Prevalence of pediatric HIV in New Delhi
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《美国医学杂志》
1 Department of Microbiology, Great Ormond Street Hospital for Children, London, UK, India
2 Department of Paediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
3 Department of Microbiology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
Abstract
Objective : This study was carried out to determine the prevalence of HIV infection in North India, as there are scanty reports from this part of India. Methods : The prevalence of HIV infection was determined by serological tests for HIV antibodies in children born to a seropositive mother or suffering from chronic diarrhea, failure to thrive or disseminated tuberculosis. Results : One hundred and twelve children were tested of which ten were seropositive (8.9%). This included six children born to seropositive mother (22%), two with chronic diarrhea (4%), one with failure to thrive (5%) and one child with disseminated tuberculosis (6.6%). Conclusion : HIV infection is an emerging reality in New Delhi. A clinically directed screening can help detect more cases.
Keywords: HIV; Chronic diarrhea; Disseminated tuberculosis
In India, most initial reports in pediatric HIV infection were focused on multi-transfused recipients such as thalassemics.[1],[2] With mandatory screening of blood products, the incidence of transfusion-associated HIV infection has reduced dramatically and is now seen only sporadically. In spite of this decrease, pediatric HIV infection has become an important public health issue due to a sharp rise in infection rates among women. This is particularly true for India where the major mode of transmission is heterosexual contact. The increasing numbers of infected women has led to an increase in the number of children infected perinatally. According to a recent UNAIDS estimate, around 1.2 lakh children are living with HIV infection in India.[3] Although the problem is well-recognized, there are scant reports on the prevalence of pediatric HIV infection from North India. In order to address this issue, this study has been carried out to determine the prevalence of HIV infection among two subgroups of children attending a tertiary care center at New Delhi. These subgroups were children of seropositive mothers or children suffering from chronic diarrhea, failure to thrive or disseminated tuberculosis. The findings of the screening are presented in this paper.
Materials and Methods
In this prospective screening, consecutive high-risk children less or equal to twelve years of age were enrolled from March 2001-2002. For the purpose of the study, the criteria for high risk of HIV infection were :
1. Children of seropositive mothers
2. Children with failure to thrive, defined as a child growing below the fifth percentile or a child whose decreased growth rate has crossed two major growth percentiles in a short time.
3. Children presenting with chronic diarrhea, defined as the passage of three or more watery stools or a change in the consistency of stools for a minimum duration of 14 days
4. Children suffering from disseminated tuberculosis ascertained by two or more organ involvement in a child with suspected tuberculosis.
After an informed consent and pre and post test counseling, these children were screened by ELISA (DETECT-HIV). A positive result was confirmed by supplemental tests (COMB-AIDS RS and Tri-Dot) and Western Blot assay. These kits were provided for the study by the National AIDS Control Organization.
Based on the criteria laid by the Center of Disease Control and Prevention, Atlanta[4], a positive serology in a child more than 18 months of age was taken as a case of proven HIV infection. However, in the absence of PCR, infection in a child of less than 18 months of age was established on the basis of specific signs and symptoms of HIV infection. A child was labeled as perinatally infected if he/she presented with non-specific symptoms and had a positive serology and was below eighteen months of age.
After the infection was established on serological grounds, a thorough history was taken and clinical examination performed. Details noted included age, gender, mode of acquisition of infection, time of onset and duration of symptoms, evidence of nutritional deficiency, fever, hepatomegaly, splenomegaly, lymphadenopathy and diarrhea. Nutritional status was determined by anthropometric measurements and then graded according to Indian Academy of Paediatrics' classification.[5] All infected children underwent extensive laboratory investigations. This included a complete blood count, ESR, Chest X-Ray, Mantoux test, Urine and stool examination, serum chemistry and an opportunistic infection screen based on the clinical presentation.
Results
A total of one hundred and twelve children were tested. This included 73 males and 39 females. Ten of these children were seropositive for HIV-1. Thus, the overall seroprevalence observed in this study was 8.9%. table1 shows the age and sex distribution of the children screened. The seroprevalence rate was highest in females in the age group of 18 months-3 years (22%), followed by males aged 4-7 years of age (14.8%), and females in the age group of 4-7 years (11%). The ten seropositive children included seven males and three females. All except one child were above eighteen months of age. Hence, infection could be confirmed on the basis of serological tests alone that are capable of detecting the HIV antibody. In one child below eighteen months of age, infection was confirmed on the basis of specific signs and symptoms of AIDS defining illnesses.
Mother to child transmission was the commonest mode of acquisition of infection as documented in seven children. The mode of transmission was uncertain in one child aged 12 years. Parents of this child were negative and history of blood transfusion or sexual transmission was not forthcoming. In two children, the route of transmission could not be ascertained, as the parents could not be tested.
All children were symptomatic at the time of detection of infection. Based on the criteria laid by the Center of Disease Control, Atlanta[6], five of the infected children were moderately symptomatic and three children were severely symptomatic. Common clinical manifestations included fever (50%), tuberculosis (50%), anemia (40%), hepatosplenomegaly (40%), lymphadenopathy (30%), and respiratory tract infections (30%). Nine of the ten infected children had some evidence of malnutrition. Four children had Grade III or Grade IV malnutrition.
The most common opportunistic infection was tuberculosis-seen in five of the ten infected children. Two children had evidence of extrapulmonary or disseminated tuberculosis. The diagnosis of tuberculosis was based on clinical and radiological grounds as microscopy and culture was not contributory. Mantoux test was negative in all children. The other opportunistic infections encountered in this study include a case of diarrhea due to Cryptosporidium spp in a child aged 12 years and recurrent bacterial infections and oral thrush in a child aged five months.
During the span of this study, five children were receiving antitubercular treatment and PCP prophylaxis. Three children could receive antiretroviral treatment with the support of social organizations.
Discussion
Pediatric HIV infection is detected as a result of screening children of HIV infected mothers, or on the basis of clinical suspicion. Chronic diarrhea, failure to thrive and disseminated tuberculosis are common clinical illnesses among hospitalized patients and are also reported as frequent manifestations of HIV infection. The prevalence of HIV infection in chronic diarrhea in our study was 4.1%, which was much lower than the rate of 18% and 24% observed in two separate studies in Mumbai.[7],[8] Also, the prevalence rate of 6.6% among children with disseminated tuberculosis was lower than those observed in this illness from Aligarh [9](18%) and Mumbai (16 and 18%). This is more likely to be the result of different selection criteria, since Delhi and Aligarh report a low prevalence for HIV infection. Nevertheless, these prevalence rates and an overall prevalence rate of 8.9% in our study suggest that pediatric HIV infection is an emerging reality in Delhi.
The prevalence rate observed in our study also raises the question of the utility of a clinically directed screening. One of the objectives of a clinically directed screening is to maximize the use of the existing resources to detect more HIV infected children, so that specific management like antiretroviral therapy or PCP prophylaxis can be provided. To this end, Karande et al[8] conducted a study in Mumbai and measured the HIV seroprevalence and risk estimate of severe malnutrition, serious pyogenic infections, disseminated tuberculosis, chronic diarrhea and oral candidiasis present singly or in combination in children. Although seroprevalence was high in all illnesses, only oral candidiasis was noted as an independent risk factor. They also observed that with the number of risk factors increasing, the chances of the child being infected increased. In the present study, four of the ten HIV infected children were detected on the grounds of a clinical directed screening alone. Hence, it is likely that such a screening could maximize the benefits from the existing resources we have.
Most children in this study presented with moderate to severe symptoms at the time of detection. Two children had AIDS defining illnesses, namely cryptosporidial diarrhea and encephalopathy. This was despite the previous contacts the children had with the hospital. This marked delay in diagnosis can be attributed to the presumed low risk of infection in this part of the country. Thus, the disease is missed when a child is asymptomatic or has only minor symptoms.
The common clinical manifestations in this study were similar to that observed in other studies.[10], [11],[12] Most children in this study had more than one clinical manifestation. Mother-to-child transmission was the commonest mode of infection. However, the mode of transmission was uncertain in one child aged 12 years of age.
The final management protocol depends on the clinical status of the child and the feasibility of antiretroviral regimes. This therapy is the backbone of management. Due to financial constraints only a few children are able to receive this therapy. During the course of this study it was possible to provide antiretroviral therapy with zidovudine and lamivudine to only three out of the ten HIV infected children. Hence, nutritional intervention and prophylaxis for opportunistic infections like tuberculosis and Pneumocystis carinii remain the mainstay of management of these children. Even diagnostic tools like PCR for the early detection and confirmation of HIV infection remain unaffordable. This was also true in this study. We encountered only one child below 18 months of age, in whom the diagnosis could be confirmed on the basis of specific signs and symptoms. With increasing awareness of this disease, more asymptomatic children early in their life are likely to be encountered. In such cases, the availability of PCR for diagnosis is crucial. To conclude, Pediatric HIV infection is an emerging reality in New Delhi and there is a need of an effective screening program to detect children early in infection.
References
1. Sen S, Mishra NM, Giri T, et al. Acquired immunodeficiency syndrome (AIDS) in multitransfused children with thalassemia. Indian Pediatrics 1993; 30: 455-460.
2. De M, Banerjee D, Chandra S, Bhattacharya DK. HBV and HIV seropositivity in multitransfused hemophilics and thalassemics in Eastern India. Indian J Med Res 1990(A), 91:63-66.
3. UNAIDS 2004. Report on the global HIV/AIDS epidemic. December 2004. UNAIDS, Geneva, Switzerland.
4. US. Center for Disease Control and Prevention .1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep 1994; 43: 1-10
5. Nutritional subcommittee of the Indian Academy of Pediatrics. Report. Indian Pediatrics 1972; 9 : 360
6. CDC. Classification system for immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987; 36:225-230,235
7. Merchant RH, Shroff RC. HIV Seroprevalence in Disseminated tuberculosis and chronic diarrhea. Indian Pediatrics 1998; 35: 883-887.
8. Karande S, Bhalke S, Kelkar A, et al. Utility of a clinically directed selective screening to diagnose HIV infection in hospitalized children in Bombay, India. Journal of Tropical Pediatrics 2002; 48 : 149-155.
9. Shahab T, Zoha MS, Ashraf Malik M, et al. Prevalence of HIV infection in children with tuberculosis. Indian Pediatrics 2004;41 : 595-599.
10. Merchant RH, Oswal JS, Bhagwat V, et al. Clinical profile of HIV Infection. Indian Pediatrics 2000; 38: 239-246.
11. Verghese VP, Cherian T, Cherian AJ, et al. Clinical features of HIV1 infection. Indian Pediatrics 2002; 39 : 57-63.
12. Lodha R, Singhal T, Jain Y et al. Pediatric HIV Infection in a Tertiary Care Center in North India: Early Impressions. Indian Pediatrics 2000; 37: 982-986.(Parthasarathy P, Mittal S)
2 Department of Paediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
3 Department of Microbiology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
Abstract
Objective : This study was carried out to determine the prevalence of HIV infection in North India, as there are scanty reports from this part of India. Methods : The prevalence of HIV infection was determined by serological tests for HIV antibodies in children born to a seropositive mother or suffering from chronic diarrhea, failure to thrive or disseminated tuberculosis. Results : One hundred and twelve children were tested of which ten were seropositive (8.9%). This included six children born to seropositive mother (22%), two with chronic diarrhea (4%), one with failure to thrive (5%) and one child with disseminated tuberculosis (6.6%). Conclusion : HIV infection is an emerging reality in New Delhi. A clinically directed screening can help detect more cases.
Keywords: HIV; Chronic diarrhea; Disseminated tuberculosis
In India, most initial reports in pediatric HIV infection were focused on multi-transfused recipients such as thalassemics.[1],[2] With mandatory screening of blood products, the incidence of transfusion-associated HIV infection has reduced dramatically and is now seen only sporadically. In spite of this decrease, pediatric HIV infection has become an important public health issue due to a sharp rise in infection rates among women. This is particularly true for India where the major mode of transmission is heterosexual contact. The increasing numbers of infected women has led to an increase in the number of children infected perinatally. According to a recent UNAIDS estimate, around 1.2 lakh children are living with HIV infection in India.[3] Although the problem is well-recognized, there are scant reports on the prevalence of pediatric HIV infection from North India. In order to address this issue, this study has been carried out to determine the prevalence of HIV infection among two subgroups of children attending a tertiary care center at New Delhi. These subgroups were children of seropositive mothers or children suffering from chronic diarrhea, failure to thrive or disseminated tuberculosis. The findings of the screening are presented in this paper.
Materials and Methods
In this prospective screening, consecutive high-risk children less or equal to twelve years of age were enrolled from March 2001-2002. For the purpose of the study, the criteria for high risk of HIV infection were :
1. Children of seropositive mothers
2. Children with failure to thrive, defined as a child growing below the fifth percentile or a child whose decreased growth rate has crossed two major growth percentiles in a short time.
3. Children presenting with chronic diarrhea, defined as the passage of three or more watery stools or a change in the consistency of stools for a minimum duration of 14 days
4. Children suffering from disseminated tuberculosis ascertained by two or more organ involvement in a child with suspected tuberculosis.
After an informed consent and pre and post test counseling, these children were screened by ELISA (DETECT-HIV). A positive result was confirmed by supplemental tests (COMB-AIDS RS and Tri-Dot) and Western Blot assay. These kits were provided for the study by the National AIDS Control Organization.
Based on the criteria laid by the Center of Disease Control and Prevention, Atlanta[4], a positive serology in a child more than 18 months of age was taken as a case of proven HIV infection. However, in the absence of PCR, infection in a child of less than 18 months of age was established on the basis of specific signs and symptoms of HIV infection. A child was labeled as perinatally infected if he/she presented with non-specific symptoms and had a positive serology and was below eighteen months of age.
After the infection was established on serological grounds, a thorough history was taken and clinical examination performed. Details noted included age, gender, mode of acquisition of infection, time of onset and duration of symptoms, evidence of nutritional deficiency, fever, hepatomegaly, splenomegaly, lymphadenopathy and diarrhea. Nutritional status was determined by anthropometric measurements and then graded according to Indian Academy of Paediatrics' classification.[5] All infected children underwent extensive laboratory investigations. This included a complete blood count, ESR, Chest X-Ray, Mantoux test, Urine and stool examination, serum chemistry and an opportunistic infection screen based on the clinical presentation.
Results
A total of one hundred and twelve children were tested. This included 73 males and 39 females. Ten of these children were seropositive for HIV-1. Thus, the overall seroprevalence observed in this study was 8.9%. table1 shows the age and sex distribution of the children screened. The seroprevalence rate was highest in females in the age group of 18 months-3 years (22%), followed by males aged 4-7 years of age (14.8%), and females in the age group of 4-7 years (11%). The ten seropositive children included seven males and three females. All except one child were above eighteen months of age. Hence, infection could be confirmed on the basis of serological tests alone that are capable of detecting the HIV antibody. In one child below eighteen months of age, infection was confirmed on the basis of specific signs and symptoms of AIDS defining illnesses.
Mother to child transmission was the commonest mode of acquisition of infection as documented in seven children. The mode of transmission was uncertain in one child aged 12 years. Parents of this child were negative and history of blood transfusion or sexual transmission was not forthcoming. In two children, the route of transmission could not be ascertained, as the parents could not be tested.
All children were symptomatic at the time of detection of infection. Based on the criteria laid by the Center of Disease Control, Atlanta[6], five of the infected children were moderately symptomatic and three children were severely symptomatic. Common clinical manifestations included fever (50%), tuberculosis (50%), anemia (40%), hepatosplenomegaly (40%), lymphadenopathy (30%), and respiratory tract infections (30%). Nine of the ten infected children had some evidence of malnutrition. Four children had Grade III or Grade IV malnutrition.
The most common opportunistic infection was tuberculosis-seen in five of the ten infected children. Two children had evidence of extrapulmonary or disseminated tuberculosis. The diagnosis of tuberculosis was based on clinical and radiological grounds as microscopy and culture was not contributory. Mantoux test was negative in all children. The other opportunistic infections encountered in this study include a case of diarrhea due to Cryptosporidium spp in a child aged 12 years and recurrent bacterial infections and oral thrush in a child aged five months.
During the span of this study, five children were receiving antitubercular treatment and PCP prophylaxis. Three children could receive antiretroviral treatment with the support of social organizations.
Discussion
Pediatric HIV infection is detected as a result of screening children of HIV infected mothers, or on the basis of clinical suspicion. Chronic diarrhea, failure to thrive and disseminated tuberculosis are common clinical illnesses among hospitalized patients and are also reported as frequent manifestations of HIV infection. The prevalence of HIV infection in chronic diarrhea in our study was 4.1%, which was much lower than the rate of 18% and 24% observed in two separate studies in Mumbai.[7],[8] Also, the prevalence rate of 6.6% among children with disseminated tuberculosis was lower than those observed in this illness from Aligarh [9](18%) and Mumbai (16 and 18%). This is more likely to be the result of different selection criteria, since Delhi and Aligarh report a low prevalence for HIV infection. Nevertheless, these prevalence rates and an overall prevalence rate of 8.9% in our study suggest that pediatric HIV infection is an emerging reality in Delhi.
The prevalence rate observed in our study also raises the question of the utility of a clinically directed screening. One of the objectives of a clinically directed screening is to maximize the use of the existing resources to detect more HIV infected children, so that specific management like antiretroviral therapy or PCP prophylaxis can be provided. To this end, Karande et al[8] conducted a study in Mumbai and measured the HIV seroprevalence and risk estimate of severe malnutrition, serious pyogenic infections, disseminated tuberculosis, chronic diarrhea and oral candidiasis present singly or in combination in children. Although seroprevalence was high in all illnesses, only oral candidiasis was noted as an independent risk factor. They also observed that with the number of risk factors increasing, the chances of the child being infected increased. In the present study, four of the ten HIV infected children were detected on the grounds of a clinical directed screening alone. Hence, it is likely that such a screening could maximize the benefits from the existing resources we have.
Most children in this study presented with moderate to severe symptoms at the time of detection. Two children had AIDS defining illnesses, namely cryptosporidial diarrhea and encephalopathy. This was despite the previous contacts the children had with the hospital. This marked delay in diagnosis can be attributed to the presumed low risk of infection in this part of the country. Thus, the disease is missed when a child is asymptomatic or has only minor symptoms.
The common clinical manifestations in this study were similar to that observed in other studies.[10], [11],[12] Most children in this study had more than one clinical manifestation. Mother-to-child transmission was the commonest mode of infection. However, the mode of transmission was uncertain in one child aged 12 years of age.
The final management protocol depends on the clinical status of the child and the feasibility of antiretroviral regimes. This therapy is the backbone of management. Due to financial constraints only a few children are able to receive this therapy. During the course of this study it was possible to provide antiretroviral therapy with zidovudine and lamivudine to only three out of the ten HIV infected children. Hence, nutritional intervention and prophylaxis for opportunistic infections like tuberculosis and Pneumocystis carinii remain the mainstay of management of these children. Even diagnostic tools like PCR for the early detection and confirmation of HIV infection remain unaffordable. This was also true in this study. We encountered only one child below 18 months of age, in whom the diagnosis could be confirmed on the basis of specific signs and symptoms. With increasing awareness of this disease, more asymptomatic children early in their life are likely to be encountered. In such cases, the availability of PCR for diagnosis is crucial. To conclude, Pediatric HIV infection is an emerging reality in New Delhi and there is a need of an effective screening program to detect children early in infection.
References
1. Sen S, Mishra NM, Giri T, et al. Acquired immunodeficiency syndrome (AIDS) in multitransfused children with thalassemia. Indian Pediatrics 1993; 30: 455-460.
2. De M, Banerjee D, Chandra S, Bhattacharya DK. HBV and HIV seropositivity in multitransfused hemophilics and thalassemics in Eastern India. Indian J Med Res 1990(A), 91:63-66.
3. UNAIDS 2004. Report on the global HIV/AIDS epidemic. December 2004. UNAIDS, Geneva, Switzerland.
4. US. Center for Disease Control and Prevention .1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep 1994; 43: 1-10
5. Nutritional subcommittee of the Indian Academy of Pediatrics. Report. Indian Pediatrics 1972; 9 : 360
6. CDC. Classification system for immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987; 36:225-230,235
7. Merchant RH, Shroff RC. HIV Seroprevalence in Disseminated tuberculosis and chronic diarrhea. Indian Pediatrics 1998; 35: 883-887.
8. Karande S, Bhalke S, Kelkar A, et al. Utility of a clinically directed selective screening to diagnose HIV infection in hospitalized children in Bombay, India. Journal of Tropical Pediatrics 2002; 48 : 149-155.
9. Shahab T, Zoha MS, Ashraf Malik M, et al. Prevalence of HIV infection in children with tuberculosis. Indian Pediatrics 2004;41 : 595-599.
10. Merchant RH, Oswal JS, Bhagwat V, et al. Clinical profile of HIV Infection. Indian Pediatrics 2000; 38: 239-246.
11. Verghese VP, Cherian T, Cherian AJ, et al. Clinical features of HIV1 infection. Indian Pediatrics 2002; 39 : 57-63.
12. Lodha R, Singhal T, Jain Y et al. Pediatric HIV Infection in a Tertiary Care Center in North India: Early Impressions. Indian Pediatrics 2000; 37: 982-986.(Parthasarathy P, Mittal S)