Tracking cryptococcal meningitis to monitor HIV program success during the Treat-All era: an analysis of national data in Botswana.

BACKGROUND: Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSION: Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era.

Tumor microbial diversity and compositional differences among women in Botswana with high-grade cervical dysplasia and cervical cancer.

INTRODUCTION: We characterized the cervical 16S rDNA microbiome of patients in Botswana with high-grade cervical dysplasia and locally advanced cervical cancer. METHODS: This prospective study included 31 patients: 21 with dysplasia and 10 with cancer. The Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray-Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using linear discriminant analysis effect size. RESULTS: Alpha diversity was significantly higher in patients with cervical cancer than in patients with cervical dysplasia (P<0.05). Beta diversity also differed significantly (weighted UniFrac Bray-Curtis, P<0.01). Neither alpha diversity (P=0.8) nor beta diversity (P=0.19) varied by HIV status. The results of linear discriminant analysis effect size demonstrated that multiple taxa differed significantly between patients with cervical dysplasia vs cancer. Lachnospira bacteria (in the Clostridia class) were particularly enriched among cervical dysplasia patients, while Proteobacteria (members of the Firmicutes phyla and the Comamonadaceae family) were enriched in patients with cervical cancer. DISCUSSION: The results of our study suggest that differences exist in the diversity and composition of the cervical microbiota between patients with cervical dysplasia and patients with cervical cancer in Botswana. Additional studies are warranted to validate these findings and elucidate their clinical significance among women living in sub-Saharan Africa, as well as other regions of the world.

Factors Related to Advanced Stage of Cancer Presentation in Botswana.

PURPOSE: Botswana, a country with a high prevalence of HIV, has an increasing incidence of cancer-related mortality in the post-antiretroviral therapy era. Despite universal access to free health care, the majority of Botswana patients with cancer present at advanced stages. This study was designed to explore the factors related to advanced-stage cancer presentation in Botswana. METHODS: Patients attending an oncology clinic between December 2015 and January 2017 at Princess Marina Hospital in Gaborone, Botswana, completed a questionnaire on sociodemographic and clinical factors as well as cancer-related fears, attitudes, beliefs, and stigma. Odds ratios (ORs) were calculated to identify factors significantly associated with advanced stage (stage III and IV) at diagnosis. RESULTS: Of 214 patients, 18.7% were men and 81.3% were women. The median age at diagnosis was 46 years, with 71.9% of patients older than 40 years. The most commonly represented cancers included cervical (42.3%), breast (16%), and head and neck (15.5%). Cancer stages represented in the study group included 8.4% at stage I, 19.2% at stage II, 24.1% at stage III, 11.9% at stage IV, and 36.4% at an unknown stage. Patients who presented at advanced stages were significantly more likely to not be afraid of having cancer (OR, 3.48; P < .05), believe that their family would not care for them if they needed treatment (OR, 6.35; P = .05), and believe that they could not afford to develop cancer (OR, 2.73; P < .05). The perception that symptoms were less serious was also significantly related to advanced stage ( P < .05). Patients with non-female-specific cancers were more likely to present in advanced stages (OR, 5.67; P < .05). CONCLUSION: Future cancer mortality reduction efforts should emphasize cancer symptom awareness and early detection through routine cancer screening, as well as increasing the acceptability of care-seeking, especially among male patients.