Internal Validation of Automated Visual Evaluation (AVE) on Smartphone Images for Cervical Cancer Screening in a Prospective Study in Zambia.

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA. Design: Prospective study. Setting: Eight public health facilities in Zambia. Participants: 8,204 women aged 25-55. Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Main outcome measures: Area under the receiver operating curve (AUC); sensitivity; specificity. Results: As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden's index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91). Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE's sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although "unseen" by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.

Anatomic and clinical pathology services and infrastructure in Zambia.

OBJECTIVES: Pathology services are limited across most of sub-Saharan Africa. We sought to ascertain the availability of anatomic and clinical pathology services and diagnostic resources in Zambia. METHODS: Two individual surveys-one for anatomic pathology and one for clinical pathology/laboratory medicine-were developed by subject matter experts. These surveys were administered to individuals involved in pathology and laboratory medicine diagnostic services at hospitals and laboratories across Zambia from May to October 2022 using the American Society for Clinical Pathology email listserv. RESULTS: A total of 20 responses were received from 17 unique laboratories-8 sites provide anatomic pathology (AP) services, 12 provide clinical pathology (CP) services, and 3 perform both AP and CP services. Anatomic pathology services are variable and generally limited to a few of the responding laboratories, as only 1 laboratory performs immunohistochemical staining on surgical pathology specimens, and only 2 perform general histochemical stains. Conversely, certain microbiology testing (eg, for HIV) is more widely available. CONCLUSIONS: This study of 17 unique laboratories represents the most complete analysis of pathology capabilities in Zambia. Despite initiatives to improve pathology services, both personnel and infrastructure challenges remain. Given a population of approximately 20 million, expansion of anatomic pathology in Zambia must be prioritized.

Validation in Zambia of a cervical screening strategy including HPV genotyping and artificial intelligence (AI)-based automated visual evaluation.

BACKGROUND: WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE). METHODS: In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer. RESULTS: HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well. CONCLUSIONS: These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.

Survey of blood collection and transfusion practices among institutions in Africa.

INTRODUCTION: Dramatic improvements in blood transfusion have occurred during the last two decades. Transfusion medicine services and practices in Africa remain underexplored. METHODS: A survey of blood bank/transfusion medicine (BBTM) practices, available blood products, blood product source(s), pre-transfusion testing, and blood donor infectious disease testing methodologies across Africa was performed using the American Society for Clinical Pathology (ASCP) listserv. Survey recipients included hospital-based laboratories/blood banks, national transfusion medicine services, and free-standing laboratories (collectively referred to as institutions). RESULTS: Responses from a total of 81 institutions across 22 countries were analyzed. All 81 institutions provide at least one type of blood product-whole blood, red blood cells (RBCs), platelets, plasma, and cryoprecipitate, with whole blood (90.1%, 73 of 81) and RBCs (79.0%, 64 of 81) most common, while cryoprecipitate is least common (12.4%, 10 of 81). Only five countries had a responding institution that provides all types of products. Among institutions that collect blood onsite, the most common sources of blood products are patients' family members (94.1%, 48 of 51) and pre-screened on-demand volunteer donors (82.4%, 42 of 51). The most commonly screened infectious agents are HIV and hepatitis B virus (both 81.5%), while 70.4% (57 of 81) test for hepatitis C virus (HCV) and Treponema pallidum. DISCUSSION: This study highlights significant variability and restrictions in blood product availability, pre-transfusion testing, and blood donor infectious disease testing across Africa. Further studies are needed to ascertain barriers to improving blood donor availability, blood product safety, and infectious disease testing.

Incidental Tuberculosis in sudden, unexpected, and violent deaths in the community Lusaka, Zambia - A descriptive forensic post-mortem examination study.

OBJECTIVES: Tuberculosis remains a global emergency. In Zambia only 55% of tuberculosis cases are diagnosed. We performed a study to determine incidental cases of tuberculosis seen at forensic autopsy of individuals who died suddenly and unexpectedly in the community in Lusaka, Zambia. METHODS: Whole-body autopsies were performed according to Standard Operating Procedures. Representative samples obtained from relevant organs were subjected to pathological examination. Information on circumstances surrounding the death was obtained. Data on patient demographics, gross and microscopic pathological findings, and cause(s) of death were analysed. RESULTS: Incidental tuberculosis was found in 52 cases (45 male, 7 female, age range 14-66) out of 4286 whole-body autopsies. 41/52 (80%) were aged 21-50 years. One was a 14-year old boy who died during a football match. 39/52 (75%) deaths were attributable specifically to tuberculosis only. Other deaths were due to acute alcohol intoxication(4), violence(7), ruptured ectopic pregnancy(1), bacterial meningitis (1). All the cases were from poor socio-economic backgrounds and lived in high-density areas of Lusaka. CONCLUSIONS: Incidental cases of active tuberculosis undiagnosed antemortem seen at forensic autopsy reflects major gaps in the national TB control programs. More investments into proactive screening, testing, treatment activities, and accurate data collection are required.

COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.

BACKGROUND: Data from Africa regarding sudden and unexpected COVID-19 community deaths and underlying pathological, demographic, and co-morbidity features require definition. METHODS: We performed a case series of COVID-19-related deaths seen at Forensic Post-Mortem examination of sudden and unexpected Community Deaths in Lusaka, Zambia, Africa. Whole-body Post-Mortem examinations were performed according to Standard Operating Procedures. Patient demographics, history, co-morbidities, pathological gross and microscopic findings, and cause(s) of death were recorded. Variables were grouped as frequencies and percentages. Comparison of data was made with autopsy findings of hospital COVID-19 deaths. FINDINGS: Of 21 COVID-19 decedents, 14/21 (66.7%) were male; 18/21, (85.7%) were below 55 years of age (mean age, 40 ± 12.3; range, 20-73). The median duration of symptoms was 1 day (range 0-2); 9/21 (42.9%) had co-morbidities, with hypertension and obesity being the most common. Main post-mortem findings were diffuse alveolar damage (DAD) (80.9%), saddle and shower emboli (38.1%, respectively), and pneumonia (14.3%). Pulmonary thromboembolism (76.2%), DAD (14.3%), and SARS-CoV-2 pneumonia (9.5%) were common causes of death. CONCLUSIONS: COVID-19 is an important cause of death to consider in forensic investigations of sudden and unexpected community deaths. Risk factors for the younger age of COVID-19 deaths and thromboembolism need to be identified.

Antimicrobial resistance patterns of bacterial pathogens their distribution in university teaching hospitals in Zambia.

Aim: To determine the antimicrobial resistance patterns of bacterial pathogens from urine, blood and wound infections and their distribution by age, sex and location. Materials & methods: A total of 49,168 samples were collected, processed and analyzed. Results: Multidrug resistance was observed in almost all bacterial pathogens in blood urine and wound swabs. In urine and females odds ratio (OR) = 0.864, p = 0.023, OR = 0.909, p = 0.013 urine and neonates were susceptible to antibiotics OR = 0.859, p = 0.003, OR = 0.741, p < 0.001. Ampicillin resistance was above 90% against Escherichia coli in blood, urine and wound swabs. Conclusion: There was a spike in resistance to imipenem, ciprofloxacin and ampicillin against E. coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus species from all three specimen sources.

Lay abstract Bacterial infections and microbial resistance are becoming the most challenging problems associated with increased morbidity and mortality. The emergence of antibiotic resistance is a growing concern for people of all ages and settings. This study aimed to determine the antimicrobial resistance patterns of microorganism from urine, blood and wound swabs and their distribution by age, sex and location. The study showed that bacterial isolates from urine and blood were more resistant than isolates from wound infections. Furthermore, bacterial isolates from neonates were resistant to antimicrobial agents used. Bacterial isolates from inpatients were more statistically significant to antimicrobial agents than those from outpatients. There was resistance of bacteria Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus species from all three specimen sources to imipenem, ciprofloxacin, and ampicillin, and the effect of age, sex and location on antibiotic resistance was also significant.

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.

First COVID-19 case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries.

Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed that it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa.