107
estimations may be helpful. We have found increases in interferon-gamma and soluble CD8 in patients with active cerebral disease.10 Increased cerebrospinal fluid neopterin concentrations have also been reported in patients with HLH." The diagnostic criteria for systemic HLH are not the same as for CNS-HLH.6 Nevertheless, the presence of any of the following findings could be indicative of this
fever, anaemia, splenomegaly, encephalopathy: neutropenia, thrombocytopenia, hypertriglyceridaemia, hypofibrinogenaemia, evidence of haemophagocytosis, or a 6
familial pttem.
for CNS-HLH is states similar to that used for familial HLH is recommended.12 Since the penetration of etoposide and teniposide across the bloodbrain barrier is limited, steroid treatment is recommended and may need to be prolonged.13 Intrathecal chemotherapy with methotrexate has been difficult to evaluate.12 Bone marrow transplantation is suggested if an HLA-identical sibling is available.14 CNS-HLH imitates several neurological disorders and may be misdiagnosed. An awareness of this condition is important because it is treatable.
Although experience
of
treatment
limited, a regimen for active inflammatory
We thank Dr Ake Ost and Dr Blaise Favara for reviewing the histopathological specimens and Dr Lennart Hedenborg for valuable comments on the manuscript. This work was supported by grants from the Children’s Cancer Foundation of Sweden and the Samariten Foundation.
REFERENCES 1. Henter J-I, Elinder G, Soder O, Öst A. Incidence in Sweden and clinical
features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand 1991; 80: 428-35.
Janka G. Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr 1983; 140: 221-30. 3. Britton S, Andersson-Anvert M, Gergely P, et al. Epstein-Barr-virus 2.
immunity and tissue distribution in a fatal case of infectious mononucleosis. N Engl J Med 1978; 298: 89-92 4. Purtilo DT, Sakamoto K, Saemundsen A, et al. Documentation of Epstein-Barr virus infection in immunodeficient patients with lifethreatening lymphoproliferative diseases by clinical, virological and immunopathological studies. Cancer Res 1981; 41: 4226-36. 5. Price DL, Woolsey JE, Rosman NP, Richardson EP. Familial lymphohistiocytosis of the nervous system. Arch Neurol 1971; 24: 270-83. 6. Henter J-I, Elinder
G, Öst A, and the FHL Study Group of the Histiocyte Society. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Semin Oncol 1991; 18: 29-33. 7. Boutin B, Routin M-C, Rocchccioli F, et al. Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis. Semin Oncol 1991; 18: 29-33. 8. Rettwitz W, Sauer O, Burow M-M, Lenard H-G, Raute-Kreinsen U, Tomow K. Neurological and neuropathological findings in familial erythrophagocytic lymphohistiocytosis. Brain Dev 1983; 5: 322-27. 9. Akima M, Sumi SM, Neuropathology of familial erythrophagocytic lymphohistiocytosis. Six cases and review of the literature. Hum Pathol 1984; 15: 161-68. 10. Henter J-I, Elinder G, Söder O, Hansson M, Andersson B, Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991; 78: 2918-22. 11. Howells DW, Strobel S, Smith I, Levinsky RJ, Hyland K. Central system involvement in the erythrophagocytic disorders of infancy: the role of cerebrospinal fluid neopterins in their differential diagnosis and clinical management. Pediatr Res 1990; 28: 116-19. 12. Henter J-I, Elinder G. Familial hemophagocytic lymphohistiocytosis: clinical review based on the findings in seven patients. Acta Paediatr nervous
Scand 1991; 80: 267-77. 13. Creaven PJ. The clinical pharmacology of VM26 and VP16-213: a brief overview. Cancer Chemother Pharmacol 1982; 7: 133-40. 14. Blanche S, Caniglia M, Girault D, Landman J, Griscelli C, Fischer A. of Treatment hemophagocytic lymphohistiocytosis with chemotherapy and bone-marrow transplantation. Blood 1991; 78: 51-54.
Parvovirus B19 outbreak in
Parvovirus B19 infection
can
cause
severe
complications in pregnant women, individuals with haemolytic anaemia, and those who are immunocompromised. In a hospital outbreak of this balance should be struck between protection of these individuals and the maintenance of medical services. The index case of an outbreak of parvovirus B19 infection among staff and patients of a paediatric ward was not identified. 58 members of staff were screened for B19 markers and 4 of the 6 susceptible men and 6 of the 24 susceptible women became infected (p = 0·05) as defined by serum IgM and viraemia. 1 of the 11 adults (10 members of staff and 1 parent) infected remained symptom-free. 12 immunocompromised patients were also assessed, and symptom-free infection developed in 2 of these. During the outbreak staff with symptoms were put on sick leave, immunocompromised patients (there were none with haemolytic anaemia) were given normal human immunoglobulin and nursed in single rooms by B19 IgG-positive, IgM-negative staff, and the ward was closed to B19 IgG-negative pregnant women. However, the limitation of spread of
infection,
a
children’s ward
infection cannot be attributed with measures
certainty
to the
taken.
Introduction
a
Parvovirus B19 infection is associated with erythema infectiosum in children, hydrops fetalis and second trimester abortion in pregnant women, aplastic crises in those with underlying haemolytic anaemias, and chronic anaemia in immunocompromised individuals. However, infection is also commonly symptomless, especially in childhood. 40-60% of the adult population have serological evidence of infection, in most cases acquired between the ages of 4 and 10.1 Studies of B19 outbreaks in schools and day-care centres have shown that this virus has high infectivity,2-4 but there are few data on hospital outbreaks5-in which pregnant women, immunocompromised individuals, and those with ADDRESSES Division of Communicable Diseases (D Pillay, PhD, C. C Kibbler, MRCPath, Prof P D. Griffiths, MD), and Occupational Health Unit (S Hurt, OHNCert), Royal Free Hospital and School of Medicine, London NW3 2PF, UK, and Department of Medical Microbiology, University College and Middlesex School of Medicine, London (G Patou, MRCPath). Correspondence to Dr D
Pillay.
108
TABLE I-SYMPTOMS IN 10ADULTS DURING PARVOVIRUS B19
INFECTION
TABLE II-SUSCEPTIBILITY OF AND SUBSEQUENT INFECTION IN CONTACTS
*Number of patients*Includes 1
anaemias may be at risk of serious B 19 disease. We describe here an outbreak of B 19 infection among staff and patients of a general paediatric ward.
underlying haemolytic
Methods Clinical and epidemiological studies On Aug 9, 1990 (day 7 of the outbreak), a nurse working on a paediatric ward became ill, with fever, a rash, arthralgia, and diarrhoea. This ward houses bone-marrow and renal-transplant recipients as well as general paediatric patients. During the subsequent month, a similar illness developed in other members of staff on the same ward. Most of them were examined at least once by D. P. and S.H., and relevant specimens were taken for laboratory investigation. During and after their illness they were questioned closely about their symptoms. Any patient on the ward with unexplained symptoms during this period was also examined and fully investigated. At least one blood sample was obtained from all affected individuals after cessation of symptoms. All 58 health care workers who worked on, or had close contact with, the ward at any time during the outbreak were identified. For most of them serum samples previously obtained routinely by the occupational health unit and stored at - 20°C were available. These stored samples and fresh samples collected from staff after onset of the outbreak were tested for B19, as were samples from immunocompromised children (7 renal-transplant and 5 bonemarrow recipients) on the ward during this period. To identify the index case of the outbreak paediatricians were questioned as to whether children admitted to the ward in the period preceding the outbreak had features ofB19 infection.
Parvovirus B 19 tests B19 specific IgG and IgM were tested for by use of ’in house’ IgG (GACRIA) and IgM (MACRIA) capture assays.6 Most of the immunocompromised children on the ward were also tested for
case
of
secondary infection.
B19 DNA by dot-blot hybridisation.’’ Individuals were designated "infected" if positive for B 19 IgM or DNA in the serum. Infection was confirmed by a polymerase chain reaction technique.8 Individuals were classed as "susceptible" to infection, for epidemiological purposes, if they lacked B 19 IgG initially, or if they became infected during the outbreak. serum
Statistics
Comparison of groups was undertaken by X2 test for trend.9 Results Clinical and laboratory details of infected individuals The nurse who was the first patient to come to our notice had her symptoms for 6 days, and parvovirus B 19 IgM was found in an acute serum sample. The 7 members of staff who subsequently became ill were also positive for B19 IgM. Serological testing identified recent infection in 3 other adults-2 members of staff and 1 parent of a patient. 2 of these had had symptoms before the first case and the other had no symptoms. 2 renal-transplant recipients also had symptom-free infection. Among the 10 adults (9 members of staff and 1 parent) who had symptoms the commmonest clinical features were rash, arthralgia, and pyrexia (table i). Usually the rash was blotchy or "lacy" and, except in the 2 subjects in whom the rash was confined to the limbs, it covered the whole body except the face. Arthralgia was commoner among women (83%) than among men (50%), and the joints affected varied. The illness lasted a mean of 6-7 days (range 3-13, figure). In all affected individuals tests for rubella IgM and stool and throat swab cultures for virus isolation were
negative.
testing and epidemiological investigation Since the first 2 patients started their illness on the same day (figure), a common source of infection was sought but our questioning of the paediatricians yielded nothing. The figure shows that infection spread in a "rolling" person-toperson manner rather than from a single virus excretor. The Parvovirus
interval between onset of symptoms in the first and that in the last case was 31 days. The incubation period for the B19 infection cannot be calculated since we are not certain of the source of infection for any of the cases. Of all staff members in contact with the outbreak 24/45 women (53%) and 6/13 men (45%) were susceptible to infection; of these proportionately more men (4/6, 67%) than women (6/24, 25%) acquired the infection (table n) (p 0.05, when analysed for trend). 9 (75%) of the immunocompromised patients were susceptible to B19, and of these 2 (22%) acquired the infection, without symptoms. =
Time of onset and duration of symptoms for adults in B19 outbreak.
109
Management of outbreak When B19 virus was confirmed to be the cause of the outbreak on day 18, infection control measures introduced on day 7 were modified. The protocol adopted was based on our finding that infection is spread by affected individuals before onset of their major symptoms:
IgG and IgM determined on all staff wholly or partly in with ward during period of outbreak. 2. B 19 IgG+ve, IgM - ve staff allocated to care for high-risk patients, in single rooms. 3. B19 IgG, IgM, and DNA status determined in high-risk patients. 4. Ward closed to high-risk patients (immunocompromised and those with haemolytic disorders) until 14 days after cessation of 1. B19
contact
symptoms in last affected individual. 5. Normal human immunoglobulin given to high-risk patients. 6. Ward closed to B 19 IgG - ve pregnant staff/parents during period of outbreak.
Affected staff were placed on sick leave debilitating symptoms persisted.
as
long
as
Discussion To our knowledge, there has been only one report of B 19 outbreak among staff of a hospital; in that outbreak the index cases were 2 children with sickle-cell crises.5 We could not identify an index case so all staff members who worked on the ward over the whole duration of the outbreak were screened. The proportion (about 50%) of staff susceptible to parvovirus B19 infection accords with previous estimates.6 The infectivity of B19 virus is underlined by the overall attack rate of 30% among the susceptible subjects, which is similar to that reported by Bell et al for a hospital outbreak.s We found that a greater proportion of susceptible men than women were infected during the outbreak. Previous studies of B19 outbreaks have noted a preponderence of disease among women,10 but the finding may have been due to investigational bias.1o,11 Our concern about the potential effect of the outbreak on immunocompromised children on the ward directed our choice of infection control measures, although they differed from the American Academy of Pediatrics recommendation that staff should wear masks and gloves when caring for B 19 infected children.s B 19 infection can lead to a chronic, severe anaemia in those with dysfunctional immune systems,12,13 but it is not clear whether this complication follows from a primary infection, reinfection, or reactivation of latent of the infection. Therefore, although 25% children had evidence of immunocompromised prior infection as indicated by the presence of IgG, they were all given a dose of normal immunoglobulin, which can reduce B19 viral load and restore erythropoiesis in with immunocompromised patients persistent infection. 13,14 In addition, they were nursed in single rooms by B19 IgG seropositive personnel, on the basis that in immunocompetent individuals immunity is long lasting and therefore infection would be unlikely to be transmitted to these children via these staff members. By the end of the outbreak, 2 immunocompromised children showed evidence of B 19 infection, without severe anaemia or symptoms. 1 case was shown to represent a secondary infection (ie, there had been previous infection with the
agent) and has been reported elsewhere.8 Since the rash and arthralgia of B 19 infection are thought to represent immune-complex-mediated processes,l the patient’s immunocompromised state may explain the lack of same
symptoms. Also immunoglobulin therapy may have attenuated the effects of infection and prevented the development of anaemia. Pregnant women, if infected, have an increased risk of second-trimester abortion.15 1 pregnant member of staff who was seronegative for B19 was thus advised against further visits to the ward during the outbreak. The ward was reopened 14 days after cessation of symptoms in the last case, on the basis that the maximum incubation period for B19 is 16 days and that virus is shed only before the onset of major symptoms.16 We managed to prevent B19 disease in high-risk patients and pregnant women, but whether this was the result of our infection-control measures is uncertain. A balance has to be struck between protecting small numbers of highly susceptible individuals and denying access to medical services to the majority unlikely to be adversely affected by parvovirus B19. Hence, instead of closing the ward completely, we denied admission only to those at high risk. We think that the balance we achieved was correct, and we would manage another outbreak in a similar manner. G. P. is
a
recipient of a Sir Jules Thorn Trust research fellowship. REFERENCES
1. Pattison
JR. Parvovirus: medical and biological aspects. In: Fields BN, Knipe DM, eds. Virology. New York: Raven, 1990: 1765-86. 2. Woolf AD, Campion GV, Chiswick A, et al. Clinical manifestations of human parvovirus B19 in adults. Arch Intern Med 1989; 149: 1153-56. 3. Gillespie SM, Carter ML, Asch S, et al. Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum. JAMA 1990; 263: 2061-65. 4. Grilli EA, Anderson MJ, Hoskins TW. Concurrent outbreaks of influenza and parvovirus B19 in a boy’s boarding school. Epidemiol Infect 1989; 103: 359-70. 5. Bell LM, Naides SJ, Stoffman P, Hodinka RL, Plotkin SA. Human parvovirus B19 infection among hospital staff members after contact with infected patients. N Engl J Med 1989; 321: 485-91. 6. Cohen BJ, Mortimer PP, Pereira MS. Diagnostic assays with monoclonal antibodies for the human serum parvovirus-like virus (SPLV). J Hyg Camb 1983; 91: 113-30.
MJ, Jones SE, Minson AC. Diagnosis of human parvovirus infection by dot-blot hybridisation using cloned viral DNA. J Med Virol 1985; 15: 163-72.
7. Anderson
8.
Patou G, Rees L, Griffiths PD. Secondary parvovirus B19 infection in an immunocompromised child. Paed Infect Dis J 1991; 10:
Pillay D,
623-24.
9. Bland M. An introduction University Press, 1987.
to
medical statistics. Oxford: Oxford
10. Cohen BJ. Human parvovirus B19 and fifth disease. In: Mortimer PP, ed. Public health virology: twelve reports. London: Public Health Laboratory Service, 1986: 130-43.
11. 12.
Morgan-Capner P, Wright J, Longley JP, Anderson MJ. Sex ratio in outbreaks of parvovirus B19 infection. Lancet 1987; ii: 98. Kurtzman GJ, Ozawa K, Cohen B, et al. Chronic bone marrow failure due to persistent B19 parvovirus infection. N Engl J Med 1987; 317: 287-94.
13. Frickhofen N, Abkowitz JL, Safford M, et al. Persistent B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anaemia in AIDS. Ann Intern Med 1990; 113: 926-33. 14. Kurtzman GJ, Cohen B, Meyers P, Amunullah A, Young NS. Persistent anaemia in children with acute lymphocytic anaemia. Lancet 1988; ii: 1159-62. 15. Public Health Service Working Party on Fifth Disease. Prospective study of human parvovirus (B19) infection m pregnancy. Br Med J 1990; 300: 1166-70.
16. Anderson
MJ, Higgins PG, Davis LR, et al. Experimental parvovirus man. J Infect Dis 1985; 152: 257-65.
infection with
estimations may be helpful. We have found increases in interferon-gamma and soluble CD8 in patients with active cerebral disease.10 Increased cerebrospinal fluid neopterin concentrations have also been reported in patients with HLH." The diagnostic criteria for systemic HLH are not the same as for CNS-HLH.6 Nevertheless, the presence of any of the following findings could be indicative of this
fever, anaemia, splenomegaly, encephalopathy: neutropenia, thrombocytopenia, hypertriglyceridaemia, hypofibrinogenaemia, evidence of haemophagocytosis, or a 6
familial pttem.
for CNS-HLH is states similar to that used for familial HLH is recommended.12 Since the penetration of etoposide and teniposide across the bloodbrain barrier is limited, steroid treatment is recommended and may need to be prolonged.13 Intrathecal chemotherapy with methotrexate has been difficult to evaluate.12 Bone marrow transplantation is suggested if an HLA-identical sibling is available.14 CNS-HLH imitates several neurological disorders and may be misdiagnosed. An awareness of this condition is important because it is treatable.
Although experience
of
treatment
limited, a regimen for active inflammatory
We thank Dr Ake Ost and Dr Blaise Favara for reviewing the histopathological specimens and Dr Lennart Hedenborg for valuable comments on the manuscript. This work was supported by grants from the Children’s Cancer Foundation of Sweden and the Samariten Foundation.
REFERENCES 1. Henter J-I, Elinder G, Soder O, Öst A. Incidence in Sweden and clinical
features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand 1991; 80: 428-35.
Janka G. Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr 1983; 140: 221-30. 3. Britton S, Andersson-Anvert M, Gergely P, et al. Epstein-Barr-virus 2.
immunity and tissue distribution in a fatal case of infectious mononucleosis. N Engl J Med 1978; 298: 89-92 4. Purtilo DT, Sakamoto K, Saemundsen A, et al. Documentation of Epstein-Barr virus infection in immunodeficient patients with lifethreatening lymphoproliferative diseases by clinical, virological and immunopathological studies. Cancer Res 1981; 41: 4226-36. 5. Price DL, Woolsey JE, Rosman NP, Richardson EP. Familial lymphohistiocytosis of the nervous system. Arch Neurol 1971; 24: 270-83. 6. Henter J-I, Elinder
G, Öst A, and the FHL Study Group of the Histiocyte Society. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Semin Oncol 1991; 18: 29-33. 7. Boutin B, Routin M-C, Rocchccioli F, et al. Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis. Semin Oncol 1991; 18: 29-33. 8. Rettwitz W, Sauer O, Burow M-M, Lenard H-G, Raute-Kreinsen U, Tomow K. Neurological and neuropathological findings in familial erythrophagocytic lymphohistiocytosis. Brain Dev 1983; 5: 322-27. 9. Akima M, Sumi SM, Neuropathology of familial erythrophagocytic lymphohistiocytosis. Six cases and review of the literature. Hum Pathol 1984; 15: 161-68. 10. Henter J-I, Elinder G, Söder O, Hansson M, Andersson B, Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991; 78: 2918-22. 11. Howells DW, Strobel S, Smith I, Levinsky RJ, Hyland K. Central system involvement in the erythrophagocytic disorders of infancy: the role of cerebrospinal fluid neopterins in their differential diagnosis and clinical management. Pediatr Res 1990; 28: 116-19. 12. Henter J-I, Elinder G. Familial hemophagocytic lymphohistiocytosis: clinical review based on the findings in seven patients. Acta Paediatr nervous
Scand 1991; 80: 267-77. 13. Creaven PJ. The clinical pharmacology of VM26 and VP16-213: a brief overview. Cancer Chemother Pharmacol 1982; 7: 133-40. 14. Blanche S, Caniglia M, Girault D, Landman J, Griscelli C, Fischer A. of Treatment hemophagocytic lymphohistiocytosis with chemotherapy and bone-marrow transplantation. Blood 1991; 78: 51-54.
Parvovirus B19 outbreak in
Parvovirus B19 infection
can
cause
severe
complications in pregnant women, individuals with haemolytic anaemia, and those who are immunocompromised. In a hospital outbreak of this balance should be struck between protection of these individuals and the maintenance of medical services. The index case of an outbreak of parvovirus B19 infection among staff and patients of a paediatric ward was not identified. 58 members of staff were screened for B19 markers and 4 of the 6 susceptible men and 6 of the 24 susceptible women became infected (p = 0·05) as defined by serum IgM and viraemia. 1 of the 11 adults (10 members of staff and 1 parent) infected remained symptom-free. 12 immunocompromised patients were also assessed, and symptom-free infection developed in 2 of these. During the outbreak staff with symptoms were put on sick leave, immunocompromised patients (there were none with haemolytic anaemia) were given normal human immunoglobulin and nursed in single rooms by B19 IgG-positive, IgM-negative staff, and the ward was closed to B19 IgG-negative pregnant women. However, the limitation of spread of
infection,
a
children’s ward
infection cannot be attributed with measures
certainty
to the
taken.
Introduction
a
Parvovirus B19 infection is associated with erythema infectiosum in children, hydrops fetalis and second trimester abortion in pregnant women, aplastic crises in those with underlying haemolytic anaemias, and chronic anaemia in immunocompromised individuals. However, infection is also commonly symptomless, especially in childhood. 40-60% of the adult population have serological evidence of infection, in most cases acquired between the ages of 4 and 10.1 Studies of B19 outbreaks in schools and day-care centres have shown that this virus has high infectivity,2-4 but there are few data on hospital outbreaks5-in which pregnant women, immunocompromised individuals, and those with ADDRESSES Division of Communicable Diseases (D Pillay, PhD, C. C Kibbler, MRCPath, Prof P D. Griffiths, MD), and Occupational Health Unit (S Hurt, OHNCert), Royal Free Hospital and School of Medicine, London NW3 2PF, UK, and Department of Medical Microbiology, University College and Middlesex School of Medicine, London (G Patou, MRCPath). Correspondence to Dr D
Pillay.
108
TABLE I-SYMPTOMS IN 10ADULTS DURING PARVOVIRUS B19
INFECTION
TABLE II-SUSCEPTIBILITY OF AND SUBSEQUENT INFECTION IN CONTACTS
*Number of patients*Includes 1
anaemias may be at risk of serious B 19 disease. We describe here an outbreak of B 19 infection among staff and patients of a general paediatric ward.
underlying haemolytic
Methods Clinical and epidemiological studies On Aug 9, 1990 (day 7 of the outbreak), a nurse working on a paediatric ward became ill, with fever, a rash, arthralgia, and diarrhoea. This ward houses bone-marrow and renal-transplant recipients as well as general paediatric patients. During the subsequent month, a similar illness developed in other members of staff on the same ward. Most of them were examined at least once by D. P. and S.H., and relevant specimens were taken for laboratory investigation. During and after their illness they were questioned closely about their symptoms. Any patient on the ward with unexplained symptoms during this period was also examined and fully investigated. At least one blood sample was obtained from all affected individuals after cessation of symptoms. All 58 health care workers who worked on, or had close contact with, the ward at any time during the outbreak were identified. For most of them serum samples previously obtained routinely by the occupational health unit and stored at - 20°C were available. These stored samples and fresh samples collected from staff after onset of the outbreak were tested for B19, as were samples from immunocompromised children (7 renal-transplant and 5 bonemarrow recipients) on the ward during this period. To identify the index case of the outbreak paediatricians were questioned as to whether children admitted to the ward in the period preceding the outbreak had features ofB19 infection.
Parvovirus B 19 tests B19 specific IgG and IgM were tested for by use of ’in house’ IgG (GACRIA) and IgM (MACRIA) capture assays.6 Most of the immunocompromised children on the ward were also tested for
case
of
secondary infection.
B19 DNA by dot-blot hybridisation.’’ Individuals were designated "infected" if positive for B 19 IgM or DNA in the serum. Infection was confirmed by a polymerase chain reaction technique.8 Individuals were classed as "susceptible" to infection, for epidemiological purposes, if they lacked B 19 IgG initially, or if they became infected during the outbreak. serum
Statistics
Comparison of groups was undertaken by X2 test for trend.9 Results Clinical and laboratory details of infected individuals The nurse who was the first patient to come to our notice had her symptoms for 6 days, and parvovirus B 19 IgM was found in an acute serum sample. The 7 members of staff who subsequently became ill were also positive for B19 IgM. Serological testing identified recent infection in 3 other adults-2 members of staff and 1 parent of a patient. 2 of these had had symptoms before the first case and the other had no symptoms. 2 renal-transplant recipients also had symptom-free infection. Among the 10 adults (9 members of staff and 1 parent) who had symptoms the commmonest clinical features were rash, arthralgia, and pyrexia (table i). Usually the rash was blotchy or "lacy" and, except in the 2 subjects in whom the rash was confined to the limbs, it covered the whole body except the face. Arthralgia was commoner among women (83%) than among men (50%), and the joints affected varied. The illness lasted a mean of 6-7 days (range 3-13, figure). In all affected individuals tests for rubella IgM and stool and throat swab cultures for virus isolation were
negative.
testing and epidemiological investigation Since the first 2 patients started their illness on the same day (figure), a common source of infection was sought but our questioning of the paediatricians yielded nothing. The figure shows that infection spread in a "rolling" person-toperson manner rather than from a single virus excretor. The Parvovirus
interval between onset of symptoms in the first and that in the last case was 31 days. The incubation period for the B19 infection cannot be calculated since we are not certain of the source of infection for any of the cases. Of all staff members in contact with the outbreak 24/45 women (53%) and 6/13 men (45%) were susceptible to infection; of these proportionately more men (4/6, 67%) than women (6/24, 25%) acquired the infection (table n) (p 0.05, when analysed for trend). 9 (75%) of the immunocompromised patients were susceptible to B19, and of these 2 (22%) acquired the infection, without symptoms. =
Time of onset and duration of symptoms for adults in B19 outbreak.
109
Management of outbreak When B19 virus was confirmed to be the cause of the outbreak on day 18, infection control measures introduced on day 7 were modified. The protocol adopted was based on our finding that infection is spread by affected individuals before onset of their major symptoms:
IgG and IgM determined on all staff wholly or partly in with ward during period of outbreak. 2. B 19 IgG+ve, IgM - ve staff allocated to care for high-risk patients, in single rooms. 3. B19 IgG, IgM, and DNA status determined in high-risk patients. 4. Ward closed to high-risk patients (immunocompromised and those with haemolytic disorders) until 14 days after cessation of 1. B19
contact
symptoms in last affected individual. 5. Normal human immunoglobulin given to high-risk patients. 6. Ward closed to B 19 IgG - ve pregnant staff/parents during period of outbreak.
Affected staff were placed on sick leave debilitating symptoms persisted.
as
long
as
Discussion To our knowledge, there has been only one report of B 19 outbreak among staff of a hospital; in that outbreak the index cases were 2 children with sickle-cell crises.5 We could not identify an index case so all staff members who worked on the ward over the whole duration of the outbreak were screened. The proportion (about 50%) of staff susceptible to parvovirus B19 infection accords with previous estimates.6 The infectivity of B19 virus is underlined by the overall attack rate of 30% among the susceptible subjects, which is similar to that reported by Bell et al for a hospital outbreak.s We found that a greater proportion of susceptible men than women were infected during the outbreak. Previous studies of B19 outbreaks have noted a preponderence of disease among women,10 but the finding may have been due to investigational bias.1o,11 Our concern about the potential effect of the outbreak on immunocompromised children on the ward directed our choice of infection control measures, although they differed from the American Academy of Pediatrics recommendation that staff should wear masks and gloves when caring for B 19 infected children.s B 19 infection can lead to a chronic, severe anaemia in those with dysfunctional immune systems,12,13 but it is not clear whether this complication follows from a primary infection, reinfection, or reactivation of latent of the infection. Therefore, although 25% children had evidence of immunocompromised prior infection as indicated by the presence of IgG, they were all given a dose of normal immunoglobulin, which can reduce B19 viral load and restore erythropoiesis in with immunocompromised patients persistent infection. 13,14 In addition, they were nursed in single rooms by B19 IgG seropositive personnel, on the basis that in immunocompetent individuals immunity is long lasting and therefore infection would be unlikely to be transmitted to these children via these staff members. By the end of the outbreak, 2 immunocompromised children showed evidence of B 19 infection, without severe anaemia or symptoms. 1 case was shown to represent a secondary infection (ie, there had been previous infection with the
agent) and has been reported elsewhere.8 Since the rash and arthralgia of B 19 infection are thought to represent immune-complex-mediated processes,l the patient’s immunocompromised state may explain the lack of same
symptoms. Also immunoglobulin therapy may have attenuated the effects of infection and prevented the development of anaemia. Pregnant women, if infected, have an increased risk of second-trimester abortion.15 1 pregnant member of staff who was seronegative for B19 was thus advised against further visits to the ward during the outbreak. The ward was reopened 14 days after cessation of symptoms in the last case, on the basis that the maximum incubation period for B19 is 16 days and that virus is shed only before the onset of major symptoms.16 We managed to prevent B19 disease in high-risk patients and pregnant women, but whether this was the result of our infection-control measures is uncertain. A balance has to be struck between protecting small numbers of highly susceptible individuals and denying access to medical services to the majority unlikely to be adversely affected by parvovirus B19. Hence, instead of closing the ward completely, we denied admission only to those at high risk. We think that the balance we achieved was correct, and we would manage another outbreak in a similar manner. G. P. is
a
recipient of a Sir Jules Thorn Trust research fellowship. REFERENCES
1. Pattison
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