Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy-Experienced Ugandans With Virologic Failure.

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. CONCLUSIONS: In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases

Retrospective review of positive newborn screening results for Isovaleric Acidemia and development of a strategy to improve the efficacy of newborn screening in the UK

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder

Integrated management of HIV, diabetes and hypertension in sub Saharan Africa: a pragmatic multi-country cluster-randomised trial

Background: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. Methods: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. Findings: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were –0·65% (95% CI –5·76 to 4·46; p=0·80) unadjusted and –0·60% (–5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were –0·37% (one-sided 95% CI –1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and –0·36% (–1·99 to 1·28; pnon-inferiority<0·0001 adjusted). Interpretation: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK.

Peer reviewed: TrueAcknowledgements: We acknowledge all staff in UK newborn screening laboratories and the clinicians in Newborn Screening Clinical Centres in the NHS. We also acknowledge Piero Rinaldo for his help and support with CLIR.Publication status: PublishedSince the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0-9.6) and 4.0 (1.8->70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in 'asymptomatic' individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8-7.1) whilst 'clinically affected' patients (n = 7), showed a median (range) C5C of 13.9 (7.7-70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder

Quantitative trait loci and differential gene expression analyses reveal the genetic basis for negatively associated β-carotene and starch content in hexaploid sweetpotato [Ipomoea batatas (L.) Lam.]

Key message: β-Carotene content in sweetpotato is associated with the Orange and phytoene synthase genes; due to physical linkage of phytoene synthase with sucrose synthase, β-carotene and starch content are negatively correlated. Abstract: In populations depending on sweetpotato for food security, starch is an important source of calories, while β-carotene is an important source of provitamin A. The negative association between the two traits contributes to the low nutritional quality of sweetpotato consumed, especially in sub-Saharan Africa. Using a biparental mapping population of 315 F progeny generated from a cross between an orange-fleshed and a non-orange-fleshed sweetpotato variety, we identified two major quantitative trait loci (QTL) on linkage group (LG) three (LG3) and twelve (LG12) affecting starch, β-carotene, and their correlated traits, dry matter and flesh color. Analysis of parental haplotypes indicated that these two regions acted pleiotropically to reduce starch content and increase β-carotene in genotypes carrying the orange-fleshed parental haplotype at the LG3 locus. Phytoene synthase and sucrose synthase, the rate-limiting and linked genes located within the QTL on LG3 involved in the carotenoid and starch biosynthesis, respectively, were differentially expressed in Beauregard versus Tanzania storage roots. The Orange gene, the molecular switch for chromoplast biogenesis, located within the QTL on LG12 while not differentially expressed was expressed in developing roots of the parental genotypes. We conclude that these two QTL regions act together in a cis and trans manner to inhibit starch biosynthesis in amyloplasts and enhance chromoplast biogenesis, carotenoid biosynthesis, and accumulation in orange-fleshed sweetpotato. Understanding the genetic basis of this negative association between starch and β-carotene will inform future sweetpotato breeding strategies targeting sweetpotato for food and nutritional security

Afri-Can Forum 2

CITATION: Mukudu, H., et al. 2016. Afri-Can Forum 2. BMC Infectious Diseases, 16:315, doi:10.1186/s12879-016-1466-6.The original publication is available at https://bmcinfectdis.biomedcentral.comENGLISH ABSTRACT: We are pleased to present peer reviewed forum proceedings of the 2nd synchronicity forum of GHRI/CHVIfunded Canadian and African HIV prevention and vaccine teams Forum objectives ∙GHRI-funded capacity building and HIV prevention research teams presented highlights of achievements ∙Teams discussed how to jointly build on achievements for sustainability ∙Provided an opportunity for inter-team collaboration, synchronize best approach to capacity building, mentoring of new researchers and building leadership ∙Provided opportunities for informal discussions and networking among the teams. ∙Teams learnt about recent advances in the area of African regulatory and ethics review process ∙The forum proceedings was a special supplement in an openaccess journal was producedhttps://bmcinfectdis.biomedcentral.com/articles/supplements/volume-16-supplement-2Publisher's versio