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BACKGROUND: Several rural public health facilities in East Central Uganda have sub-optimal, below 50%, levels of uptake of cervical cancer screening services among women with HIV. This is attributed to low cervical cancer screening literacy: limited ability to access, understand, appraise, and apply cervical cancer screening information. This research identified multi-level (health facility, community, interpersonal and individual) barriers, and facilitators of accessing, understanding, and applying cervical cancer screening information among rural women with HIV attending rural public health facilities in East Central Uganda to inform interventions. METHODS: We conducted ten Focus Group Discussions with rural women aged 25-49 years with HIV attending four selected rural public health facilities: thirty women who had ever screened for cervical cancer and thirty women who had never screened for cervical cancer across different age categories. Data was collected using a guide based on the Integrated model of health literacy. Thematic analysis was used for analysis. Competences (accessing, understanding and applying cervical cancer screening information) and categories of factors (health system, community, interpersonal and individual factors) of the integrated model of health literacy were deductively derived whereas barriers and facilitators were deductively derived from women's statements. RESULTS: Lack of communication materials and inability to access information were health facility and individual barriers of accessing cervical cancer screening information respectively. Facilitators of accessing information were access to information at health facility, community, and interpersonal levels and women's ability to access information. Barriers and facilitators of understanding cervical cancer information were related to communication materials, provision of health education and women's concentration during health education. Barriers and facilitators of applying cervical cancer screening information were related to communication and provision of cervical cancer screening services at health facility level, and interpersonal level from peers, partners and other family members as well as women's ability to: understand information and access to cervical cancer screening services at individual level. CONCLUSIONS: This study emphasizes the influence of multi-level factors on cervical cancer screening literacy among rural women with HIV attending rural public health facilities in East Central Uganda. Improving uptake of cervical cancer screening services among these women requires multi-level interventions.

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Background: Short-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AE) could differ in routine settings. Real-world data on AE type, frequency, and timing is crucial for health systems considering 3HP programmatic scale-up. Methods: We reviewed AEs among people living with HIV (PLHIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including lab tests, diagnoses made, medications prescribed, and treatment interruptions. Results: Among 1655 PLHIV treated between July 2020-September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE. Conclusions: In a routine setting, 3HP was safe with 16% of PLHIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention.

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CONTEXT: Some patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing the cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF) may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some untreated classic CAH patients. OBJECTIVE: Develop and validate an LC-MS/MS method for free cortisol and free 21DF to quantify these steroids in untreated patients with classic CAH (n=29), non-classic CAH (NCCAH, n=5), other forms of adrenal insufficiency (AI, n=3), and controls (n=11) before and 60 minutes after Synacthen® administration. RESULTS: Unstimulated total cortisol concentrations of untreated classic CAH patients (median 109 nmol/L) were lower than in untreated NCCAH patients (249 nmol/L, p=0.010) and controls (202 nmol/L, p=0.016), but free cortisol concentrations were similar. Basal free 21DF concentrations were high in 21OHD patients (median 5.32 nmol/L) and undetectable in AI patients and controls (<0.19 nmol/L). After Synacthen® administration, free 21DF concentrations increased in 21OHD patients, while free cortisol concentrations did not change. CONCLUSIONS: Free cortisol concentrations in classic CAH patients were similar to those in controls and NCCAH patients, indicating comparable cortisol availability. Additionally, 21OHD patients produce high concentrations of 21DF, possibly explaining the low occurrence of symptoms in some classic 21OHD patients. Free cortisol and 21DF levels should be considered in evaluating adrenal insufficiency in patients with CAH.

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Sequencing of plasma microbial cell-free DNA (mcfDNA) has gained increased acceptance as a valuable adjunct to standard-of-care testing for diagnosis of infections throughout the body. Here, we report the analytical and clinical validation of a novel application of mcfDNA sequencing, the non-invasive detection of seven common antimicrobial resistance (AMR) genetic markers in 18 important pathogens. The AMR markers include SCCmec, mecA, mecC, vanA, vanB, blaCTX-M, and blaKPC. The AMR markers were computationally linked to the pathogens detected. Analytical validation showed high reproducibility (100%), inclusivity (54 to 100%), and exclusivity (100%). Clinical accuracy was assessed with 114 unique plasma samples from patients at seven study sites with concordant culture results for target bacteria from a variety of specimen types and correlated with available phenotypic antimicrobial susceptibility test results and genotypic results. The positive percent agreement (PPA), negative percent agreement (NPA), and diagnostic yield (DY) were estimated for each AMR marker. DY was defined as the percentage of tests that yielded an actionable result of either detected or not detected. The results for the combination of SCCmec and mecA for staphylococci were PPA 19/20 (95.0%), NPA 21/22 (95.4%), DY 42/60 (70.0%); vanA for enterococci were PPA 3/3 (100%), NPA 2/2 (100%), DY 5/6 (83.3%); blaCTX-M for gram-negative bacilli were PPA 5/6 (83.3%), NPA 29/29 (100%), DY 35/49 (71.4%); and blaKPC for gram-negative bacilli were PPA 0/2 (0%), NPA: 23/23 (100%), DY 25/44 (56.8%). The addition of AMR capability to plasma mcfDNA sequencing should provide clinicians with an effective new culture-independent tool for optimization of therapy. IMPORTANCE: This manuscript is ideally suited for the Innovative Diagnostic Methods sections as it reports the analytical and clinical validation of a novel application of plasma microbial cell-free DNA sequencing for direct detection of seven selected antimicrobial resistance markers in 18 target pathogens. Clearly, it has potential clinical utility in optimizing therapy and was incorporated into the Karius test workflow in September 2023. In addition, the workflow could readily be adapted to expand the number of target bacteria and antimicrobial resistance markers as needed.

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Stretching an elastic material along one axis typically induces contraction along the transverse axes, a phenomenon known as the Poisson effect. From these strains, one can compute the specific volume, which generally either increases or, in the incompressible limit, remains constant as the material is stretched. However, in networks of semiflexible or stiff polymers, which are typically highly compressible yet stiffen significantly when stretched, one instead sees a significant reduction in specific volume under finite strains. This volume reduction is accompanied by increasing alignment of filaments along the strain axis and a nonlinear elastic response, with stiffening of the apparent Young's modulus. For semiflexible networks, in which entropic bending elasticity governs the linear elastic regime, the nonlinear Poisson effect is caused by the nonlinear force-extension relationship of the constituent filaments, which produces a highly asymmetric response of the constituent polymers to stretching and compression. The details of this relationship depend on the geometric and elastic properties of the underlying filaments, which can vary greatly in experimental systems. Here, we provide a comprehensive characterization of the nonlinear Poisson effect in an affine network model and explore the influence of filament properties on essential features of both microscopic and macroscopic response, including strain-driven alignment and volume reduction.

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BACKGROUND: Human Papilloma Virus (HPV) vaccination can prevent more than 90% of cancers caused by HPV. Although this vaccination is recommended and provided at no cost to all adolescent girls aged 9 to19 years in Uganda, its uptake remains low. We sought to determine the uptake of, and factors associated with HPV vaccination among adolescent girls living with HIV in Uganda. METHODS: We conducted an explanatory sequential mixed methods study, among adolescent girls living with HIV, attending HIV care at the Mulago ISS HIV clinic in Kampala, Uganda. We administered a structured questionnaire to elicit data on HPV vaccination and its covariates to a systematic random sample of 264 adolescent girls with HIV. A participant who had received all the three recommended HPV vaccine doses was classified as fully vaccinated. We then conducted four focus group discussions among adolescent girls living with HIV (n = 32), eight in-depth interviews among their parents and five Key informant interviews among their healthcare providers. We conducted descriptive statistics and logistic regression analyses for the quantitative data before thematic analysis for the qualitative data. RESULT: Of 264 adolescent girls, 31% (83/264) had at least one HPV vaccine dose; 22% (59/264) two doses, while 8.0% (21/264) were fully vaccinated (received three doses). While most participants received their first and second doses (48% (40/83)) and 57.6% (34/59), respectively) from school, the largest number of participants (47.1% (12/21)) received their third dose at community outreaches. Participants who received counseling from community members were three times more likely to get fully vaccinated compared to those who did not receive counseling (aOR 3.28, Cl:1.07-10.08, P = 0.038). From the qualitative follow-up, three major themes were identified: (1): Limited information about HPV vaccination, which gave room for misconceptions and doubts about the vaccine; (2) Parental influence on adolescent decisions was strong despite parents having limited knowledge about HPV vaccination and (3) Inadequacy of HPV vaccination services at the hospital and in the schools. CONCLUSION: Full HPV vaccination was low among adolescent girls living with HIV. Counseling of the adolescents by community members, alongside HPV vaccination community outreaches, provided a platform for vaccination. There should be strategies to provide adequate information about HPV vaccine to health workers, parents, and the adolescents. In addition to schools, community-based initiatives, including outreaches and lay-health workers can be utilized to improve HPV vaccine uptake among girls with HIV.

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Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5-36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient.

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Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Methods: Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. Results: All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. Discussion: We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed.

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BACKGROUND: Following the World Health Organization's declaration of COVID-19 as a global pandemic, several countries implemented population-wide lockdowns. However, these responses to COVID-19 caused severe healthcare system disruptions to service delivery. The TB case notification rate in Uganda decreased by 22% between January and April 2020, which coincided with a lockdown and an increase in COVID-19 cases. In this study, we tested the effect of screening all patients with both COVID-19-positive and negative symptom screen for TB at a National Referral Hospital. DESIGN/METHODS: Following our formative assessment, we identified potential barriers to and facilitators of integrating screening for COVID-19 and TB at Kiruddu National Referral Hospital. To address the barriers, in February 2021 we trained healthcare providers on integrated COVID-19-TB screening tools and provided COVID-19/TB screening tools/Standard operating procedures and personal protective equipment. From March 1, 2021, to June 30, 2021, we screened patients presenting to the emergency and outpatient departments for COVID-19 symptoms, and subsequently, we performed TB symptom screening for both patients with COVID-19 positive and negative symptom screen using the intensified tuberculosis case-finding (ICF) guide. We then compared the outcomes of TB symptom screening for patients initially with a positive COVID-19 symptom screen with those who initially had a negative COVID-19 symptom screen. RESULTS: From March 2021 to June 2021, we screened 1464 patients (44.3% male and 55.7% female) for COVID-19 symptoms. Out of these participants, 1252 (85.5%) screened positive for COVID-19 symptoms, while 212 (14.5%) screened negative. The majority of patients with a positive COVID-19 symptom screen, 717 (57.3%), also screened positive for TB symptoms compared to 19 (8.9%) among patients with a negative COVID-19 symptom screen. Out of the total 736 presumptive TB cases identified, 717 (97.4%) initially screened positive for COVID-19 symptoms. TB was diagnosed in 110 individuals including 104 who had positive COVID-19-symptom screen and six who had a negative COVID-19 symptom screen. All of the 110 newly diagnosed TB cases were linked to TB treatment. CONCLUSIONS: Patients who screen positive for COVID-19 symptoms should be routinely screened for TB to mitigate missed opportunities for TB case identification.

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Strain-controlled criticality governs the elasticity of jamming and fiber networks. While the upper critical dimension of jamming is believed to be d_{u}=2, non-mean-field exponents are observed in numerical studies of 2D and 3D fiber networks. The origins of this remains unclear. In this study we propose a minimal mean-field model for strain-controlled criticality of fiber networks. We then extend this to a phenomenological field theory, in which non-mean-field behavior emerges as a result of the disorder in the network structure. We predict that the upper critical dimension for such systems is d_{u}=4 using a Gaussian approximation. Moreover, we identify an order parameter for the phase transition, which has been lacking for fiber networks to date.

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Chronic diseases such as HIV, hypertension, and diabetes increase the risk of severe coronavirus disease 2019 (COVID-19) and death. Thus, COVID-19 vaccine uptake data among these priority populations are needed to inform immunization programs. We assessed COVID-19 vaccine uptake among people living with HIV (PLWH) and those with hypertension/diabetes without HIV (PWoH) in Southwestern and Southcentral Uganda and determined factors influencing vaccination. We conducted a cross-sectional study from January to April 2023. We enrolled a random sample of participants aged 18 years and older seeking HIV, hypertension, or diabetes care at two regional referral hospitals (RRHs) in Mbarara and Masaka in Uganda. Using vaccination records abstraction and interviewer-administered questionnaires, we collected data on COVID-19 vaccine uptake, sociodemographic data, and reasons for non-uptake in unvaccinated persons. We compared COVID-19 vaccination uptake between PLWH and PWoH and applied modified Poisson regression to determine sociodemographic factors associated with vaccine uptake. The reasons for non-vaccine uptake were presented as percentages. Of the 1,376 enrolled participants, 65.6% were fully vaccinated against COVID-19. Vaccination coverage was 65% among PWLH versus 67% among PWoH. Higher education attainment and older age were associated with COVID vaccination. Participants with secondary education and those aged ≥50 years achieved >70% coverage. Fear of side effects was the most cited reason (67%) for non-vaccination among 330 unvaccinated participants, followed by vaccine mistrust (24.5%). People with chronic diseases in Southwestern Uganda had slightly lower than 70% COVID-19 vaccine coverage as recommended by WHO. Higher educational attainment and older age were linked to increased vaccine uptake. However, mistrust and fear of vaccine side effects were the main reasons for non-vaccination. To increase COVID-19 vaccine uptake, programs must reach those with lower educational attainment and younger age groups, and address the fear of vaccine side effects and mistrust among persons with underlying diseases in Uganda.

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Background: Oral HIV self-testing (HIVST) among men is relatively low and still inadequate in Sub-Saharan Africa. Delivering HIVST kits by pregnant women attending antenatal care to their partners is a promising strategy for increasing HIV testing among men. However, even amidst the interventions, most men do not know their HIV status. This study, aimed to determine the proportion of partners who received and used oral HIVST kits delivered by pregnant women, associated factors, barriers, and facilitators for uptake among partners. Methods: We conducted an exploratory sequential mixed methods study among 380 sampled partners. Lists of partners in the HIVST log books whose women picked an HIVST kit were obtained and systematic random sampling was done to obtain participants. 14 male partners were purposively selected for in-depth interviews (IDIs) to identify barriers and facilitators. We used modified poison regression to determine the association between oral HIVST and independent variables. We used an inductive analysis for the qualitative analysis. Results: Out of 380 participants, 260(68.4%) received an oral HIVST kit from their pregnant women, and 215(82.7%) used the kit for HIVST. Oral HIVST was associated with; Information Education and Communication (CPR = 1.64, 95%CI 1.48-1.82), being reached at home (CPR = 1.04, 95%CI 1.01-1.08), and being aware of the woman's HIV status (CPR = 1.04, 95%CI 0.99-1.09). In-depth results identified barriers to uptake as, lack of trust in the HIVST kit results, fear of test outcome in the presence of the partner and inclination that the HIV status of their women is the same as theirs, and facilitators included convenience, ease to use, prior awareness of their HIV status, and fear of relationship consequences and breakup. Conclusion: Delivery of oral HIVST kits to men through pregnant women reached a high number of men and achieved a high uptake. Accessing information, education, communication and convenience nature were the major reasons for uptake among men who received the Oral HIVST kit as trust issues of the kit affected use among partners. Scaling up the delivery of oral HIVST kits at all departments of the hospital through women seeking health services is paramount to support HIV screening among men to reach the UNAIDS 95 strategy.

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Fibrous networks such as collagen are common in biological systems. Recent theoretical and experimental efforts have shed light on the mechanics of single component networks. Most real biopolymer networks, however, are composites made of elements with different rigidity. For instance, the extracellular matrix in mammalian tissues consists of stiff collagen fibers in a background matrix of flexible polymers such as hyaluronic acid (HA). The interplay between different biopolymer components in such composite networks remains unclear. In this work, we use 2D coarse-grained models to study the nonlinear strain-stiffening behavior of composites. We introduce a local volume constraint to model the incompressibility of HA. We also perform rheology experiments on composites of collagen with HA. Theoretically and experimentally, we demonstrate that the linear shear modulus of composite networks can be increased by approximately an order of magnitude above the corresponding moduli of the pure components. Our model shows that this synergistic effect can be understood in terms of the local incompressibility of HA, which acts to suppress density fluctuations of the collagen matrix with which it is entangled.

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Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. The antiviral effect of NTP was investigated using an in vitro model of HSV-1 epithelial infection that involved the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. It was found that NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggests the potential of NTP as a therapeutic agent effective against HSV-1 infection.

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Background: HIV pre-exposure prophylaxis (PrEP) is underutilized by cisgender female sex workers (FSW) despite its proven effectiveness. This study aimed to understand the experiences of FSW with PrEP services in Uganda to inform HIV programming for this key population. Methods: We conducted qualitative interviews with 19 FSW between June and July 2022 at the Most at Risk Populations Initiative clinic, Mulago Hospital, Kampala, to explore experiences with accessing PrEP Indepth interviews explored: (1) descriptions of where and how PrEP was obtained; (2) perspectives on current approaches for accessing PrEP; and (3) individual encounters with PrEP services. Data were analyzed through inductive thematic analysis. Results: Three key themes emerged for FSW perspectives on PrEP service delivery. FSW highlighted the positive impact of a welcoming clinic environment, which motivated FSW to initiate PrEP and fostered a sense of connectedness within their community. They also reported feeling accepted, secure, and free from prejudice when accessing PrEP through facility-based services. The second explores the obstacles faced by FSW, such as lengthy wait times at clinics, inadequate provider support, and lack of sensitivity training which hindered their access to PrEP The third sheds light on how HIV-related stigma negatively impacted the delivery of community-based PrEP for FSW. While community-based distribution offered convenience and helped mitigate stigma, clinic-based care provided greater anonymity and was perceived as offering higher-quality care. Overall, FSWs emphasized the critical role of friendly healthcare providers, social support, and non-stigmatizing environments in promoting successful utilization of PrEP. Conclusion: The study findings offer insights that can support HIV programs in optimizing PrEP delivery for FSW. Establishing easily accessible drug pick-up locations, prioritizing privacy, addressing and improving health workers' attitudes, and providing regular reminders could enhance PrEP access for FSW and decrease HIV acquisition.

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OBJECTIVE: To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. DATA EXTRACTION AND SYNTHESIS: Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. RESULTS: Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). CONCLUSIONS: A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO REGISTRATION NUMBER: CRD42020219363.

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BACKGROUND: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART). METHODS: 897 ART-initiators were recruited irrespective of symptoms and sputum induction offered. For triage (n=800), we evaluated point-of-care blood-based CRP testing, compared with the WHO-recommended four-symptom screen (W4SS). For sputum-based confirmatory testing (n=787), we evaluated Xpert Ultra versus Xpert MTB/RIF (Xpert). For urine-based confirmatory testing (n=732), we evaluated Xpert Ultra and LF-LAM. We used a sputum culture reference standard. FINDINGS: 463 (52%) of 897 participants were female. The areas under the receiver operator characteristic curves for CRP was 0·78 (95% CI 0·73-0·83) and for number of W4SS symptoms was 0·70 (0·64-0·75). CRP (≥10 mg/L) had similar sensitivity to W4SS (77% [95% CI 68-85; 80/104] vs 77% [68-85; 80/104]; p>0·99] but higher specificity (64% [61-68; 445/696] vs 48% [45-52; 334/696]; p<0·0001]; reducing unnecessary confirmatory testing by 138 (95% CI 117-160) per 1000 people and number-needed-to-test from 6·91 (95% CI 6·25-7·81) to 4·87 (4·41-5·51). Sputum samples with Xpert Ultra, which required induction in 49 (31%) of 158 of people (95% CI 24-39), had higher sensitivity than Xpert (71% [95% CI 61-80; 74/104] vs 56% [46-66; 58/104]; p<0·0001). Of the people with one or more confirmatory sputum or urine test results that were positive, the proportion detected by Xpert Ultra increased from 45% (26-64) to 66% (46-82) with induction. Programmatically done haemoglobin, triage test combinations, and urine tests showed comparatively worse results. INTERPRETATION: CRP is a more specific triage test than W4SS in those initiating ART. Sputum induction improves diagnostic yield. Sputum samples with Xpert Ultra is a more accurate confirmatory test than with Xpert. FUNDING: South African Medical Research Council, EDCTP2, US National Institutes of Health-National Institute of Allergy and Infectious Diseases.

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BACKGROUND: HIV mostly affects people with severe mental illnesses (SMIs) than the general population. In 2015, the World Health Organization (WHO) introduced assisted partner notification (APN) as a strategy to increase HIV testing. Although research has demonstrated the effectiveness of APN in the general population, its use among people living with HIV (PLHIV) who have SMI is not well understood. This study sought to determine the acceptance of the APN strategy among PLHIV who had a diagnosis of SMI. METHODS: This study used a cross-sectional study design that was retrospective to determine acceptance of APN among PLHIV with a documented diagnosis of SMI. We enrolled participants with a diagnosis of both HIV and SMI from August 2018 to January 2022, attending the HIV clinic at Butabika Hospital. We used pretested questionnaires to extract participants' demographic and clinical data from their existing clinical charts, antiretroviral therapy (ART) registers and APN registers. We defined acceptance of APN as the number of PLHIV with SMI diagnoses who agreed to provide information about their sexual partners. We used modified Poisson regression analysis to assess the factors associated with the acceptance of APN. RESULTS: A total of 125 participants were enrolled, of whom 83 (66.4%) were female. The median age was 30 (interquartile range (IQR) (25-34)), and 41 (33%) of them accepted APN (95% CI: 25.05-41.61). Receipt of at least three counselling sessions before enrollment in APN (aPR = 1.8, 95% CI: 1.72-1.98) was the most significant factor associated with increased acceptance of APN. Poor adherence to ART (aPR = 0.62, 95% CI: 0.54-0.80), being escorted to hospital by a distant relative (aPR = 0.55, 95% CI: 0.39-0.80), being married/cohabiting (aPR = 0.65, 95% CI: 0.60-0.81), and being a Seventh Day Adventist (SDA) (aPR = 0.53, 95% CI: 0.45-0.71) or Pentecostal (aPR = 0.44, 95% CI: 0.22-0.98) by faith were associated with reduced acceptance of APN. CONCLUSION AND RECOMMENDATION: The acceptance of APN is low among PLHIV with a diagnosis of SMI. More structured counselling would facilitate earlier identification of undiagnosed HIV-positive partners. We recommend a follow-up study to compare acceptance of APN among PLHIV with SMI and those without SMI.

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Introduction: Diseases caused by bacteria can be managed with medicinal plants with rightful dosage that will not affect body physiology and organs. Aim: This research aimed to evaluate the antioxidants and the effects of Anogeisus leiocarpus on liver function. Materials and methods: Ethanol leaf extracts were processed for antioxidants and hepatotoxic effects using animal models. Group one (negative control) was given access to water and regular feed, group two (positive control) was dosed with 107 CFU/ml of Escherichia coli O157:H7, and groups 3-6 were dosed with 107 E. coli O157:H7 for 3 days and treated with extract concentrations of 12, 25, 50 and 100 mg/kg bw respectively for seven days. Results: Higher ascorbic acid values in Ferric reducing antioxidant property (FRAP) and Hydroxyl radical scavenging (HRS) were recorded in the positive control (0.05 ± 0.01, 41 ± 0.05) than in the extract-treated (0.02 ± 0.14, 30 ± 0.02). Increase in DPPH (47 ± 0.1268 ± 0.05 %), Free radical scavenging property (FRAP) (0.03 ± 0.02-0.08 ± 0.14 %), and HRS (38 ± 0.14-68 ± 0.12 %) was observed in the extract. The lipid peroxidation (LPO) of the quote was 78.51 ± 2.16, GSH was 36.18 ± 3.18, and catalase was 78.42 ± 4.713. In the extract-treated, decreased values were recorded for LPO ((108.36 ± 1.12-70.19 ± 1.68 µM/g), while increased values were observed in Glutathione (GSH) (25.11 ± 2.64-33.62 ± 1.35 µM/g), and catalase (54.18 ± 2.14-60.25 ± 1.4 µM/g). The values of negative control for Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphate (ALP) were lesser than what was received in the extract treated. Conclusion: The plant's traditional medicine usage is effective at low dosage and could be a suitable candidate for drug development which will not affect the body's physiology and organs. The subjecting of A. leiocarpus ethanol leaf extract to antioxidants assays and its effect on liver function have further proved its value in folklore medicine.