Indian Pediatrics - Editorial

Original Articles

Indian Pediatrics 2000;37: 831-836

CLINICAL SPECTRUM OF HIV INFECTION

Rachita Dhurat*, Mamta Manglani, Ratna Sharma and N.K. Shah

From the *Department of Dermatology and Division of Pediatric Hematology-Oncology, L.T.M.M. College and L.T.M.G. Hospital, Sion, Mumbai 400 022, India.

Reprint requests: Dr. Rachita Dhurat, 116/3813, Kedarnath Society, Nehru Nagar, Kurla (E), Mumbai 400 024, India.

Manuscript received: June10, 1999; Initial review completed: August 3, 1999; Revision accepted: February 22, 2000.

Objective: To study the modes of transmission of pediatric HIV infection, to categorize clinical manifestations and to compare clinical spectrum of perinatal with transfusion acquired HIV infection. Design: Case series study. Setting: Hospital based pediatric HIV clinic. Methods: Children confirmed to have HIV infection were evaluated and relevant details recorded. Results: 55 children were enrolled of whom 41 (74.5%) had perinatal transmission of HIV, 12 (21.8%) were infected through blood transfusions and 2 (3.6%) through other routes. Thirty-seven (90.2%) of the 41 perinatally infected children were symptomatic. Tuberculosis was seen in 25 (67.5%) of these children and failure to thrive in 18 (48.6%). Nonspecific features such as recurrent bacterial infection, oral candidiasis and chronic diarrhea were other manifestations. Eight (26.3%) of the 30 children available for follow up for a median period of 9 months died at the median age of 8.5 months. Amongst the transfusion acquired HIV infection, 11 (91.6%) of the 12 were asymptomatic at presentation. Six (50%) of these children died at the median age of 3 years and the remaining 6 had no major symptoms at a median follow up of 3.5 years. Conclusions: Perinatal route is the major route of HIV transmission in children and clinical manifestations are different from those of adults.

Key words: HIV infection; Perinatal transmission.

Pediatric HIV infection today represents a major setback to child health. As of 1st January 1998, WHO has estimated that there are 30.6 million people living with HIV/AIDS worldwide, of which 5.8 million have been newly infected during 1997, including 590,000 children. More than 3,800 children with AIDS have been reported from the ten countries of the South East Asia region. A majority of these children are from Thailand and India(1). Children can be infected through HIV positive mother (more than 90% of pediatric AIDS reported in 1994 occurred as a consequence of mother to infant transmission)(2), by trans-fusion of contaminated blood products, especially with multiple transfusions as in thalassemics and hemophiliacs or by sexual abuse(3). In the developing countries, pediatric AIDS comprises as much s 15-20% of all AIDS cases(4). HIV-1 infection in children may involve a wide spectrum of clinical diseases(5,6). In view of the varying clinical manifestations of HIV infection in children and paucity of relevant data from India the present study was conducted with the following aims: (i) to study the modes of transmission and categorize clinical manifestations; and (ii) to compare the clinical manifestations of perinatal HIV infection with those of transfusion acquired HIV infection.

Subject and Mehods

Children confirmed to have HIV infection were included in the present study, which was conducted from January 1995 to December 1998. Children who tested positive for HIV IgG antibody with 2 different antigen based ELISA kits (United Biomedical, Beijing and Lab Systems,Finland) were considered HIV infected. However perinatal HIV infection was confirmed on the basis of the revised CDC criteria in children(7) which included persist-ence of antibodies beyond 18 months of age or a positive PCR(8).

In the present study all 17 infants between 3 months to 18 months of age were subjected to PCR using DNA amplication method on gel electrophoresis. The sequences studied included SK 38, 39 for gag region and SK 145, 435 for pol region.

A thorough history and clinical examination was performed in all these children, the details of which were noted in a predesigned proforma. These included age, sex, risk factors for HIV infection, time of onset of symptoms, duration of symptoms, examination findings with special reference to growth failure, fever, hepato-megaly, splenomegaly, lymphadenopathy, parotitis, diarrhea, secondary infectious diseases and other associated diseases. A descriptive analysis was performed to outline the various clinical manifestations in these children. All these children were followed up regularly for further evaluation. Routine laboratory investigations including a complete blood count, erythrocyte sedementation rate (ESR), X-ray chest, Mantoux test and urine and stool examination was done in all children. Specific investigations which included cerebrospinal fluid (CSF) examination, gastric lavage for acid fast bacilli (AFB), fine needle aspiration cytology (FNAC), blood culture, relevant imaging studies and ELISA for IgG and IgM antibodies for Toxoplasma gondii and cyto-megalovirus infections were done when indicated.

Results

A total of 55 children were enrolled in the present study. Forty one (74.5%) had acquired HIV through perinatal transmission (21 boys and 20 girls), 12 (21.8%) were infected through blood transfusions (6 boys and 6 girls), 1 boy had a history of sexual abuse (1.8%) and in 1 girl (1.8%) no risk factor for transmission was documented.

Perinatal HIV Infection

The age of 41 children, who acquired HIV infection through their mothers, ranged between 2 months and 8 years (Table I ). Thirty seven (90.2%) out of 41 children were symptomatic. When data was analyzed age wise it was found that of the 15 children below one year of age, 11 (73.3%) were symptomatic. The median age at onset of symptoms was 3.2 years (range: 0.2 to 8 years). The clinical spectrum in these 37 symptomatic children is shown in Table II. The commonest presentation was tuberculosis seen in 25 (67.5%) children; of them, 16 had pulmonary tuberculosis which was diagnosed on the basis of clinical and radiological evidence at the discretion of the clinician. Mantoux test was negative in all children (Mantoux was considered positive when induration was more than 5 mm). Twelve of these 16 children had typical clinical manifestations of lower respiratory tract infection in the form of fever, cough and breathlessness and 4/16 were diagnosed as pulmonary tuberculosis only on the basis of radiological findings (persistent patch). Nine children had extrapulmonary tuberculosis, out of which 4 had both extrapulmonary and pulmonary tuberculosis. Extrapulmonary sites included abdominal tuberculosis(4), neuro-tuberculosis(2) and tuberculous lymph-adenitis(3). Four of 16 children had moderate to severe clubbing.

Eighteen of 37 (48.6%) children had failure to thrive and of these, 15 had associated tuberculosis. Nineteen children had hepato-splenomegaly, 13 each had oral candidiasis and generalized lymphadenopathy, 10 had chronic diarrhea, and bacterial infections were seen in 14 children in the form of lower respiratory tract infection, Gram negative sepsis (Salmo-nella typhimurium and Klebsiella species organisms), pyoarthrosis and meningitis. The other bacterial infections were otitis media(5) and pyoderma(6). Various cutaneous mani-festations seen included seborrhoeic dermatitis in 6 children, multidermatomal herpes zoster in 2 and chickenpox in 4, of which hemorrhagic type was seen in 2 children. All the 6 children with varicella infection were treated with oral Acyclovir in the dose of 10 mg/kg/dose in 3 divided doses for 7 days.

During the median follow up of 9 months (range: 2 to 28 months), 11/41 (27.5%) children were lost to follow up. Eight (26.3%) of 30 children died at a median age of 8.5 months (range: 0.3 to 2 years).

Transfusion Acquired HIV Infection

In the present study 12 (21.8%) of the 55 children had acquired HIV through blood transfusions. Amongst these, 11 were thalas-semics and one child had received transfusions for refractory anemia. The median age of these children at presentation was 9 years (range: 1-13 years) (Table I), the youngest being the child with refractory anemia who manifested with extrapulmonary tuberculosis, severe failure to thrive, recurrent anemia, hepatosplenomegaly and lower respiratory tract infections (Table II). All thalassemic children had hepatospleno-megaly due to their disease and complications arising out of their treatment, but were otherwise asymptomatic at presentation. Six (50%) of these children died at a median follow up of 3 years (range: 2 to 9 years), 3 died due to HIV related causes and 3 died due to causes related to thalassemia. The remaining 6 children had no major symptoms of HIV at a median follow up of 3.5 years (range: 1-5 years).

HIV Infection Through Sexual Abuse

One child in the present study had acquired HIV infection through sexual abuse and was diagnosed as HIV related thrombocytopenic purpura. During the 4 year follow up, he had recurrent lower respiratory tract infections, pulmonary tuberculosis, hemorrhagic chicken pox and unresponsive chronic thrombo-cytopenia.

Table I - Age Distribution and Mode of Transmission

	Mode of Transmission
Age (yrs)	Perinatal (n = 41)	Transfusion acquired (n = 12)	Sexual abuse (n = 1)	Unknown (n = 1)	Total (n = 55) (%)
0-1	15	–	–	–	15 (27.2)
1-2	7	2	–	–	9 (16.3)
2-4	4	–	–	–	4 (7.2)
4-6	7	–	1	–	8 (14.5)
6-8	7	3	–	1	11 (20.0)
8-10	–	2	–	–	2 (3.6)
10-12	–	3	–	–	3 (5.4)
> 12	1	2	–	–	3 (5.4)

Table II - Clinical Spectrum of HIV in Symptomatic Children (n=38)

Presenting symptoms	Perinatal Transmission n = 37 (%)	Transfusion acquired n = 1
Tuberculosis	25 (67.5)	1
Failure to thrive	18 (48.6)	1
Hepatomegaly	19 (51.9)	1
Splenomegaly	18 (48.6)	–
Oral Candidiasis	13 (35.1)	1
Lymphadenopathy	13 (35.1)	–
Diarrhea	10 (27.2)	–
Recurrent pneumonia	9 (24.3)	1
Gram –ve sepsis	3 (8.7)	–
Pyoarthrosis	1 (2.7)	–
Cutaneous bacterial infections	3 (8.7)	–
Anemia	12 (32.4)	–
Seborrheic dermatitis	6 (16.2)	–
Chicken pox	4 (10.8)	–
Herpes zoster	2 (5.4)	–
Parotitis	5 (13.5)	–

Discussion

Pediatric HIV infection is assuming alarming proportions in the developing countries, especially in urban India(1). HIV infection in children is primarily restricted to perinatal transmission or is transfusion acquired. The present study has shown similar results. The patterns of disease expression and progression differ among HIV infected children from those in adults(9). Infected children have a varied and wide spectrum of clinical signs and symptoms as reported in literature(5,6). HIV encephalopathy and opportunistic infections are typical and often early manifestations of HIV disease in children(10,11). Some infants present with features of severe immunodeficiency, whereas others have findings such as hepato-splenomegaly, failure to thrive, unexplained fever, parotitis and gastroenteritis. During the first year, lymphadenopathy, splenomegaly and hepatomegaly singularly or combined, have been observed in more than 50% of children. Other signs including failure to thrive, fever, diarrhea and AIDS defining secondary infections are frequent, but can also be present at a later age(12). Most of the children in the present study had nonspecific findings such as hepatosplenomegaly, lymphadenopathy, failure to thrive, diarrhea and recurrent fever as the presenting features. Tuberculosis has emerged as a major infectious complication of HIV infection in the developing countries(13), as was also seen in the present study. Though several studies have indicated that infected children in Africa present with many of the signs and symptoms similar to those in industrialized countries(14), this was not observed in the present study.

A low incidence of PCP has been reported amongst African, Caribbean and Indian children(14-16). However, recently anecdotal report of PCP in children with a presumptive diagnosis of PCP with HIV have been published from India(16). Whether the apparent differences in the occurrence of P. carinii pneumonia reflect difficulties in establishing the diagnosis, differences in disease susceptibility or geographic variation in the prevalence of the organism needs to be explored.

In the present study, 26.3% of the perinatally infected children died at the median age of 8.5 months (range: 0.3-2 years), due to various infections including tuberculosis, Gram negative sepsis, lower respiratory tract infec-tions and diarrhea. Since these children were not on PCP prophylaxis, there is a possibility of undiagnosed PCP as a cause of death.

Out of the 12 children with transfusion transmitted HIV infection, 2 children were below 2 years of age. It is imperative to highlight that these 2 children had been infected through transfusions received long after government regulations mandating HIV screening of blood donors. In the light of these observations the need for judicious use of blood and stringent donor screening requires further emphasis.

Children infected by blood products had symptoms and signs different from children who acquired perinatal infection. Of the 12 children with transfusion acquired HIV infection, 11 were asymptomatic. Various studies have shown that incubation period of AIDS for transfusion associated cases was longer than perinatally acquired cases but shorter than adult transfusion associated cases (median 3.5 vs 1.75 vs 4.5 years)(17). Similar results were found by others(18-20). Since 11 out of the 12 children with transfusion acquired HIV infection were asymptomatic, a compari-son of manifestations between perinatally acquired and transfusion acquired HIV infection was not possible in the present study. However, as reported in literature HIV acquired through either of these routes has similar manifestations, except that in transfusion acquired HIV, lymphoid interstitial pneumo-nitis was less common as compared to oppor-tunistic infections and HIV encephalo-pathy(17).

In conclusion, perinatal transmission is a major route of acquiring pediatric HIV infection. Emphasis must therefore be laid on treatment in seropositive mothers to prevent or reduce this transmission. Clinical manifesta-tions of HIV infection are protean and mimic a number of other illnesses. A high index of suspicion would therefore help in early and appropriate diagnosis.

Acknowledgements

We wish to acknowledge Dr. R.G. Shirahatti, Dean, L.T.M.M.C. and L.T.M.G.H. for permitting us to publish this data and Dr. M.V. Kulkarni, Professor and Head, Department of Pediatrics and Dr. H.R. Jerajani, Professor and Head, Department of Dermatology for their constant guidance and help in doing this work.

Contributors: RD coordinated the study by participating in data collection, designing, drafting and also helped in interpretation of the paper. She will act as the guarantor for the paper. MM coordinated in design, drafting and interpretation of the paper. RS participated in drafting and interpretation of the paper. NKS participated in data collection.

Funding: None.
Competing interests: None stated.

Key Messages

• Perinatal infection is the major route of transmission of HIV in pediatric age group.

• Tubeculosis is one of the commonest co-existing infections in children with HIV infection.

• Perinatally infected children tend to manifest earlier and have a poorer prognosis as compared to children infected through blood products.

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