Early
Human
Development,
29 (1992)
221
221-224
Elsevier Scientific Publishers Ireland Ltd. EHD 01279
Clinical presentation of HIV/AIDS in the high risk neonate in Zambia M.P. Shilalukey-Ngoma,A. Mushanga, X. Wang and M. Watanabe Neonatal
Intensive
Care Unit,
University
Teaching
Hospital, (Zambia)
School
of Medicine.
P. 0. Box 501 IO. Lusaka
A prospective case series study was conducted Jan 1991-Ott 1991 on 108 neonates admitted to NICU, Lusaka. 90 patients satisfied inclusion criteria, 45 cases and 45 controls. Symptomatic seropositive babies born to seropositive mothers presented with failure to thrive, fever, persistant or recurrent thrush, severe Sepsis and large liver. Tendency to prematurity among cases was high. Diarrhoea, Sepsis and Haemolytic Anaemia appear to be terminal signs. Neonates suffer the most aggressive form of HIV/AIDS, with symptomatic cases dying 3-4152 of onset of symptoms. Over one quarter of the mothers were symptomatic. Congenital malformations and Lymphadenopathy were not significantly associated. Microcephaly occurred in association with failure to thrive and was not an isolated finding. Key words: symptomatic Zambia
seropositive babies; seropositive mothers; HIV/AIDS;
Introduction The Neonatal Intensive Care Unit (NICU), admits between 250 and 350 neonates per month requiring special or intensive care. These include Premature, Birth Asphyxia, Sepsis and Congenital Malformations. HIV and AIDS constitutes about 5% of all ‘high risk’ admissions to the NICU (1990) [ 11. Two hundred neonates diagnosed as HIV infection were treated on NICU, 1990. The positive antibody under 18 months of age may merely reflect maternal antibody (3.67). However, neonates with suggestive symptoms and positive antibodies, made the diagnosis of HIV/AIDS more likely in our highly select infants.
Correspondence to: M.P. Shilalukey-Ngoma, Neonatal Intensive Care Unit, University Teaching Hospital, School of Medicine, P.O. Box 50110, Lusaka, Zambia.
222
Patients and methods A prospective study of high risk neonates with symptoms of immunodeticiency and positive antibody to HIV, was conducted between Jan 1991 and Oct. 1991, on the basis of the 1990 observations. Cases were aged 3 months and less at recruitment. All 45 cases had informed consent. Mothers received pretest and post test counselling and were tested for HIV antibody as well. Forty-five controls were tested anonymously [2]. Controls were matched for gestation, with cases. A further 18 babies who tested positive and had no special features were excluded, but are under follow-up. In total 108 babies were documented.
Of the 45 mothers, age 16-38 years, (average 22.9 years), 43 out of 45(95.6%) were seropositive, while 2 out of 45 mothers were seronegative (4.4%), but had seropositive babies. Seven out of 45 (15.6%) were also positive for syphilis. Some mothers, 12 out of 45 (26.7%) were already ill, 3 with proven pulmonary tuberculosis, 2 terminally ill, 2 vaginal warts and 1 with Herpes Genitalis, 1 pelvic abscess, 1 malaria, 1 sickle cell disease and 1 had died. We had limited or no contact with most fathers. All mothers of the 45 gestation - matched controls were well with the exception of 1 who had Rheumatic Heart Disease. Mothers were not tested as babies had been tested anonymously, to avoid unwarranted anxiety [2]. Of the 45 cases, 33 (73.3%) were preterm, 12 (26.7%) term and none post term, suggesting that babies with HIV infection tend to be born prematurely. More than half, 26 (57.8%) were small for dates, with 17 (37.8%) appropriate for dates and only 2 (4.4%) large for dates. Controls had 28 out of 45, (62.2%) small for dates. Small for dates is not significant in the population under study. Of all cases, 1 out of 45 became seronegative at 9 months (Margin of Error 2.2%). We lost 8 (17.8%) to follow up, presumably parents fell ill. Twenty-six out of 45, (57.8%) are dead, while 11 out of 45(24.4%) are still alive. Symptoms occurred from birth to 4 weeks of life, with peak onset 2-3 weeks of age. Death occurred 18 days to 9 months of life, with most deaths occurring 3-4 weeks of onset of symptoms. The majority (66.7%) of our cases presented with failure to thrive, after the second week of life and despite adequate feeds. The failure to thrive was generalised. Microcephaly was the direct result of the failure to thrive and not an isolated or initial finding. Infants had an ‘old man look,’ related to Marasmus. Only 4.5% of our controls showed failure to thrive. As compared to controls, with only 9% infants with fever, our cases had 55.6% showing fever. Most had signs of bacterial infection, i.e. Bronchopneumonia, abscesses, etc. Temperatures ranged from 37.5”C to 39°C. Hepatomegaly (liver size greater than 2 cm below the costal margin) featured in 15 (33.3%) and Splenomegaly in 8 (17.8%). Only 1 infant had palpable lymphnodes. Oral thrush appeared under 1 month of age and was persistent and recurrent, while only 6.7% controls had thrush which cleared easily.
223
Fourteen cases (31.1%) presented for the first time with a haemolytic anaemia (rising serum bilirubin with falling haematocrit and high reticulocytes during the second and third weeks of life. Ten out of the 14 cases required transfusion, and 9 out of 14 died within 2-3 weeks of the appearance of the anaemia with an associated Disseminated Intravascular Coagulation Syndrome. Other clinical conditions which were terminal included diarrhoea, septicaemia and bronchopneumonia (see Table I). Septic spots, bullous eruption, necrotising fasciitis of the scrotal sac, papulardermatoses, herpes and generalised eczema were observed among infants. Urticaria occurred in infants older than 3 months. A miscellaneous collection of cases included Trichomonas Vaginalis Urinary Tract Infection, dactylitis, supraventricular tachycardia and hydrops foetalis. Discussion
Seropositive symptomatic neonates were born of mothers who were mostly seropositive and young, average age 22.9 years. Over one quarter of these mothers were already ill, an unhappy fact of the rising problem of orphans of AIDS in Zambia. It is difficult to explain the 2 seronegative mothers with seropositive infants. There is a tendency to prematurity among our cases [3], while both controls and cases demonstrate a tendency to be small for dates [3-51. Only one of our 45 cases reverted to negative and is well and healthy. Given 25-40% rates of mother-to-child transmission [3,6,7] some margin of error is to be expected inspite the stated inclusion criteria. Once symptomatic, infants become ill and die between 3 to 4 weeks of onset. The disease in these high risk neonates is extremely aggressive. The earlier the onset of symptoms, the more aggressive the disease. TABLE I Clinical features. Feature
Case
Control
Failure to Thrive Fever Hepatomegaly Thrush Haemolytic Anaemia Bronchopneumonia Septicaemia Rash Diarrhoea Spleen Eye Discharge Umb Sepsis Abscesses Other: UT1 (T.V.), Downs, Dactylitis, SVT, Nodes
30 (66.7%) 25 (55,6%) 15 (33.3%) 14 (31.1%) 14 (31.l%)T 13 (28.9%)T 10 (22.2%)T 9 (20%) 8 (17.8%)T 8 (17.8%) 7 (15.6%) 5 (11.1%) 4 (8.9%) 1 (2.2%) of each
2 (4.5%) 4 (9%) 3 (6.7%) 1 (2.2%) 2 (4.5%)
T, terminal.
3 (6.7%) -
224
Prematurity too takes its toll e. g. infants under 1000 G on NICU have almost looo/ mortality [l] complicating the overall presentation and mortality. Failure to thrive is the leading abnormality. The failure to thrive is usually gross, inspite of adequate feeds [3] Microcephaly is related to the failure to thrive and not an initial presentation. Controls show a head growth of 0.2-0.5 cm per week in the first 3 months of life while cases remain static. No special facies or congenital malformations were noted, in contrast to reports from N. America [3]. Fever is a variable indicator of infection in the normal newborn [4,5]. Fifty-five percent of our cases developed fever. Older children have prolonged fever [8] while neonates appear to respond with fever mainly during infection. Hepatosplenomegaly is an indicator of intrauterine infection [4,5]. When Splenomegaly occurred in HIV, it often did not regress with Penicillin therapy. Lymphadenopathy was not a feature among our patients [8]. An unusual haemolytic anaemia reported in 14 cases was terminal in 9 out of 14 cases. Further haemotological assessment is required. One of these cases received 8 transfusions in 14 days before he died. DIC seems to be associated with anaemia and is terminal. Other features, which are difficult to explain include Supraventricular Tachycardia resistant to simple therapy, Trichomonas Vaginalis Urinary Tract Infection, Dactylitis and Hydrops Foetalis. Conclusions 0 While our case series suggest the clinical features to be due to AIDS/HIV, contirmation of these findings is necessary. Clinical diagnosis remains the most useful diagnostic tool. 0 Common forms of presentation - failure to thrive, fever, persistent or recurrent thrush, severe Sepsis and Hepatomegaly. 0 Tendency to prematurity is high in HIV infection. 0 Diarrhoea, Severe Sepsis and Haemolytic anaemia are terminal events. 0 High risk neonates suffer the most aggressive form of HIV/AIDS. 0 The earlier the onset of symptoms, the more aggressive the course of illness. l Policy change, to screen all preterm admissions for HIV. 0 Further studies required to confirm clinical findings. References 1 The care of High Risk Neonates in a Developing Country. Editors: M.P. Shilalukey-Ngoma, C. Chintu and K. Mukelabai (in press). 2 Editorial (1990): Anonymous HIV Testing. Lancet, 10 March, Vol. 35. 3 P&o, P.A. (1991): Wilfert Paediatric AIDS. The Challenge of HIV Infection in Infants, Children and Adolescents, Williams & Wilkins, Baltimore. 4 Vaughan McKay (1979): Nelson Textbook of Paediatrics. W.B. Saunders, Philadelphia. 5 Forfar, J.O. and Aneil, C.G. (1984): Textbook of Paediatrics. Editors: Vaughan, McKay and Berhman, 3rd edn, Vol. 1, Churchill Livingstone, New York. 6 Hira, SK., Kamanga, S. and Bhat, G.J. et al. (1989): Perinatal Transmission of HIV in Zambia. Br. Med. J., 299, 1250-1252. 7 Ryoler, R.R. Nsa, W. and Hassig, S. et al. (1989): Perinatal transmission of human immunodeficiency Virus Type 1 to infants of seropositive women in Zaire. New Engl. J. Med., 320 (25) 1637-1642. 8 AIDS Surveillance, Ministry of Health: DDMS (PHC) Zambia, D649 4189.
Human
Development,
29 (1992)
221
221-224
Elsevier Scientific Publishers Ireland Ltd. EHD 01279
Clinical presentation of HIV/AIDS in the high risk neonate in Zambia M.P. Shilalukey-Ngoma,A. Mushanga, X. Wang and M. Watanabe Neonatal
Intensive
Care Unit,
University
Teaching
Hospital, (Zambia)
School
of Medicine.
P. 0. Box 501 IO. Lusaka
A prospective case series study was conducted Jan 1991-Ott 1991 on 108 neonates admitted to NICU, Lusaka. 90 patients satisfied inclusion criteria, 45 cases and 45 controls. Symptomatic seropositive babies born to seropositive mothers presented with failure to thrive, fever, persistant or recurrent thrush, severe Sepsis and large liver. Tendency to prematurity among cases was high. Diarrhoea, Sepsis and Haemolytic Anaemia appear to be terminal signs. Neonates suffer the most aggressive form of HIV/AIDS, with symptomatic cases dying 3-4152 of onset of symptoms. Over one quarter of the mothers were symptomatic. Congenital malformations and Lymphadenopathy were not significantly associated. Microcephaly occurred in association with failure to thrive and was not an isolated finding. Key words: symptomatic Zambia
seropositive babies; seropositive mothers; HIV/AIDS;
Introduction The Neonatal Intensive Care Unit (NICU), admits between 250 and 350 neonates per month requiring special or intensive care. These include Premature, Birth Asphyxia, Sepsis and Congenital Malformations. HIV and AIDS constitutes about 5% of all ‘high risk’ admissions to the NICU (1990) [ 11. Two hundred neonates diagnosed as HIV infection were treated on NICU, 1990. The positive antibody under 18 months of age may merely reflect maternal antibody (3.67). However, neonates with suggestive symptoms and positive antibodies, made the diagnosis of HIV/AIDS more likely in our highly select infants.
Correspondence to: M.P. Shilalukey-Ngoma, Neonatal Intensive Care Unit, University Teaching Hospital, School of Medicine, P.O. Box 50110, Lusaka, Zambia.
222
Patients and methods A prospective study of high risk neonates with symptoms of immunodeticiency and positive antibody to HIV, was conducted between Jan 1991 and Oct. 1991, on the basis of the 1990 observations. Cases were aged 3 months and less at recruitment. All 45 cases had informed consent. Mothers received pretest and post test counselling and were tested for HIV antibody as well. Forty-five controls were tested anonymously [2]. Controls were matched for gestation, with cases. A further 18 babies who tested positive and had no special features were excluded, but are under follow-up. In total 108 babies were documented.
Of the 45 mothers, age 16-38 years, (average 22.9 years), 43 out of 45(95.6%) were seropositive, while 2 out of 45 mothers were seronegative (4.4%), but had seropositive babies. Seven out of 45 (15.6%) were also positive for syphilis. Some mothers, 12 out of 45 (26.7%) were already ill, 3 with proven pulmonary tuberculosis, 2 terminally ill, 2 vaginal warts and 1 with Herpes Genitalis, 1 pelvic abscess, 1 malaria, 1 sickle cell disease and 1 had died. We had limited or no contact with most fathers. All mothers of the 45 gestation - matched controls were well with the exception of 1 who had Rheumatic Heart Disease. Mothers were not tested as babies had been tested anonymously, to avoid unwarranted anxiety [2]. Of the 45 cases, 33 (73.3%) were preterm, 12 (26.7%) term and none post term, suggesting that babies with HIV infection tend to be born prematurely. More than half, 26 (57.8%) were small for dates, with 17 (37.8%) appropriate for dates and only 2 (4.4%) large for dates. Controls had 28 out of 45, (62.2%) small for dates. Small for dates is not significant in the population under study. Of all cases, 1 out of 45 became seronegative at 9 months (Margin of Error 2.2%). We lost 8 (17.8%) to follow up, presumably parents fell ill. Twenty-six out of 45, (57.8%) are dead, while 11 out of 45(24.4%) are still alive. Symptoms occurred from birth to 4 weeks of life, with peak onset 2-3 weeks of age. Death occurred 18 days to 9 months of life, with most deaths occurring 3-4 weeks of onset of symptoms. The majority (66.7%) of our cases presented with failure to thrive, after the second week of life and despite adequate feeds. The failure to thrive was generalised. Microcephaly was the direct result of the failure to thrive and not an isolated or initial finding. Infants had an ‘old man look,’ related to Marasmus. Only 4.5% of our controls showed failure to thrive. As compared to controls, with only 9% infants with fever, our cases had 55.6% showing fever. Most had signs of bacterial infection, i.e. Bronchopneumonia, abscesses, etc. Temperatures ranged from 37.5”C to 39°C. Hepatomegaly (liver size greater than 2 cm below the costal margin) featured in 15 (33.3%) and Splenomegaly in 8 (17.8%). Only 1 infant had palpable lymphnodes. Oral thrush appeared under 1 month of age and was persistent and recurrent, while only 6.7% controls had thrush which cleared easily.
223
Fourteen cases (31.1%) presented for the first time with a haemolytic anaemia (rising serum bilirubin with falling haematocrit and high reticulocytes during the second and third weeks of life. Ten out of the 14 cases required transfusion, and 9 out of 14 died within 2-3 weeks of the appearance of the anaemia with an associated Disseminated Intravascular Coagulation Syndrome. Other clinical conditions which were terminal included diarrhoea, septicaemia and bronchopneumonia (see Table I). Septic spots, bullous eruption, necrotising fasciitis of the scrotal sac, papulardermatoses, herpes and generalised eczema were observed among infants. Urticaria occurred in infants older than 3 months. A miscellaneous collection of cases included Trichomonas Vaginalis Urinary Tract Infection, dactylitis, supraventricular tachycardia and hydrops foetalis. Discussion
Seropositive symptomatic neonates were born of mothers who were mostly seropositive and young, average age 22.9 years. Over one quarter of these mothers were already ill, an unhappy fact of the rising problem of orphans of AIDS in Zambia. It is difficult to explain the 2 seronegative mothers with seropositive infants. There is a tendency to prematurity among our cases [3], while both controls and cases demonstrate a tendency to be small for dates [3-51. Only one of our 45 cases reverted to negative and is well and healthy. Given 25-40% rates of mother-to-child transmission [3,6,7] some margin of error is to be expected inspite the stated inclusion criteria. Once symptomatic, infants become ill and die between 3 to 4 weeks of onset. The disease in these high risk neonates is extremely aggressive. The earlier the onset of symptoms, the more aggressive the disease. TABLE I Clinical features. Feature
Case
Control
Failure to Thrive Fever Hepatomegaly Thrush Haemolytic Anaemia Bronchopneumonia Septicaemia Rash Diarrhoea Spleen Eye Discharge Umb Sepsis Abscesses Other: UT1 (T.V.), Downs, Dactylitis, SVT, Nodes
30 (66.7%) 25 (55,6%) 15 (33.3%) 14 (31.1%) 14 (31.l%)T 13 (28.9%)T 10 (22.2%)T 9 (20%) 8 (17.8%)T 8 (17.8%) 7 (15.6%) 5 (11.1%) 4 (8.9%) 1 (2.2%) of each
2 (4.5%) 4 (9%) 3 (6.7%) 1 (2.2%) 2 (4.5%)
T, terminal.
3 (6.7%) -
224
Prematurity too takes its toll e. g. infants under 1000 G on NICU have almost looo/ mortality [l] complicating the overall presentation and mortality. Failure to thrive is the leading abnormality. The failure to thrive is usually gross, inspite of adequate feeds [3] Microcephaly is related to the failure to thrive and not an initial presentation. Controls show a head growth of 0.2-0.5 cm per week in the first 3 months of life while cases remain static. No special facies or congenital malformations were noted, in contrast to reports from N. America [3]. Fever is a variable indicator of infection in the normal newborn [4,5]. Fifty-five percent of our cases developed fever. Older children have prolonged fever [8] while neonates appear to respond with fever mainly during infection. Hepatosplenomegaly is an indicator of intrauterine infection [4,5]. When Splenomegaly occurred in HIV, it often did not regress with Penicillin therapy. Lymphadenopathy was not a feature among our patients [8]. An unusual haemolytic anaemia reported in 14 cases was terminal in 9 out of 14 cases. Further haemotological assessment is required. One of these cases received 8 transfusions in 14 days before he died. DIC seems to be associated with anaemia and is terminal. Other features, which are difficult to explain include Supraventricular Tachycardia resistant to simple therapy, Trichomonas Vaginalis Urinary Tract Infection, Dactylitis and Hydrops Foetalis. Conclusions 0 While our case series suggest the clinical features to be due to AIDS/HIV, contirmation of these findings is necessary. Clinical diagnosis remains the most useful diagnostic tool. 0 Common forms of presentation - failure to thrive, fever, persistent or recurrent thrush, severe Sepsis and Hepatomegaly. 0 Tendency to prematurity is high in HIV infection. 0 Diarrhoea, Severe Sepsis and Haemolytic anaemia are terminal events. 0 High risk neonates suffer the most aggressive form of HIV/AIDS. 0 The earlier the onset of symptoms, the more aggressive the course of illness. l Policy change, to screen all preterm admissions for HIV. 0 Further studies required to confirm clinical findings. References 1 The care of High Risk Neonates in a Developing Country. Editors: M.P. Shilalukey-Ngoma, C. Chintu and K. Mukelabai (in press). 2 Editorial (1990): Anonymous HIV Testing. Lancet, 10 March, Vol. 35. 3 P&o, P.A. (1991): Wilfert Paediatric AIDS. The Challenge of HIV Infection in Infants, Children and Adolescents, Williams & Wilkins, Baltimore. 4 Vaughan McKay (1979): Nelson Textbook of Paediatrics. W.B. Saunders, Philadelphia. 5 Forfar, J.O. and Aneil, C.G. (1984): Textbook of Paediatrics. Editors: Vaughan, McKay and Berhman, 3rd edn, Vol. 1, Churchill Livingstone, New York. 6 Hira, SK., Kamanga, S. and Bhat, G.J. et al. (1989): Perinatal Transmission of HIV in Zambia. Br. Med. J., 299, 1250-1252. 7 Ryoler, R.R. Nsa, W. and Hassig, S. et al. (1989): Perinatal transmission of human immunodeficiency Virus Type 1 to infants of seropositive women in Zaire. New Engl. J. Med., 320 (25) 1637-1642. 8 AIDS Surveillance, Ministry of Health: DDMS (PHC) Zambia, D649 4189.
