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BackgroundGuidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking.SettingWe studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART.MethodsSerum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART.ResultsPretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment.ConclusionsQuantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

BackgroundPregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy.MethodsIMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics.ResultsOf 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P

Educational contexts around the world are increasingly characterized by diversity, including a rise in students from refugee backgrounds. Much research has focused on the educational needs of these students and the particular struggles they experience in educational contexts. The increasing number of refugee and asylum-seeking children in Australia calls for rethinking approaches to enhance the acculturation process in ways that build on individuals' prior knowledge and understanding of self. This paper draws on data from a larger case study that focused on Sudanese young people in regional Australia and investigated their out-of-school activities, networks, and practices and how these contributed to their success across a range of contexts. Drawing on perspectives of identity and theories of social capital, we discuss the role of social networks in generating social capital and what this means in terms of the (re)formation of students' identities in regional locations, and we consider how this can contribute to educational success. We suggest that the resources in regional areas present both a challenge and an opportunity for young former-refugee people in terms of repositioning themselves in new social, cultural, and educational contexts. The paper examines how the young people developed their own momentum, rationality, and legitimacy in their identity (re)formation, and suggests that educational settings need to connect with and understand young people's out-of-school resources to avoid deficit narratives that lead to poor educational outcomes.

BackgroundMedication adherence is a critical issue in achieving viral suppression targets, particularly in resource-limited countries. As HIV-related cognitive impairment (CI) impacts adherence, we examined frequency and predictors of CI in the African Cohort Study.SettingCross-sectional examination of enrollment data from President's Emergency Plan for AIDS Relief supported clinic sites.MethodsIn a 30-minute cognitive assessment, CI was defined as -1SD on 2 tests or -2SD on one, as compared with 429 controls. We performed univariable and multivariable logistic and linear models examining clinical and demographic factors associated with CI and global neuropsychological performance (NP-6).ResultsTwo thousand four hundred seventy-two HIV+ participants from Kenya (n = 1503), Tanzania (n = 469), and Uganda (n = 500). The mean (SD) age was 39.7 (10.7) years, and 1452 (59%) were women. The majority reported completing or partially completing primary school (n = 1584, 64%). Mean (SD) current and nadir CD4 count were 463 (249) and 204 (221) cells/mm, respectively; 1689 (68%) were on combination antiretroviral therapy. Nine hundred thirty-nine (38%) HIV+ versus 113 (26%) HIV- individuals showed CI: (P < 0.001). We found significant effects of literacy [odds ratio (OR): 0.3; 95% CI: 0.2 to 0.4; P < 0.001] and World Health Organization stage 4 (OR: 1.5; 95% CI: 1.0 to 2.q; P = 0.046) on CI. Tanzanians (OR: 3.2; 95% CI: 2.4 to 4.3; P < 0.001) and Kenyans (OR: 2.0; 95% CI: 1.6 to 2.6; P < 0.001) had higher risk of CI compared with Ugandans. Results were relatively unchanged in predictive models of NP-6, with the only difference being an additional significant effect of current CD4 cell count (coeff: 0.0; 95% CI: 0.0 to 0.0; P = 0.005).ConclusionsLiteracy, country, World Health Organization stage, and current CD4 cell count were associated with increased risk of cognitive dysfunction. Our findings help optimize care practices in Africa, illustrating the importance of strategies for early and effective viral-immunological control.

BackgroundMild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART.MethodsChemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response.ResultsOf 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks.ConclusionsAmong HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low.Clinical trials registrationNCT01352117.

OBJECTIVES: The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. METHODS: IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. RESULTS: IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho 0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. CONCLUSIONS: We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.

Purpose: To evaluate the effect of behavioral, empowerment-focused interventions on the incidence of pregnancy-related school dropout among girls in Nairobi's informal settlements. Method: Retrospective data on pregnancy-related school dropout from two cohorts were analyzed using a matched-pairs quasi-experimental design. The primary outcome was the change in the number of school dropouts due to pregnancy from 1 year before to 1 year after the interventions. Results: Annual incidence of school dropout due to pregnancy decreased by 46% in the intervention schools (from 3.9% at baseline to 2.1% at follow-up), whereas the comparison schools remained essentially unchanged (p < 0.029). Sensitivity analysis shows that the findings are robust to small levels of unobserved bias. Conclusions: Results suggest that these behavioral interventions significantly reduced the number of school dropouts due to pregnancy. As there are limited promising studies on behavioral interventions that decrease adolescent pregnancy in low-income settings, this intervention may be an important addition to this toolkit.

The seeds of Khaya anthotheca , (Welv.) yielded two undescribed limonoids, 1α,7α-diacetoxyhavanensin-16-one (1) and 3α,7α-diacetoxyhavanensin-16-one (2), as well as three known limonoids, khayanthone (3), 3,7-di- O -acetyl-14,15-deoxyhavanensin (4) and 1,7-di- O -acetyl-14,15-deoxyhavanensin (5). The antiplasmodial activities of the CH 2 Cl 2 extract and the pure compounds were evaluated in vitro against Plasmodium falciparum (Dd2-B2 strain). Khayanthone (3) showed the highest activity of all the compounds isolated in this study, with an IC 50 of 1.32 µg/mL. [Display omitted] • Two undescribed havanensin derivatives along with three known limonoids were isolated from the seeds of Khaya anthotheca. • The extract and the pure compounds were evaluated for antiplasmodial activity. • Khayanthone showed moderate activity against Plasmodium falciparum (Dd2-B2 strain). [ABSTRACT FROM AUTHOR]

Rape occurs at high rates in South Sudan and Kakuma refugee camps, a region characterized by armed conflict, gender inequity, and economic crisis. To date, we know little about how to prevent rape in this region of the world. As such, the purpose of this study was to examine outcomes of Empowerment Transformation Training (ETT) (an adapted empowerment self-defense program; empowerment self-defense) among female participants in South Sudan and the Kakuma refugee camp. Schools were assigned to the treatment (ETT) condition (n = 7) or control (life skills) condition (n = 9) and used as the unit of analysis given the cluster-randomized design. Female participants anonymously completed a baseline (T1) and 12-month follow-up (T2) paper and pencil survey. Annual rape victimization rates decreased from 10.7% to 5.5% in the ETT schools (risk ratio [ RR ] = 0.51); there was no change in the control schools (10.0%–9.0%). Empowerment Transformation Training (ETT) schools had increased confidence at T2 (T1: 42.4%; T2: 75.4%; RR = 1.79) and greater rates of confidence at T2 compared to control schools (54.3%; RR = 1.39). Knowledge of effective self-defense strategies (T2) was greater for ETT schools (47.4%) compared to control schools (30.1%) (RR = 1.57). The ETT program reduced rates of rape, increased confidence, disclosures of rape (among victims), and knowledge of effective self-defense strategies. Empowerment self-defense programs are a critical component to rape prevention across global communities, including those characterized by armed conflict, gender inequity, and economic crisis. [ABSTRACT FROM AUTHOR]