A Case of HIV (Human Immunodeficiency Virus) Infected Child Born to HIV Positive Mother

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A Case of HIV (Human Immunodeficiency Virus) Infected Child Born to HIV Positive Mother Corry S Matondang,1 Siti D. Wisnuwardhani,2 Rulina Suradi,1 Hindra I. Satari1 Graham RR,3Sjawitri P Siregar1, Arwin AP Akib1, Zakiudin Munasir1 (Departments of Child Health1and Obstetrics and Gynecology,2 Medical School, University of Indonesia, and Namru-2 Laboratory,3Jakarta) ABSTRACT a case of HIV infected Indonesian baby girl bom from an HIV positive mother is reported. This is the first HIV infected child reported in Indonesia. The diagnosis was based on the positive DNA HIV and HIV culture in the baby's blood taken at 3 days old. At this time the baby is still asymptomatic. Despite this we gave her prophylactic treatment against Pneumocystis Carinii infection to prevent the possibility of Pneumocystis Carinii Pneumonia which is usually fatal under 1 year old. The positive HIV at 3 days old may indicative of intrauterine nans mission. Because she is still asymptomatic, the intrauterine infection may be occured during late gestation. In spite of this we hope that the HIV- infection in this baby is not a progressive one. [Paediatr Indones 1997;37:216-220] Case Report A full term baby girl was bom spontaneously at Cipto Mangunkusumo Hospital on July 20, 1996. with a body weight o f 3380 grams, body length 49 cm and Apgar score 9/10. She was the second o f 2 siblings. The first child was 5 years old and was in good condition. The first child was from her first husband and they were divorced. The mother, 36-37 weeks gestation was sent to the Q pto Mangunkusumo hospital on July 3, 1996, because it was thought that she was going to deliver a baby. But it seemed that the contraction o f the uterus subsided and she was sent home. Ultrasonography o f the fetus revealed no congenital or growth developmental abnormalities. Author's address: Crorry S Matondang, MD, Department of Child Health, Medical School, University of Indonesia, Jalan Salemba 6, jakarta, Indonesia 10430 TelOp (62)(21) 390-3372, Fax. 390-7743.

Corry S Matondang et al 217 The mother was known as an HIV infected woman about 4 years ago without any symptoms. For this reason she got AZT (azidotimidine, zidovudine) 5x100 mg/day orally, started on July 15, 1996. On July 19, 1996 she was referred again to the Cipto Mangunkusumo hospital for delivery. The mother G ^ A ^ 36-38 weeks gestation was in good condition. AZT was given orally 300 mg every 3 hours until the baby was bom. She got oxytocin drips because of the presence o f inertia uteri. The delivery occurred spontaneously on July 20, 1996 and was uneventful. The labor took for about 18 hours, paying attention to the preventive measures o f infection. The baby was given AZT 5 mg orally every 6 hours, for 6 weeks. Physical examination revealed a female infant in good condition. Pulse rate was 140 per minute, respiration rate 48 per minute and body temperature 36,5 C. Head circumference was 34 cm. The heart and lungs were normal. The abdomen was supple, the liver and spleen were not enlarged, there was no lymphadenopathy and there were no abnormalities in the extremities. She was fed with infant formula and the mother, got bromocriptine orally to suppress the lactation. Blood taken from the umbilical cord showed positive HIV antibody. At 3 days old, the blood was examined for DNA HIV by means o f PCR (polymerase chain reaction) and HIV culture. Then the baby was discharged from the hospital in a good condition with a body weight o f 3550 grams. A t 1 week old (July 27, 1996) she suffered from diarrhea and was treated with co-trimoxazole, and the diarrhea subsided. The result o f DNA HIV PCR revealed positive for HIV, subtype E (see Figure 1). On followed up at 1 month old (August 21, 1996) the baby was still in a good condition with a body weight o f 4240 grams, a body length o f 53 cm and a head circumference o f 38 cm. Her hemoglobin content was 16,2 g/dl, white blood cell count w as 13.400/ il with normal differential count (lymphocyte 54%). W e gave her co-trimaxazol which consisted o f thrimethoprim 150 mg/m2 body surface orally in two divided doses, 3 days per week intermittently. The HIV culture revealed positive result. The baby was planned to be followed up at a primary health care and to visit the child outpatient clinic of Cipto Mangunkusumo Hospital periodically. Discussion This case was the first HIV infection in children reported in Indonesia. The diagnosis o f HIV infection was based on the DNA HIV PCR, which showed positive for HIV, subtype E and also positive HIV culture. Although the IgG HIV antibody was positive in th e blood taken from the umbilical cord, the diagnosis o f H IV infection in this baby could not be performed based only on this. IgG HIV antibody from the mother can be transferred transplacentally to the baby, so that the presence o f IgG HIV antibody alone cannot be taken as an indication o f HIV infection in the baby. In order to be able to diagnose HIV infection in babies under 15 months old an other examination should b e

218 A case of HIV infected child born to HIV positive mother performed such as HIV culture, detection of p 24 antigen or DNA HIV.2,3 In connection with this we performed the DNA HIV PCR and HIV culture. Fig 1. PCR product of mother's and baby's, visualized on 2 % agarose gel stained with ethidium bromide. Lane 1-4 (from left to right): primer B, lane 1 mother's PCR product, lane 2 baby s PCR product, lane 3 positive control, lane 4 negative control. Lane 5-8: primer E, lane 5 mother's PCR product, lane 6 baby's PCR product, lane 7 positive control, lane 8 negative control. As mentioned in the literature, the most common way o f HIV transmission in children (>80%) is vertically from HIV infected mothers to their babies.46 It is estimated that maternal to infant transmission occurs in 15% to 50% o f instances710and one o f the factors that may play a role in the transmission is maternal virus load or viraemia.71 '. To reduce the virus load it is suggested to treat HIV infected pregnant women during the prenatal period and through labor with antiretroviral.12,13 The mother in this case had gotten A Z T started only 5 days before delivery and orally. Actually, it is recommended13 that to reduce the maternal infant transmission about 68 %, the antiretroviral treatment should be started at 24-32 weeks gestation ( Zidovudine 5 x 100 mg/day, orally ) and continued to labor (during the first hour, 2 mg/kg body weight IV and followed by 1 mg/kg body weight IV until the baby bom). In regions with limited health care resources, a short-course Zidovudine program was

Carry S Matondang et al 219 proposed.14the sub-saharan African countries model14 consists of 2 doses o f 300 mg zidovudine orally per day for the last 2 to 6 weeks prior to delivery and 300 m g zidovudine orally every 3 hours during labor. It was estimated that this model could reduce the perinatal HIV transmission approximately one h alf of the effect o f the longercourse zidovudine. Anyhow the fact is that the baby has been infected. Although the baby was infected by HIV, she did not show any abnormal physical findings and clinical signs of infection at birth. Indeed, it is reported that the majority o f perinatally infected infants are completely asymptomatic at delivery, but will have a more rapid progression from asymptomatic to symptomatic infection compare to adult.6 More than 50% may develop AIDS by 2 years o f age.1516 Infants infected in utero (early gestation) may be more likely to develop early severe disease and opportunistic infection compare to those infected intrapartum.6 In our case, DNA HIV and HIV were already detected in her blood at 3 days old and this may indicative o f intra- uterine infection.17 Because this baby still showed no abnormalities on physical examination at birth, the intrauterine transmission may be occurred during late gestation. Children with perinatally HIV infection are prone to get opportunistic infection and the most common1 is Pneumocystis Carinii Pneumonia (PCP). PCP in HIV infected children can be fatal, especially under 1 year old and more than half of the reported pediatric AIDS related cases of PCP occur in less than 6 months old.18 For this background it is suggested,18 to give all HIV infected children under 1 year prophylactic treatment for PCP. From 1 to 5 years, prophylaxis was recommended if CD4 counts are less than 500 or less than 15% of total T-cell number. For this reason we decided to give the baby prophylactic treatment against PCP, starting at 4 weeks old. In the beginning we gave the baby formula to avoid the possibility of transmission through breast feeding. It is stated that transmission through breast feeding can happen in ll% -29% cases.19 But the fact was that the baby had been infected. After knowing that the baby was infected, we recommended breast feeding, but unfortunately there was no breast milk any more, and we continued to give infant formula. Two types of clinical presentations occur in perinatally HIV infected children.6 The first are children with earlier severe disease and progress rapidly. They are usually infected in utero. The disease may occur within the first 6 months o f life and the mortality within the first 2 years o f life. The second are those with a more indolent course and some are surviving into early adolescence or more. The positive HIV culture and DNA HIV in blood taken at 3 days old, suggested that this baby may be infected in utero. Despite this, we still hope of course that she is one o f the slow progessors. References 1. Directorate General CDC and EH National Institute of Health, Research and Development, Department of Health Republic of Indonesia, Jakarta,

220 A case of HIV infected child born to HIV positive mother 2. Lane HC, Davey RT. Diagnosis of HIV Infection. Immunol. Allergy Clin N Amer 1995; 15:367-86. 3. Nelson RP, Price LJ; Halsey AB, et al. Diagnosis of pediatric human immuno deficiency virus infection by means of a commercially available polymerase chain reaction gene amplification. Arch Pediatr Med 1996;150:40-5. 4. Falloon j, Eddy J, Wiener L, Pizzo PA. Human Immuno deficiency virus infection in children. J Pediatr 1989:1-30. 5. Prober CG, Gershon AA. Medical management of newborns and infants bom to human immuno deficiency virus-seropositive Mothers. Pediatr Infect Dis J 1991;10:684-695. 6. Esquilin IO, Hutto C: Mechanisms of HIV transmission and clinical presentation. Immunol Allergy Clin N Amer 1995; 15:2:205-23. 7. Andiman WA, Simpson BJ, Olson B, Dember L, Silva TJ, Miller G. Rate of transmission of human immuno deficiency virus type 1 infection from mother to child and short-term out come of neonatal infection. Am J Dis Child 1990; 144:758-66. 8. Oxtoby MJ. Perinatally acquired HIV infection. In Pizzo PA, Wilfert CM, eds. Pediatric AIDS 2nd ed. Baltimore: Williams & Wilkins Baltimore 1994:3-20. 9. European Collaborative Study. Risk factors for mother-to-child transmission of HIV-1. Lancet 1992; 339:1007-12. 10. Sirisanthana V, Hammadhum D. Outcome of children bom to HIV-infected mothers at Chiang Mai University Hospital. (Abstract) presented at Thai. Perinatal Society Meedng on Nov 11-12, 1993 at Pattaya, Chonburi, Thailand. Cited from Sirisanthana V: Pediatric AIDS: An overview including the Chiang Mai experience. JAMA S-E ASIA 1994;10:18-20. 11. Borkowsky W, Krasinslti K, Cao Y, et al. Correlation o f perinatal transmission of human immuno deficiency vims type 1 with maternal vircmia and lymphocyte phenotypes. J Pediatr 1994:125:345-51. 12. Bayer PJ, Dillon M, Novaic M, et al. Factors predictive of maternal-fetal transmission of HIV-1. JAMA 1994; 271:1925-30. 13. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immuno deficiency virus type 1 with zidovudine treatment: Results of AIDs Clinical Trials Group Protocol 076. N Engl J med 1994; 331:1173-80. 14. Mansergh G, Haddix AC, Steketee RW, et al. Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a Sub-Saharan African developing country setting. JAMA 1996; 276:139-45. 15. Gibb D, Newell ML. HIV infection in children. Arch Dis childh 1992; 67:138-41. 16. European Collaborative Study: Children bom to women with HIV-1 infection. Natural history and risk of transmission. Lancet 1991; 337:254-60. "17. Rogers MG, Du CY, Rayfield M, Thomas PA, et al. Use of polymerase chain reaction for early detection of the proviral sequences of HIV in infants bom to seropositive Mothers. N Engl J Med 1989; 320:1649-54. 18. Hughes PA. Opportunistic infections in HIV-infected children. Immunol Allergy Clin North Am 1995;15:2:261-84. 19. Dunn DT, Newell ML, Ades AE, Peckham CS. Risk of human immuno-deficiency vims type 1 transmission through breastfeeding. Lancet 1992; 340:585-8.