HIV SEROPOSITIVITY IN HOSPITALIZED CHILDREN ON CLINICALLY DIRECTED SELECTIVE SCREENING: AN EXPERIENCE FROM CENTRAL INDIA
Amit Agrawal, Sharad Thora, Rashmi Agrawal
Department of Pediatrics, Gandhi Medical College, Bhopal, MP, India
Address for Correspondence
Dr Amit Agarwal, 28, Ravidas Nagar, Near Nizamuddin Colony, Indrapuri, Bhopal, MP, India.
Email
agrawaldramit@yahoo.co.in
Abstract
Background: Probability of HIV infection in a given clinical manifestation has been examined in a very few studies.

Aims: To assess the probability of HIV infection in children hospitalized with the selected manifestations included in either World Health Organization (WHO) or South African criteria.

Methods: Patients aged 18 months to 14 years hospitalized with at least two of the following clinical features: marasmus, prolonged pyrexia, persistent cough, chronic diarrhoea, repeated common infections, generalized lymphadenopathy, hepatosplenomegaly, generalized dermatosis, oral candidiasis were tested for HIV by ELISA test using WHO-UNAIDS strategy-II.

Results: Out of the recruited 110 cases, 9 cases were HIV positive with a seropositivity rate of 8.2%. In our study, only oral candidiasis was found to be an independent risk factor to predict HIV infection in children. However, probability of HIV infection increases with increase in the number of risk factors present concomitantly.

Conclusion: Number and nature of the clinical features present determine the probability of HIV infection in children, which increases with increase in number of risk factors.
Keywords
HIV, AIDS, Pediatrics, WHO clinical case definition
Introduction
HIV infection in children exhibits a variety of manifestations including prolonged fever, prolonged diarrhea, weight loss, recurrent or opportunistic infections, lymphadenopathy, and hepatosplenomegaly.(1,2) However, in developing countries like in India, there is high prevalence of malnutrition, poor hygiene and of infectious diseases like malaria and tuberculosis leading to childhood admissions without HIV infection but similar clinical features, thus to make a clinical diagnosis of HIV infection becomes very difficult.(3,4) As routine HIV testing is not a feasible option, especially in resource poor countries, clinically directed selective screening to diagnose HIV infection is the foremost way to detect maximum number of cases without wasting resources.(5)

For this purpose, first clinical case definition (CCD) was developed by World Health Organization (WHO), especially for use in countries where testing for HIV antibodies was not routinely available.(6) This has been evaluated in different settings in an attempt to determine the likelihood of HIV infection in a given clinical situation and to formulate their own screening criteria.(1,7-10) Of these, one study was conducted at Bloemfontein, South Africa (SA) and the proposed CCD was claimed to be easier to use, less subjective, and more sensitive (63.2% vs. 14.5%) than WHO-CCD.(1) However, as clinical profile of HIV in children vary greatly in different epidemiological settings, it is difficult to adopt one particular criteria for all the settings. Therefore, we conducted this prospective study to assess the probability of HIV infection in children hospitalized with at least two of the selected manifestations. We selected these clinical features as they were found to be associated with high probability of HIV infection in children and were included in either WHO or SA criteria for HIV screening.

Methods & Materials
This prospective study was conducted in pediatrics department of a tertiary care teaching institution of central India, over a period of 12 months. Clearance from the institutional ethics committee was obtained and written informed consent from the parents or legal guardians and assent from children above seven years of age was obtained before recruitment. Patients between 19 months and 14 years of age hospitalised with any two of the following clinical presentations were included in the study: prolonged fever for more than one month, prolonged diarrhoea for more than one month, marasmus (weight less than 60% or less than third percentile of the expected weight for age and sex), chronic cough persisting for more than one month, generalized dermatitis, repeated common infections (e.g. upper respiratory tract infections), oropharyngeal candidiasis, generalized lymphadenopathy, hepatosplenomegaly. We selected these clinical features as they were included in either WHO case definition or SA criteria. Children with other known causes of immunosuppression e.g. cancer, severe malnutrition, on long-term steroid or chemotherapy, children aged below 18 months and children whose parents refused to participate in the study were excluded. Pre-test counselling was provided including information on high risk behaviour in relation to HIV infection, technical aspects of screening and possible implications of result being found positive. After recruitment, demographic data including age, sex, weight, height, parents education and occupation, socioeconomic status and any high risk behaviour in parents were noted in pre-designed patient data form. Present and past history along with physical examination finding was recorded.

Blood sample was drawn by venepuncture and sent to laboratory for HIV testing by ELISA using Pareekshak rapid membrane ELISA kits (a sandwich enzyme immunoassay) and Enzaids HIV 1&2 ELISA kits (an indirect heterogeneous enzyme immunoassay). Diagnosis of HIV infection was confirmed as per WHO-UNAIDS strategy II.(11) We could not confirm HIV positive cases by Western Blot or other confirmatory tests because of financial constraints. Parents of seropositive children were offered post-test counselling including information on antiretroviral therapy, providing support and exploring the possibility of achievable solutions to personal problems.

Data were analyzed using SPSS version 16.0. Data were presented as percentage and compared by fisher's exact test, whenever appropriate. P value < 0.05 was considered significant.
Results
Total 138 children were eligible for recruitment on the basis of clinical examination. Of these, 28 children were excluded from study due to various reasons (16 children were aged less than 18 months, 7 cases had other known causes of immunodeficiency and parents of 5 children refused to participate in the study). The mean age of the study population was 62.3 + 26.7 months with a male: female ratio of 1.4: 1. Most of the cases (46, 41.8%) belonged to 18 months to 5 years age group.
On admission, the most common presentation was repeated common infections in 75 (68.2%) cases followed by prolonged pyrexia in 66 (60%) cases. On examination, 64 (58.2%) cases had marasmus while 61 (55.5%) cases had hepatosplenomegaly. Forty (36.4%) cases had different forms of tuberculosis including tubercular meningitis (TBM) in 14 (12.7%) cases. Generalized dermatosis was seen in only 4 (3.6%) cases (Table 1).

Out of the 110 cases, 9 cases (8.2%) were HIV positive on ELISA. HIV seropositivity rate for various clinical manifestations varies from 0% for generalized dermatosis to 23.6% for oral candidiasis. Seropositivity rate for common clinical manifestations like repeated infections and prolonged pyrexia were 6.7% and 4.6% respectively (Table 1). In our study, only oropharyngeal candidiasis was found to be an independent risk factor for predicting HIV infection (P=0.03).

The probability of HIV seropositivity increased significantly with increase in the number of risk factors present. As depicted in table 2, seropositivity rate increases from 3.3% for two risk factors to 25% when six risk factors were present.

Both the parents of 5 seropositive cases were HIV positive, parents of 3 cases were seronegative, while in 1 case parental status was undetermined as they didn't present themselves for HIV testing. Thirty-two cases received blood transfusion in past for various reasons, of which 3 were HIV positive. Most common mode of transmission was vertical (55.6% cases), 3 cases (33.3%) got it through blood transfusion. In 1 case, exact mode of transmission was undetermined as parental status was unknown.

Table 1 - HIV serostatus in relation to each clinical feature
Clinical
Manife
stations
Total Cases HIV +ve Cases HIV-ve Cases Sensiti
vity
Specifi
city
PPV P Value
Repeated
common
infections
75 5 70 55.6% 30.7% 6.76 0.46
Prolo
nged
pyrexia
66 3 63 33.3% 37.6% 4.55 0.15
Marasmus 64 6 58 66.7% 36.6% 8.57 1.00
Hepato
spleno
megaly
61 4 57 44.4% 53.7% 7.84 0.50
Persi
stent
Cough
49 2 47 22.2% 53.7% 0.50 0.29
Genera
lized
Lympha
denopathy
37 3 34 33.3% 66.3% 8.11 1.00
Oro-pha
ryngeal
Candi
diasis
17 4 13 44.4% 87.1% 23.57 0.03
Chronic
diarrhea
11 1 10 11.1% 90.1% 9.09 1.00
Genera
lized
derma
tosis
4 - - 0 96.0% 0 1.00


PPV = Positive predictive value

Table 2 - HIV seropositivity and number of risk factors present
Number of
risk factors
present
Number of
total cases
HIV positive Cases HIV negative
Cases
Seropositivity rate
Two 30 1 29 3.3%
Three 26 1 25 3.9%
Four 38 4 34 10.5%
Five 12 2 10 16.7%
Six 4 1 3 25%


Discussion
Clinically directed selective screening to diagnose HIV infection in children requires awareness among pediatricians about the spectrum of clinical manifestations of HIV infection in a particular area or community. Therefore, constant work is necessary in this field so as to determine clinical manifestations of HIV in different geographical regions, as these manifestations differ from community to community. Although actual prevalence of pediatric HIV infection in India is unknown, seroprevalence in hospitalized children was estimated to be 2.3% by Shah I et al.(12) In our study, overall HIV seropositivity rate was 8.18% in clinically directed selective screening, which is lesser than that of high prevalence areas e.g. 15% - 20% in Mumbai.(13,14)

Many studies have demonstrated the role of clinically directed selective screening to detect HIV infection(14-16) and WHO-CCD was proposed for the same purpose but its sensitivity varied greatly in different studies, e.g. 69% in Zambian study(17) to 19% in Ivory Coast study (18). Also, WHO-CCD contains 9 items, divided into major and minor signs and 6 of 9 signs require medical history, which can not be objectively verified. So that sometimes it becomes difficult to use it in outpatient department with a heavy patient load. Additionally, accompanying person?s inability to recollect the history and duration of symptoms also creates situation more difficult. Therefore in our study, we tried to include more objective signs which be obtained by simple physical examination without dividing them into minor or major criterion.

We have replaced the sign 'weight loss or abnormally slow growth' included in WHO-CCD, which depends on the subjective observation of caretaker, with an objective finding i.e. marasmus as included in SA criteria. On applying this weight criterion in our study, only 58.2% cases had marasmus compared to history of weight loss in 88.2% cases. Other Indian studies also reported a high incidence of severe malnutrition in these children, ranging from 44.56% by Merchant et al(19) to 81.9% by Lahiri et al. (20) Seropositivity rate for severe malnutrition was reported to be 26% by Bavdekar et al(14) as against the seropositivity rate of 9.38% for marasmus in our study.

In this study, seropositivity rates of chronic diarrhoea, marasmus and oropharyngeal candidiasis were higher than overall seropositivity rate of 8.18%. However, only oropharyngeal candidiasis was an independent predictor of HIV infection (P=0.03).

Oropharyngeal candidiasis is one of the most consistently identified risk factor for predicting HIV infection.(14, 21-23) Many different independent risk factors for pediatric HIV infection were identified in other studies including generalized dermatitis(14) lymphadenopathy(14,21), malnutrition(21), chronic diarrhea(22,23), and pneumonia.(24) However, in our study we did not find chronic diarrhea, dermatitis, marasmus or lymphadenopathy as significant risk factor for HIV infection. This indicates the variability of significant risk factors from one community to other and making it imperative to conduct studies in different population groups to determine significant risk factors for that particular group.

In our study, repeated common infections, chronic fever, marasmus, and hepatosplenomegaly were the common clinical manifestations of HIV infection, which are same as seen in other studies from India(25-29) as well as other tropical countries.(21-24) However, none of these was significantly associated with HIV seropositivity, which could be explained by the fact, that in developing countries other common causes of childhood admissions e.g. malaria and tuberculosis present with the similar clinical presentations. The probability of HIV infection increased progressively with increase in number of risk factors concomitantly present, which can be explained by the presence of more manifestations in children with advanced stage of the disease or greater immunosuppression.

In our study, most common mode of transmission was vertical followed by transfusion related(33.3%), which is collaborating to results of other Indian studies.(25-29) It indicates towards a worrisome fact that despite regulations requiring screening of donors, transfusion-associated HIV continues to occur in India, which can be either due to poor adherence to screening procedures or due to unsafe injection practices. In the present study, of the 40 tubercular patients, one patient was HIV positive (2.5%). Merchant et al reported seropositivity 24% and 18% in children with chronic diarrhea and disseminated tuberculosis respectively(19), while Karande S et al reported 6.5% seropositivity in TBM patients.(30)

Few study limitations were that we could not confirm positive ELISA tests by PCR or other confirmatory tests because of financial constraints. Secondly, present study was conducted on relatively small number of hospitalized children so it may not present true picture of HIV prevalence in community.

In conclusion, probability of HIV infection increases with increase in the number of risk factors and these risk factors differ from community to community. Therefore, further large scale community trials are needed to determine these risk factors for that particular population group, especially for use by paramedical workers to screen suspected HIV cases on outpatient basis.
Funding
None
Conflict of Interest
None
References :
  1. Van Gend CL, Haadsma ML, Sauer PJ, Schoeman CJ. Evaluation of the WHO clinical case definition for pediatric HIV infection in Bloemfontein, South Africa. J Trop Pediatr 2003; 49: 143-147  [Pubmed]  [CrossRef]
  2. Pol RR, Shepur TA, Ratageri VH. Clinico-laboratory profile of pediatric HIV in Karnataka. Indian J Pediatr 2007; 74: 1071-5.  [Google Scholar]  [Pubmed]  [CrossRef]
  3. Roy RN, Shrivastava P, Das DK, Saha I, Sarkar AP. Burden of Hospitalized Pediatric Morbidity and Utilization of Beds in a Tertiary Care Hospital of Kolkata, India. Indian J Community Med 2012; 37: 252-5.  [Google Scholar]
  4. Awasthi S, Agrawal S. Determinants of childhood mortality and morbidity in urban sums in India. Indian Pediatr 2003; 40:1145-61.  [Pubmed]
  5. Colebunders R, Ndumbe P. Priorities for HIV testing in developing countries? Lancet 1993; 342: 601-602  [Google Scholar]  [Pubmed]  [CrossRef]
  6. World Health Organization. Provisional WHO clinical case definition for AIDS. Wkly Epidem Rec 1986; 61 (10): 72-73.
  7. Banerjee T, Pensi T, Banerjee D. Sensitivity of paediatric AIDS score vs. WHO case classification in Indian children-a retrospective study. J Trop Pediatr 2009; 55: 91-96  [Google Scholar]  [Pubmed]  [CrossRef]
  8. Colebunders RI, Greenberg A, Nguyen-Dinh P, Francis H, Kabote N, Izaley L et al. Evaluation of a clinical case definition on AIDS in African Children. AIDS 1987; 1: 151-153  [Google Scholar]  [Pubmed]
  9. Emodi IJ, Okarfor GO. Clinical Manifestation of HIV infection in children at Enugu, Nigeria. J Trop Pediatr 1998; 44: 73-6  [Google Scholar]  [Pubmed]  [CrossRef]
  10. Leepage P, Van de Perre P, Dabis F, Commenges D, Orbinski J, Hitimana DG, et al. Evaluation and simplification of the World Health Organization clinical case definition for pediatric AIDS. AIDS 1989; 3: 221-225  [Pubmed]  [CrossRef]
  11. UNAIDS/WHO working group on global HIV/AIDS/STI surveillance. Guidelines for Using HIV Testing Technologies in Surveillance. Available from: URL: http://www.unaids.org/en/media/unaids/contentassets/dataimport/ publications/irc-pub02/jc602-hivsurvguidel_en.pdf. Accessed Nov 30 2012.
  12. Shah I, Katira B. Seroprevalence of HIV infection in hospitalized paediatric patients at a tertiary care centre in western India. HIV Medicine 2007; 8: 265?266  [Google Scholar]  [Pubmed]  [CrossRef]
  13. Agrawal M, Koppikar GV, Ghildiyal R, Charvakar M, Joshi SM, Lahiri KR. Seropositivity rate for HIV infection in hospitalized children on selective screening. Indian Pediatr 2001; 38: 267-271  [Pubmed]
  14. Bavdekar SB, Agrawal R. Clinically directed selective screening for HIV infection in hospitalized children. Indian Pediatr 2005; 42: 1191-1197  [Google Scholar]  [Pubmed]
  15. Bandyopadhyay A, Bhattacharyya S, Banerjee A. Clinicoepidemiological scoring system for early diagnosis of pediatric HIV. Indian Pediatr 2009; 46: 512-515  [Google Scholar]  [Pubmed]
  16. Karande S, Bhalke S, Kelkar A, Ahuja S, Kulkarni M, Mathur M. Utility of clinically-directed selective screening to diagnose HIV infection in hospitalized children in Bombay, India. J Trop Pediatr 2002; 48: 149-155.  [Google Scholar]  [Pubmed]  [CrossRef]
  17. Chintu C, Malek A, Nyumble M, Luo C, Mesono J, Dufont HL et al. Case definition for Pediatric AIDS: the Zambian experience. Int J STD AIDS 1993; 4: 83-85  [Google Scholar]  [Pubmed]
  18. Vetter KM, Djomand G, Zadi F Diaby L, Brattegaard K, Timité M, et al. Clinical Spectrum of human immunodeficiency virus disease in children in a West African city. Pediatr Infect Dis J 1996; 15: 438-442  [Google Scholar]  [Pubmed]  [CrossRef]
  19. Merchant RH, Shroff RC. HIV seroprevalence in disseminated tuberculosis and chronic diarrhea. Indian Pediatr 1998; 35: 883-887  [Google Scholar]  [Pubmed]
  20. Lahiri S, Shahaf T, Alan S, Malik L. HIV seropositivity in hospitalized children with high clinical likelihood of AIDS. Indian Pediatr 2002; 39: 372-375.  [Google Scholar]  [Pubmed]
  21. Prazuck T, Tall F, Nacro B, Rochereau A, Traore A, Sanou T, et al. HIV infection and severe malnutrition: A clinical and epidemiological study in Burkina Faso. AIDS 1993; 7: 103-108  [Google Scholar]  [Pubmed]
  22. Akpede GO, Ambe JP, Robasa Al, Akuhwa TR, Ajayi Akoma MA, Bukbuk DN, et al. Presentation and outcome of HIV-1 infection in hospitalization infants and other children in North Eastern Nigeria. E Afr Med J 1997; 74: 21-27  [Google Scholar]  [Pubmed]
  23. Thea DM, St. Louis ME, Atido LI, Kanjinga K, Kembo B, Matondo M, et al. Prospective study of diarrheas and HIV-1 infection among 429 Zairian infants. N Engl J Med 1993; 329: 1696-1702  [Google Scholar]  [Pubmed]  [CrossRef]
  24. Mann JM, Francis H, Davachi F, Quinn TC, Baudoux P, Nzilambi N, et al. Risk factors for HIV seropositivity among children 1-24 months old in Kinshasa, Zaire. Lancet 1986; 20: 654-656  [Google Scholar]  [Pubmed]
  25. Verghese VP, Cherian T, Cherian AJ, Babu PG, John TJ, Kirubakaran C, et al. Clinical Manifestation of HIV-1 infection. Indian Pediatr 2002; 39: 57-63
  26. Sehgal R, Baveja UK, Chattopadhya D, Chandra J, Lal S. Pediatric HIV infection. Indian J Pediatr 2005; 72: 925-930  [Google Scholar]  [Pubmed]  [CrossRef]
  27. Lodha R, Upadhyay A, Kapoor V, Kabra SK. Clinical profile and natural history of children with HIV infection. Indian J Pediatr 2006; 73: 201-204  [Google Scholar]  [Pubmed]  [CrossRef]
  28. Shah I. Age related clinical manifestations of HIV infection in Indian children. J Trop Pediatr 2005; 51: 300-303  [Google Scholar]  [Pubmed]  [CrossRef]
  29. Dhurat R, Manglani M, Sharma R, Shah NK. Clinical spectrum of HIV infection. Indian Pediatr 2000; 37: 831-836  [Google Scholar]  [Pubmed]
  30. Karande S, Gupta V, Kulkarni M, Joshi A, Rele M. Tuberculous Meningitis & HIV. Indian J Pediatr 2005; 72: 755-760  [Google Scholar]  [CrossRef]
Last Updated : Tuesday, January 01, 2013 Vol 10 Issue 1 Art #4
DOI: 10.7199/ped.oncall.2013.4
How to Cite URL :
Agrawal A, Thora S, Agrawal R. HIV SEROPOSITIVITY IN HOSPITALIZED CHILDREN ON CLINICALLY DIRECTED SELECTIVE SCREENING: AN EXPERIENCE FROM CENTRAL INDIA . Pediatric Oncall [serial online] 2013[cited 2013 January 1];10. Art #4. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=536&type=J&tid=&imgid=&reportid=60&tbltype=
Disclaimer: The information given by www.pediatriconcall.com is provided by medical and paramedical & Health providers voluntarily for display & is meant only for informational purpose. The site does not guarantee the accuracy or authenticity of the information. Use of any information is solely at the user's own risk. The appearance of advertisement or product information in the various section in the website does not constitute an endorsement or approval by Pediatric Oncall of the quality or value of the said product or of claims made by its manufacturer.
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.