|Year : 2006 | Volume
| Issue : 4 | Page : 244-249
|Pediatric HIV: There is hope
Subhasish Bhattacharyya, Aparna Mukherjee
Deparment of Pediatrics, Pediatric HIV/AIDS Clinic, Medical College, Kolkata, India
B-3/8, Purbasha Housing Estate, 160, Maniktola Main Road, Kolkata - 700 054
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bhattacharyya S, Mukherjee A. Pediatric HIV: There is hope. Indian J Dermatol 2006;51:244-9
| Introduction|| |
The threat of HIV/AIDS is one of the major menace that mankind is facing today, with HIV/AIDS having made a huge global impact permeating the social, cultural and economic fabric of all nations of the world. Today an estimated 40.3 million people worldwide are infected with HIV with roughly 4.9 million new cases reported in 2005 alone and 3.1 million deaths reported in 2005. The current estimate is that India has the largest number of AIDS cases -5.7 million in 2005. The adult prevalence of HIV in the country is 0.91%. Out of this 38.4% are females and 57% are from rural population.
| The Scenario in Paediatric Population|| |
The picture in the paediatric population is no less grim. According to UNICEF Executive Director Ann M. Veneman, 'children are the missing face of AIDS, but what is still missing is a global recognition of the impact of AIDS on children's lives. An estimated 2.5 million children of less than 15 years are living with HIV/AIDS globally. 1500 new cases are being detected everyday. 15 million children have lost at least one of their parents to the disease. In India, according to UNAIDS 1, 20,000 children were living with HIV in 2004. National Aids Control Organization (NACO) estimated that 60000 new infections occurred last year and activists estimate that around 2,50,000 Indian children are positive today, but there are no accurate data. The director general of NACO commented that children would be awarded greater priority in the next NACP III.
| Modes of Transmission|| |
With the rising concern of HIV/AIDS in children our focus shifts to the modes of transmission in children, which are different from that in adult. The main mode of transmission is PTCT (parent to child transmission), which can occur during pregnancy, at time of delivery and through breast-feeding. In the developing countries like India, there is 25-30% chance of the baby being infected from an infected mother. Currently more than 27 million women, including over 92,000 HIV infected women, give birth in India every year. Thus we can perceive the danger, which our young population is facing today.
It is generally accepted that 30-40% of infected newborns are infected in-utero with infection occurring as early as the 10th week of gestation. The largest fraction of infection is intrapartum occurring in 60-70% of cases of vertical transmission presumed to be due to exposure to infected blood and cervico-vaginal secretions. Breast-feeding is also an important route of transmission in the developing countries. A meta-analysis of prospective studies found that the additional risk of transmission through breast-feeding in women with HIV infection before pregnancy was 14% compared with a 29% increase in breast-feeding women who acquired HIV postnataly. The risk factors of vertical transmission are: preterm delivery (<34 week gestation), a low maternal antenatal CD4 count, use of illicit drugs during pregnancy, >4 hour duration of ruptured membranes and birth weight <2500 g. Transfusions of infected blood or blood products have accounted for 3-6% of all pediatric AIDS cases. In the pediatric population, sexual transmission is infrequent, but a small number of cases resulting from sexual abuse have been reported. In contrast, sexual contact is a major route of transmission in the adolescent population, accounting for most of the cases.
| Clinical Features|| |
HIV/AIDS in children is classified on the basis of clinical status and degree of immunological impairment.
Currently, it is the latest WHO clinical staging of HIV/AIDS for children, which is preferred than the earlier CDC classification, especially in resource limited regions.
WHO clinical staging for HIV/AIDS for children with confirmed HIV infection is as follows [Table - 1],[Table - 2]:
Clinical staging 1:
- Persistent generalized lymphadenopathy
Clinical staging 2:
- Unexplained persistent hepatosplenomegaly
- Papular pruritic eruptions [Figure - 1]
- Extensive warts
- Extensive molluscum contagiosum
- Fungal nail infections
- Recurrent oral ulcerations
- Unexplained persistent parotid enlargement
- Linear gingival erythema
- Herpes zoster
- Recurrent or chronic upper respiratory tract infections
Clinical staging 3:
- Unexplained moderate malnutrition not adequately responding to standard treatment
- Unexplained persistent diarrhoea (14 days or more)
- Unexplained persistent fever (37.5șC, for one month or longer)
- Persistent oral candidiasis
- Oral hairy leukoplakia
- Acute necrotizing ulcerative gingivitis or periodontitis
- Lymph node tuberculosis
- Pulmonary tuberculosis
- Severe recurrent bacterial pneumonia
- Symptomatic lymphoid interstitial pneumonitis
- Chronic HIV-associated lung disease including bronchiectasis
- Unexplained anemia (les than 8 g/dL), neutropaenia (<500/cmm) and or thrombocytopaenia (<50000/cmm).
Clinical staging 4:
- Unexplained severe wasting, stunting or severe malnutrition not adequately responding to standard treatment
- Pneumocystis pneumonia
- Recurrent severe bacterial infections
- Chronic herpes simplex infection
- Extrapulmonary tuberculosis
- Kaposi sarcoma
- Esophageal candidiasis
- Central nervous system toxoplasmosis
- HIV encephalopathy
- Cytomegalovirus infection
- Extrapulmonary cryptococcosis (including meningitis)
- Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
- Chronic cryptosporidiosis
- Chronic isosporiasis
- Disseminated non-tuberculous mycobacterial infection
- B-cell non Hodgkin lymphoma
- Progressive multifocal leukoencephalopathy
- Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy
| Opportunistic Infections|| |
Pneumocystis jiroveci (carinii) pneumonia (PCP)
Pneumocystis carinii, earlier thought to be protozoan, now believed to be more closely related to fungi, is the most common opportunistic infection in HIV infected children. PCP is an infection of early infancy and most children are affected at between 3-6 months of age. The risk of PCP in the first year of life for perinatally infected children not receiving prophylaxis is estimated to be approximately 12%. Children with PCP present with acute onset tachypnea, dyspnea, cough, and fever. Physical examination findings include tachycardia, tachypnea and diffuse chest retractions. Pulmonary auscultation is typically non-specific. PCP is characterized by rapidly progressive and marked hypoxemia. Early radiographic findings may be normal or can include hyperinflation with peribronchial thickening. As the disease progresses, the chest radiographic findings typically evolve to reveal bilateral alveolar or interstitial infiltrates usually spreading peripherally from the perihilar region to involve both lung fields. Focal or patchy infiltrates, cavities or effusions may also be found. Fiberoptic bronchoscopy with bronchoalveolar lavage has been shown to be a safe and sensitive method for the diagnosis of PCP.
Recurrent bacterial infections
Recurrent bacterial infections is defined as two or more bacteriologically documented systemic bacterial infections including septicemia or bacteraemia, meningitis, pneumonia, osteomyelitis, septic arthritis or abscess of an internal organ or body cavity occurring within a period of 2 years. The major bacterial pathogens in children with HIV are found to be similar to those in immunologically healthy children, Streptococcus pneunoniae and Salmonella More Details sp. being common isolates.
Infection with Mycobacterium tuberculosis is a very important and probably the commonest coinfection in paediatric HIV /AIDS, particularly in developing countries. Although most children seem to have primary pulmonary infection, extrapulmonary disease has been reported in 10-50% of children with tuberculosis.
Mycobacterium avium-intercellulare (MAC)
Disseminated infection with MAC occurs almost exclusively in children with advanced HIV disease (CD4 count <100 cells/cmm).
Most children present with fever, weight loss, poor weight gain, abdominal pain, and anemia. Night sweats, diarrhea, malaise, neutropenia, and hepatomegaly have also been described
Although systemic fungal infections are relatively rare in children with HIV infection, mucosal and cutaneous fungal infections are commonly diagnosed. Oral candidiasis is the most common fungal infection in HIV infected children, with esophagitis present in 20% of children [Figure - 2]. Cryptococcus neoformans, Aspergillius Sp., Histoplasma capsulatum , and Coccidiodes immitis are other fungal pathogens.
Parasitic infections like intestinal cryptosporidiosis, microsporidiosis, isosporidiosis and rarely giardiasis causes significant morbidity in HIV infected children.
Disseminated CMV infections are found in children with very low CD4 count of less than 50 cells/cmm and presents with chorioretinitis, esophagitis, pneumonitis, and colitis. Cytomegalovirus colitis is characterized by non-specific complaints of diarrohoea, abdominal pain, weight loss, anemia, and fever. Patients with CMV pneumonitis present with cough, shortness of breath and progressive hypoxemia.
HIV infected children are at risk for persistent, recurrent, chronic infections with varicella-zoster virus. Atypical measles without the typical rash may occur in spite of immunization.
Central nervous system (CNS) features
Progressive and static encephalopathy with cognitive deterioration, loss of developmental milestones, acquired microcephaly, behavioral problems and symmetric motor manifestations has been described in HIV-infected children. Focal neurological signs may be due to CNS tumour like lymphoma, stroke or opportunistic infections like toxoplasmosis (particularly in adolescents). Neuroimaging and CSF studies are important for diagnosis.
Respiratory tract features
Recurrent otitis media and sinusitis are very common in HIV infected children. Pneumonia with S. pneumoniae, P. cariinii and M. tuberculosis are common.
Lymphoid interstitial pneumonitis (LIP), a chronic lymphocytic infiltrative disease of the lung is a unique manifestation of HIV infection, found in about 25% of infected children. It presents insidiously with cough, tachypnoea, and hypoxaemia with minimal auscultatory findings. In more severe cases, significant clubbing occurs. The diagnosis of LIP in children is usually based on a typical chest radiograph with persistent reticulonodolar bilateral infiltrates.
Cardiac lesions described in patients with HIV include pericardial effusions; pericarditis; myocarditis; dilated cardiomyopathy; endocarditis; and vascular lesions, such as aneurysms, atherosclerosis and pulmonary hypertension.
Ulcers in the oral cavity may be due to HSV, CMV, and Coxsackie A infection. Oral thrush and esophagitis due to candidiasis may be present. Development of chronic bilateral enlargement of the parotid glands may occur in as many as 15% of children with HIV infection and usually does not require any treatment. Parotitis is in fact a good prognostic marker. Diarrhea is a common manifestation of HIV infection. Although an infectious cause is frequently suspected, other important causes include side effects of medications, malignancies and HIV enteropathy. Infectious cause may include bacteria, parasites, fungi and virus.
Failure to thrive is almost universal amongst HIV infected children, particularly in developing countries. Impairment of linear growth is more common.
Seborrheic dermatitis, drug allergies, and infectious disorders like scabies and bacterial infections tend to be more disseminated and unresponsive to conventional therapy [Figure - 3].
Anemia occurs in about 20-70% of HIV infected children. Anemia is generally multifactorial in HIV infection. The most common causes include nutritional deficiencies of iron, folic acid and, less commonly, vitamin B12; immune hemolysis; hemorrhage; drug toxicities; and bone marrow suppression caused by the HIV virus, other infectious agents like Parvovirus B-19 and malignancy.
Neutropenia may occur secondary to infection, nutritional deficiencies or drug toxicity. Some drugs used to treat HIV infection, such as zidovudine and co-trimoxazole, are associated with the development of neutropenia.
Thrombocytopenia is a common problem among HIV-infected children. It may occur in the absence of other symptoms and, in some patients, is the initial presenting illness. Although a specific cause is usually not found, it should be investigated.
Malignant diseases are infrequent in HIV infected children, unlike the adults. They include CNS lymphomas, and leiomyosarcomas.
| Diagnosis of HIV Infection (WHO Definition)6|| |
In adults and children 18 months or older, HIV infection is diagnosed based on:
- Positive HIV antibody testing (rapid or laboratory-based enzyme immunoassay). This is usually confirmed by a second HIV antibody test (rapid or laboratory-based enzyme immunoassay) relying on different antigens or of different operating characteristics.
- A positive virological test for HIV or its components (HIV-RNA or HIV-DNA or ultrasensitive HIV p24 antigen) confirmed by a second virological test obtained from a separate determination.
In children younger than 18 months, HIV infection is diagnosed based on:
- A positive virological test for HIV or its components (HIV-RNA or HIV-DNA or ultrasensitive HIV p24 antigen), confirmed by a second virological test obtained from a separate determination taken more than four weeks after birth. Positive antibody testing is not recommended for definitive or confirmatory diagnosis of HIV infection in children until 18 months of age, as maternally acquired antibodies remain positive till this age.
| Treatment|| |
Specific therapy with HAART
Decision-making process for initiation of antiretroviral therapy (ART) in infants and children depends on clinical and immunological assessment. WHO emphasizes the importance of clinical parameters, rather than CD4 measurement because this investigation is not widely available in our resource poor setting. However, if available, using the results of CD4 count is valuable in deciding the need of ART in less ill children
Recommended first line ART
Ziduvudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP)/ Efavirenz (EFV)
Stavudine (d4T) + Lamivudine (3TC) + Nevirapine (NVP)/ Efavirenz (EFV)
EFV is recommended in HIV and TB coinfection. It should not be used below 3 years and in adolescent girls.
AZT + d4T should not be used together.
AZT is not recommended in anemic children (Hb%<9 gm/dL)
Recommendations for initiating ART in HIV infected infants and children depend on clinical stage and availability of immunological markers. (WHO 2006)
Components of follow up in children receiving ART
- Clinical follow up
- Laboratory follows up
- Counseling of caregivers
- Efficacy evaluation
- Adherence monitoring
- Monitoring of adverse events
- Diagnosis of opportunistic infections (OI)
- Immune reconstitution syndrome
There are three types of treatment failures-clinical failure, immunological failure and virological failure, diagnosed on the basis of clinical manifestations, CD4 count and blood viral load.
Management of OIs
TMP-SMX (trimethoprim-sulfamethoxazole) is the treatment of choice for children with Pneumocystis carinii pneumonia. The dose is 20 mg/kg divided into four daily doses for 21 days. Pentamidine 4 mg/kg given as a single dose for 21 days is generally reserved for children who cannot tolerate TMP-SMX secondary to adverse effects and for those who fail therapy. Several other medications (i.e., dapsone-trimethoprim, clidamycin-primaquone, atovaquone, and trimetrexate-leucovorin) have been approved for the treatment of adults with PCP but none of these medications have been evaluated in children. Comprehensive respiratory support, including supplemental oxygen, ventilatory support and good pulmonary toilet is essential to ensure a satisfactory outcome for patients with this disease
Prophylaxis of PCP
Prophylaxis should be administered to:
- All HIV infected and indeterminate children from 4 weeks to 12 months of life (prophylaxis can be stopped if HIV infection has been excluded after 4 months of age)
- All symptomatic HIV infected children (WHO clinical stage 2 and above, when CD4 count is not available) [Table - 3]
- All HIV infected children treated for PCP
- All HIV infected children with CD4% less than appropriate for age, severe immune suppression. TMP-SMX is given in a dose of 6-8 mg/kg of TMP (trimethoprim) daily in two divided doses.
The other opportunistic infections and co-infections should be appropriately treated. Prophylaxis is recommended for MAC, contact with open cases of tuberculosis. Secondary prophylaxis is recommended for MAC, cytomegalovirus infection, and toxoplasmosis.
The parents should be properly counseled about importance of good nutritious diet with adequate calories and protein. Also, the importance of simple measures in preventing serious infections should be stated. These include hand washing, consuming properly washed and cooked food, avoiding bathing in ponds, keeping away from pets like cats, etc.
HIV infected children should receive all vaccine as detailed under immunization schedule recommended by the WHO Expanded Program on Immunization (EPI) for children in developing countries. Only children classifying under WHO clinical stage 4 should not receive live vaccination like OPV or BCG. Hepatitis B, pneumococcal vaccines and H. influenzae vaccines are also recommended. Yearly influenza vaccines in children beyond 6 months of age may be administered if available.
In the context of our country where lack of proper awareness regarding HIV/AIDS has lead to a lot of social discrimination, psychosocial support is very important for the HIV infected children and their families. Moreover, many of these children are becoming orphans having lost both the parents to the disease and require a lot of economical and psychological support.
| Conclusion|| |
With more access to antiretroviral therapy along with good nutrition there is hope that more and more HIV positive children would cross adolescence stage to adulthood. Regular clinical follow up along with better understanding of HIV among doctors and society will bring rays of hope for these unfortunate innocent victims of a deadly virus.
| References|| |
|1.||UNAIDS/AIDS epidemic update. World Health Organization: Geneva, Switzerland; 2005. [cited on 2006 Sep 29]. Available from: http://www.unicef.org/aids/index_1.php. |
|2.||UNAIDS Report on the Global HIV/AIDS Epidemic. UNAIDS AIDS epidemic. World Health Organization: Geneva, Switzerland; 2006. [cited on 2006 Sep 29]. Available from: http://www.unicef.org/aids/index_1.php. |
|3.||Monthly updates on AIDS, NACO, 31 July 2005. [cited on 2006 Sep 30]. Available from: http://www.nacoonline.org/directory_pptct.htm. |
|4.||UNAIDS Report on the Global HIV/AIDS Epidemic. UNAIDS AIDS epidemic: Executive summary 2006.; World Health Organization: Geneva, Switzerland; 2006. [cited on 2006 Sep 29]. Available from: http://www.unicef.org/aids/index_1.php. |
|5.||Hiddleston S, Left out - children with AIDS. The HINDU May 31, 2006. [cited on 2006 Sep 29]. Available from: http://www.thehindu.com/2006/05/31/01hdline.htm. |
|6.||WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. World Health Organization: Geneva, Switzerland; 2006. [cited on 2006 Sep 29]. Available from: http:/www.who.int/hiv. |
|7.||Bhattacharyya S. HIV positive children of Calcutta- survival strategies without antiretroviral drugs. In : 15th International AIDS conference, International proceedings, Medimond S.R.L; 2004. p. 81-5. |
|8.||Khilnani P, Rajdev SK, Uttam R. Pediatric Aids - Part 1. Indian J Crit Care Med 2003;7:257-72. |
|9.||Ruff A, Guay L, Halsey N. Medical Management of Newborns and Infants in Developing countries. In : Pediatric AIDS. Pizzo PA, Wilfert CM, editors. The Challenge of HIV Infection in Infants, Children and Adolescents. 3rd ed. Lippincott Williams and Wilkins: Philadelphia; 1998. p. 593-613. |
|10.||WHO Recommendation for Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: Towards universal access. World Health Organization: Geneva, Switzerland; 2006. |
|11.||Bhattacharyya S. Regular multivitamin and multimineral supplementation improves quality of life and prolongs survival of HIV positive children in India. In : 3rd IAS conference on HIV pathogenesis and treatment. Rio de Janerio, Brazil: 2005 Abs no MoPe 9.2C05. |
|12.||Bhattacharyya S. Effect of cotrimoxazole prophylaxis on morbidity and mortality of HIV positive children in Eastern India. In : XVI International AIDS conference. Toronto, Canada; 2006 Abs no THPE0056. |
|13.||Bhattacharyya S. Clinico-epidemiological scoring system for early diagnosis of pediatric HIV/AIDS in India. In : 7th International congress on AIDS in Asia and the Pacific. 2005 Abs no SaPA0029. |
|14.||Bhattacharyya S. Early diagnosis of pulmonary tuberculosis in HIV positive children by scoring system during regular out patient follow-up. In : XVI International AIDS conference. Toronto, Canada: 2006 Abs no MOPE0397. |
[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2], [Table - 3]
|This article has been cited by|
||A web-based electronic health care system for the treatment of pediatric HIV
| ||Paul, S., Das Bhattacharya, S., Sudar, A., Patra, D., Majumdar, A.K., Mukhopadhyay, J., Majumdar, B. |
| ||2009 11th IEEE International Conference on e-Health Networking, Applications and Services, Healthcom 2009. 2009; : 175-180 |
| Article Access Statistics|
| Viewed||6706 |
| Printed||146 |
| Emailed||3 |
| PDF Downloaded||322 |
| Comments ||[Add] |
| Cited by others ||1 |