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The lack of culturally and contextually appropriate adaptations of health-related quality of life (HRQoL) tools hinders HIV patient outcomes. This study aims to assess the validity and reliability of a Tswana version of the Medical Outcome Survey-HIV (MOS-HIV) tool among diverse HIV sub-populations in Botswana. In terms of the methodology the study will comprise of several steps. Firstly, forward and back-translation of the original U.S. English MOS-HIV tool into Setswana, followed by the review of the translated tool. Phase 1 will evaluate content, construct validity, and reliability of the newly developed tool among HIV outpatients at Gaborone Infectious Diseases Clinics (IDCC). A Cronbach's alpha coefficient >0.7 across the 35 items and 11 dimensions of the MOS-HIV tool will indicate internal consistency reliability. Phase 2 will employ the use of logistic regression models to identify predictors of poor HRQoL among randomly selected IDCC sites, both in urban and rural centers. Phase 3 will investigate predictors of poor HRQoL among inpatients receiving treatment for HIV-associated cryptococcal meningitis (CM) using longitudinal data analysis methods. Ethical approval has been obtained from the University of Botswana, Walter Sisulu University, Human Research and Development Unit, Ministry of Health, and Princess Marina Hospital. Prospective participants will provide written informed consent, with proxy consent explored when feasible. Voluntary participation and confidentiality will be ensured during data collection and analysis. Data will be securely stored under lock-and-key. Dissemination of study findings will adhere to strict privacy protocols, avoiding the sharing of personal identifiers. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of scabies is poorly understood, particularly in regions with high disease burden. This lack of epidemiological data, especially in sub-Saharan Africa, hampers the control and preventative measures. This study is aimed at estimating the prevalence and associated risk factors of scabies and impetigo in the Nata and Sowa catchment areas of Tutume district. Methodology: A cross-sectional study was conducted in the Tutume District, targeting the settlements of Manxhotae, Malelejwe, Ndutshaa, and Tshwaane. Participants were randomly selected from households in the settlements. Data were collected using questionnaires, and participants were classified as having scabies typical lesions if they met criteria B and or C of International Alliance for the Control of Scabies (IACS) consensus criteria. Statistical significance was set at p<0.05, with a 95% confidence interval for precision. Results: A total of 429 participants were enrolled across the four settlements. The overall prevalence of scabies was found to be 18.18% (95%CI 14.8–22.1). The highest prevalence of scabies was in Manxhotae at 27.1% (95%CI 21.2–34.0) and Ndutshaa at 23.4% (95%CI 13.4–37.3). Malelejwe and Tshwaane had lower prevalence of 10.4% (95%CI 6.2–16.8) and 3.4% (95%CI 0.8–12.7), respectively. Only five (5) cases of impetigo were identified. Multivariable logistic regression analysis revealed that younger age of 0–4 years, 5–18 years and a household member with an itch were strongly associated with scabies, with adjusted odds ratios (aOR) of 7.9 (95%CI 2.4–25.6) p-value 0.001, 5.7(95%CI 2.7–11.7), p-value 0.001 and 14.3(95%CI 5.3–38.5) p-value 0.001 respectively. Conclusion: The prevalence of scabies in the Nata catchment area was noted to be high. The risk factors included younger age, a household member with an itch, and less frequent bathing. Prospective studies are needed to explore household disease transmission dynamics and risk factors specific to the youth. Author summary: This study was carried out in the Nata catchment area in Tutume district, Botswana. It aimed to assess the burden, risk factors informing effective disease control programs. The survey involved interviews and skin examination by a health worker. Findings revealed a higher prevalence of scabies cases, while impetigo cases were less prevalent. These results highlight the need for community-wide interventions to mitigate the disease's impact. Identified risk factors include younger age, residing with an individual experiencing itchiness, and infrequent bathing. Overall, this study supports advocating for scabies as a neglected tropical disease. [ABSTRACT FROM AUTHOR]

Background: Single, high-dose liposomal amphotericin B (LAmB; AmBisome, Gilead Sciences) has demonstrated non-inferiority to amphotericin B deoxycholate in combination with other antifungals for averting all-cause mortality from HIV-associated cryptococcal meningitis. There are limited data on the pharmacokinetics (PK) of AmBisome. The aim of this study was to describe population PK of AmBisome and conduct a meta-analysis of the available studies to suggest the optimal dosing for cryptococcal meningoencephalitis.Methods: Data from a Phase II and Phase III trial of high-dose, short-course AmBisome for cryptococcal meningoencephalitis were combined to develop a population PK model. A search was conducted for trials of AmBisome monotherapy and meta-analysis of clinical outcome data was performed.Results: A two-compartment model with first-order clearance of drug from the central compartment fitted the data best and enabled the extent of inter-individual variability in PK to be quantified. Mean (SD) population PK parameter estimates were: clearance 0.416 (0.363)  L/h; volume of distribution 4.566 (4.518) L; first-order transfer of drug from central to peripheral compartments 2.222 (3.351)  h-1, and from peripheral to central compartment 2.951 (4.070)  h-1. Data for the meta-analysis were insufficient to suggest optimal dosing of AmBisome for cryptococcal meningoencephalitis.Conclusions: This study provides novel insight into the PK of AmBisome at the population level and the variability therein. Our analysis also serves to highlight the paucity of data available on the pharmacodynamics (PD) of AmBisome and underscores the importance of thorough and detailed PK/PD analysis in the development of novel antifungals, by demonstrating the challenges associated with post hoc PK/PD analysis. [ABSTRACT FROM AUTHOR]

Background Evidence to inform cryptococcal antigen (CrAg)–screening guidelines among ART-experienced populations is lacking. We performed a study evaluating the utility of reflex CrAg screening in Gaborone, Botswana. Methods CD4 count data were collected from the HIV reference laboratory from 2014–2016. CrAg screening was performed on samples with CD4 ≤100 cells/µL beginning January 2015. The proportion of CD4 counts ≤100 cells/µL was determined and the frequency of repeat CrAg testing described. Analyses ascertained the impact of ART status on CrAg prevalence and outcomes, and whether CrAg titers could be used for risk stratification. Results Overall, 5.6% (3335/59 300) of individuals tested had CD4 ≤100 cells/μL; 2108 samples with CD4 ≤100 cells/μL from 1645 unique patients were CrAg tested. Over half of samples were from ART-experienced individuals: 40.9% (863) on ART and 12.1% (255) defaulters; 22% (463) of CrAg tests were on repeat samples. CrAg prevalence was 4.8% (72/1494; 95% CI, 3.8–6.0%) among outpatients and 21.9% (32/151; 95% CI, 15.3–28.5%) among inpatients. CrAg prevalence rates did not differ by ART status, but 6-month mortality was significantly lower in CrAg-positive individuals on ART at screening. Ten CrAg positives were identified through repeat testing. A CrAg titer cutoff ≥1:80 provided the best discrimination for 6-month survival. Conclusions CrAg-positivity rates in an ART-experienced population were comparable to those seen in ART-naive populations. Repeat screening identified individuals who seroconverted to CrAg positivity and were at risk of cryptococcal disease. CrAg titers ≥1:80 can help identify the individuals at highest risk of death for more intensive management. [ABSTRACT FROM AUTHOR]

Background We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana. Methods Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day. Results Eighty participants were enrolled. EFA for daily L-AmB was –0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was –0.11 (95% CI, –.29 to.07) log10 CFU/mL/day faster with single dose (n = 16); –0.05 (95% CI, –.20 to.10) log10 CFU/mL/day faster with 2 doses (n = 18); and –0.13 (95% CI, –.35 to.09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated. Conclusions Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial. Clinical Trials Registration ISRCTN 10248064. [ABSTRACT FROM AUTHOR]