LASSA FEVER

Lassa fever

Background

Lassa Fever is a viral hemorrhagic fever (VHF) illness caused by the arenavirus Lassa. It was first discovered in the village Lassa in Nigeria in 1969.

It is endemic in areas of West Africa. Sierra Leone, Liberia and Guinea are the most affected, but the disease is also found in Burkina Faso, Côte d´Ivoire, Gambia, Ghana, Mali, Nigeria, Central African Republic and Senegal. There are estimated 300,000-500,000 infections per year with estimated 5,000 deaths per year.

Lassa fever affects all age groups and has seasonal clustering in the late rainy and early dry season. The peak incidence of cases is during the months of January to May.

Lassa Fever has been endemic in eastern Sierra Leone since first diagnosed in 1971 as part of an epidemic originating in Panguma. The area of endemicity is defined as the triangle between Kailahun, Tongo and Kenema (also called "Lassa Belt"). The highest infection rates are seen in the region immediately north of Kenema district in the mining towns of Segbwema, Panguma and Tongo.

An outbreak of Lassa Fever was first declared in 1996 when 470 cases with 110 deaths were reported (case fatality rate 23%) for Kenema district. Since then Lassa cases were continuously reported.

Since 1996 a specialised Lassa Ward has been established in the compound of the Kenema Government Hospital. The ward has been supported by an NGO, Merlin, who still is the main partner to MoHS (Ministry of Health and Sanitation) in the Lassa Ward.

At 14 September 2004 a sub regional strategic plan for Lassa Fever 2004-2008 was adopted and a MOU signed by the ministers of health of Liberia, Guinea and Sierra Leone. This plan includes collaboration in the fields of patient management, laboratory, surveillance, information-education-communication, environmental control, Training § Supervision, Monitoring § Evaluation and Operational Research.

The lassa virus is chronically carried by a particular rat, the "multimammate rat" (Mastomys species complex). The rat community serves as the "reservoir" for the disease. Occasionally there are outbreaks within the health sector (nosocomial).

The rat lives close to the houses, in the fields and cleared forest. The rat is a prolific breeder and has about 8-12 pups per litter. The rat is infected at birth and does not get ill but becomes a chronic asymptomatic carrier of the Lassa virus. The virus is shed in the urine and the faeces. 

Modes of transmission of Lassa virus

a. Rat to human

            -Food or drinking water contaminated with rat urine or faeces

            -Direct contact with rat (bite or consumption of rat)

            -Direct contact with droplets of containing virus above rat urine or faeces (aerosol)

b. Human to human

-Contact with blood or body fluids

o    Household transmission (open wound, unprotected sexual contact)

o    Nosocomial (in the health sector)

Community Control

a. rat trapping

b. minimizing human-rat contact

c. Good Village Hygiene : disposal of garbage; appropriate storage of food; avoid rodents as a food     source, keep cats and do not have close contact with household members with compatible febrile illnesses.

No Lassa vaccine currently available

 

Clinical presentation

Incubation period: 5-21 days

STAGE I           Day 1-3

Ø  Flu-like symptoms: malaise,  weakness

Ø  Fever > 38 º C with constant peaks of 40-41 º C

STAGE II           Day 4-7

Ø  Headache

Ø  Back / chest / side / abdominal pain

Ø  Red eyes

Ø  Sore throat, very common

Ø  Nausea / vomiting / diarrhoea

Ø  Anaemia

Ø  Protein in the urine

Ø  Low blood pressure

Ø  Sometimes swelling  of the lymph nodes

Ø  Sometimes productive cough

STAGE III          Day 7-14

Ø  Facial oedema

Ø  Convulsions

Ø  Mucosal bleeding : mouth, nose, eyes

Ø  Spontaneous abortion following fever

Ø  Internal bleeding

Ø  Sometimes tinnitus, dizziness

Ø  Sometimes maculopapular rash

(Bleeding only in 15-20 % of cases)

STAGE IV         Day 14 <

Ø  Difficult breathing

Ø  Coma

Ø  Death

Evolution

Ø  Patients die from combination of increased capillary permeability, cardiac suppression and coagulopathy leading to a low effective circulating volume leading to shock, NOT loss of blood

Ø  Particularly severe in pregnant women and their fetuses (fetal death rate > 95%)

Deafness a common complication, up to 1/3 cases

Case fatality rate:          1-50%

20-25% of hospitalised cases, ( Lassa ward in Kenema)

How to deal with contacts of patients?

a.   Casual contacts

o    Same office, room, hotel, etc. but with no physical contact

o    Physical contact before or after acute phase of illness (except unprotected sexual contact)

o    No surveillance needed ( use of condom for 21 days)

b.   Close contacts

o    Physical contact with patient and/or body fluids during the symptomatic phase of the illness

o    Follow patient daily for fever and other signs of illness for 21 days after the last exposure. Isolate immediate if ill

c.   High risk contacts

o    Needle stick, exposure to body fluids, sexual contact

o    Consider post-exposure ribavirin

Case definitions used in Sierra Leone

MOHS/WHO Surveillance definition for Lassa fever:

Unexplained fever > 38 degrees Celsius with no response to standard treatment for most likely causes of fever (e.g. malaria, typhoid fever) within 72 hours.

and any one of the following:

Ø  Swollen neck or face

Ø  Abnormal bleeding (from mouth, nose, vagina, haematemesis)

Ø  Retrosternal pain

Ø  Sore throat

Ø  Spontaneous abortion following fever

Ø  Hearing loss during a febrile illness

Ø  Conjunctivitis or subconjunctival haemorrhage

Ø  Known exposure to a confirmed case of Lassa fever

This case definition is valid for people living in; or having travelled in the past six to twenty-one days to the endemic zone; and is the field definition for places with minimal health care or laboratory facilities e.g. PHUs.

A decision to refer must be made as soon as possible as Ribavirin is most useful if started in the first 6 days of illness.

MOHS/WHO Case Definition for Lassa fever at Referral Hospital Level:

A patient with fever > 38 degrees Celsius not responding to effective antimalarial and broad spectrum antibiotics within 2 hours, with no obvious localizing signs of infection and at least two major or one major and at least two minor criteria. This patient must either be living in, or travelled to the endemic zone in the past six to twenty-one days.

This definition is for a conventional referral hospital setting with adequate laboratory and diagnostic facilities.

Major criteria

Ø  Abnormal bleeding (including mouth, nose, haematemesis, or from the vagina)

Ø  Swollen neck or face

Ø  Conjunctivitis or subconjunctival haemorrhage

Ø  Spontaneous abortion

Ø  Unexplained tinnitus or altered hearing during a febrile illness

Ø  Persistent low systolic blood pressure

Ø  Known exposure to a confirmed Lassa patient or readmitted within three weeks of inpatient care for illness with fever

Ø  Markedly elevated SGOT/AST

Minor criteria

Ø  Headache

Ø  Sore throat

Ø  Persistent vomiting

Ø  Diffuse abdominal pain/tenderness

Ø  Retrosternal pain

Ø  Diarrhoea

Ø  Generalized myalgia and arthralgia

Ø  Profuse weakness

Ø  Proteinuria

Ø  WBC count < 4000 mL

Laboratory investigations

Common laboratory findings:

o    Early Low White Blood Cell count (phase I-II), later High WBC count

o    Mild-to-moderate low trombocytes (platelets)

o    Elevated Liver enzymes (AST>ALT, also have prognostic value)

 

Blood sampling for ELISA and PCR

Ø  Blood sample should be taken before starting the treatment

Ø  Wear protective gear (gloves, glasses, mask and gown) all this are available in Gondama Referral Centre (VHF protection kit in Emergency room and Pharmacy).

Ø  BE CAREFUL, avoid contamination and insure closed system before handing over the sample.

Ø  The tube should be sent without separating the serum.

Ø  The tube should be filled so there is no empty space.

Ø  Transport: preferably cold chain. Avoid temperature changes. Label the tube. Transport the tube in a safety container. ( see details in "specimen handling guidelines"). Containers should be available in the Protection Kit.

Ø  The tubes should be sent to the Lassa laboratory in Nzerekore in Guinee and Germany, if nothing else is instructed by MEDCO Sierra Leone / MEDCO Cell 3 Brussels. Keep one sample in Sierra Leone until result of tests have come back.

(The Lassa ward in Kenema  have been doing a car kiss with the Lassa laboratory in Nzerekore in Guinee. A Lassa laboratory is under construction in Kenema)

Treatment of patient with Lassa Fever

The decision to start treatment should be done by a medical doctor in collaboration with the Lassa specialist in Kenema  after discussion with the MEDCO Sierra Leone / Cell 3 Brussels (but don´t delay the treatment). Efficacy of Ribavirin is high as long as it is started within the first 6 days of illness.

Hospitalization for treatment

a.   The staff should be admitted in a temporary isolation unit in Gondama Referral Centre. One of   the offices will be changed into an isolation room.

b.   Barrier nursing and droplet precautions should be taken (gloves, gowns, masks, glasses) . Realize patients are generally infectious only while symptomatic, and only by direct contact with blood or body fluids

c.   Close observation with hourly monitoring should be done if needed.

d.   The MD and one international nurse should follow the patient and be the only ones in contact with the patient before repatriation. The staff in contact with the patient should take oral Ribavirin prophylaxis, if he/she gets into direct contact with blood or body fluids from the patient.

e.   The room, and all items (linen, cups, spoon, medical instruments etc.) should be disinfected with chlorine, following the WHO/CDC guidelines for Viral Hemorrhagic Fevers.

f.    Supportive treatment should be given : fluid replacement, control of fever, control of convulsions, control of bleeding. Blood should be made available if needed. Aspirin and IM injections should be avoided to prevent any additional bleeding.

o    Intensive care unit if possible

o    Limit movement of patient

o    Fluid and electrolyte balance, supplemental O2,

o    Consider capillary leak and risk of pulmonary edema when rehydrating

Steroids not indicated

VHF (viral hemorrhagic fever) protection kits are available in Gondama Referral Centre (emergency room and pharmacy) and Bo pharmacy

Ribaverin

Ribavirin: 1200 mg / vial             (available in the office in Bo, Field Co office)

Contraindications                      (unless life saving)

1. Pregnancy
2. Severe cardiac disease
3. Sever debilitating medical conditions
4. Hepatic dysfunction
5. renal failure
6. Uncontrolled thyroid disease
7. History of sever psychiatric disease
8. Severe anemia

Side effect of Ribaverin therapy

1. Reversible haemolytic anemia
2. Irritability, anxiety, depression
3. Headache, dizziness
4. Myalgia, athralgia, paraesthesia
5. Dry skin, rash
6. Leucopenia, thrombocytopenia, hyperuricaemia
7. Blurred vision, taste disturbance
8. Aggravation of existing thyroid disorder

IV treatment procedure

Ø  Ribavirin should be diluted with Dextrose 5% or NaCl 0.9%.

Ø  Time of infusion should be at least 10-15 minutes (20 cc syringe and needle ID 26G in the IV set could be used). No specific requirement for the volume of dilution, whatever volume facilitates the 10-15 minutes of giving can be used.

Ø  Major side-effect is a reversible, most-often mild anemia

Ø  Technically contra-indicated in pregnant women, but may still merit consideration given high maternal and fetal death rates associated with LF

Dosage IV Ribavirin- total 10 days

Loading dose of           30 mg/kg

6 hours later                  15 mg/kg every 6 hours for 4 days         (16 doses)

8 hours later                  7.5 mg/kg every 8 hours for 6 days        (18 doses)

example

Day 1                           Hrs 0    Loading dose, 30 mg/kg

                                    Hrs 6    15 mg/kg

                                    Hrs 12   15 mg/kg

                        Hrs 18   15 mg/kg

Day 2-3-4                      Hrs 24   15 mg/kg

                                    Hrs 6    15 mg/kg

                                    Hrs 12   15 mg/kg

                                    Hrs 18   15 mg/kg

Day 5                           Hrs 24   15 mg/kg

                                    Hrs 8    7.5 mg/kg

                                    Hrs 16   7.5 mg/kg

Day 6-10                       Hrs 24   7.5 mg/kg

                                    Hrs 8    7.5 mg/kg

                                    Hrs 16   7.5 mg/kg

Day 11                          Hrs 24   7.5 mg/kg

Ribavirin prophylaxis with tablets (200 mg)- total 10 days

< 65 kg             2 tablets (400 mg) two times a day for 10 days

> 65 – 85 kg      2 tablets (400 mg) in the morning and 3 tablets (600 mg) at night for 10 days

> 85 kg             3 tablets (600 mg) two times a day for 10 days

Lactating mothers should discontinue breastfeeding

Efficacy of oral Ribavirin as treatment or post-exposure prophylaxis unknown

Notes:

For a total treatment of 1 adult of 80 kg,                        27 vials are required.

For a total prophylaxis of 1 adult of 80 kg,     50 tablets are required

The price per vial is about 80 euro, so ensure safe storage.