Tanvier Omar

Background and Objectives: Existing literature on ovarian masses necessitating intervention in children by pediatric surgeons and gynecologists in Low‐ and Middle‐Income Countries is sparse and lacks collaborative standardization in management between the two subspecialties. Therefore, this study seeks to assess the range of ovarian masses presenting to these two specialties and to explore variations in management. Methods: A 15‐year retrospective review of surgically biopsied or excised ovarian masses between subspecialties at two academic hospitals in Johannesburg. Results: We identified 288 patients, six with bilateral disease and 294 ovarian masses. The mean age was 13.34 years (SD ±5.12). The most common presentation was abdominal pain in 149/288 (51.74%); 117 patients (40.62%) were from pediatric surgery and 171 (59.38%) from gynecology departments. There were 127/288 (44.09%) non‐neoplastic and 161/288 (55.90%) neoplastic lesions, of which 110/161 (68.33%) were benign and 51/161 (31.67%) malignant. The neoplastic lesions consisted of 107/161 (66.45%) germ cells, 28/161 (17.39%) surface epithelial tumors, and 26/161 (16.14%) sex cord‐stromal tumors. Ovarian‐sparing surgery was done in 56/288 (19.44%) patients, 22/117 (18.80%) in pediatric surgery, and 34/171 (19.88%) in gynecology. Laparoscopy was done in 57/288 (19.79%) patients, 24/117 (20.51%) in pediatric surgery, and 19/171 (19.29%) in gynecology. The survival rate in benign masses was 100%, and 86.28% in malignancies. Conclusion: This study highlights the diverse spectrum of ovarian masses managed by pediatric surgeons and gynecologists. A laparoscopic approach combined with ovarian preservation, which was comparable between specialties, should be the preferred method for managing benign lesions whenever feasible. These findings underscore the need for standardized, collaborative guidelines between pediatric surgeons and gynecologists to ensure consistent and optimal management of ovarian masses in children.

Background: Mortality among people living with HIV (PLWH) in developing settings remains elevated, despite high coverage with antiretroviral therapy (ART), with 70% – 80% being virally suppressed (VS). Objectives: This study aimed to determine cause-specific mortality in PLWH in South Africa. Method: An autopsy study with detailed medical record review was undertaken in PLWH dying in hospital. Minimally invasive autopsies were performed on 38 VS and 21 unsuppressed PLWH (≥ 18 years) dying in hospital between May 2018 and April 2022. We assessed clinical and histological findings to determine underlying, contributing, and immediate causes of death (CODs). Results: Median CD4 counts were 180 and 42 cells/mm3 in patients with and without VS respectively. Leading immediate CODs in both VS and unsuppressed PLWH were respiratory failure, sepsis, and septic shock; leading contributing CODs in decreasing order of frequency in both groups were acute kidney injury (AKI), bacterial pneumonia, immunological failure, gastroenteritis and current tuberculosis. Leading underlying CODs in both groups were hypertension, current tuberculosis, malignancies, and chronic obstructive pulmonary disease. VS was associated with lower risk of septic shock and AKI. Conclusion: VS on ART appeared to reduce risk of death from specific pathologies. However, infections, multi-organ failure, non-AIDS-defining malignancies, and metabolic diseases remain important CODs. Incomplete immune reconstitution appears to be a key contributor to premature death.

Background: HIV is associated with an increased risk of aggressive lymphomas. Lymphadenopathy is common at the time of presentation; therefore, we set out to understand the time to lymphoma diagnosis in people with HIV (PWH) undergoing fine needle aspiration (FNA). Methods: A prospective, observational cohort of PWH, age ≥ 18 years, undergoing FNA in Soweto, South Africa was established between September 2021 and December 2022. Participants were followed up for up to 8 months and provided consent for a medical record review. Results: One hundred and forty-six participants were enrolled, including 76 females (52%) with a median age of 40 years and a median CD4 count of 216 cells/μL. TB was the most common diagnosis (n = 62; 42%), followed by lymphoma (n = 21; 14%), of whom 10 (48%) died either prior to diagnosis or initiating chemotherapy. An additional 2 participants (10%) were still awaiting a biopsy confirmation at 8 months. One participant’s FNA was suggestive of both lymphoma and TB. The median healthcare provider interval, the time from presentation to diagnosis, was 85 days. Conclusions: While TB was the most common diagnosis among PWH undergoing FNA, lymphoma was the leading cause of death. As most deaths occurred prior to chemotherapy, interventions to expedite a lymphoma diagnosis in this high-risk population are needed.

Background: Liver disease is the leading cause of non-AIDS-related mortality in people living with HIV (PLWH). Steatotic liver disease (SLD) is increasingly recognised as an important aetiological factor in liver dysfunction in PLWH. Objectives: This study aimed to determine the post-mortem prevalence and severity of SLD and determine HIV- and non-HIV-related risk factors associated with it. Method: We conducted a retrospective cross-sectional study in which liver histology from 59 deceased people who were infected with HIV was assessed for steatosis, and findings correlated with clinical, epidemiological, and biochemical data. Results: Decedents were predominantly men (33/59); 63% (37/59) were virologically supressed. Median CD4+ T-cell count was 139 cells/µL (interquartile range [IQR]: 47–344). Steatosis was present in 39% (23/59) of decedents: 74% mild, 9% moderate, and 17% severe steatosis. There were no cases of steatohepatitis, and one case with mild fibrosis. Factors associated with SLD were: CD4 T-lymphocyte count > 200 cells/µL (odds ratio [OR]: 3.69; 95% confidence interval [CI]: 1.19–11.44), female sex (OR: 8.5; 95% CI: 2.57–28.17), hypertension (OR: 6.5; 95% CI: 2.05–21.00), and being normal or overweight (OR: 6.75; 95% CI: 1.12–40.56). Virological suppression and duration of antiretroviral drug use were not associated with steatosis. Conclusion: We found a high proportion of SLD with heterogeneous causes in deceased people who were infected with HIV, exceeding previously reported prevalences from elsewhere in Africa. A preserved CD4 count and being female conferred the highest risk for steatosis, underscoring the need for screening in this subgroup and further research to delineate risks in a Southern African population.

PURPOSE: Diagnosis of AIDS lymphoma in low-resource settings, like South Africa, is often delayed, leaving patients with limited treatment options. In tuberculosis (TB) endemic regions, overlapping signs and symptoms often lead to diagnostic delays. Assessment of plasma cell-free DNA (cfDNA) by next-generation sequencing (NGS) may expedite the diagnosis of lymphoma but requires high-quality cfDNA.METHODS: People living with HIV with newly diagnosed aggressive B-cell lymphoma and those with newly diagnosed TB seeking care at Chris Hani Baragwanath Academic Hospital and its surrounding clinics, in Soweto, South Africa, were enrolled in this study. Each participant provided a whole blood specimen collected in cell-stabilizing tubes. Quantity and quality of plasma cfDNA were assessed. NGS of the immunoglobulin heavy chain was performed.RESULTS: Nine HIV+ patients with untreated lymphoma and eight HIV+ patients with TB, but without lymphoma, were enrolled. All cfDNA quantity and quality metrics were similar between the two groups, except that cfDNA accounted for a larger fraction of recovered plasma DNA in patients with lymphoma. The concentration of cfDNA in plasma also trended higher in patients with lymphoma. NGS of immunoglobulin heavy chain showed robust amplification of DNA, with large amplicons (> 250 bp) being more readily detected in patients with lymphoma. Clonal sequences were detected in five of nine patients with lymphoma, and none of the patients with TB.CONCLUSION: This proof-of-principle study demonstrates that whole blood collected for cfDNA in a low-resource setting is suitable for sophisticated sequencing analyses, including clonal immunoglobulin NGS. The detection of clonal sequences in more than half of patients with lymphoma shows promise as a diagnostic marker that may be explored in future studies.

Background: Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa. Methods and findings: WLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today. Conclusions: In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

Mycobacterial infection, tuberculosis (TB) in particular, remains one of the world's deadliest communicable diseases in adults and particularly in children, in low and middle income countries. The combination of human immunodeficiency virus (HIV) and TB is often lethal with TB accounting for 25% of deaths in the HIV population. One of the cornerstones for reducing the TB epidemic is early case detection using high quality diagnostic techniques. Cytology, especially fine needle aspiration biopsy (FNAB) is able to diagnose mycobacterial infection in a rapid and cost-effective manner without requiring surgery, thus allowing appropriate management to be quickly instituted. Confirmatory ancillary tests can effectively be performed on cytologic material. In this review, the pertinent cytomorphology of mycobacterial infection in various exfoliative and FNAB specimens is presented, in both immunocompetent and immunosuppressed patients. In the immunosuppressed, the typical cytomorphology of caseating granulomatous inflammation may not be seen but suppurative necrotic inflammation, mycobacterial spindle pseudotumour or a specimen comprised entirely of necrosis may be seen instead. This review includes discussion of currently available ancillary tests that can be performed on cytologic specimens. Diagn. Cytopathol. 2016;44:255–262.

Xpert MTB/RIF (Xpert) is recommended for human immunodeficiency virus (HIV)-associated pulmonary tuberculosis but not extrapulmonary tuberculosis. We assessed the performance of Xpert for HIV-associated lymph node tuberculosis (LNTB), the most common type of extrapulmonary tuberculosis. Among HIV-infected adults suspected of LNTB presenting for fine needle aspirate (FNA) at a South African hospital, we assessed the diagnostic accuracy of Xpert using either FNA culture or a composite of microscopy, culture, and cytology as the reference standard, and evaluated the impact of different diagnostics on patient management. Among 344 adults with valid FNA culture and Xpert results, 84 (24 %) were positive on microscopy, 149 (43 %) on culture, 152 (53 %) on Xpert, and 181 (57 %) had a cytology result suggestive of tuberculosis. Using liquid culture as the reference standard, the specificity of a single Xpert was suboptimal (88.2 %) but the sensitivity was high [93.3 %, 95 % confidence interval (CI) 87.6–96.6] and increased with decreasing CD4 count (from 87.0 % for CD4 >250 to 98.6 % for CD4 3). Using a composite reference standard reduced the sensitivity to 79.2 % but increased the specificity to 98.6 %. All Xpert-positive patients initiated treatment within one day, compared to 70 % of culture-positive but Xpert-negative and 13 % of culture- and Xpert-negative but cytology-positive patients. Xpert is accurate and effective and could be endorsed as the initial diagnostic for HIV-associated LNTB.