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POSTNATAL TRANSMISSION OF AIDS-ASSOCIATED RETROVIRUS FROM MOTHER TO INFANT
896
POSTNATAL TRANSMISSION OF AIDS-ASSOCIATED RETROVIRUS FROM MOTHER TO INFANT DAVID A. COOPER JOHN B. ZIEGLER RICHARD O. JOHNSON JULIAN GOLD for the Sydney AIDS Study Group* Prince of Wales Children’s and St Vincent’s Hospitals, Centre for Immunology, University of NSW; and Albion Street Centre, Sydney Hospital, Sydney NSW Australia
The third child of a previously healthy woman was delivered by caesarean section. Because of intraoperative blood loss, a blood transfusion was given after the delivery. The baby was breast-fed for 6 weeks. One unit of blood came from a male in whom the acquired immunodeficiency syndrome (AIDS) developed 13 months later. On recall, the mother proved to have lymphadenopathy, serum antibody to the AIDS virus, and a reduced T4/T8 ratio. The infant, who failed to thrive and had atopic eczema from 3 months, has likewise proved to have antibody to the AIDS virus. Since his mother was transfused after his birth, he is presumed to have been infected via breast milk or by way of some other form of close contact with his mother.
Summary
Introduction
_
THE aetiological agents of the acquired immunodeficiency syndrome (AIDS) are a group of recently described lymphocytopathic retroviruses known as lymphadenopathyassociated virus (LAV),’ human T-lymphotropic virus type III (HTL V-III),2 and AIDS-associated retrovirus (ARV).3 Groups at risk of acquiring this disease are male homosexuals or bisexuals, intravenous drug abusers, recipients of blood and blood products, Haitians, and the heterosexual partners of individuals in these groups.4-7 Affected infants, who account for about 1% of cases of AIDS, have usually been born to women in these at-risk groups.A smaller number of infants seem to have acquired the disease from blood transfusions.9 Where the mother has been the apparent source of infection in infants, all reports have been consistent with transmission in utero or during the birth process. 10-12 *Sydney AIDS Study Group Consultant: A. I. Adams. Project coordinators: D. A. Cooper, J. Gold. Centre for Immunology, St Vincent’s Hospital, Sydney: R. Penny, G. Chapman, A. Imre, J. Kramer, L. McKenzie, P. Maclean, P. Meyer, A. Norris, A. Ryan, E. Scheuers, B. Spinks, B. Tindall. Prince of Wales Children’s Hospital: J. B. Ziegler, O. Westcott. School of Public Health and Tropical Medicine, University of Sydney: G. Berry, J. Mandryk, P. Mock. Albion Street Centre, Sydney Hospital: J. Burcham, P. McCarthy, P. Todd, J. Watts. STD Centre, Sydney Hospital: C. Brown, R. Philpot, R. P. Jones, J. Roberts. Participating Medical Practitioners: T. G. Barnes, P. Brooke, B. Donovan, R. Finlayson, P. Haynes, H. M. Michelmore, K. Mutimer, R. Price. Gays Counselling Service of NSW and AIDS Support Group, Sydney: T.
Goulden, J. Dykes.
29. Taasan VC, Block AJ, Boysen PG, et al. Alcohol increases sleep apnoea and oxygen desaturation in asymptomatic men. Am J Med 1981; 71: 240-45. 30. Issa FG, Sullivan CE. Alcohol, snoring and sleep apnoea. J Neurol Neurosurg Psychiatry 1982; 45: 353-59. 31. Cherniack NS. Respiratory dysrhythmias during sleep. N Engl J Med 1981; 305: 325-30 32. Schroeder JS, Motta J, Guilleminault C. Hemodynamic studies in sleep apnoea. In: Guilleminault C, Dement WC, eds. Sleep apnoea syndromes. New York: Alan R Liss, Inc, 1978: 177-96.
favours
evidence
Epidemiological
transplacental
transmission, since infants of at-risk parents tend to show signs of infection earlier than do those receiving affected transfusions post-partum.13 Since the virus has been isolated from lymphocytes14 and since viable maternal lymphocytes can reach a fetus transplacentally,15 it seems certain that this mode of transmission operates, perhaps in addition to other routes. We report here the case of a child who appears to have acquired ARV from his mother who was not exposed to a source of infection until after the child was delivered. Transmission via breast milk seems the likely route of infection. Methods Serum concentrations of immunoglobulins G, A, and M were measured by rate nephelometry (Beckman) and IgE by paper radioimmunoabsorbent assay (Pharmacia). To quantitate circulating lymphocyte subsets, circulating mononuclear cells were isolated on ’Ficoll-Hypaque’, stained with fluoresceinated monoclonal antibodies against surface membrane markers (Ortho Corporation, Raritan NJ, USA), and analysed by flow cytometry (Epics C, Coulter Corporation, Hialeah, FL, USA). Serum antibodies to ARV were detected by indirect immunofluorescence assay, with an ARV infected cell line, test sera at a dilution of 1:10, and fluoresceinated goat anti-human Ig. 16 Positive sera identified in this way werechecked by an enzyme-linked immunosorbent assay for antibodies to HTLV-111 and by a radioimmunoprecipitation assay for antibodies to the LAV antigen p25 which is less sensitive but has greater specificity.
Case-report The
patient is the third child of a previously healthy white woman. There is a family history of a mild form of congenital dysfibrinogenaemia inherited in an autosomal dominant fashion: his mother and older brother are affected but symptomless. The two older siblings had been delivered vaginally without haemostatic complications. The mother had not previously received blood or blood products. Apart from mild eczema in two paternal cousins, there is no family history of atopy. The third pregnancy was complicated by polyhydramnios and moderate third-trimester vaginal bleeding due to placenta praevia. The child was delivered at term by lower-segment caesarean section performed because of fetal bradycardia. 1200 ml of blood loss was recorded during this procedure and placental-bed oozing was noted. 15 min after completion of the third stage of the delivery, a transfusion of 2 units of whole blood was begun. The second of these had been donated by a male homosexual who was then well but in whom Kaposi’s sarcoma and Pneumocystis carinii pneumonitis developed simultaneously 13 months later; he was immunodeficient and had antibody to ARV. Birthweight was 4100 g, Apgar scores were 9 and 10, and no serious neonatal disorders were reported. The mother received a further blood transfusion of 2 units on the second day. Breast-feeding was established on the first day and continued for 6 weeks. No problems with breast feeding were reported and there were no nipple difficulties. The baby had gastro-oesophageal reflux, subsequently demonstrated by barium studies, from day 1 and this persisted for several months. Apart from one episode of impetigo, no infections have been noted. Atopic dermatitis developed at age 3 months and poor weight gain was noted from that time. Iron-
33. Kales A, Bixler Lancet 1984;
EO, Cedieux RJ,
1005-08. 34. Yasue H, Omote S, Takizawa A,
et
al.
Sleep
apnoea in
a
hypertensive population
n:
Nagao M, Miwa K, Tanaka S. Circadian variation of patients with Prinzmetal’s variant angina: Role of exerciseinduced coronary arterial spasm. Circulation 1979; 59: 938-48. 35. Yasue H. Pathophysiology and treatment of coronary arterial spasm. Chest 1980, 78: exercise
216-23.
capacity
in
897 TABLE I-ANTIBODIES TO HTLV-III
*IF, Immunofluorescence; ELISA, enzyme-linked immunosorbent RIPA, radio-immunoprecipitation assay.
assay;
TABLE II-IMMUNOLOGICAL STUDIES ON THE PATIENT AND HIS MOTHER
been infected after the delivery. Her husband is seronegative and no other risk factors are operating. The persistence of such passively acquired antibodies to age 17 months is unlikely. The child may have been immunised by noninfectious material of viral origin-present, for example, in breast milk-but a recent prospective study has documented infection in every instance of seroconversion in a homosexual population.16 The most likely explanation is that the child was infected with the AIDS virus. Since he has not been transfused and since his mother has been infected she represents the most likely source of his infection. The virus can be demonstrated in semen 14 and saliva,17 and there is no reason to expect that it will not be found in milk; so breast feeding represents a likely mode of infection. Since clinical disease has been documented within 6-13 days of exposure to virus, 16,18 there is no reason to doubt the possibility of the mother’s infectivity during the 6 weeks of breast feeding. The existence of active eczema for most of the child’s life raises another hypothesis-viral entry from maternal saliva or other secretions in contact with the skin. Eczema is a common observation in children with AIDSIO-13 but has been assumed to be a consequence rather than a predisposing factor in their
disease.
ND = not determined.
responsive anaemia was diagnosed at age 13 months at which time he was being fed almost entirely on cow’s milk. Upper gastrointestinal endoscopy at 16 months showed a mild oesophagitis with
no evidence of candida infection. At age 17 months his dermatitis has been controlled by topical corticosteroids and skin moisturisers; with resolution of reflux and introduction of solid foods he has gained 1 kg weight in 2 months. He is now of normal height, weight is at 3rd percentile, development is normal, mild flexural eczema is present, and he has inguinal, axillary, and cervical lymphadenopathy. Liver and spleen are of normal size, mucosae are clear, and his respiratory system is normal. The child’s mother is aged 34 years, weighs 58’7kg, and is well.
She has bilateral axillary lymphadenopathy with soft, discrete, nontender nodes up to 1 cm in length. The thyroid gland is diffusely enlarged to twice normal size and a single firm nodule 0 -5cm in diameter is palpable at the lower pole of the right lobe. The child’s father denies homosexual contact.
The likelihood of future development of ARV-related illness in this child is unknown and, since incubation periods can be as long as 5 years, it will be some time before we can presume that he will continue in good health. It is possible, however, that his eczema and failure-to-thrive were symptomatic of an AIDS-related illness from which he has recovered. Such recovery has been previously reported.19 The questions raised by the observations reported here could be addressed in a primate model; breast milk of other infected women could be examined for virus; and comparison of breast-feeding rates among infected and uninfected children of carrier mothers would show whether breast feeding represents an important mode of transmission from mother to infant (as may be the case for hepatitis B). Until these issues are resolved, lactating women falling into high risk groups for infection with AIDS virus should be advised of the possibility of transmission via breast milk. We thank Dr Ian Gust, Queen’s Memorial Hospital for Infectious Diseases, Fairfield, Victoria, Australia, for performing ELISA and RIPA antibody tests.
Correspondence should be addressed to J. B. Z., Prince of Wales Children’s Hospital, High Street, Randwick, NSW 2031, Australia. REFERENCES 1. Barré-Smoussi
from
Results
Discussion The observation that this child has antibody to the AIDS virus could have several explanations. These antibodies could have been transplacentally transmitted in utero, but this seems unlikely since the mother must be assumed to have
F, Chermann JC, Rey F, et al. Isolation ofa T-lymphotropic retrovirus patient at risk for acquired immune deficiency syndrome (AIDS). Science
1983; 220: 2. Gallo
When the blood-donor was diagnosed as having AIDS, the mother and child were examined and found also to be seropositive. Results of these assays are shown in table I and results of the immunological analyses in table II. The infant is immunologically normal. The mother has reduced numbers of circulating T4 positive (helper/inducer) and T8 positive (cytotoxic/suppressor) T cells and a reduced T4/T8 ratio. The child’s father and two older siblings are seronegative.
a
868-71.
RC, Shearer GM, Kaplan
M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.
Science 1984; 224: 500-03. Hoffman AD, Dramer SM, Landis JA, Shimabukuro JM, Oshiro LS. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984; 225: 840-43. 4. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. N Engl J Med 1981; 305: 1425-31 5. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia. N Engl J Med 1981; 305: 1431-38. 6. Curran JW, Lawrence DN, Jaffe H, et al. Acquired immune deficiency syndrome 1984; 310: 69-75. (AIDS) associated with transfusions. N Engl Med J 7. Harris C, Small CB, Klein RS, et al. Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome. N Engl J Med 1983; 308: 1181-84. 8. CDC. Update: Acquired immunodeficiency syndrome (AIDS)-United States. MMWR 1984; 33: 661-64. 9. Ammann AJ, Cowan MJ, Wara DW, et al. Acquired immunodeficiency in an infant: possible transmission by means of blood products. Lancet 1983; i: 956-58. 3.
Levy JA,
898
MEASUREMENT OF GASTRIC EMPTYING RATES BY RADIOACTIVE ISOTOPE SCANNING AND EPIGASTRIC IMPEDANCE
J. Human
A. SUTTON
SYLVIA THOMPSON
Pharmacology Unit, Beecham Research Laboratories, Coldharbour Road Harlow, Essex CM19 5AD R. SOBNACK
Radioisotope Department,
London
Hospital,
London
When
liquids of low electrical conductivity the stomach the impedance of the epigastric mA, 100 kHz current increases. There follows a decline, which logically represents gastric emptying. This method of measuring gastric emptying was compared against scintigraphy in six volunteers, and similar results were obtained. Impedance monitoring is entirely noninvasive, inexpensive, simple, and quick. The method merits further exploration.
Summary
enter region to a 4
Fig 1-Impedance measuring equipment. Zo=basal impedance level.
Introduction IMPEDANCE is the alternating current equivalent of direct current resistance. It has long been used to monitor volumes of air in pneumography, and impedance cardiography is a sensitive and accurate method of measuring blood volume. 1,2 Impedance has also been used to measure gastric volume and hence gastric emptying rates-for example, after metoclopramide.3,4 Rates measured by impedance are as5 reliable as those measured by a dye-dilution method. Scintigraphy is an accurate method of measuring gastric emptying.6-8 In this study we compared impedance methods against scintigraphy in monitoring the gastric emptying of a liquid meal.
Methods
Fig 2-Electrode positions for epigastric impedance. electrodes (Hewlett Packard), one anterior and one posterior to the stomach (fig 2). Fluctuations in the current as it passed through the
epigastric region were collected via two recording electrodes and amplified, demodulated, and recorded directly onto a y-t chart-
Study Design The volunteers were six men of average age 44 years (range 34 to 55) who gave their informed consent to participate. London Hospital ethical committee approval was obtained. The volunteers were asked to abstain from food and tobacco overnight. They lay supine beneath the gamma camera, which meant that the test meal had to be drunk through a wide-bore plastic tube. The meal was a 600 ml mixture of 110 ml orange flavoured ’Quosh’, 490 ml water, and 20 g 99Tc-diethylene triamine penta-acetic acid (DTPA), drunk as rapidly as possible.
Impedance The impedance epigastrograph closely resembles standard respiratory impedance equipment except that it has a 0 1 Hz lowpass filter to exclude much respiratory and all cardiac interference (fig 1). A small (4 mA) AC current at 100 kHz was derived from 2-9 volt batteries so that volunteers were isolated from mains supply. The current was passed through silver/silver chloride input
recorder. The impedance half-emptying time is defined as the time taken to reverse half the initial deflection consequent upon taking the liquid meal.
Scintigraphy A small-field-of-view gamma camera (CE 1 Elscint, Haifa) centred the 140 KeV 99mTc-photopeak with a j:200/0 windows, was positioned anteriorly on the upper left quadrant and lowered to within 5 cm of the abdomen. Immediately after 99mTc DTPA was swallowed data collection began as 40 sequential 1-min or alternating 30 s frames. Data was stored in a 128x 128 matrix. A ’Nodecrest NMS 1000’ computer was used to define the region of interest (ROI) from a composite of frames taken over 10 min intervals. Counts accumulated in the ROI during 1 min or 30 second intervals were computed after correction for physical decay of on
99mTc.
10. Oleske 11
J, Minnefor A, Cooper R, et al Immune deficiency syndrome in children. JAMA 1983; 249: 2345-49. Rubinstein A, Sicklick M, Gupta A, et al. Acquired immunodeficiency with reversed T4/T8 ratios in infants born to promiscuous and drug-addicted mothers JAMA
1983, 249: 2350-56. 12. Scott GB, Buck BE, Letterman JG, Bloom FL, Parks WP. Acquired immunodeficiency syndrome in infants N Engl J Med 1984; 310: 76-81. 13 Thomas PA, Jaffe HW, Spira TJ, Reiss R, Guerrero IC, Auerbach D. Unexplained 14
immunodeficiency in children A surveillance report JAMA 1984; 252: 639-44. Zagury D, Bernard J, Leibow itch J, et al HTLV-III in cells cultured from semen of two patients with AIDS Science 1984; 236: 449-51. J, Conte FA, Grumbach MM Practical and theoretical
15 Walnowska
implications of
16.
fetal/maternal lymphocyte transfer Lancet 1969, i: 1119-22. Cooper DA, Gold J, Maclean P, Donovan B, Barnes TG, Michelmore MB, Brooke P. Penny R Acute AIDS retrovirus infection. Definition of aclinical illness associated with
17.
seroconversion.
Lancet 1985,
i:
537-40
Groopman JE, Salahuddin SZ, Sarngadharan MG, et al. HTLV-III in saliva of people with AIDS-related complex and healthy homosexual men at risk for AIDS Science
1984; 226: 447-49. 18. Editorial Needlestick transmission of HTLV-III from a patient infected in Africa Lancet 1984; ii: 1376-77. 19. Brun-Vezinet F, Rouzioux C. Montagnier L, et al. Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS. Science 1984; 226: 453-56.
POSTNATAL TRANSMISSION OF AIDS-ASSOCIATED RETROVIRUS FROM MOTHER TO INFANT DAVID A. COOPER JOHN B. ZIEGLER RICHARD O. JOHNSON JULIAN GOLD for the Sydney AIDS Study Group* Prince of Wales Children’s and St Vincent’s Hospitals, Centre for Immunology, University of NSW; and Albion Street Centre, Sydney Hospital, Sydney NSW Australia
The third child of a previously healthy woman was delivered by caesarean section. Because of intraoperative blood loss, a blood transfusion was given after the delivery. The baby was breast-fed for 6 weeks. One unit of blood came from a male in whom the acquired immunodeficiency syndrome (AIDS) developed 13 months later. On recall, the mother proved to have lymphadenopathy, serum antibody to the AIDS virus, and a reduced T4/T8 ratio. The infant, who failed to thrive and had atopic eczema from 3 months, has likewise proved to have antibody to the AIDS virus. Since his mother was transfused after his birth, he is presumed to have been infected via breast milk or by way of some other form of close contact with his mother.
Summary
Introduction
_
THE aetiological agents of the acquired immunodeficiency syndrome (AIDS) are a group of recently described lymphocytopathic retroviruses known as lymphadenopathyassociated virus (LAV),’ human T-lymphotropic virus type III (HTL V-III),2 and AIDS-associated retrovirus (ARV).3 Groups at risk of acquiring this disease are male homosexuals or bisexuals, intravenous drug abusers, recipients of blood and blood products, Haitians, and the heterosexual partners of individuals in these groups.4-7 Affected infants, who account for about 1% of cases of AIDS, have usually been born to women in these at-risk groups.A smaller number of infants seem to have acquired the disease from blood transfusions.9 Where the mother has been the apparent source of infection in infants, all reports have been consistent with transmission in utero or during the birth process. 10-12 *Sydney AIDS Study Group Consultant: A. I. Adams. Project coordinators: D. A. Cooper, J. Gold. Centre for Immunology, St Vincent’s Hospital, Sydney: R. Penny, G. Chapman, A. Imre, J. Kramer, L. McKenzie, P. Maclean, P. Meyer, A. Norris, A. Ryan, E. Scheuers, B. Spinks, B. Tindall. Prince of Wales Children’s Hospital: J. B. Ziegler, O. Westcott. School of Public Health and Tropical Medicine, University of Sydney: G. Berry, J. Mandryk, P. Mock. Albion Street Centre, Sydney Hospital: J. Burcham, P. McCarthy, P. Todd, J. Watts. STD Centre, Sydney Hospital: C. Brown, R. Philpot, R. P. Jones, J. Roberts. Participating Medical Practitioners: T. G. Barnes, P. Brooke, B. Donovan, R. Finlayson, P. Haynes, H. M. Michelmore, K. Mutimer, R. Price. Gays Counselling Service of NSW and AIDS Support Group, Sydney: T.
Goulden, J. Dykes.
29. Taasan VC, Block AJ, Boysen PG, et al. Alcohol increases sleep apnoea and oxygen desaturation in asymptomatic men. Am J Med 1981; 71: 240-45. 30. Issa FG, Sullivan CE. Alcohol, snoring and sleep apnoea. J Neurol Neurosurg Psychiatry 1982; 45: 353-59. 31. Cherniack NS. Respiratory dysrhythmias during sleep. N Engl J Med 1981; 305: 325-30 32. Schroeder JS, Motta J, Guilleminault C. Hemodynamic studies in sleep apnoea. In: Guilleminault C, Dement WC, eds. Sleep apnoea syndromes. New York: Alan R Liss, Inc, 1978: 177-96.
favours
evidence
Epidemiological
transplacental
transmission, since infants of at-risk parents tend to show signs of infection earlier than do those receiving affected transfusions post-partum.13 Since the virus has been isolated from lymphocytes14 and since viable maternal lymphocytes can reach a fetus transplacentally,15 it seems certain that this mode of transmission operates, perhaps in addition to other routes. We report here the case of a child who appears to have acquired ARV from his mother who was not exposed to a source of infection until after the child was delivered. Transmission via breast milk seems the likely route of infection. Methods Serum concentrations of immunoglobulins G, A, and M were measured by rate nephelometry (Beckman) and IgE by paper radioimmunoabsorbent assay (Pharmacia). To quantitate circulating lymphocyte subsets, circulating mononuclear cells were isolated on ’Ficoll-Hypaque’, stained with fluoresceinated monoclonal antibodies against surface membrane markers (Ortho Corporation, Raritan NJ, USA), and analysed by flow cytometry (Epics C, Coulter Corporation, Hialeah, FL, USA). Serum antibodies to ARV were detected by indirect immunofluorescence assay, with an ARV infected cell line, test sera at a dilution of 1:10, and fluoresceinated goat anti-human Ig. 16 Positive sera identified in this way werechecked by an enzyme-linked immunosorbent assay for antibodies to HTLV-111 and by a radioimmunoprecipitation assay for antibodies to the LAV antigen p25 which is less sensitive but has greater specificity.
Case-report The
patient is the third child of a previously healthy white woman. There is a family history of a mild form of congenital dysfibrinogenaemia inherited in an autosomal dominant fashion: his mother and older brother are affected but symptomless. The two older siblings had been delivered vaginally without haemostatic complications. The mother had not previously received blood or blood products. Apart from mild eczema in two paternal cousins, there is no family history of atopy. The third pregnancy was complicated by polyhydramnios and moderate third-trimester vaginal bleeding due to placenta praevia. The child was delivered at term by lower-segment caesarean section performed because of fetal bradycardia. 1200 ml of blood loss was recorded during this procedure and placental-bed oozing was noted. 15 min after completion of the third stage of the delivery, a transfusion of 2 units of whole blood was begun. The second of these had been donated by a male homosexual who was then well but in whom Kaposi’s sarcoma and Pneumocystis carinii pneumonitis developed simultaneously 13 months later; he was immunodeficient and had antibody to ARV. Birthweight was 4100 g, Apgar scores were 9 and 10, and no serious neonatal disorders were reported. The mother received a further blood transfusion of 2 units on the second day. Breast-feeding was established on the first day and continued for 6 weeks. No problems with breast feeding were reported and there were no nipple difficulties. The baby had gastro-oesophageal reflux, subsequently demonstrated by barium studies, from day 1 and this persisted for several months. Apart from one episode of impetigo, no infections have been noted. Atopic dermatitis developed at age 3 months and poor weight gain was noted from that time. Iron-
33. Kales A, Bixler Lancet 1984;
EO, Cedieux RJ,
1005-08. 34. Yasue H, Omote S, Takizawa A,
et
al.
Sleep
apnoea in
a
hypertensive population
n:
Nagao M, Miwa K, Tanaka S. Circadian variation of patients with Prinzmetal’s variant angina: Role of exerciseinduced coronary arterial spasm. Circulation 1979; 59: 938-48. 35. Yasue H. Pathophysiology and treatment of coronary arterial spasm. Chest 1980, 78: exercise
216-23.
capacity
in
897 TABLE I-ANTIBODIES TO HTLV-III
*IF, Immunofluorescence; ELISA, enzyme-linked immunosorbent RIPA, radio-immunoprecipitation assay.
assay;
TABLE II-IMMUNOLOGICAL STUDIES ON THE PATIENT AND HIS MOTHER
been infected after the delivery. Her husband is seronegative and no other risk factors are operating. The persistence of such passively acquired antibodies to age 17 months is unlikely. The child may have been immunised by noninfectious material of viral origin-present, for example, in breast milk-but a recent prospective study has documented infection in every instance of seroconversion in a homosexual population.16 The most likely explanation is that the child was infected with the AIDS virus. Since he has not been transfused and since his mother has been infected she represents the most likely source of his infection. The virus can be demonstrated in semen 14 and saliva,17 and there is no reason to expect that it will not be found in milk; so breast feeding represents a likely mode of infection. Since clinical disease has been documented within 6-13 days of exposure to virus, 16,18 there is no reason to doubt the possibility of the mother’s infectivity during the 6 weeks of breast feeding. The existence of active eczema for most of the child’s life raises another hypothesis-viral entry from maternal saliva or other secretions in contact with the skin. Eczema is a common observation in children with AIDSIO-13 but has been assumed to be a consequence rather than a predisposing factor in their
disease.
ND = not determined.
responsive anaemia was diagnosed at age 13 months at which time he was being fed almost entirely on cow’s milk. Upper gastrointestinal endoscopy at 16 months showed a mild oesophagitis with
no evidence of candida infection. At age 17 months his dermatitis has been controlled by topical corticosteroids and skin moisturisers; with resolution of reflux and introduction of solid foods he has gained 1 kg weight in 2 months. He is now of normal height, weight is at 3rd percentile, development is normal, mild flexural eczema is present, and he has inguinal, axillary, and cervical lymphadenopathy. Liver and spleen are of normal size, mucosae are clear, and his respiratory system is normal. The child’s mother is aged 34 years, weighs 58’7kg, and is well.
She has bilateral axillary lymphadenopathy with soft, discrete, nontender nodes up to 1 cm in length. The thyroid gland is diffusely enlarged to twice normal size and a single firm nodule 0 -5cm in diameter is palpable at the lower pole of the right lobe. The child’s father denies homosexual contact.
The likelihood of future development of ARV-related illness in this child is unknown and, since incubation periods can be as long as 5 years, it will be some time before we can presume that he will continue in good health. It is possible, however, that his eczema and failure-to-thrive were symptomatic of an AIDS-related illness from which he has recovered. Such recovery has been previously reported.19 The questions raised by the observations reported here could be addressed in a primate model; breast milk of other infected women could be examined for virus; and comparison of breast-feeding rates among infected and uninfected children of carrier mothers would show whether breast feeding represents an important mode of transmission from mother to infant (as may be the case for hepatitis B). Until these issues are resolved, lactating women falling into high risk groups for infection with AIDS virus should be advised of the possibility of transmission via breast milk. We thank Dr Ian Gust, Queen’s Memorial Hospital for Infectious Diseases, Fairfield, Victoria, Australia, for performing ELISA and RIPA antibody tests.
Correspondence should be addressed to J. B. Z., Prince of Wales Children’s Hospital, High Street, Randwick, NSW 2031, Australia. REFERENCES 1. Barré-Smoussi
from
Results
Discussion The observation that this child has antibody to the AIDS virus could have several explanations. These antibodies could have been transplacentally transmitted in utero, but this seems unlikely since the mother must be assumed to have
F, Chermann JC, Rey F, et al. Isolation ofa T-lymphotropic retrovirus patient at risk for acquired immune deficiency syndrome (AIDS). Science
1983; 220: 2. Gallo
When the blood-donor was diagnosed as having AIDS, the mother and child were examined and found also to be seropositive. Results of these assays are shown in table I and results of the immunological analyses in table II. The infant is immunologically normal. The mother has reduced numbers of circulating T4 positive (helper/inducer) and T8 positive (cytotoxic/suppressor) T cells and a reduced T4/T8 ratio. The child’s father and two older siblings are seronegative.
a
868-71.
RC, Shearer GM, Kaplan
M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.
Science 1984; 224: 500-03. Hoffman AD, Dramer SM, Landis JA, Shimabukuro JM, Oshiro LS. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984; 225: 840-43. 4. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. N Engl J Med 1981; 305: 1425-31 5. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia. N Engl J Med 1981; 305: 1431-38. 6. Curran JW, Lawrence DN, Jaffe H, et al. Acquired immune deficiency syndrome 1984; 310: 69-75. (AIDS) associated with transfusions. N Engl Med J 7. Harris C, Small CB, Klein RS, et al. Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome. N Engl J Med 1983; 308: 1181-84. 8. CDC. Update: Acquired immunodeficiency syndrome (AIDS)-United States. MMWR 1984; 33: 661-64. 9. Ammann AJ, Cowan MJ, Wara DW, et al. Acquired immunodeficiency in an infant: possible transmission by means of blood products. Lancet 1983; i: 956-58. 3.
Levy JA,
898
MEASUREMENT OF GASTRIC EMPTYING RATES BY RADIOACTIVE ISOTOPE SCANNING AND EPIGASTRIC IMPEDANCE
J. Human
A. SUTTON
SYLVIA THOMPSON
Pharmacology Unit, Beecham Research Laboratories, Coldharbour Road Harlow, Essex CM19 5AD R. SOBNACK
Radioisotope Department,
London
Hospital,
London
When
liquids of low electrical conductivity the stomach the impedance of the epigastric mA, 100 kHz current increases. There follows a decline, which logically represents gastric emptying. This method of measuring gastric emptying was compared against scintigraphy in six volunteers, and similar results were obtained. Impedance monitoring is entirely noninvasive, inexpensive, simple, and quick. The method merits further exploration.
Summary
enter region to a 4
Fig 1-Impedance measuring equipment. Zo=basal impedance level.
Introduction IMPEDANCE is the alternating current equivalent of direct current resistance. It has long been used to monitor volumes of air in pneumography, and impedance cardiography is a sensitive and accurate method of measuring blood volume. 1,2 Impedance has also been used to measure gastric volume and hence gastric emptying rates-for example, after metoclopramide.3,4 Rates measured by impedance are as5 reliable as those measured by a dye-dilution method. Scintigraphy is an accurate method of measuring gastric emptying.6-8 In this study we compared impedance methods against scintigraphy in monitoring the gastric emptying of a liquid meal.
Methods
Fig 2-Electrode positions for epigastric impedance. electrodes (Hewlett Packard), one anterior and one posterior to the stomach (fig 2). Fluctuations in the current as it passed through the
epigastric region were collected via two recording electrodes and amplified, demodulated, and recorded directly onto a y-t chart-
Study Design The volunteers were six men of average age 44 years (range 34 to 55) who gave their informed consent to participate. London Hospital ethical committee approval was obtained. The volunteers were asked to abstain from food and tobacco overnight. They lay supine beneath the gamma camera, which meant that the test meal had to be drunk through a wide-bore plastic tube. The meal was a 600 ml mixture of 110 ml orange flavoured ’Quosh’, 490 ml water, and 20 g 99Tc-diethylene triamine penta-acetic acid (DTPA), drunk as rapidly as possible.
Impedance The impedance epigastrograph closely resembles standard respiratory impedance equipment except that it has a 0 1 Hz lowpass filter to exclude much respiratory and all cardiac interference (fig 1). A small (4 mA) AC current at 100 kHz was derived from 2-9 volt batteries so that volunteers were isolated from mains supply. The current was passed through silver/silver chloride input
recorder. The impedance half-emptying time is defined as the time taken to reverse half the initial deflection consequent upon taking the liquid meal.
Scintigraphy A small-field-of-view gamma camera (CE 1 Elscint, Haifa) centred the 140 KeV 99mTc-photopeak with a j:200/0 windows, was positioned anteriorly on the upper left quadrant and lowered to within 5 cm of the abdomen. Immediately after 99mTc DTPA was swallowed data collection began as 40 sequential 1-min or alternating 30 s frames. Data was stored in a 128x 128 matrix. A ’Nodecrest NMS 1000’ computer was used to define the region of interest (ROI) from a composite of frames taken over 10 min intervals. Counts accumulated in the ROI during 1 min or 30 second intervals were computed after correction for physical decay of on
99mTc.
10. Oleske 11
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