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ORIGINAL ARTICLE
Year : 2009  |  Volume : 21  |  Issue : 3  |  Page : 107-113 Table of Contents   

Prevalence of orofacial manifestations in HIV-positive South Indian children and the co-relation with CD4 counts


Department of Oral Medicine and Radiology, Dayananda Sagar College of Dental Sciences, Shavige Malleshwara Hills, Kumaraswamy Layout, Bangalore, India

Date of Web Publication7-Jan-2010

Correspondence Address:
Rachna Kaul
Department of Oral Medicine and Radiology, Dayananda Sagar College of Dental Sciences, Shavige Malleshwara Hills, Kumaraswamy Layout, Bangalore - 560 078
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.58750

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   Abstract 

Objectives : Orofacial manifestations (OFMs) are seen early in the course of HIV disease in children and can also act as indicators for the presence of the disease. The objective of the study were to find the prevalence of OFMs of HIV in infected children, co-relate them with their CD4 counts and establish whether OFMs could be used as markers for disease progression. Materials and Methods : Using the diagnostic criteria recommended by the European Collaborative Clearinghouse (ECC) on oral problems related to HIV infection and WHO Collaborating Centre on oral manifestations of the HIV, 48 HIV-infected children were examined at the baseline and their CD4 counts were obtained. A follow-up was conducted 6 months later. Chi-Square test was used to analyse the data obtained. Results : OFM showed a high prevalence in HIV-infected children. The degree of immunosuppression was found to co-relate with the presence of OFMs. But, it could not be established that the presence of OFMs could be a marker for HIV disease progression. Conclusion : The results of our study indicated a high prevalence of OFMs in HIV-infected South Indian children. A decline in CD4 counts was found to be associated with more number of OFMs. However, we were unable to establish OFMs as markers for HIV disease progression. The sample size in our study being about 48 patients and the variability in the initiation and duration of HAART therapy, use of other drugs not being considered, may have an influence on the result of our study. Larger population groups, with parameters such as nutritional status and HAART initiation included, can probably give a more conclusive result..

Keywords: CD4 cells, HIV, immunosuppression, orofacial manifestations


How to cite this article:
Kaul R, David CM, Savitha G, Rema J, Ramnarayan B K. Prevalence of orofacial manifestations in HIV-positive South Indian children and the co-relation with CD4 counts. J Indian Acad Oral Med Radiol 2009;21:107-13

How to cite this URL:
Kaul R, David CM, Savitha G, Rema J, Ramnarayan B K. Prevalence of orofacial manifestations in HIV-positive South Indian children and the co-relation with CD4 counts. J Indian Acad Oral Med Radiol [serial online] 2009 [cited 2019 Dec 12];21:107-13. Available from: http://www.jiaomr.in/text.asp?2009/21/3/107/58750


   Introduction Top


HIV infection was first recognized in children in November 1982. [1] However, according to some authors, the first case of HIV infection in children was described in 1983. [2],[3],[4],[5],[6] As in 2007, approximately 40 million people are living with HIV infection worldwide, of whom 2.5 million are children. [7] According to an estimate in 2006, by UNAIDS, approximately 1.2 lakh children are living with HIV infection in India alone. [8] India has the second highest number of people living with HIV/AIDS in the world being next only to South Africa. The six high-prevalence states are Maharashtra, Karnataka, Andhra Pradesh, Tamil Nadu, Manipur, and Nagaland. [9]

Although HIV disease shows similarities in children and in adults, there are also a number of differences, such as risk factors, primary mode of transmission, patterns of seroconversion, natural history, and spectrum of disease which includes the oral manifestations. [10] HIV infection has been studied extensively in adults, but pediatric HIV infection is a relatively newer field and has not been extensively studied. [7] Since orofacial manifestations (OFMs) are a common presentation in HIV-infected children and adults, and often the only manifestation of the disease, an OFM could be an early identifying point in HIV positivity in high-risk groups.

Pediatric HIV infection is rapidly advancing in the South Indian scenario; we conducted a study on HIV-infected South Indian children to assess the prevalence of OFMs and to assess their corresponding CD4 counts, which would indicate whether an OFM can be used as a marker of disease progression. This would help in an early identification of the disease and its progression, thus helping in the important factor of management protocols, which in turn, affects the quality of life and lifespan too.


   Materials and Methods Top


A randomized comparative study was conducted at the Infectious Diseases Clinic at Indira Gandhi Institute of Child Health Care, Bangalore (Karnataka, India) from the time period between July 2007 and March 2008. HIV-infected children in the age group of 2-12 years were randomly selected with informed consent of their parent or guardian. The study consisted of two phases; at the baseline, 48 children in the study group were examined. Six months later, a follow-up was conducted and these children were re-examined. In all, four children were lost to the follow- up; three children could not be traced while one child had unfortunately succumbed to HIV.

The findings of the clinical examination were recorded in a prepared format for the study. Three examiners (a specialist in the field of Oral Diagnosis, Medicine and Radiology; a specialist in Pediatrics, and the third examiner held a bachelor's degree in Dental Surgery) conducted a thorough orofacial examination. The examiners were not calibrated and each one of them individually examined all the children. The examination was carried out in a hospital set-up with the children comfortably seated on a chair. Disposable mouth mirrors and probes were used to examine the children under the light from a pen torch. The diagnostic criteria followed were as given by the Collaborative Work-Group on the oral manifestations of pediatric HIV infection in March 1994 and May 1995 for the diagnosis and management of HIV-related oral diseases in children. The framework was adapted from the classification system of the European Collaborative Clearinghouse (ECC) on oral problems related to HIV infection and WHO Collaborating Centre on oral manifestations of the HIV. The diagnosis was based on visual examination alone and culture tests for candida were not done and no biopsies for other oral lesions were carried out.

The study group was subjected to analysis of their CD4 counts within a period of a week of their oral examination. Information regarding their date of HIV conformity, other illness they were suffering from, and medications they were on apart from HAART was also gathered from the records at the Infectious Diseases Clinic. The children receiving HAART were on a combination of zidovudine, lamivudine, and stavudine. The individual doses differed according to the guidelines by National AIDS Control Organization (NACO), India.


   Results Top


It was found that at the baseline, the prevalence of OFMs was 64.58% and 6 months later, the same was 61.36% [Table 1], [Figure 1]. The threshold level of the CD4 count at which an OFM was seen was 119 at the baseline and 212 6 months later. The mean CD4 count of the children with OFMs at the baseline was found to be 532.64, while that of those without OFMs was 1062.76. Six months later, the mean CD4 count of the children with OFMs was found to be 650.67 for those with and 758.94 for those without OFMs indicating that children with OFMs had lower CD4 counts as compared to those without OFMs in both the phases.

On categorizing the children based on their level of immunosuppression, at the baseline, out of 31 children with OFMs, 29 were immunosuppressed while 6 months later, out of 27 children with OFMs, 23 were immunosuppressed [Table 2],[Figure 2]. Though the immunosuppression levels of children with OFMs were found to be more in majority of children both at the baseline and 6 months later when considered individually, no significant association was found at both time intervals when compared with each other [Table 2].

The distribution of individual OFMs both at the baseline and 6 months later was found as shown in [Table 3] and [Table 4] and [Figure 3] and [Figure 4]. Other lesions like those of molluscum contagiosum, dermatological infections, otitis media, fissured tongue, and mesiodens were also come across in the study group.

The mean duration of time for which the children were on HAART was 4.6 months and 8.9 months at the baseline and 6 months later, respectively. At the baseline, 17 children were on HAART and 6 months later, this number had increased to 22.

In the study group, the mean age of children was 6.98 years and 7.2 years at the baseline and 6 months later, respectively. The minimum age at which an OFM was seen at the baseline was 3 years and 6 months later, it was 5 years. Considering the gender distribution, at the baseline among the children examined, 25 were males and 23 females and 6 months later, 23 were males and 21 females. OFMs were more prevalent in males at the baseline while 6 months later, females had more OFMs [Figure 5]. On comparing the mean CD4 counts of males and females in the study group, it was found that at the baseline, females had a higher mean CD4 count of 751.91 compared to a lower value of 691.28 in males. However, there was a reversal in the mean CD4 count of females and males 6 months later with females having a lower mean CD4 count [Figure 6].

Minitab version 14 was used for the statistical analysis of the data; Microsoft Excel was used for generating the graphs and the statistical test used was the Chi-square test.


   Discussion Top


Among the various modes of transmission of HIV in human beings, transplacental transmission (85% cases) is important in causing pediatric HIV infection. [11] HIV-infected children are classified into mutually exclusive categories according to their infection status, their clinical status, and their immunologic status. [1] Three mutually exclusive immunological categories defined according to the degree of immunosuppression are no suppression, moderate suppression, and severe suppression. HIV-infected children can also be divided into three groups (fast progressors, intermediate progressors, and nonprogressors) according to the progression of disease they show, [12] and majority belong to the intermediate progressor group.

Among the various types of manifestations of HIV infection in children, OFMs are the first signs of the infection in approximately half of the infected children and are indicative of progression. [11],[13],[14],[15],[16],[17],[18] OFMs seen in these HIV-infected children have been broadly divided based on the frequency under three groups. [3],[4],[10] Group I comprises lesions like oral candidiasis (OC), herpes simplex virus (HSV) infections, linear marginal gingivitis (LMG), parotid enlargement (PE), and recurrent aphthous ulcers (RAU). Group II comprises necrotizing gingival/periodontal disease, necrotizing stomatitis, xerostomia, etc., and Group III comprises Kaposi's sarcoma, oral hairy leukoplakia, etc. These lesions are usually clearly visible and can be diagnosed reliably from the clinical features alone. [19]

In our study, we examined 48 HIV-positive children between the ages of 2 and 12 years. The levels of maternal antibodies in infected children may mask the actual CD4 levels and also provide some added immunity to the infant against the infections. Hence, the above age group was considered. The same children were re-examined after a period of 6 months as considered by other investigators such as Kozinetz et al. in 2001. [21] The CD4 counts were obtained for all the children examined both at the baseline and 6 months later.

OFM prevalence of 64.58% was found at the baseline and of 61.36% 6 months later. This implies that more than half of the infected children both at the baseline and the follow-up had one or more OFMs. Considering that most of the children in our study sample were destitute from orphanages, they usually report to an institution very late. During this time, there is progression of HIV infection which leads to various manifestations including OFMs. Also, following the diagnostic criteria of the Collaborative Work-Group on the oral manifestations of pediatric HIV infection, the diagnosis of OFMs was based on visual examination alone considering that ours is a preliminary study.

In our study, the observations regarding the CD4 counts implied that the presence of OFMs was more at lower CD4 counts. Previous studies show that a reduced CD4 count in children usually determines a greater frequency and severity of oral manifestations associated with HIV infection. [11,25] There was an increase in the number of children on HAART during the 6-month follow-up period indicating that there was deterioration in the immune status of these children and hence they had to be put on HAART. A common baseline regarding the initiation of HAART was unavailable to us since many of the children were already on HAART for some duration at the time when they were first examined. The mean duration for which children at baseline were on HAART was 4.6 months and 6 months later, it was 8.9 months. Most of the children in the study were on other drugs like antitubercular therapy (ATT), antimicrobial agents, etc. Since we did not take into account the number of children on these drugs and the duration of therapy, we cannot comment on the exact effect of these drugs on the immune systems.

The lowest age at which OFMs were seen in our study was 3 years at the baseline and 5 years after 6 months suggesting that in a developing country like India, one may encounter the oral manifestations of HIV at a very early age. This could be attributed to a prevailing immunodeficient state along with the effects of malnutrition, lack of medical facilities, etc. In our study, among the children with OFMs, majority belonged to moderate and severe immunosuppression categories. Normally children have considerably higher CD4 counts than do adults. [17] In HIV-infected children, like in adults, CD4 cells are the prime target of the virus and are destroyed. The pace of this destruction, however, is varied and the immune system of majority of children behaves in an intermediate manner. Only when their CD4 counts fall below a certain level, do they become immunocompromised and hence prone to various infections. The findings of our study point toward the weak immune system that prevailed in our study sample. The threshold level of the CD4 count at which OFMs were observed at the baseline was 119 and 6 months later it was 212. It is well known that as the immune status of the HIV-infected children deteriorates, they are more prone to infections. [28] To say that OFMs can be used as an indicator for the progression of HIV disease, we needed to establish that as the immunosuppression progresses, OFMs show an increase or as the immunosuppression reverses, OFMs decrease.

However, on comparison, no significant association was found between immunosuppression levels and the presence of lesions at the two time intervals. Hence, we could not find a significant relation to justify that OFMs increased or decreased with time at different degrees of immunosuppression. This could be because the influence of HAART and other drug therapies was not taken into consideration.

In our study, at the baseline, oral candidiasis (OC) was found to be the most prevalent OFM, followed by CL, parotid enlargement (PE), herpes labialis (HL), angular cheilitis (AC), and linear marginal gingivitis (LMG). There were no children with recurrent aphthous ulcers (RAU) and dental caries (DC) was seen in 12 (25%) of children. At the follow-up, CL was most prevalent followed by recurrent aphthous ulcers (RAU)., oral candidiasis (OC), parotid enlargement (PE), herpes labialis (HL), and linear marginal gingivitis (LMG). There were no children with angular cheilitis (AC) and dental caries (DC) was seen in 17 (38.63%) of children.

Oral candidiasis (OC) is the most prevalent OFM in HIV-infected children. [19],[20],[21] In HIV-infected children, we come across two major types-pesudomembranous candidiasis (PC) and erythematous candidiasis (EC). Some authors consider angular cheilitis (AC) as a variant of oral candidiasis (OC). [14] In our study, oral candidiasis (OC) was found to be of erythematous type in majority of the patients. Considering that majority of these children had weak immune systems, they were more prone to oral candidiasis (OC). Hence, the role of nutritional standards needs to be taken into account as most of the children in our study were malnourished which along with their immune deficiency accounts for the prevalence of oral candidiasis (OC) at the baseline. Six months later, oral candidiasis (OC) was seen in 4.55% of the children. This implied that there was a decrease in the prevalence of oral candidiasis (OC). The initiation of HAART improves the CD4 counts. [29] Once the CD4 count increases, OFMs are on decline; this could explain the decrease in the prevalence of OFMs. The response shown, however, varies from one child to the other. Since we do not have a common baseline regarding children on HAART, we cannot completely justify the decrease in the prevalence of oral candidiasis (OC). Adenopathy is most common in cervical nodes in HIV-infected children. [14] In our study, CL was seen in 14.58% children at the baseline and in 13.64% children 6 months later. HL is also a common feature of infection caused by HSV. In our study, at the baseline, HL was seen in 12.5% children and in 2.27% 6 months later. Non-HIV-infected children also commonly have primary HSV infection. However, in HIV-infected children, HL is more prevalent. In our study, the prevalence of HL at the baseline was higher than reported in most of the studies. This could be attributed to poor nutritional standards and hence immune systems in the children in our study. It is important to note that HSV infection is not considered to be a useful indicator of HIV-related immunosuppression or viral burden, possibly reflecting the difficulty of being able to delineate infection that would have arisen even in the absence of HIV disease. [31] parotid enlargement (PE) may be the first clinical manifestation of HIV infection. [32] In the present study, parotid enlargement (PE) was seen in 12.50% children at the baseline and in 4.55% at the follow-up. This remains persistent throughout the life and many children also experience xerostomia due to lymphocytic infiltration of salivary glands. However, our study did not take into consideration the changes in salivary flow rates. angular cheilitis (AC) in immunocompromised individuals is usually the result of a fungal infection caused by Candida albicans. It was seen in 8.33% children at the baseline but 6 months later, none of the children had angular cheilitis (AC). Linear marginal gingivitis (LMG), also called as red-band gingivitis by some authors is a common feature seen in HIV-infected children. [27] At baseline, linear marginal gingivitis (LMG), was found to be present in 6.25% children and 6 months later, it was present in 2.27%. Due to a diminished immune response in HIV-infected children, they are more prone to gingival and periodontal pathogens. This is supplemented by the lack of good oral hygiene and nutritional deficiencies and can account for the occurrence of linear marginal gingivitis (LMG) in many of the children in our study. Recurrent aphthous ulcers (RAU) was not seen in any of the children at the baseline. However, 6 months later, 6.82% children had recurrent aphthous ulcers (RAU). The presence of recurrent aphthous ulcers (RAU) at follow-up can be attributed to the malnutrition in the children we examined in our study. Also the presence of HIV infection by itself causes stress which further contributes to the occurrence of recurrent aphthous ulcers (RAU).

Apart from all the above-mentioned OFMs, 25% children at the baseline had dental caries (DC). Six months later, it was present in 38.63% children of the group. It has been speculated that HIV-positive children display a different decay pattern, which may be related to the decreased salivary flow and the use of viscous sugary nutritional supplements. Dental caries (DC), as such is a common finding even among non-HIV-infected children. The prevalence of dental caries (DC) in non-HIV-infected children has been found to be 41% by Chawla et al. [29] and 44% by Sarvanan et al. [33]


   Conclusion Top


The impact of HIV infection on the populations of developing countries is worse as compared to that in developed nations. Pediatric population, which in coming years will have to bear the burden of nation as adults, is showing an increased incidence of HIV infection since the time of its discovery in 1982. Since complex diagnostic tests may not be available to the health care professionals in developing countries, there is a need to identify certain manifestations of the disease which can serve as indicators of the disease.

Not many studies regarding the OFMs in HIV-infected children and the co-relation with CD4 counts have been conducted in India. We conducted this study keeping these two objectives in mind and also made an attempt at categorizing the OFMs as markers for the progression of the disease.

The results of our study indicated a high prevalence of OFMs in HIV-infected South Indian children. The CD4 counts of the examined children were found to be low. A decline in CD4 counts was found to be associated with more number of OFMs. However, we were unable to establish OFMs as markers for HIV disease progression. The sample size in our study being about 48 patients and the variability in the initiation and duration of HAART therapy, use of other drugs not being considered, may have an influence on the result of our study. However, the effectiveness of the HAART treatment may be co-related to the decline of OFMs thus making it of prognostic value. Another valid observation made was that an increase in OFMs would indicate an increase in immunosuppression levels. Larger population groups, with parameters such as nutritional status and HAART initiation included, can probably give a more conclusive result.[34]

 
   References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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