Pediatric Nephrology
Pediatr Nephrol (1992) 6: 335-338 9 IPNA 1992
Original article Clinical characteristics of haemorrhagic fever with renal syndrome in children Amira Peco-Antidl, Milana Popovid-Rolovidl, Ana Gligid 2, Divna Popovidt, Olga Jovanovid~, and Mirjana Kostit31 1 Nephrology Department, University Children's Hospital, Tirsova 10, 11000 Belgrade, Yugoslavia 2 Institute of Immunology and Virology "Torlak", Belgrade, Yugoslavia Received February 26, 1991; received in revised form January 30, 1992; accepted February 7, 1992
Abstract. From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3 - 1 2 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Children's Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, s6vere haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2 - 3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fatal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS. Key words: Hantavirus - Acute renal failure ~- Haemorrhagic fever in children
Introduction Haemorrhagic fever with renal syndrome (HFRS) is an acute illness transmitted by small rodents such as field mice or voles. It is characterised by fever, haemorrhagic syndrome and renal involvement. Gastrointestinal disorders, enlarged liver and spleen are more frequently seen Correspondence to: A. Peco-Anti6
in children than adults. The disease is mild in 10%-20%, moderate in 66.6% and severe in 23% of HFRS-affeeted children [1, 2]. The diagnosis is based on clinical manifestations, epidemiological data and the appearance of specific, complement-fixing antibodies to hantaviruses in the serum. Following the identification of the aetiological agent in Korea [3], HFRS has been recognised in many countries throughout the world [4-12]. In Europe, most HFRS patients have been described in the Soviet Union and Yugoslavia [13]. Up to 1988 there were 471 patients with HFRS in Yugoslavia, of whom 69 were children. Only 7 patients were below 7 years [13]. However, the disease is most probably underdiagnosed, because only patients with acute renal failure are registered. In this report we describe the first seven patients who were identified and treated for HFRS at the University Children's Hospital of Belgrade.
Patients and methods Patients. From January 1988 to September 1989, seven patients with HFRS (3 boys and 4 girls, aged 3 - 1 2 years) were treated at the University Children's Hospital of Belgrade. Four were siblings, while the others were sporadic cases. Epidemiological investigation of the affected family revealed a link with rodents. All captured rats (Rattus novegicus) and half of the captured mice (Mus musculus) were infected with hantaviruses. These rodents are currently under investigation at the United States Army Institute in Fort Detric (Frederick, Maryland) under suspicion that new hantaviruses circulate in southern Yugoslavia [14]. The remaining three patients mentioned contacts with rodents, and in one the disease began 2 weeks after vacations spent in Rudnik, a forest area endemic for HFRS.
Serological techniques. Serum antibodies were detected by an indirect immunofluorescence assay (1FA) employing slides spotted with Vero-E6 cells infected with either Hantaan virus (strain 76-118), Puumala virus (strain H~lniis B 1) or Soeul virus [ 15]. Antibody titres were expressed as a reciprocal of the highest dilution of serum giving fluorescence. Negative human sera ~ind uninfected Vero-E6 cells served as controls. An enzyme-linked immunosorbent assay or IFA were used to detect IgM antibodies to Hantaan virus.
336 Table 1. Clinical and laboratory findings in seven patients with haemorrhagic fever with renal syndrome Patient no. Sex/age (years)
1 M/3
2 F/4
3 M/12
4 F/7
5 M/10
6 M/6
7 F/12
Illness duration prior to admission to hospital (days)
3
3
3
10
6
illness onset in hospital
9
3 + -
10 + -
+ +
-
7 + + -
+4 170/110 + Moderate 78
-26 b 140/100 + Moderate 944 47 0.82 0.45
+3 120/80 + Mild 451
+ + + +
-
Epidemiological assessment
Family outbreak
Infective syndrome Febrility (duration in days) Gastrointestinal illness Maculopapnlar exanthema Facial erythema Lymphadenopathy Hepatosplenomegaly
4 + + . + +
Renal syndrome Oedema a Hypertension (maximum mmHg) Haematuriae Proteinuriad Maximum serum creatinine (I.tmol/1) Haemodialysis (duration in days) Serum C3 (g/l) Serum C4 (g/l)
+ NT NT NT NT . -
Haemorrhagic syndrome Melaena Haernatemesis Haematoma Petechia
. + .
7 + +
Sporadic
10 + +
.
.
.
+ +
+ +-
+7 170/130 + Mild 75
+ 11 170/100 + Moderate 73 . 0.16 0.27
.
. 0.16 0.47 -
.
+9 145/85 + Normal 71
-
0.22 0.56
.
.
.
.
.
.
.
+ .
.
7 + + . + +
0.16 0.56
-
-
-
+
0.82 0.34
-
NT, Not tested a Percentage difference in body weight during hospital stay b The patient was oedematous, with loss in body weight
c Patients 2 - 5 had glomerular-type haematuria Mild
Pediatr Nephrol (1992) 6: 335-338 9 IPNA 1992
Original article Clinical characteristics of haemorrhagic fever with renal syndrome in children Amira Peco-Antidl, Milana Popovid-Rolovidl, Ana Gligid 2, Divna Popovidt, Olga Jovanovid~, and Mirjana Kostit31 1 Nephrology Department, University Children's Hospital, Tirsova 10, 11000 Belgrade, Yugoslavia 2 Institute of Immunology and Virology "Torlak", Belgrade, Yugoslavia Received February 26, 1991; received in revised form January 30, 1992; accepted February 7, 1992
Abstract. From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3 - 1 2 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Children's Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, s6vere haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2 - 3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fatal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS. Key words: Hantavirus - Acute renal failure ~- Haemorrhagic fever in children
Introduction Haemorrhagic fever with renal syndrome (HFRS) is an acute illness transmitted by small rodents such as field mice or voles. It is characterised by fever, haemorrhagic syndrome and renal involvement. Gastrointestinal disorders, enlarged liver and spleen are more frequently seen Correspondence to: A. Peco-Anti6
in children than adults. The disease is mild in 10%-20%, moderate in 66.6% and severe in 23% of HFRS-affeeted children [1, 2]. The diagnosis is based on clinical manifestations, epidemiological data and the appearance of specific, complement-fixing antibodies to hantaviruses in the serum. Following the identification of the aetiological agent in Korea [3], HFRS has been recognised in many countries throughout the world [4-12]. In Europe, most HFRS patients have been described in the Soviet Union and Yugoslavia [13]. Up to 1988 there were 471 patients with HFRS in Yugoslavia, of whom 69 were children. Only 7 patients were below 7 years [13]. However, the disease is most probably underdiagnosed, because only patients with acute renal failure are registered. In this report we describe the first seven patients who were identified and treated for HFRS at the University Children's Hospital of Belgrade.
Patients and methods Patients. From January 1988 to September 1989, seven patients with HFRS (3 boys and 4 girls, aged 3 - 1 2 years) were treated at the University Children's Hospital of Belgrade. Four were siblings, while the others were sporadic cases. Epidemiological investigation of the affected family revealed a link with rodents. All captured rats (Rattus novegicus) and half of the captured mice (Mus musculus) were infected with hantaviruses. These rodents are currently under investigation at the United States Army Institute in Fort Detric (Frederick, Maryland) under suspicion that new hantaviruses circulate in southern Yugoslavia [14]. The remaining three patients mentioned contacts with rodents, and in one the disease began 2 weeks after vacations spent in Rudnik, a forest area endemic for HFRS.
Serological techniques. Serum antibodies were detected by an indirect immunofluorescence assay (1FA) employing slides spotted with Vero-E6 cells infected with either Hantaan virus (strain 76-118), Puumala virus (strain H~lniis B 1) or Soeul virus [ 15]. Antibody titres were expressed as a reciprocal of the highest dilution of serum giving fluorescence. Negative human sera ~ind uninfected Vero-E6 cells served as controls. An enzyme-linked immunosorbent assay or IFA were used to detect IgM antibodies to Hantaan virus.
336 Table 1. Clinical and laboratory findings in seven patients with haemorrhagic fever with renal syndrome Patient no. Sex/age (years)
1 M/3
2 F/4
3 M/12
4 F/7
5 M/10
6 M/6
7 F/12
Illness duration prior to admission to hospital (days)
3
3
3
10
6
illness onset in hospital
9
3 + -
10 + -
+ +
-
7 + + -
+4 170/110 + Moderate 78
-26 b 140/100 + Moderate 944 47 0.82 0.45
+3 120/80 + Mild 451
+ + + +
-
Epidemiological assessment
Family outbreak
Infective syndrome Febrility (duration in days) Gastrointestinal illness Maculopapnlar exanthema Facial erythema Lymphadenopathy Hepatosplenomegaly
4 + + . + +
Renal syndrome Oedema a Hypertension (maximum mmHg) Haematuriae Proteinuriad Maximum serum creatinine (I.tmol/1) Haemodialysis (duration in days) Serum C3 (g/l) Serum C4 (g/l)
+ NT NT NT NT . -
Haemorrhagic syndrome Melaena Haernatemesis Haematoma Petechia
. + .
7 + +
Sporadic
10 + +
.
.
.
+ +
+ +-
+7 170/130 + Mild 75
+ 11 170/100 + Moderate 73 . 0.16 0.27
.
. 0.16 0.47 -
.
+9 145/85 + Normal 71
-
0.22 0.56
.
.
.
.
.
.
.
+ .
.
7 + + . + +
0.16 0.56
-
-
-
+
0.82 0.34
-
NT, Not tested a Percentage difference in body weight during hospital stay b The patient was oedematous, with loss in body weight
c Patients 2 - 5 had glomerular-type haematuria Mild
