The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) occurs more frequently in some developing countries compared to developed countries. Infection with HIV and/or high-risk human papillomavirus (hrHPV) are risk factors for penile cancer development. The tumor microenvironment of PSCC may predict prognosis and may inform on the best targets for immunotherapy. We evaluated the immune microenvironment of penile tumors histologically, and determined whether and/or how HIV and/or hrHPV infections affect this tumor microenvironment. We conducted a prospective analytical cross-sectional study in which penile cancer tumors from 35 patients presenting at the University Teaching Hospital in Lusaka, Zambia were histologically staged and assessed for presence of tumor infiltrating immune cells and expression of immune checkpoints. Immunohistochemistry was used to evaluate immune checkpoints and infiltrating immune cells, while multiplex real-time polymerase chain reaction was used for hrHPV genotyping. The median age of all participants was 55 years. About 24% had advanced histological stage, 83% were HIV+, and 63% had hrHPV detected in their tumors using multiplex real-time polymerase chain reaction. PDL1 expression was significantly higher in HIV- participants than HIV+ participants (p = 0.02). Tumors with multiple hrHPV infections had a significantly higher number of cells expressing TIM3 than those with one hrHPV (p = 0.04). High grade tumors had a significantly higher infiltrate of FoxP3+ cells (p = 0.02), CD68+ cells (p = 0.01), CD163+ cells (p = 0.01), LAG3+ cells (p = 0.01), PD1+ cells (p = 0.01) and TIM3+ cells (p = 0.03) when compared with low grade tumours. There was significant moderate to strong positive correlation of cells expressing PD1 and LAG3 (⍴ = 0.69; p = 0.0001), PD1 and TIM3 (⍴ = 0.49; p = 0.017) and TIM3 and LAG3 PDL1 (⍴ = 0.61; p = 0.001). In conclusion, the tumor microenvironment of penile squamous cell carcinoma seems to be affected by both HIV and HPV infections. TIM3 appears to be a potential therapeutic target in PSCC patients with hrHPV infections.

Development of an online teaching platform to improve access to postgraduate pathology training in sub-Saharan Africa.

Background: Resource barriers to the provision of accessible training in cancer diagnosis in lower- and middle-income countries (LMICs) limit the potential of African health systems. Long-term provision via teaching visits from senior pathologists and trainee foreign placements is unsustainable due to the prohibitive costs of travel and subsistence. Emerging eLearning methods would allow pathologists to be trained by experts in a cheaper, more efficient, and more scalable way. Purpose: This study aimed to develop an online teaching platform, starting with hematopathology, for trainee pathologists in sub-Saharan Africa, initially in Nairobi, Kenya, and Lusaka, Zambia. Methods: Course materials were prepared for both Canvas and the Zoom eLearning platforms using digitally scanned slides of lymph nodes and bone marrow trephines. Initial in-person visits were made to each site to establish trainee rapport and maximize engagement, evaluate different methods and course content, and obtain feedback to develop the project. The knowledge of trainees before and after course completion was used to measure initial effectiveness. Online teaching with the preferred platform is to be continued for 1 year before re-evaluation for long-term effectiveness. Results: Canvas was selected as the preferred delivery platform as it is freely available and has good functionality to support all required tasks. Face-to-face teaching was considered optimal to establish the initial rapport necessary to maximize subsequent engagement with online teaching. Challenges have included sub-optimal internet speeds and connections and scheduling issues. Weekly online hematopathology teaching sessions using live image capture microscope sessions, Zoom, and Canvas have been delivered to students in Kenya and Zambia, with good attendance and interaction in case discussions. Conclusion: Our team has successfully designed and delivered an online training program in hematopathology to trainee pathologists in Kenya and Zambia, which has been ongoing for over a year. This project is now being scaled to other sub-Saharan countries and other sub-specialties.

HIV and inflammatory markers are associated with persistent COVID-19 symptoms.

BACKGROUND: A proportion of COVID19 survivors may present with long-COVID, which is persistent symptoms lasting four or more weeks post SARS-CoV-2 infection. These symptoms may be mild to severe, and may affect different organ-systems of the body. AIMS: The main objective of this study was to determine the demographic, clinical and immunological factors associated with long COVID. MATERIALS & METHODS: We conducted a nested case control study, with a total of 94 study participants initially included, and 64 participants matched for age and sex for biomarker analyses. RESULTS: 32/94 (34.1%) of all the participants had long COVID. Respiratory symptoms were the most common (59.5%) followed by the musculoskeletal symptoms (28.1%). HIV was an independent predictor of long COVID (adjusted odds ratio = 2.7; p = .037). In all the 64 matched cases and controls, IFN-ß was significantly higher among controls than cases. After stratifying by HIV, IL6 was significantly higher among cases than controls in the HIV- group (2.06 vs. 0.81 pg/mL; p = .02). On the other hand, IFN-ß was significantly higher among controls than cases in the HIV+ group (251 vs. 0 pg/mL; p = .01). CONCLUSION: HIV infection is a risk factor for long COVID, and inflammatory markers associated with long COVID may be slightly different for HIV- and HIV+ individuals.

SARS-CoV-2-Specific T Cell Immunity in HIV-Associated Kaposi Sarcoma Patients in Zambia.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus is the cause of coronavirus disease 2019 (COVID-19). It has caused millions of infections and deaths globally over a 2-year period. Some populations including those living with HIV and/or cancer are reported to be at a higher risk of infection and severe disease. HIV infection leads to a depletion of CD4+ T cells which impairs cell-mediated immunity and increases the risk of malignancies such as Kaposi sarcoma (KS) and viral infections such as SARS-CoV-2. However, several other factors including level of immunosuppression and chemotherapy may also affect the immune response against SARS-CoV-2. In this study, we investigated factors affecting SARS-CoV-2-specific T cell immunity towards the spike, nucleoprotein, membrane protein, and other open reading frame proteins in individuals with HIV-associated KS. The KS patients were SARS-CoV-2 seropositive with detectable T cell responses, but had no history of symptomatic SARS-CoV-2 infection. We observed that the T cell responses increase from baseline levels during follow-up, with responses towards the NMO peptide pool being statistically significant. Low CD4 counts below 200 cells/µl were associated with lower SARS-CoV-2-specific T cell responses. Cancer chemotherapy and KS T staging did not have a significant effect on the T cell responses.

Rapidly progressive glomerulonephritis in two Zambian children: a case report.

Rapidly progressive glomerulonephritis (RPGN) is a rare syndrome which is marked by a sudden rise in serum creatinine and the presence of crescents on renal biopsy. If appropriate and timely treatment is not instituted, as many as 90% of affected patients may develop End Stage Renal Disease (ESRD). There is only limited access to renal replacement therapy in many low resource countries, thus it is important that awareness of this entity is raised. We narrate the clinical course of two children who were admitted with rising serum creatinine, hypertension and haematuria and who were subsequently diagnosed with crescentic glomerulonephritis on biopsy. Despite having received immunosuppressive therapy, both children had a poor renal outcome, perhaps due to delays in institution of appropriate treatment. It is imperative that all clinicians who manage children are made aware of this clinical syndrome so that timely referrals to nephrology are done. This will help to improve renal outcomes.

Histopathological Evaluation of Deceased Persons in Lusaka, Zambia With or Without Coronavirus Disease 2019 (COVID-19) Infection: Results Obtained From Minimally Invasive Tissue Sampling.

BACKGROUND: Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. METHODS: We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. RESULTS: From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40-64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. CONCLUSIONS: Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.

BACKGROUND: Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa. METHODS: We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages. FINDINGS: Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%). CONCLUSIONS: A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation.

Acquired Acrodermatitis Enteropathica in a 28-Year-Old Male with Type 1 Diabetes.

Acrodermatitis enteropathica (AE) is a rare disorder arising from inherited or acquired zinc deficiency. It is mainly characterized by acral dermatitis, periorificial dermatitis, alopecia, and gastrointestinal symptoms in the form of diarrhea. There are many complications of AE including local and systemic infections that may develop as a result of untreated AE. In addition, due to the role of zinc in glucose metabolism, chronic zinc deficiency may pose a challenge in the control of blood glucose levels in diabetics. We report the case of a 28-year-old male with type 1 diabetes who presented with signs and symptoms of AE.

Pleomorphic Adenoma Presenting as an Atypical Nasal Mass in a 26-Year-Old Female.

Pleomorphic adenoma (PA) is a salivary gland tumor that may rarely occur in the nasal cavity. It can be a clinical diagnostic dilemma in many instances due to many possible differential diagnoses. We report the case of a 26-year-old female who presented with a 3-year history of a right nasal growth associated with ipsilateral nasal blockage, nasal pain, and rhinorrhea. Radiological image showed a mild enhancing lesion in the right nasal cavity. The patient underwent a lateral rhinotomy with wide excision of the mass. Histopathological exam was consistent with PA. Nasal PA is a rare entity and should be suspected as a diagnosis for intranasal tumors.

Demonstration of an algorithm to overcome health system-related barriers to timely diagnosis of breast diseases in rural Zambia.

BACKGROUND: Long delays to diagnosis is a major cause of late presentation of breast diseases in sub-Saharan Africa. AIMS: We designed and implemented a single-visit breast care algorithm that overcomes health system-related barriers to timely diagnosis of breast diseases. METHODS: A multidisciplinary team of Zambian healthcare experts trained a team of mid- and high-level Zambian healthcare practitioners how to evaluate women for breast diseases, and train trainers to do likewise. Working collaboratively, the two teams then designed a clinical platform that provides multiple breast care services within a single visit. The service platform was implemented using a breast outreach camp format, during which breast self-awareness, psychosocial counseling, clinical breast examination, breast ultrasound, ultrasound-guided biopsy, imprint cytology of biopsy specimens and surgical treatment or referral, were offered within a single visit. RESULTS: Eleven hundred and twenty-nine (1129) women attended the camps for breast care. Mean age was 35.9 years. The majority were multiparous (79.4%), breast-fed (76.0%), and reported hormone use (50.4%). Abnormalities were detected on clinical breast examination in 122 (10.8%) women, 114 of whom required ultrasound. Of the 114 who underwent ultrasound, 48 had identifiable lesions and were evaluated with ultrasound-guided core needle biopsy (39) or fine-needle aspiration (9). The concordance between imprint cytology and histopathology was 100%, when breast specimens were classified as either benign or malignant. However, when specimens were classified by histopathologic subtype, the concordance between imprint cytology and histology was 85.7% for benign and 100% for malignant lesions. Six (6) women were diagnosed with invasive cancer. Eighteen (18) women with symptomatic breast lesions had next-day surgery. SIGNIFICANCE: Similar to its impact on cervical cancer prevention services, a single visit breast care algorithm has the potential to overcome health system-related barriers to timely diagnosis of breast diseases, including cancer, in rural African settings.