxygen, ECG monitoring.

• Treat intercurrent illnesses

Limitation of disability

• Hearing aids

• Dialysis

Rehabilitation

• Psychotherapy

• Assisted Reproductive Techniques

• Organ transplant

Rehabilitation

• Issuance of medical certificate of fitness

• Re-integration into the community

• Employment

• Physiotherapy for disuse atrophy

The Nigerian Response so far

The Nigerian Response so far:

• Coordination• NCDC/FMOH is taking leadership for coordination supported by partners

• Daily review meeting at the EOC

• Technical guidance is being provided to states based on available capacities (coordination, surveillance, case management and IPC) within states

• Production of daily Situation report

The Nigerian Response so far

• Case Management and Infection Prevention and Control • 71,000 tabs of Ribavirin, 20,750 vials of parenteral Ribavirin and 960 pieces of

PPE distributed to the affected states as of today.

• Isolation centers have been identified in most states

• NCDC/Niger state team supervised the safe burial of a suspected case today

• Surveillance• Continuing outbreak investigation in the affected states

• Nationwide alert to SMOH on current situation and need for preparedness

• Contact tracing ongoing in affected states

• Clinician sensitization ongoing in affected states

The Nigerian Response so far

• Laboratory • 5 National laboratories with PCR capability are currently conducting analysis

of samples

• 101 samples analyzed and 42 tested positive for Lassa fever, other VHFs were negative

• Some laboratory results are currently awaited.

The Nigerian Response so far

• Communication and Social Mobilization• Training for NCDC call centre operators conducted today

• Radio and television jingles are ongoing in the states

• Lassa fever information website ( www.lassaalert.org ) linked to the NCDC website has been developed and has gone live.

• Community health education ongoing

• Challenges• Coordination of laboratory network leading to delay in sending laboratory

results

• Logistics support for contact tracing in the states Logistics for sample transportation for prompt laboratory diagnosis

The Nigerian Response so far

• Next steps • Reinforce active surveillance, contract tracing and continue outbreak

investigation

• Continue clinician sensitization to ensure early detection and reporting

• Continue health education and community sensitization

• Capacity building at state level for coordination, surveillance, case management and IPC, communication and social mobilization

• Coordinate laboratory network for prompt release of documented results.

CONCLUSION• Lassa Fever is still present in our Country Nigeria.

• Diagnosis requires a high index of suspicion for every patient presenting with a fever.

• Travel history to neighboring states still plagued by a Lassa Fever and history of contact is pertinent.

• Treatment is mostly symptomatic.

• Prevention is KEY!

• NEVER LET DOWN YOUR GUARD.!!!!

References

• Akpede GO, Kayode-Adedeji BO, Dawodu SO(2012) Manifestations and outcomes of lassa fever in Nigerian children: a case series. Arch Dis Child 2012;97:A38-A39 doi:10.1136/archdischild-2012-301885.96

• Deborah UE, Danny AA, Jacqueline E, Peter OO et. Al (2012). Hospital based surveillance for lassa fever in Edo state, Nigeria, 2005 – 2008. Tropical Medicine and International health J. 2012; 17(8):1001-1004

• Nigeria Centre for disease control (NCDC). FMoH, Summary Table (IDSR weekly report as at 16/01/2015).http://www.health.gov.ng/doc/EpidRpt_Wk_2 2015.pdf.accessed on 27/3/15.

• Durham, Jerry D. and Felissa R. Lashley. Emerging Infectious Diseases-Trends and Issues. Springer Publishing Company. (2002)

References

• LASSA FEVER OUTBREAK IN NIGERIA Daily Situation Report No. 11: 19 January, 2016 Nigeria Centre for Disease Control (NCDC). http://reliefweb.int/sites/reliefweb.int/files/resources/Lassa11.pdf

• LSHTM Jan- Feb 2015 online course materials on Ebola in context: understanding transmission, response and control.

• Centers for Disease Control. Lassa Fever. Fact sheet. http://www.cdc.gov/vhf/lassa/pdf/factsheet.pdf

• WHO (2010).Technical guidelines for Integrated Disease Surveillance and Response in the African Region 2nd edition. http://www.cdc.gov/globalhealth/dphswd/idsr/pdf/Technical%20Guidelines/IDSR%20Technical%20Guidelines%202nd%20Edition_2010_English.pdfaccessed on 28/3/2015.