Background
Children and adolescents infected with HIV/AIDS (CA-HIV) are at increased risk of developmental and neuropsychological disturbances owing to both the direct and indirect effects of the HIV virus [
1,
2]. HIV has direct neurotoxic effects on brain structures involved in the regulation of emotion, behavior, and cognition, this effect is thought to result primarily from HIV’s ability to induce inflammatory factors that cause neuronal cell damage and eventual cell death [
1]. The indirect effects of HIV include social stressors, poverty, illness and trauma on morbidity and mortality [
1,
2]. Previous research suggests that HIV-1 mutations differ by subtype, which may lead to increased resistance to anti-retroviral therapy (ART) thus resulting in persistence of neurological and neurodevelopmental disorders among CA-HIV receiving ART [
2].
In sub Saharan Africa, with the exception of epilepsy, few studies have attempted to determine the prevalence of neurologic disease among children and adolescents and therefore characterize their clinical correlates [
1]. In one study conducted in East Africa, approximately two-thirds of new patients presenting to a child and adolescent psychiatry service had epilepsy [
3], and seizures are also common among individuals with HIV/AIDS [
4]. Although neurological disorders are reported to be associated with HIV/AIDS [
1,
2,
5], no such studies have been conducted among CA-HIV in Uganda. The primary objectives of the present study were to (a) document the prevalence of neurological disorders among a large sample of CA-HIV attending rural and urban HIV clinics in Uganda, (b) characterize the relation of neurological disorders with a wide range of commonly studied clinical correlates, (c) establish the co-occurrence of neurological and psychiatric disorders, and (d) investigate the relation of neurological disorders with important indices of functioning.
Discussion
This study aimed to determine the prevalence of neurological disorders among CA-HIV in Uganda and their association with commonly studied mental health clinical correlates, associated psychiatric comorbidities, and functioning. The prevalence of at least one neurological disorder among CA-HIV was 18.5%, which is consistent with findings from previous studies that suggest a high prevalence of neurological disorders among CA-HIV [
2,
4].
The prevalence of probable epilepsy in this study was 4%, which is within the range reported in prior studies both in the West and in South Africa. Kellinghaus and colleagues (2008) found that among HIV positive adult patients attending a neurological clinic in Germany, 6.1% had epilepsy [
12]. Pascual-Sedano and colleagues (1999) reported a 3% prevalence for new-onset seizures during a one year follow-up period among an adult HIV cohort in Spain [
13]. In one of the few studies in this area from sub-Saharan Africa, Samai and colleagues (2013) noted that among HIV positive youth in South Africa, 7.6% had epilepsy [
14].
The prevalence of enuresis/encopresis in this study was 10%, and we were unable to locate any other studies in the extant literature about these problems among CA-HIV for purposes of comparison. A rate of enuresis of 5–9% [
15‐
17] and that of encopresis of 1–3% [
15‐
17] have been reported among general population samples of children. In this study, the prevalence for motor/vocal tics was 5.3%, a figure within the 4–12% range reported among children in the general population [
18].
In this study, the only variable that was marginally associated with probable epilepsy was ethnicity. Belonging to an ethnic group that was not indigenous to the study area conferred an increased risk for epilepsy. Ethnicity could be associated with epilepsy for two reasons. Firstly, ethnicity may be a pointer to the genetic underpinnings of epilepsy [
19]. Secondly, ethnicity may be a marker for socio-economic disadvantage with respondents who were not indigenous to the study area being more likely to experience medical complications while growing up that are associated with both social disadvantage and epilepsy such as birth trauma, other central nervous system infections (including complicated malaria), and traumatic brain injury [
20].
In this study, enuresis/encopresis were significantly associated with younger age and marginally higher among males than in females. Both enuresis and encopresis have previously been reported to decrease with increasing age [
16,
21,
22] and to be higher among males than among females [
21,
22]. In this study, enuresis/encopresis was significantly associated with living in a rural area. Living in a rural area was probably an index of low socio-economic status. Indeed, in a Turkish study [
16], enuresis was reported to be associated with low maternal education and with low monthly income, indices of poor socio-economic status. Ethnicity was significantly associated with enuresis/encopresis in this study. As previously discussed under probable epilepsy, the association between enuresis/encopresis and ethnicity may be underlined by the same reasons namely, as a pointer to an underlying genetic underpinning for enuresis/encopresis [
23], secondly, as a marker for socio-economic disadvantage. The association between enuresis/encopresis and ‘less HIV viral load suppression’ observed in this study may be due to the direct neurotoxic effect of HIV or/ and to the increased psychological distress associated with a worse HIV clinical state. Lastly, enuresis/encopresis were the only neurological disorders significantly associated with both externalising and internalising psychiatric disorders. Previous research has reported that 20–40% of all children with enuresis have additional comorbid psychiatric disorders which include the externalising disorders of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) and the internalising disorder of depression [
21]. In a large community study, children with encopresis were reported to have increased rates of the externalising disorders of ADHD and ODD and the internalising disorders of separation anxiety, specific phobia and generalised anxiety disorders [
24].
In this study motor/vocal tics were more common in females than in males. Scahill and colleagues (2014) in a review involving eleven community studies reported great variation in the female to male ratio of motor/vocal tics ranging from 1 to 1, 1 to 4, through to 1 to 10 [
25]. The factors significantly associated with motor/ vocal tics in this study included increasing age and ethnicity. Metzger and colleagues (2012) observed that as children progress into young adulthood, tics often go into remission [
18]. The significant association between motor/vocal tics and ethnicity as discussed under probable epilepsy is probably underlined by two factors, a genetic underpinning [
26] and social disadvantage.
Having any neurological disorder in this study was associated with an earlier onset of sexual intercourse. The reasons for this association were not immediately clear, however this relationship could be mediated through psychiatric comorbidity [
6].
This study has several strengths that include a large sample size, comprehensive assessment battery, and cross-cultural orientation, however, there were also several limitations. Firstly, it is not possible to comment on the casual direction of obtained associations given the cross-sectional design. Secondly, neurological disorders were assessed using single-item questions which increased the risk of false positives. Thirdly, because we did not have a comparable sample of sero-negative youth from the same geographic areas, it is not possible to know whether relations between neurological and putative mental health factors and functional outcomes are influenced by HIV status. This does not, however, detract from the clinical implications of our findings for CA-HIV. Lastly, by design, the present study focused on CA-HIV living in Uganda, and owing to considerable cultural variation in East Africa, our results may not be generalizable to other countries in the region.
Conclusions
In summary, approximately 18% of CA-HIV living in Uganda met DSM-5 symptom count plus impairment criteria for neurological disorder. Risk factors of neurological disorders among CA-HIV as hypothesised in the conceptual framework fell under two broad domains of HIV related factors (less viral load suppression at baseline) and socio-demographic factors (age, gender, ethnicity and residence in the rural area). However, the association between neurological disorders on one hand and ethnicity and externalising disorders on the other seem to suggest a genetic vulnerability component. The association between ‘having a neurological disorder’ and earlier age of sexual intercourse, may have important implications for clinical management, quality of life, long-term outcome and possible disease transmission. Moving forward, there is a definite need to integrate neurological/mental health services into routine HIV care for youth in low-and middle-income settings such as those in sub-Saharan Africa. This should include the development of cost effective assessment and treatment strategies that have high probability of success in challenging interventional settings.
Acknowledgments
The authors wish to thank the managers of the five study sites (Lubowa Joint Clinical Research Centre, Nsambya homecare department Children’s HIV Care clinic; Nsambya hospital, the Children’s clinic at The AIDS Support Organisation; TASO Masaka, Uganda Cares / Masaka Regional Referral Hospital and Kitovu Mobile AIDS Organisation, Masaka) for permitting the study to be conducted at their specialised HIV/AIDS clinics. The authors extend appreciation to the Medical Research Council, Uganda (MRC, Uganda) for funding and facilitating the study. Special gratitude is extended to the staff working at the five specialised HIV/AIDS clinics where the study was conducted. Appreciation is extended to the diligent work of research assistants. Appreciation is extended to the participants for their time and trust.