The prevalence of human papillomavirus in ocular surface squamous neoplasia in HIV positive and negative patients in a South African population.

PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

A Review of Human Ocular RNA Virus Infections Excluding Coronavirus, Human T-Cell Lymphotropic Virus, and Arboviruses.

We provide an updated review of pre-selected RNA viruses causing ocular inflammation in humans. RNA viruses such as coronaviruses and arboviruses are reviewed elsewhere. A Google Scholar search was conducted to identify recent publications on ocular inflammation caused by the RNA viruses specified here. Human RNA viruses target a wide range of ocular tissues from the anterior to the posterior. Influenza, measles and mumps cause anterior segment manifestations including conjunctivitis and keratitis, while retinitis and optic neuritis may be seen posteriorly. Newcastle disease and RSV cause conjunctivitis, whereas HIV causes characteristic anterior uveitis. Cataracts, microphthalmos, and iris abnormalities are common in congenital Rubella, while Rubella virus is associated with Fuchs uveitis syndrome. Newer technologies make it possible to detect more than one pathogen if present simultaneously. RNA viruses may produce significant ocular morbidity, and care should be taken to investigate ocular symptoms during disease outbreaks.

CXCL13, CXCL10 and CXCL8 as Indicators of Ocular and Neurological Involvement in Patients With Ocular Syphilis: An Observational Descriptive Study.

Aim: To investigate the role of the chemokines CXCL13, CXCL10 and CXCL8 in the diagnosis of ocular- and neurosyphilis by examining the serum, aqueous humour (AH) and cerebrospinal fluid (CSF) of patients with ocular syphilis. Methods: An observational descriptive study was performed prospectively at Tygerberg Academic Hospital in Cape Town, South Africa from 1 February 2018 till 31 January 2021 which enrolled 23 participants. 14 Patients were male and 9 female, 15 patients were HIV positive, and all patients were newly diagnosed with ocular syphilis. Upon diagnosis of ocular syphilis, the HIV status of each patient was determined, and 3 samples (AH, serum and CSF) were collected to measure the levels of CXCL13, CXCL10 and CXCL8 in each. All patients were treated with 14 days of intravenous Penicillin G and topical corticosteroid drops for uveitis. Results: The mean concentrations of all 3 biomarkers were higher in the AH and CSF than in the serum. The mean concentrations of the 3 measured biomarkers were markedly different when comparing both AH and CSF levels to serum levels. The level of CXCL13 measured in the AH correlated well with the concentrations found in the CSF of patients with neurosyphilis. In patients with neurosyphilis, mean AH levels of CXCL13 and CXCL10 were markedly higher than in serum while mean CSF levels of CXCL10 were also markedly higher than in serum. Also, the AH/serum ratio of CXCL13 and CXCL10, as well as the CSF/serum ratio of CXCL10, was much higher in patients with neurosyphilis than without. In patients with HIV infection, mean AH CXCL13 levels were much higher than in patients without HIV infection. Conclusion: The levels of CXCL13, CXCL10 and CXCL8 in the AH of patients with neurosyphilis are similar to previously reported levels in the CSF of patients with neurosyphilis and can potentially be an adjunct in the diagnosis of ocular syphilis. Patients with ocular syphilis who tested negative for neurosyphilis with conventional CSF testing showed features of neurosyphilis when analysing the CSF chemokines.

Evaluation of Potential Antigen-specific Host Biomarkers in QuantiFERON Supernatants as Candidates for the Diagnosis of Ocular Tuberculosis.

Purpose: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB).Methods: We investigated 47 host markers in QuantiFERON supernatants from 92 individuals with uveitis using the Luminex platform. We evaluated the potential of individual and combined biomarkers to distinguish between patients with possible, probable, and no OTB.Results: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1ß, in individuals with OTB versus no OTB regardless of HIV status. Individuals with probable and possible OTB only differed regarding GM-CSF. We identified a four-marker biosignature (CD40 L, IL-33, IFN-γ, and SAP) which diagnosed OTB with an area under the ROC curve of 0.80, sensitivity = 56.3% and specificity = 90.0%.Conclusion: This represents the first attempt at screening QuantiFERON supernatants for biomarkers to diagnose OTB. We identified candidate biosignatures which may aid in diagnosing OTB in both HIV positive and negative patients.

Identification of Potential Biomarkers in Peripheral Blood Supernatants of South African Patients with Syphilitic and Herpetic Uveitis.

Purpose: To identify potential diagnostic biomarkers for herpetic and syphilitic uveitis.Methods: Blood samples were collected from 92 uveitis patients. Concentrations of 47 biomarkers were evaluated in unstimulated Quantiferon supernatants using the Luminex platform.Results: Results showed 11 patients (12%) had herpetic uveitis, 11 (12%) syphilis, 40 (43.5%) other infectious causes, 16 (17.4%) established noninfectious causes and 14 (15.2%) were idiopathic. Biomarker analysis revealed three proteins (Apo-A1, Apo-CIII, CRP) that differed between syphilis and other causes. A three-marker biosignature (CCL4/MIP-1ß, Apo-CIII and CRP) separated syphilis from other groups with AUC = 0.83 (95% CI: 0.68-0.98). Apo-CIII and CRP differed between herpetic cases and other groups (p < .05). A three-analyte biosignature (Apo-A1, SAP and CRP) separated the herpetic group from other groups with AUC = 0.79 (95% CI: 0.65-0.93).Conclusion: We have identified candidate biomarkers with potential to differentiate between herpetic, syphilitic and other causes of uveitis. These results warrant further investigation in larger future studies.

Eyelid and Orbital Involvement in HIV Infection - An African Perspective.

Both infective and neoplastic eyelid and orbital conditions in human immunodeficiency virus (HIV) infected patients are often the result of opportunistic or co-infections (OI). In most cases, these clinical findings in younger patients alert the physician to suspected underlying HIV infection. When the eyelids and periorbital skin are primarily involved in OI with varicella-zoster virus it is called Herpes Zoster Ophthalmicus. Co-infection with a Pox virus manifests as molluscum contagiosum eruptions. Orbital cellulitis is secondary to various organisms (Mycobacterium tuberculosis, Candida albicans, Aspergillus). Neoplastic disorders are also often associated with OI such as human herpes virus 8 in Kaposi Sarcoma, Epstein-Barr virus in Hodgkin Lymphoma and human papillomavirus 16 and 18 in squamous cell carcinoma. In this review we share our personal clinical experience with HIV disease in Sub-Saharan Africa over more than two decades and provide photographs of cases to illustrate pertinent aspects of the conditions discussed.

Ocular Tuberculosis in HIV-infected Individuals.

Aim: To review the current literature and publications to assess the clinical features, recommended investigations and treatment for ocular tuberculosis in HIV infected patients. Methods: Literature review. Results: The human immunodeficiency virus (HIV) epidemic affects as many as 37.9 million people. Mycobacterium tuberculosis infection is common in HIV infection and is a leading cause of death and morbidity. Common clinical presentations include anterior uveitis (granulomatous or otherwise), choroidal granulomas/tubercles, chorioretinitis, subretinal abscess, panophthalmitis, retinal detachment and vasculitis. The majority of clinical findings were in the posterior segment, appeared primarily infective (tubercles/chorioretinitis/abscess) and were largely seen in the context of pulmonary tuberculosis or disseminated disease. Current investigational patterns include corroborative tests such as tuberculin skin test or Interferon-γ release assay. Systemic testing includes Computed Tomography, MRI or PET/CT scans. Newer Molecular techniques such as GeneXpert MTB/RIF assay and Line Probe assays (LPA) are increasingly important. Apart from standard ocular anti-inflammatory protocols, anti-tubercular treatment as per the clinical staging (latent or active) needs to be initiated. Initiation of anti-retroviral therapy (ART) is important and can be started soon after ATT. Conclusions: Ocular manifestations within this group are distinct and unique investigational and therapeutic approaches are needed.

Double Trouble: Challenges in the Diagnosis and Management of Ocular Syphilis in HIV-infected Individuals.

Syphilis and HIV infection may coexist in the same individual. Ocular syphilis and/or neurosyphilis may develop at any stage of coinfection, with a stronger association between ocular and neurosyphilis in individuals living with HIV, than in HIV-uninfected individuals. The diagnosis of ocular syphilis in HIV-infected and -uninfected patients remains with some controversy due to unspecific clinical manifestations and limited diagnostic tests. Penicillin is the mainstay of treatment of ocular syphilis, but alternative options are warranted. This review describes the epidemiology, pathophysiology, and clinical manifestations, as well as the diagnostic and therapeutic challenges posed by ocular syphilis against the background of HIV coinfection.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis. METHODS: Prospective cross-sectional study. RESULTS: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+. CONCLUSION: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.

The Etiology of Intraocular Inflammation in HIV Positive and HIV Negative Adults at a Tertiary Hospital in Cape Town, South Africa.

PURPOSE: To describe the patterns of uveitis in South Africa. METHODS: Prospective cross-sectional study. RESULTS: One hundred and six patients were enrolled and 37.7% had human immune-deficiency virus (HIV) infection. Anterior and panuveitis occurred most frequently. Infectious, non-infectious and idiopathic uveitis were diagnosed in 66.0%, 17.0% and 17.0% of all cases, respectively. Eighty percent of HIV+ cases had infectious uveitis. Overall, intraocular tuberculosis (IOTB), herpetic and syphilitic uveitis were the commonest infectious causes. Sarcoidosis and HLA-B27-associated uveitis were the commonest non-infectious causes. In anterior uveitis, HIV+ cases most frequently had probable IOTB, syphilitic or idiopathic uveitis while HIV- cases had possible IOTB, idiopathic or HLA-B27-associated uveitis. In panuveitis, HIV+ cases mostly had syphilis, probable IOTB, toxoplasma and varicella-zoster virus whereas HIV- cases mostly had possible IOTB, sarcoidosis and idiopathic uveitis. CONCLUSION: Infectious uveitis is common in South Africa, especially amongst HIV+ patients. Causes of anterior and panuveitis differ between HIV+ and HIV- patients.

The Role of QuantiFERON®-TB Gold and Tuberculin Skin Test as Diagnostic Tests for Intraocular Tuberculosis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To compare QuantiFERON®-TB Gold and tuberculin skin testing as diagnostic tests for intraocular tuberculosis in HIV positive and negative patients. METHODS: A prospective study evaluating two different tests to help diagnose intraocular tuberculosis. RESULTS: Thirty-five of 106 patients (33.0%) were diagnosed with intraocular tuberculosis including 11 (31.4%) with HIV infection. Patients were 6.95 times more likely to have intraocular tuberculosis if TST alone was positive (p < 0.001) versus 2.19 times more likely if Quantiferon alone was positive (p = 0.04). Tuberculin skin testing showed superior specificity (60.3% vs 33.3%) (p = 0.001) but similar sensitivity (90.3% vs 85.7%), positive (54.9% vs 40.5%) and negative predictive values (92.1% vs 81.5%) compared to Quantiferon. Specificity did not increase significantly if both skin testing and Quantiferon were positive. CONCLUSIONS: In South Africa, with its high HIV burden and limited public health resources, Quantiferon testing should not replace tuberculin skin testing as it provides little additional diagnostic information.

The Prevalence of Intraocular Tuberculosis in HIV-positive and HIV-negative Patients in South Africa Using a Revised Classification System.

PURPOSE: To report the prevalence of intraocular tuberculosis in South Africa using a revised classification system. METHODS: A prospective study to determine the underlying etiology in patients presenting with uveitis to a tertiary Eye Clinic. RESULTS: A total of 35 out of 106 patients (33.0%) were diagnosed with intraocular tuberculosis, of which 11 (31.4%) had HIV infection; 23 patients (65.7%) had possible intraocular tuberculosis and 12 (34.3%) had probable intraocular tuberculosis. Patients with probable intraocular tuberculosis were younger than those with possible intraocular tuberculosis (p = 0.003). More males (66.7%) had probable intraocular tuberculosis and more females (73.9%) had possible intraocular tuberculosis (p = 0.031). More HIV-positive patients had probable intraocular tuberculosis and more HIV-negative patients had possible intraocular tuberculosis (p = 0.002). CONCLUSIONS: South Africa has a high prevalence of intraocular tuberculosis. Younger, male, HIV-positive patients are more likely to have probable intraocular tuberculosis, while older, female, HIV-negative patients are more likely to have possible intraocular tuberculosis.