Lassa fever in children

Journal of Infection (I982) 4, 73-77

Lassa fever in children P. C. Sharp* Nixon Methodist Memorial Hospital, Segbwema, Sierra Leone Summary A study was made of fifty febrile children admitted at the children's ward at Nixon Methodist Memorial Hospital, Segbwema, Sierra Leone. Five of these children were shown to have Lassa fever. Their illnesses are described.

Introduction Lassa fever is an arenavirus infection t r a n s m i t t e d by the small b r o w n multim a m m a t e rat Mastomys natalensis. T h e disease was first reported from Lassa, N o r t h East Nigeria, in I969 .1 Since that sime m u c h work has been done on the epidemiology, epizootiology and clinical manifestions of the disease. ~ Several outbreaks have been reported and m a n y cases in adults described. 3-~ T h e effect of the virus on children, however, has not been well documented. Observations in the I97o outbreak in Jos, Nigeria, 6 and the presence of a n t i b o d y w i t h o u t a history of illness in the child of a missionary f r o m Telekaro, Guinea, have suggested that children m a y have a milder infection than adults. In contrast, however, in the outbreak of Zorzor, Liberia, in I972, two infants newly born to m o t h e r s with Lassa fever died. s I n the I97O-72 outbreak in P a n g u m a - T o n g o the incidence of overt disease was less in the age group o - I 9 years, a l t h o u g h a n t i b o d y was evident, again suggesting that the infection in childhood runs a milder course. 7 T h e purpose of this study was to determine the effect of the virus on children.

Methods T h e patients studied were those a d m i t t e d to hospital with a temperature equal to, or greater than, 38"5 °C. A full history was taken and a complete examination performed, with particular attention being paid to s y m p t o m s and signs observed in adult patients. 8 Patients were examined daily and any changes in s y m p t o m s or signs were recorded. Blood samples were obtained from each child on admission and one week later. Antibodies to Lassa fever virus were detected by means of an indirect immunofluorescence test2 A diagnosis of Lassa fever was made in those patients having a fourfold or greater rise in a n t i b o d y titre, and in those with titres of I in 256 or greater. Samples were obtained and sent for isolation of virus but results have not so far been received. O t h e r investigations included a full blood count, a blood smear for malarial parasites and sickle cell anaemia. O n admission, each child received chloroquine and if clinically indicated a course of antibiotics. * Present address: ~i, Osprey Close Guisborough, Cleveland. oi63-4453/82/oioo73 + 05 $oi.oo/o

© I982 T h e British Society for the Study of Infection

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T a b l e I Results for children in a serological survey (for antibodies to Lassa fever virus) of people from 2o houses in a village with an outbreak of disease Age range of children tested O-I I months I-4 years 5-9 years IO-I 4 years

No of children tested I5 42 51 34

No with Percentage antibody with antibody o 5 14 Io

o I 1.9 27.4 29'4

Patients

(I) J.S. was a six-year-old b o y admitted with a two weeks' history of fever, cough and vomiting. Apart from fever (38"9 °C) there was little to find on examination except one small n o n - t e n d e r l y m p h node in the right axilla, x cm hepatomegaly, 2 cm splenomegaly and a small tropical ulcer on the inner aspect o f his right calf. H i s t e m p e r a t u r e and illness were unaffected b y anti-malarial therapy or antibiotics. A H e a f test was positive (grade 2) so anti-tuberculous therapy was begun. In spite of this, fever lasted 23 days with a m a x i m u m t e m p e r a t u r e o f 4o °C. Hallucinations on the 38th day of illness i m p r o v e d after the dose o f streptomycin was reduced. Otherwise he made a good recovery, being discharged after 3o days in hospital. A rise in antibody titre to Lassa fever virus from x in 32 to x in 5x2 was demonstrated. (2) G . N . , a girl aged six years, was admitted with a t e m p e r a t u r e of 39"8 °C and a history of fever, cough, anorexia and vomiting for one month. She complained also o f abdominal pain, headache, dizziness and diarrhoea. O n examination an ulcerated sore m o u t h and small vesicular ulcer on the fauces were found. Scattered crepitations were heard in the chest. Investigations revealed n u m e r o u s pus cells in the urine, and a white b l o o d cell count of 9"25 x io9/1. A blood smear was negative for malarial parasites. A H e a f t e s t was positive (grade I). A n t i b o d y titres of I in xo24 to Lassa fever virus on the 29th day of illness, and a titre greater than i in xo24 on the 4ISt day of illness were demonstrated. (3) J . M . , a three-year-old girl, was admitted with a t e m p e r a t u r e of 39"8 °C and a two days' history of fever, headache, weakness and pain in the back, a b d o m e n and joints. T h e pevious day she had had convulsions. O n examination her spleen and liver were b o t h palpable 4 cm b e l o w the costal margin. T h e white b l o o d cell count was 6.2 x xog/1. Lassa fever virus antibody titres rose from x in 4 on the 5th day of illness, to x in 256 on the x4th day of illness. She m a d e a good recovery and w h e n seen at h o m e on the 2oth day of illness was well, although her liver and spleen were still palpable. (4) J.V., a b o y five years of age, was the half b r o t h e r of case 3. F o u r days after her admission he was b r o u g h t to the hospital with a two-days history o f weakness and pain in the a b d o m e n and joints, as well as fever, vomiting and

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a sore mouth. He had an episode of febrile convulsions on the day of admission. Examination revealed fever (38"9 °C), bilaterally enlarged cervical and axillary lymph nodes and I cm splenomegaly. His liver was tender to palpation 2 cm below the costal margin. On the Ioth day of illness he was still febrile and vomiting, and still had abdominal pain. One week later he had fully recovered, his spleen and liver were no longer palpable. Antibody titres to Lassa fever virus were i in 64 on the 3rd day of illness and I in 512 on the Ioth day of illness. (5) K.A. was a two-month-old baby of a woman with proven Lassa fever. T h e mother's antibody test on the fifth day of illness was negative. By the I Ith day of illness her antibody titres was I in I28. This increased to r in Io24 by the 27th day of illness. T h e baby was seen I7 days after the mother's illness began, when he had a temperature of 39"3 °C and a three days' history of fever and slight cough. T h e r e was little to find on examination except small white patches on the hard palate and anterior fauces. On the fifth day of illness he developed grossly enlarged bilateral cervical lymph nodes, lesions on the fauces and an enlarged liver palpable two cm below the costal margin. Apart from a cough the respiratory system was clear. T h a t day he had an episode of convulsions. T h e white blood cell count was Io'3 × Io9/1, and haemoglobin was 9 g/dl. A blood smear was negative for malarial parasites and sickle cell anaemia. T h e Lassa fever virus antibody titre was less than I in 4 on the third day of illness but was greater than I in Io24 on the I2th day of illness. On this last occasion the child was febrile (37"8 °C), his liver was I cm enlarged and he still had obvious enlargement of cervical lymph nodes. Discussion

O f the 50 children admitted with fever, five were found to have Lassa fever. T w o of them also had tuberculosis, resulting in a mixed clinical picture. What is striking about these children is the relatively mild course of the disease compared with that in adults. It is now thought that the disease has been prevalent in this part of West Africa for some years. Rose 1°, 11 working in Segbwema, in I955, described an epidemic of a disease known locally as Yengema fever and which had features very suggestive of Lassa fever. During the period of this study there was an outbreak of disease in a village 15 miles from Segbwema and a serological survey of people living in 2o houses was made. Results for the children in this study are shown in Table I. As none of the children were ill at the time of testing, this gives an incidence of 2o'4 per cent of children having been infected at some time with Lassa fever virus. Conclusion

Lassa fever virus is clearly an important cause of fever in children in this area. This fact is relevant not only to local physicians but also to those treating febrile children who have recently travelled from these parts. T h e importance of preventing international spread of diseases such as Lassa fever is well underlined

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SHARP

Sore throat

I

Back pain Dizziness Crepitations Enlarged lymph nodes: cervical and axillary Enlarged lymphnodes: cervical Enlarged lymph nodes:

axillary

Diarrhoea Dysuria Joint pain Sore mouth Headache Malaise Cough Abdominal pain Seizures Splenomegaly Hepatomegaly and splenomegaly Vomiting Hepatomegoly Fever

| I

0

I0 20

5'o 6'0 ;o B'O

,6o

Percentage of children

Fig. x. Prevalance of clinical features in five children with Lassa fever.

by Galbraith and colleagues. 12 Early and accurate diagnosis obviously plays a significant part in their control. T o this end, greater understanding of the clinical manifestations and of the serological response to infections are of value. T h e histogram (Fig. I) shows the prevalence of clinical features among the children in this study. From this it may be seen that the most prominent features were fever, enlargement o f the liver and spleen, vomiting, seizures, abdominal pain, cough and malaise. (I would like to express my grateful thanks to Dr J McCormick of the Center for Disease Control, Atlanta, Georgia, U.S.A. and to the staff of the Nixon Methodist Memorial Hosptial, Segbwema, for their invaluable help in the course of this project. Many thnks are due also to Dr M Longson, Consultant Virologist, Manchester, for his advice and help in the preparation of this paper. This study was made in the course of an elective period during the final year at Manchester Medical School.) References i. Frame JD, Baldwin JM Jnr, Cocke D J, Troup JM. Lassa fever, a new virus disease of man from West Africa. Clinical description and pathological findings. Am J Trap Med Hyg 1970; I9 : 670--679 • 2. M o n a t h T P , M e r t e n s P E , P a t t o n R, M a s e r C R , Baum JJ, Pinneo L. A hospital epidemic of Lassa fever in Zorzor, Liberia, March-April z972. Amff TrapMedHyg I973; e2: 773-779.

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3- Keane E, Gilles H M . Lassa fever in Panguma Hospital, Sierra Leone 1973-6. Br Med ff 1977; x: 1399-I4o2. 4. Woodruff A W , Month T P , M a h m o u d A A F , Pain A K , Morris CA. Lassa fever in Britain: an imported case. Br M e d J 1973; 3: 616-617. 5. Bowen G D , Tomori O, Wulff H, Casals J, Noonan A., Downs W G . Lassa fever in Onitsha, East Central State, Nigeria, in 1974. Bull WHO 1975; 52: 599-6o4. 6. Carey DE, K e m p GE, White HA, et al. Lassa fever: Epidemiological aspects of the 197o epidemic, Jos, Nigeria. Tram R Soc Trop Med Hyg 1972; 66: 402-408. 7. Monath TP. Lassa fever: review of epidemiology and epizootiology. Bull WHO 1975; 52: 577-592 • 8. Monath T P , Casals J. Diagnosis of Lassa fever and the isolation and management of patients. Bull WHO 1975; 52: 7o5-715. 9. Wulff W, Lang JV. Indirect immunofluoresence for the diagnosis of Lassa fever infection. Bull WHO i975; 52: 429-436. 1o. Rose JR. A new clinical entity. Lancet 1956; 2: I97. I I . Rose JR. An outbreak of encephalitis in Sierra Leone. Lancet I957; 2: 914-916. 12. Galbraith NS, Berrie J R M , Forbes P, Young S. Public health aspects of viral haemorrhagic fevers in Britain. R Soc Health J I972; 98 (4): I52-I6O-