Tracking Cryptococcal Meningitis to Monitor HIV Program Success During the Treat All Era: An Analysis of National Data in Botswana.

BACKGROUND: Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM 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 analyzed 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. CM case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [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 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSIONS: CM 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 CM as key metric of program success in the Treat All era.

How does episodic memory develop in adolescence?

Key areas of the episodic memory (EM) network demonstrate changing structure and volume during adolescence. EM is multifaceted and yet studies of EM thus far have largely examined single components, used different methods and have unsurprisingly yielded inconsistent results. The Treasure Hunt task is a single paradigm that allows parallel investigation of memory content, associative structure, and the impact of different retrieval support. Combining the cognitive and neurobiological accounts, we hypothesized that some elements of EM performance may decline in late adolescence owing to considerable restructuring of the hippocampus at this time. Using the Treasure Hunt task, we examined EM performance in 80 participants aged 10-17 yr. Results demonstrated a cubic trajectory with youngest and oldest participants performing worst. This was emphasized in associative memory, which aligns well with existing literature indicating hippocampal restructuring in later adolescence. It is proposed that memory development may follow a nonlinear path as children approach adulthood, but that future work is required to confirm and extend the trends demonstrated in this study.

The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana.

Background: Tuberculous meningitis (TBM) disproportionately impacts high-HIV prevalence, resource-limited settings where diagnosis is challenging. The GeneXpert platform has utility in TBM diagnosis, but uptake remains limited. In Botswana, before the introduction of GeneXpert, tuberculosis (TB) testing was only available through mycobacterial culture at the National TB Reference Laboratory. Data describing routine use of Xpert MTB/RIF for cerebrospinal fluid (CSF) testing in resource-limited settings are scarce. Methods: Electronic records for patients with CSF tested in government facilities in Botswana between 2016 and 2022 were obtained from a central online repository as part of ongoing national meningitis surveillance. Samples were excluded from 1 site where Xpert MTB/RIF is performed universally. The proportion receiving TB-specific investigation on CSF and the number positive for Mycobacterium tuberculosis following increased Xpert MTB/RIF capacity were determined. Results: The proportion of CSF samples receiving TB-specific investigation increased from 4.5% (58/1288) in 2016 to 29.0% (201/693) in 2022, primarily due to increased analysis with Xpert MTB/RIF from 0.9% (11/1288) to 23.2% (161/693). There was an overall decline in the annual number of CSF samples analyzed, but the proportion with microbiologically confirmed TBM increased from 0.4% to 1.2%. The proportion of samples tested for TB that were collected from health care facilities >100 km from the National TB Reference Laboratory increased with Xpert MTB/RIF rollout from 65.9% (87/132) to 78.0% (494/633). Conclusions: In Botswana, access to TB culture is challenging in remote populations; more accessible near-patient testing using Xpert MTB/RIF increased the number of patients receiving TB-specific testing on CSF and the number of confirmed TBM cases.

Measuring the impact of COVID-19 social distancing measures on sexual health behaviours and access to HIV and sexual and reproductive health services for people living with HIV in Botswana.

Introduction: Uninterrupted access to HIV and sexual and reproductive health (SRH) services is essential, particularly in high HIV prevalence settings, to prevent unintended pregnancy and vertical HIV transmission. Understanding the challenges that COVID-19 and associated social distancing measures (SDMs) posed on health service access is imperative for future planning. Methods: This cross-sectional study was conducted in Botswana between January-February 2021. A web-based questionnaire was disseminated on social media as part of the International Sexual Health and REproductive Health (I-SHARE) Survey. Respondents answered questions on SRH, before and during COVID-19 SDMs. Subgroup analysis and comparison of descriptive data was performed for people living with HIV (PLWH). Results: Of 409 participants, 65 were PLWH (80% female, 20% male). During SDMs, PLWH found it more difficult to access condoms and treatment for HIV and STIs; attend HIV appointments; and maintain adherence to antiretroviral therapy. Compared to HIV-negative women, a higher proportion of women living with HIV used condoms as their primary method of contraception (54% vs. 48%), and had lower use of long-acting reversible contraception (8% vs. 14%) and dual contraception (8% vs. 16%). Discussion: Mirroring global trends, COVID-19 disrupted HIV and SRH service access in Botswana. However, in high HIV-prevalence settings, disruption may more severely impact population health with disproportionate effects on women. Integration of HIV and SRH services could build health system capacity and resilience, reduce missed opportunities for delivering SRH services to PLWH and limit the consequences of future restrictions that may cause health system disruption.

Venous malformations: Coagulopathy control and treatment methods.

Venous malformations (VMs) are ectatic channels which arise as a result of vascular dysmorphogenesis, commonly caused by activating mutations in the endothelial tyrosine kinase receptor (TIE2)/phosphatidylinositol 3-kinase (PI3Kinase) pathway. With a prevalence of 1% in the general population, and a diverse clinical presentation depending on site, size and tissue involvement, their treatment requires a personalised and multidisciplinary approach. Larger lesions are complicated by local intravascular coagulopathy (LIC) causing haemorrhagic and/or thrombotic complications which can progress to disseminated intravascular coagulopathy (DIC). METHODS: We performed a literature review using a PubMed® search and identified 15 articles to include. References of these texts were examined to further expand the literature review.Principle findings: Several treatment options have been explored, including compression, sclerotherapy, laser therapy, cryoablation and surgery in addition to the management of LIC with low-molecular-weight-heparin (LMWH) and other anticoagulants. Targeted molecular therapies acting on the phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway are newly emerging. CONCLUSION: Despite a wealth of literature, larger, multi-centric, randomised and prospective trails are required to offer further clarification on the therapeutic management of coagulopathy control and to provide symptomatic benefit to patients with VMs. There should be efforts to provide long term follow up and to use standardised risk stratification tools and quality of life (QOL) questionnaires to aid comparison of agents and treatment protocols.