Tackling the Public Health Challenge of Lassa fever

Dr S.A. OkogbeninConsultant Obstetrician, Irrua Specialist

teaching Hospital.

Lecturer, College of Medicine, Ambrose Alli University.

Presentation outline.

• Introduction• History• Epidemiology• Transmission• Clinical course• Pregnancy Issues• Response• Conclusion

Introduction

• This is a viral haemorrhagic fever• caused by an arena virus• First discovered in Lassa town in Northern

Nigeria• Also endemic in countries of the Manu river basin

in West Africa. Sierra leone, Guinea and Liberia.• Zoonosis, with reservoir in the multimammate

rat. Mastomys natalensis.• Naturally Causes disease only in humans.

History• Lassa mission hosp• In lassa town, • In the Yedseram river valley at the south end of Lake Chad.• Borno state, Northeastern Nigeria

• 19th January 1969 • Laura Wine, 65 year old female• American missionary nurse• Described as very hardworking and hardly taking a holiday• became acutely ill, she had been in Lassa for four years • Had fever, back pain, sore throat

LAURA WINE.

• Dr Hamer the only doctor at the station became worried over her deteriorating condition

• She had – petechiae haemorrhage, – anuria. – Cloroquine, procaine penicillin – but no improvement – She started convulsing,

• Flown to Evangel hospital formerly Bingham Memorial hospital in Jos.

Laura wine

Evangel hosp jos• Dr Jeanette Troup continued treatment• But Laura Wine

– had internal haemorrhage, – went into shock – and DIED.

• Charlotte Shaw, – nurse at the Evangel hospital in Jos – Described as kind loving and generous. – nursed Laura Wine intimately

Charlotte Shaw

• On the day before Laurie Wine died,

– Charlotte Shaw had given her oral toileting

– cleaning her mouth with gauze wrapped round her index finger.

– She had earlier that morning pricked her finger while plucking flowers for another patient.

• Soon after Laura Wine died, Charlotte Shaw became ill.

• Dr. Jeanette Troup, the female doctor again began to treat Charlotte Shaw. – Her note describes an illness similar to

the one that killed Laura Wine. • 11 days after she became ill, Charlotte

Shaw died.

Charlotte Shaw

CHARLOTTE SHAW

• Dr. Jeanette Troupe– Worried and confused by the death of Laura Wine and Charlotte

Shaw, – decided to do an autopsy on Shaw.

• She was assisted by the head nurse Penny Pinneo. • A week later Penny Pinneo became ill. • Realizing this illness does not respond to Chloroquine and

Penicillin injections • Penny Pinneo was flown to New York.

• Dr. Jeanette Troup herself later developed similar illness and died.

• Penny Pinneo arrived New York alive.– Her specimens were sent to the Yale arbovirus

research laboratory.

• In Yale, a new virus was isolated by a team of Scientist led by jordi Casals after a couple of them got infected and one died.

• Penny Pinneo survived and returned to Nigeria to continue her missionary work.

• The virus that was isolated was named Lassa Virus.

• This was the pattern for all haemorrhagic fevers. They were named after the town where the index case got infected.

• In this case in Lassa town, in the Yeserdam river valley in the Southern part of lake Chad, Borno State, North Eastern Nigeria.

• In this way, Lassa virus first announced itself, by claiming a team of missionary health workers.

• That has continued to be the pattern of epidemic outburst.

• Lassa Fever has been known to erase families teams of health workers and communities.

• The Ihumudumu epidemic was equally dramatic.

• In 1984 in Ihumudumu Community of

Ekpoma, Edo state,– a woman had just died – while her burial arrangements were being made,

her husband also died of a similar febrile illness.

• They had 2 sons – One was a Medical doctor in Ekpoma – The second was a Chicago based Engineer. – They had all attended the burial. – They gave their parents befitting Burials– Afterall Esan men crave befitting Burials.

• Shortly after, the medical doctor in Ekpoma became ill.

• with fever, sore throat and proternuria, • a couple of days later he was bleeding from all

orifices including injection sites • His Colleagues desperately tried to save him• A few days after burying his parents, he died.

• With the death of a father, Mother, and a son, in a typical rural community in Nigeria.

• Of course a young girl was implicated by the Community as the witch that was responsible after all she had “confessed”.

• What happened to the Chicago based Engineer, he also attended the burial

• Your guess is as good as mine.

• The engineer who had travelled back to Chicago

• became ill in America. • His blood was taken again to the Yale

arbovirus laboratory.• He died on his hospital bed. • A few days later, the real witch was isolated. • It was the Lassa Virus.

• In between these recorded epidemics, • it is believed that in many communities in Nigeria, Lassa fever

continues to cause death undiagnosed and unchallenged.

• It only comes to prominence if – it affects American missionary heath workers, – Chicago based engineers – other high ranking members of our country.

• When it affects the voiceless,– it goes unannounced, – commonly taking refuge and misdiagnosed as resistant Malaria or

Typhoid fever.

• But for time constraints I would have told this audience about the Abakaliki, Jos, Plateau, Abuja and other epidemics in Nigeria.

Public health impact.• Wiping out of entire family members at once

(Ihumudumun/Ekpoma).

• High death rates among health workers (Lassa village, Jos, Imo, Abakalike)

• Untimely death of friends, sympathizers and mourners as in the Abuja episode

• Deafness: This occurs in 30% of survivors and results in impaired learning, frustration, and misery especially among students.

• Panic in health Care institutions, among family members and community members

Public health impact.• Dissertations of Villages, and health care facilities

• Reluctance to take up employment in health care institutions in endemic cares.

• Loss of bread winner and Economic consequence on dependants

• Stigmatization of affected Family: Courses on Family for evil done/witch craft accusation

• Devastating effects of Lassa fever are beyond causing death, – it leaves in its wake misery, Panic, stigmatization,

wrong accusation, Dissertation and economic deprivation.

• The Upper level estimates of disease burden in Nigeria are suggested to be as follows: – At risk population of 51 million, – 3 million annual illness and– annual death of 58,330.

(Richmond DJ, Baglole DJ. Lassa fever: epidemiology, clinical features, and social consequences. Br Med J 2003; 327:1271-5).

• Because of the devastating effect – it has been categorized by the Centre of Disease

Control as a category A select Agent for Bioterrorism

– along with lethal agents like Bacilli Anthrax, Plague and Small pox.

– This gives the virus an international appeal.

• Since its isolation in 1969, – endemic in countries of the Manu river basin ie– Guinea, – Sierra Leone – Liberia.

• There also reports in other countries – West Africa(Ghana) – Central Africa (Congo and Senegal).

• It is also the most commonly exported viral haemorrhagic fever – Germany, America and the United Kingdom.

• The dissemination of the infection can be assessed by prevalence of antibodies to the virus in populations: – Sierra Leone 8-52%, – Guinea 4-55% – Nigeria 21%.

• In Nigeria the disease has now been reported in 24 states as at December, 2012.

• In Serrie Leone, – 6-15% of cases of fever in hospital patients– 10-15% of hospital admissions are due to Lassa fever.

• In Irrua Specialist Teaching Hospital about – 6% of patient with fever had PCR confirmed Lassa fever

while– 6.8% of admissions to children’s emergency unit had

suspected Lassa and 3.2% were PCR confirmed.

• In University of Maiduguri Teaching Hospital, – 16% of patients with fever had serological evidence of

previous, possibly recent infection.

Transmission

• Lassa fever disease is a zoonosis• vector of transmission is the multimamate rat • known as mastomys natalensis, • recognized by the multiple breasts on its ventral surface and • its relative hairless tail. • They are peridomestic in nature, • living around houses where they often feed and then return to

surrounding bushes. • The breed copiously producing up to a dozen offspring in a single

birth. • Once infected, the rats are infected for life and• transmit the virus to their offspring. • The rats are however not affected by the virus.

Transmission

• There are 2 major modes of transmission, • Rodent to Human

– inhalation of aerosolized virus,– ingestion of food or material contaminated by infected

rodent excrement – catching and preparing the rats as food.

• Human to human transmission – direct contact with blood, tissue secretion or excrement. – Needle stick or cuts facilitate the transmission. – Inhalation of aerosolized virus can also transmit the

infection from human to human.

Clinical course

• Once the virus enters human body, it is asymptomatic in 80%

• It is only in 20% that it takes a complicated course of varied symptoms

• incubation period of 1-3 weeks, • thereafter, illness last for another 3-weeks

resulting in death or recovery.

Clinical features cont.• Symptoms

-Because symptoms are varied and nonspecific, diagnosis is difficult.

• Insidious onset - Fever, Malaise, headache, myalgia, back pain, • sore throat, cough, retrosternal pain, abdominal pain, vomiting, and

diarrhea

• conjunctivitis and sub conjuctival haemorrhage, facial and neck swelling.

• hypotension

• Bleeding occurs in less than 20% of those admitted.

Clinical features cont.

• Renal failure

• Neurological symptoms include tremors , convulsions and encephalitis

• Permanent hearing loss occurs in one third of all cases

• Breast and areola pain, tenderness, enlargement and tenseness. (in pregnancy alone)

Definition for a Suspected Case of Lassa

• Fever > 38oC for LESS than 3 weeks AND

• ABSENCE of a clinical response after 72 hours of anti-malarial treatment and/or a broad-spectrum antibiotic AND

• 2 major signs OR• 1 major sign AND 2 minor signs

Surveillance for Viral Hemorrhagic Fevers in theMano River Union Countries

2 major signs or 1 major and 2 minor

• Major Signs• Abnormal bleeding (from the mouth,

nose, rectum, and/or vagina)• Edema of the neck and/or face• Conjunctival or sub-conjunctival

haemorrhage• Jaundice• Spontaneous abortion• Buzzing in the ears or acute deafness• Persistent hypotension• Confirmed contact with a patient

suffering from Lassa fever• Elevated liver transaminases (SGOT/AST)

• Minor Signs• General malaise• Headache• Retrosternal pain• Muscle or joint pain• Vomiting• Cough• Sore throat• Abdominal pain• Diarrhoea• Proteinuria• Leucopenia < 4000/μL

• Confirmatory test can be done only in 2 laboratories in Nigeria, – the Irrua Specialist Teaching Hospital – Lagos University Teaching Hospital virology laboratory of

prof. Omilabu– private laboratory of Professor Agbonlahor in Benin City.

• The Laboratory confirmation utilizes – Elisa test for antigen and 1gM antibodies – Reverse transcriptase PCR.

• Viral Culture and Histochemistry are usually for research purposes.

Treatment.

• The specific drug for treatment is Ribavirin which should be given intravenously within 6 days of symptoms.

• Patients are best treated in isolated facilities.• Facilities for intensive care and renal dialysis• Personal protective equipment• Universal precautions.

Issues with pregnancy

– 15% mortality in non-pregnant women– 30-60% in pregnant women– Perinatal mortality 90%– Abortion– Intrauterine fetal death– Late intrauterine fetal death

Issues with pregnancy.

• The high maternal and perinatal mortality has been attributed to many factors. – Lassa virus has a high affinity for placenta and

vascular tissues – Fetal immunity is low– maternal immunity diminishes in pregnancy. – The result is :

• infected pregnant woman habours significantly higher viral load than in the non-pregnant population

• high viral load correlates with poorer out come.

– Lassa fever in pregnancy is an enigma.– With special challenges in diagnosis, management

and consequences

Challenges of diagnosisEarly LF Symptoms mimic Pregnancy Symptoms

• Diagnosis and treatment is delayed with poorer outcome• Convulsions in late LF can mimic Eclampsia• Haemorrhage in LF can mimic Obstetric Haemorrhage.• Sepsis out look of LF can mimic Obstetric related sepsis

• Viewed against the background that Eclampsia, Obstetric Haemorrhage and Sepsis are the 3 commonest causes of maternal mortality in Nigeria,

• in settings of low index of suspicion• Where facilities are lacking for laboratory diagnosis, • many cases of LF may have been misdiagnosed • thus LF may be a cause, a HIDDEN cause of Maternal

mortality.

• LF accounts for 25% of maternal death in Serra leone. • In Irrua Specialist Teaching Hospital it accounts for 20%

• This may be the picture in other Lassa fever endemic communities in Nigeria.

• Yet maternal death due to Lassa fever ….not previously reported in Nigeria nor has its contribution to material mortality be acknowledged.

• Lassa Fever could be a significant but hidden cause of maternal deaths in several communities in Nigeria.

• Lassa Fever could be a significant but hidden cause of maternal deaths in several communities in Nigeria.

• This is worrisome considering Nigeria has one of the highest maternal mortality rates which have seemingly defied intervention attempts.

Challenges in pregnancy.

• 2 individuals involved, fetus and mother.• Fetus

– Catastrophic, neonatal Lassa fever is rare.– IUD can be case defining.– High affinity for vascular tissues and placenta– Fetal immune system is still immature.– Perinatal mortality of 85-95%

Management

• The issue is the presence of the fetus and placenta

• Evacuation reported to improve outcome

• Termination of pregnancy has been suggested– It improves response to ribavirin– Fetus is usually dead anyway

• It improves overall maternal outcome.

• These were mainly from sierrie Leone studies. Where termination was a main treatment modality.

Management cont

• What if the fetus is alive. Is termination the most appropriate management?

• Early sacrifice of the fetus was questioned• Optimum management in such instances need

further evaluation• the big question here is what is optimum

management of pregnant women infected with lassa fever.

• To answer the question we reviewed 26s cases of PCR diagnosed lassa fever in pregnancy.

• Our observations pointed towards new lessons that have implications for management and gives some direction and hope.

mortality• 26 RT-PCR confirmed cases.• 12 maternal deaths• 14 maternal survivors• 46.2% mortality

• 6 of the 12 deaths occurred within 24 hours • 4 within 24-48 hours.

– Ie 10/12 (85%) deaths occurred within 48hours.

• Many of those with intrauterine fetal death could not achieve delivery before death.

Factors associated with mortality.

• Intrauterine fetal death.– 7 women presented with IUFD, all died– 2 of the 7 women with spont. abortion died.

• Viable pregnancy– 10 women came with viable pregnancy 9 survived– Of the 14 women who survived 9 came with viable

pregnancy 5 had a spontaneous abortion

• When patients presented with viable pregnancy, Treatment with ribavirin was significantly associated with survival

• Patients with an intrauterine fetal death were significantly more likely to die irrespective of ribavirin use.

• These preliminary findings suggested that presentation with a viable fetus may be predictive of improved maternal and fetal outcome and conservative management with ribavirin rather than evacuation should be considered.

• Evacuation of the Uterus was fundamental to survival only when an intrauterine fetal death has occurred..”

• This finding significantly changed the approach to management of pregnant women infected with Lassa virus.

• Professor Pardis Saberti – “If untreated, Lassa fever has extremely high fatality for pregnant

women and nearly 100% fatality for their fetuses, as such, ribavirin is indicated even for pregnant women”.

• American ribavirin registry which was designed to evaluate the potential human teratogenicity of prenatal exposure to ribavirin.

• • Findings after 5 Years of Enrollment, 2003- 2009 “Although the

registry has not reached sample size goals, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin

significance

• IUFD….prognosis….rescue mission..– Ribavirin, expedite delivery, bleeding problems

• Fetus Alive ..prognosis…Evacuation may not be optimal. And need not be first option of management…..ribavirin and symptomatic– Even if baby becomes compromised– If fetus dies during treatment then commence process of evacuation.

• After discharge…IUFD still possible(50%)…monitor fetus(ctg) deliver at 37 wks.

Summary of treatment• Co manage with physician, best isolated.• supportive care

– Fluids– Monitor urine output– E/U/Cr, LFT, FBC,} correct as necessary.– Clotting profile.– Antibiotics, avoid gentamycin

• Give Ribavirin• Conservative if the fetus is viable, • Expedite delivery if there is fetal demise• Breast symptoms improve as disease is being treated.

Out come for the fetus

• Of the 26 pregnancies• 7 presented with intrauterine fetal death• 3 more intrauterine death during treatment• 7 spontaneous abortion• 1 early neonatal death• 2 late intrauterine fetal deaths.• 2 women presented in the pueperium• 1 lost to follow up.• 3 term deliveries• Fetal wastage… 20/23 (87.0%). • Take home baby rate….3/23

• After discharge…IUFD still possible(40%)…• monitor fetus • deliver at 37 wks.

Response to the LF scouge

• Who should respond?• The federal govt?• The state govt?• The local government?• Irrua specialist teaching hospital?• World health Organization?• Development partners and NGOs?• Individuals?

• ALL• Every one ought to respond.• But what has been the response• For a long time, there was no significant National

response to Lassa fever epidemic in Nigeria. • we usually or oftentimes respond with fire

brigade measures and then go back to sleep or worse still, we may not respond at all but adopt an awake ostrich-like state.

• In 2002, 3 Federal Teaching Hospital were designated centre of excellence – Irrua Specialist Teaching Hospital, – Federal medical centre owerri, – University of maiduguri teaching hosp).

• In Irrua Specialist Teaching Hospital – A ward was build and – A pick up van given to the hospital and – Ribavirin was provided albeit erratically.– Diagnosis was however made in Germany – Results usually come long after many patients have died.

• More coordinated efforts were needed.

Co-ordinated Response• 1n 2007, the Irrua Specialist Teaching Hospital included it in

its vision and mission statement

• “the vision of the hospital is to become a centre of excellence in Medicine, particularly in the areas of rural and sub-urban medicine and the diagnosis and management of viral haemorrhagic fevers especially Lassa fever”

• Special Credit must be given to Professor G.O. Akpede – Initiated and drove the country’s response– Put Irrua Specialist Teaching Hospital on the path to playing its

current dominant role in the control of the Lassa fever scourge.

ISTH ROLE: why the choice• Disease was prevalent in this locality• Very little information was available in the

literature.(diagnosis, treatment, control)• Disease, prevalent in West Africa.• Has international appeal. (terrorism)• Disease with high epidemic potential and high

mortality.• Disease is likely to be around for a long time.• Lessons learnt can be applied to other ds.• Losing staffs, students on a regular basis.

• A regional conference was held in Abuja ( Dec 2007)• Experts were invited from various countries, • the Federal Ministry of Health was in the picture fully. • Individuals were identified to champion building of local capacity.

• Following the conference, a National Lassa fever stakeholder’s forum was formed. (2007)– Federal Ministry of Health, – World Health Organization, – Edo State Ministry of Health,– Federal and State University Teaching Hospital,– National Hospital Abuja, – Federal Medical Centres – Private Hospital like ST Nicholas, Evangel hospital Jos, – Colleges of Medicine of University of Ibadan, Lagos and the Ambrose

Alli University.

OBJECTIVES OF THE NLFSFN

• To articulate and coordinate the national response to the LF epidemic

• To apply the lessons and experience gained in LF control to the control of other emergent VHFs in the country

• To collaborate with regional groups and international agencies with similar interests

Constraints in Control.

• In carrying out its objection the forum identified several constraints in the Lassa fever control efforts in Nigeria. – Lack of facilities for Laboratory diagnosis.– Erratic supply of ribavirin– Lack of isolation wards– Limited supply of consumables and protective

clothing for staff.– Dearth of capacity in case management and infection

control practices within health care facilities.

Constraints in Control.

• Limited surveillance of the epidemic and it trends.

• Inadequate logistics support and provision of materials for community awareness campaigns.

• Lack of political will.• Poor funding.• Lack of awareness of the disease.• Low index of suspicion amongst health workers.• Inadequate knowledge of disease burden

• At the Irrua Specialist Teaching Hospital front– Development of the Institute of Lassa Fever Research

and Control.

– The philosophy of the institute was to• develop an indigenous initiative • organize and push an aggregate response to

comprehensively address the L.F. Epidemic in line with the the objectives of the NLFSHF.

– Fundamental to the institute was the need to build indigenous capacity in the diagnosis, case management, research and control of the Lassa fever scourge.

Objectives of the institute.

• TO FORMULATE POLICIES FOR THE CONTROL AND MANAGEMENT OF LF

• TO DESIGN MEASURES AND PROTOCOL FOR THE DIAGNOSIS AND TREATMENT OF LF

• TO UNDERTAKE THE EDUCATION AND ENLIGHTENMENT OF THE PUBLIC ON THE PREVENTIVE MEASURES

The institute sought to articulate• community awareness campaign, • sanitize health workers around the state and

country, • build up an effective surveillance and reporting

system. • There was also the need to build an effective

partnership with the State and Federal government through its relevant ministry

• and also collaborate with international partners with similar interest.

The department/units in the Institute

• Diagnostic Laboratory• Clinical Management support Laboratory• Critical care (Renal dialysis)• Isolation ward• Administration• Health Education• Training• Community out reach• Case Management/Research

• The laboratory was built in the hospital and was commissioned by the then Minister of health. Professsor Babatunde Osotimehin. 2009.

• We received significant support from Harvard University – trained 2 of our scientists in Harvard Boston. – received diagnostic equipment.

• The Institute of tropical medicine Hamburg Germany – training for our scientist in Hamburg.– Provision of equipment.–

• As we began to take diagnosis locally, research efforts grew and various papers were then presented in international conferences – international conference on infection disease Miami, – we then held several meetings with Key stake holders in Boston,

German and Sierra Leone.

Some gains• Reduction in mortality in the community• Providing Excellent services for diagnosis and

treatment for the country• Helping to reduce mortality amongst health workers in

the country.• Reducing deaths in ISTH staff due to Lassa fever to zero

in the last 4 years.• Creating an environment for research, capacity

building, • Gaining recognition in local and international circles• Presently recognized by WHO.

THANK YOU