will be orphaned because of AIDS or related conditions. Since foster or adoptive families are rarely available for children of HIV-infected, IVDU mothers, many of them remain in hospital or are institutionalised for long periods. This in itself further increases the risk of abnormal development, irrespective of the HIV infection status of the child. We suggest that one of our main objectives should be to help children of HIV-positive parents to live with this family disease and its consequences. National agencies and working groups on paediatric AID S should identify and educate extended families and foster families to take care of these children. These families need much support and should be prepared for the grief and trauma of illness and death in some of these children, as well as the death of their infected parents. CARLO GIAQUINTO VANIA GIACOMET ALESSANDRA PAGLIARO EZIA RUGA Department of Paediatrics, SANDRA COZZANI University of Padova, RUGGIERO D’ELIA 35128 Padova, Italy Institute of Child Health, London, UK 1. Italian Multicentre 2.
Study. Epidemiology, clinical features, and prognostic factors
paediatric HIV infection. Lancet 1988; n: 1043-46. European Collaborative Study. Children born to women with HIV-1 infection: natural history and nsk of transmission. Lancet 1991; 337: 253-60.
Formulations of didanosine overload
(ddl) and salt
SIR,-Didanosine (2,3-dideoxyinosine or ddl) is a reverse transcriptase inhibitor under investigation for antiretroviral activity in HIV-positive patients in whom zidovudine intolerance has developed. Adverse events associated with ddl include acute pancreatitis (which may be fatal), peripheral neuropathy, neutropenia, mental confusion, seizures, rashes, diarrhoea, and hypokalaemia.",2 We report an association between the use of ddl and exacerbations of acute left-ventricular failure (LVF). A 33-year-old former intravenous drug abuser had an AIDS defming diagnosis of Pneumocystis carinii pneumonia (PCP) in April, 1990. 4 months later he started treatment with ddl in a randomised double-blind trial of two dose levels (Medical Research Council trial "Alpha"). Apart from initial abdominal pain this drug was tolerated well at the allocated dose given as one sachet twice daily. Treatment was withheld for two 3-week periods at 6 and 12 weeks after initiation of ddl on account of two further eposides of PCP; and on resumption of ddl the dose was decreased to one sachet daily. HIV-related cardiomyopathy was diagnosed on the basis of echocardiography and endomyocardial biopsy in December, 1990.
He was put on captopril, intermittent frusemide, and fluid and salt restriction (2 g [87 mmol] sodium daily). His clinical course was thereafter punctuated by repeated eposides of acute LVF until his death in June, 1991. Necropsy revealed cardiomyopathy and pulmonary oedema. It was noted that several of the episodes of LVF occurred when he restarted treatment with ddl (which was stopped intermittently for short periods while he was in hospital). ddl was stopped permanently in May, 1991, after which the patient had no further episodes of acute LVF until immediately before death. He was taking no other drugs likely to exacerbate cardiac failure. The ddl was made up in citrate/phosphate/sucrose buffer containing 56 mmol sodium dissolved in 100 ml water. This sodium content is of some importance when set beside a normal dietary intake of 217-870 mmol but is a large amount for a patient on a sodium restricted diet of 87 mmol daily. ddl, as a buffered sachet preparation, is now available in the UK on a named patient basis from the drug company. ddl as tablets, formulated for use in further research trials, contains 12 mmol sodium as dihydroxyl aluminium sodium carbonate and sodium citrate dihydrate, this being the equivalent of 0-7 g of sodium chloride. A patient taking four tablets per day would be ingesting 48 mmol sodium from this source. Although an association is not proved in this case, nor can we distinguish between the contribution of ddl or the sodium content of the buffer to the development of cardiac failure in our patient, we suggest caution with the use of the current formulation of ddl in the presence of cardiac disease. We thank Bristol-Myers MRC trial.
Regional Infectious Diseases Unit, City Hospital, Edinburgh EH10 5SB, UK
LORNA WILLOCKS RAY BRETTLE JEREMY KEEN
MRC HIV Clinical Trials Centre, Department of Clinical Epidemiology,
Royal Brompton and National Heart London SW3
CHRIS VALENTINE J. PINCHING
R, Pluda JM, Thomas RV, et al. Long term toxicity/activity profile of 2’,3’-dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990; 336:
526-29. 2 Katlama C, Tubiana R, Rosenheim M. Lancet 1991; 337: 183.
Ribavirin aerosols and respiratory virus infection
SIR,-Wilcox and colleagues! have described the administrative and clinical difficulties in caring for infants in hospital with severe lower-respiratory-tract infections due to respiratory syncytial virus (RSV). Management would be simplified if the rate of nosocomial RSV infection could be reduced. Substantial reductions in the spread of RSV among health-care workers and uninfected patients can be achieved by implementing the following precautions: (1) Wash hands before and after contact with patient or specimen (2) Wear gloves for potential contact with body fluids (3) Wear protective eyewear and do not touch your eyes or nose before washing your hands (4) Wear gowns when splash with body fluids is anticipated (5) Handle all linen as potentially infectious (6) Process all laboratory specimens as potentially infectious (7) Get tested for RSV if you have symptoms of conjunctivitis, headache, sore throat and/or cough, fever, hoarseness, nasal congestion, or wheezing (8) Notify your supervisor if you test positive for RSV (9) Parents should use the same protective measures when handling RSV-infected children
Clinical evidence (2"", for example) suggests that the management of RSV-infected patients can be aided by ribavarin (’Virazid’) aerosol therapy. In a double-blind, placebo-controlled study of 28 RSV-infected infants who presented with respiratory arrest, Smith et aF recorded substantial reductions in duration of mechanical ventilation, need for supplemental oxygen, and length of time in hospital for those patients who received ribavirin therapy. Another benefit is the rapid elimination of viral shedding. 5,6** RSV is a major cause of fatal respiratory tract disease during the first year of life.7 The American Academy of Pediatrics’
recommends ribavirin for infants at high risk of severe or complicated RSV infection, infants admitted to hospital with RSV
lower-respiratory-tract disease who are severely ill, and infants who may be at increased risk of progressing to a more severe condition: Consider ribavirin therapy in infants and young children admitted to hospital with lower-respiratory-tract RSV infections, and with: Congenital heart disease
Bronchopulinonary dysplasia Other chronic lung conditions Certam premature infants
Immunodeficiency (severe combined, recent transplant, chemotherapy for malignancy) Pa02 < 65 mm Hg Increasing PACO,
We thank Dr McKendrick and other clinicians for providing specimens and our colleagues at the Public Health Laboratory, Sheffield, for technical assistance.
Less than 6 weeks of age
Multiple congenital anomalies or neurological or metabolic diseases Increased risk of disease progression from reports to American Infectious Diseases, 1991B
ICN Pharmaceuticals, Costa Mesa, California 92626, USA
CRAIG SHERMAN HUMBERTO FERNANDEZ
J Med 1991, 325: 24-29. et
al Ribavirin aerosol for acute bronchiolitis. Arch Dis Child
Public Health Laboratory, Northern General Hospital, Sheffield S5 7AU, UK
T. C. J. BOSWELL G. KUDESIA
1 Wilcox MH, Williams O, Camp SJ, Spencer RC, Barker I. Characteristics of successive epidemics of respiratory syncytial virus infection. Lancet 1991; 338: 943-44. 2. Smith D, et al. Aerosolized ribavirin m infants requiring mechanical ventilation for severe lower respiratory tract infection caused by respiratory syncytial virus. N Engl
3. Barry W,
These results indicate that a substantial proportion of patients with campylobacter gastroenteritis have antibodies that crossreact serologically with legionella by IFAT. This is important diagnostically since campylobacter infection may present as pyrexia of unknown origin, diarrhoea can be a prominent feature of legionnaires’ disease, and both infections may be acquired abroad. We therefore recommend caution in interpretation of positive legionella serological tests, especially in patients with a recent history of diarrhoea, and suggest culture of stool samples in all such
W, Kim H, et al. Aerosolized ribavirin m the treatment of patients with respiratory syncytial virus disease. Pediatr Infect Dis J 1987; 6: 159-63. 5. Sung R, et al Ribavarin treatment of severe respiratory syncytial viral infection in infants and young children: a local experience. J Hong Kong Med Assoc 1990, 42: 4. Rodriguez
80-82 6. Hall C, McBride J, et al. Aerosolized ribavirin treatment of infants with respiratory 1983; 308: 1443-47. syncytial viral infection. N Engl Med J 7. Lau Y, et al. Evaluation of ribavirin for treatment of respiratory syncytial virus. Sem Pediatr Infect Dis 1991; 2: 279-84. 8 Report of the Committee on Infectious Diseases, American Academy of Pediatrics,
22nd ed. 1991: 581-87.
Seropositivity for legionella in campylobacter infection SIR,-Despite the development of suitable culture media and other methods for direct detection of Legionella pneumophila, legionnaires’ disease is still diagnosed in most patients by serological testing. Crossreactions with other organisms that are seen when heat-killed antigens are used1,2 have generally not been found with a formatinised yolk-sac antigen (FYSA) of L pneumophila serogroup 1 in the indirect fluorescence antibody test (IFAT).3The specificity of IFAT is high, even for low titres of 16 or 32,4 and since 1978 there has been, as far as we are aware, only one reported case in which a diagnostic rise in titre of legionella antibodies by IFAT was due to a crossreaction with another organism.’ We have identified high legionella antibody titres in a 41-year-old man who presented with a 12-day history of diarrhoea, vomiting, fever, joint aches, and extreme fatigue. On admission this titre was 2048. However, the patient had no respiratory symptoms, chest radiography was unremarkable, and he had no epidemiological features suggesting legionellosis. Other initial investigations were negative but Campylobacter jejuni was subsequently isolated from three stool cultures. These findings prompted us to examine 50 serum samples (36 from 34 acutely ill and 14 from 11 convalescent patients) for legionella antibodies with IFAT in 45 inpatients with cultureproven campylobacter gastroenteritis. 1 sample (2-8%) from acutely ill patients and 10 (71 %) of 14 from convalescent patients were positive. The positive sample at the acute stage of illness had a titre of only 16 whereas 7 samples at the convalescent stage had titres between 128 and 2048. These antibodies could be absorbed by killed suspensions of campylobacter-a process that had no effect on serum legionella antibody from a patient with culture-proven legionnaires’ disease. 45 serum samples from 41 patients with salmonella gastroenteritis all had legionella antibody titres of less than 16 by IFAT.
1. Wilkinson HW, Farshy CE, Fikes BJ, Cruce DD, Yealy LP. Measure of immunoglobulin G-, M-, and A- specific titers against Legionella pneumophila and inhibition of titers against non-specific, gram-negative bacterial antigens in the indirect immunofluorescence test for legionellosis. J Clin Microbiol 1979; 10: 685-89. 2. Edelstein PH, McKinney RM, Meyer RD, Edelstein MAC, Krause CJ, Finegold SM. Immunologic diagnosis of legionnaires’ disease; cross-reactions with anaerobic and microaerophilic organisms and infections caused by them. J Infect Dis 1980; 141: 652-55. 3. Taylor AG, Harrison TG, Dighero MW, Bradstreet CMP. False positive reactions in the indirect fluorescent antibody test for legionnaires’ disease eliminated by use of formolised yolk-sac antigen. Ann Intern Med 1979; 90: 686-89. 4. Harrison TG, Taylor AG. The diagnosis of legionnaires’ disease by estimation of antibody levels. In. Harrison TG, Taylor AG, eds. A laboratory manual for legionella. Chichester. John Wiley, 1988. 113-35. 5. Gray JJ, Ward KN, Warren RE, Farrington M Serological cross-reaction between Legionella pneumophila and Citrobacter freundii in indirect immunofluorescence and rapid microagglutination tests. J Clin Microbiol 1991; 29: 200-01.
SIR,-Dr Koten and Professor den Otter (Nov 9, p 1189) suggest that omental milky spots constitute a type of primary lymphoid organ, which processes gut-derived antigens and can cause disease in its own right. We think that this proposal is improbable. For some decades it has been suggested that gut-associated lymphoid tissue (GALT) has a role as a primary lymphoid organ. The basis for this largely relates to the existence of the bursa of Fabricius, by which the pattern of B-cell reactivity is thought to be regulated in birds. In mammals, Peyer’s patches, mesenteric lymph nodes, and the large number of lymphocytes within intestinal villi are thought to constitute a primary and secondary lymphoid organ, with the joint function of regulating potentially autodestructive responses to ubiquitous antigens while retaining the ability to react specifically with and inactivate antigens associated with lifethreatening pathogens. The proposal that omental milky spots are part of or even the main component of GALT with a predominantly primary function seems untenable. We prefer the notion of the omentum and its milky spots as the abdominal policeman rather than a misplaced thymus, and argue that their important association is not with the gut lumen but with the peritoneal cavity. Milky spots are reactive structures that increase in both size and number after appropriate stimulation. Situated in direct contact with the peritoneal cavity, glomus-like collections of vascular capillaries form a framework for milky spot macrophages and dendritic cells.1 Activation of these alarm cells can trigger a rapid exudation of neutrophils and macrophages in response to peritoneal infection.2 Although minute quantities of ingested particulate material find their way from the intestinal lumen to omental milky spots (and, importantly, to parathymic lymph nodes and thymic cortex), these amounts are considerably less than those entering GALT.3 The presence of milky spots might qualify the omentum to be a peripheral lymphoid organ.4 However, it should be remembered that in circumstances that include various autoimmune, infectious, and neoplastic conditions, lymphoreticular tissue can appear almost anywhere in the mesenchyme.5 In mice, repeated intraperitoneal injection of antigen leads to the appearance of IgM and IgG forming cells in omental milky spots, cells that almost certainly derive, via the circulation, from other remote lymphoid organs, including the