with blindness (chapter 4) [62]. Increased time interval between onset of symptoms and first presentation to the facility was associated with late-stage ocular complications (chapter 4) [62]. This is most likely due to delayed initiation of antiviral treatment as early initiation thereof (≤72 hours after onset of rash) reduces the risk of progression of early- to late-stage ocular complications [50, 63]. Specific reasons for this delay remain unclear and requires further investigation. Most likely, both patient- and healthcare system-associated factors like referral delay have played a role. Our results emphasize the importance of early recognition of cutaneous HZO and ocular involvement, prompt initiation of appropriate antiviral treatment even at PHC level with swift referral to hos- pitals with ophthalmology departments to reduce sight-threatening ocular complica- tions. Appropriate antiviral treatment should be available at PHC level, even in rural and resource-limited settings (chapter 4) [62]. To achieve early recognition of cutaneous HZO and ocular involvement, training of healthcare providers at both PHC facilities and hospitals is of paramount importance and should include basic ophthalmological training and training around prescription and instalment of topical and oral antiviral treatment. Moreover, these efforts should result in the development of clinical guide- lines and standardized training programs to prevent ocular morbidity among patients with HZO. Also to reduce delay in patients seeking medical care, community campaigns should be initiated to increase awareness among HIV-infected individuals and prevent visual impairment.
In our study, HIV infection was common among patients presenting with HZO and intraocular complications were more common among HIV-infected than HIV naïve in- dividuals which is in line with previous studies [45, 49-51]. Even though several studies have advocated that HZO can be a HIV presenting clinical disease, 4/39 (10%) of HIV- infected individuals presenting with HZO were tested reactive for HIV for the first time at the ophthalmology outpatient department [45, 49, 64-65]. We therefore advocate that HIV testing and counselling should be standard practice in patients presenting with HZO in high HIV prevalence settings and encourage discussion among healthcare providers about the introduction of HIV testing and counselling in all patients presenting with HZO (chapter 4) [62].
uVEItIS
Uveitis is a sight-threatening eye condition that is a common cause of visual impairment in low-resource settings [66]. The aetiology of uveitis is diverse and includes infectious and non-infectious disorders [66-67]. Data from sub-Saharan African countries are limited, but suggest that infectious diseases play an important role in uveitis [66]. The high HIV prevalence in these countries most likely contributes to the role of infectious
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diseases in uveitis as HIV-infected individuals are at increased risk of developing infec- tious uveitis [66, 68-69].
In this thesis we conducted a cross-sectional study among patients presenting with uveitis (n=103) and found that infectious uveitis is common in our population, especially among HIV-infected individuals. The most prevalent uveitogenic pathogens identified were HHVs (51%), Mycobacterium tuberculosis (24%) and Treponema pallidum (7%) (chapter 5) [70]. The data implicate that infectious uveitis is considerably more common in the setting studied, than reported in other regions of the world [66]. For example, infectious uveitis only accounts for about 10-20% of uveitis cases in high-resource coun- tries like the USA, Portugal, United Kingdom and the Netherlands [66]. Herpetic uveitis, mainly VZV, was the major cause of infectious uveitis in our South African patient cohort and is most likely due to the high HIV prevalence and high HHV seroprevalence in our setting [34, 71]. The predominant role for VZV is in line with a study from Congo that reported VZV infection as the most common associated condition among HIV-infected uveitis patients, but in contrast to studies from high-resource settings like the USA that report a predominant role for CMV, especially in the pre-ART era [71-74]. Despite of a CMV seroprevalence of 100% among HIV-infected ART-naïve individuals in our setting, we observed only a single case of CMV uveitis [34]. A possible reason for the observed low prevalence of CMV uveitis and high prevalence of VZV uveitis in our study is the rela- tive high CD4 cell count among HIV-infected individuals at inclusion (chapter 5) [70]. CMV uveitis typically occurs in patients with CD4 cells ≤50 cells/mm³, whereas herpes zoster ophthalmicus and associated VZV uveitis already occurs in patients with CD4 cells ≤500 cells/mm³ [13, 72, 75]. In our study, only 3 (5%) HIV-infected uveitis patients presented with CD4 cells ≤50 cell/mm³, making them at risk of CMV uveitis (chapter 5) [70]. In contrast, 54 (82%) HIV-infected uveitis patients presented with CD4 cell counts between 50 and 500 cells/mm³. However, other factors like virus or host origin factors might contribute to the geographic differences in CMV uveitis prevalence as a study from Tanzania reported low prevalence of CMV uveitis (1.3%) even among HIV-infected uveitis patients with CD4 cells ≤100 cells/mm³ [76].
In addition to HHVs, M. tuberculosis was a common cause of uveitis in our study confirming previous reports from other low-resource settings like India that showed an increasing uveitogenic role of M. tuberculosis (chapter 5) [70, 77-78]. However, avail- able data on ocular tuberculosis (TB) is predominantly from non-sub-Saharan African counties where the TB epidemic differs substantially from the TB epidemic of South Africa [79]. In South Africa, the TB epidemic is fuelled by the high HIV prevalence and HIV-infected individuals are at increased risk of developing ocular TB [79-81]. Our results are of great importance and warrant recognition of M. tuberculosis infection as cause of uveitis in South Africa. Currently, there is a paucity of data and limited awareness among policy makers and healthcare providers, even among those working at the
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