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Background The 2019 WHO screening and diagnostic algorithm for tuberculosis in people living with HIV (PLHIV) has 2 components: the WHO Xpert MTB/RIF (Xpert) algorithm and WHO Alere Determine TB-LAM (AlereLAM) algorithm. According to the WHO Xpert algorithm, WHO recommends that PLHIV be routinely screened for tuberculosis with the WHO foursymptom screen (W4SS; comprising any one of current cough, fever, night sweats, or weight loss) and, if the screen is positive, receive Xpert or Xpert MTB/RIF Ultra (Xpert Ultra) confirmatory testing. According to the WHO AlereLAM algorithm, WHO also recommends that PLHIV be routinely screened for tuberculosis using screening criteria and, if the screen is positive, receive urine lateral-flow lipoarabinomannan (LF-LAM) confirmatory testing with AlereLAM. We aimed: i. To determine the diagnostic accuracy of the W4SS and alternative screening tools and strategies in ambulatory PLHIV, including key subgroups, and to compare the diagnostic accuracy of the WHO Xpert algorithm with Xpert confirmatory testing for all ambulatory PLHIV ii. To determine the performance of the W4SS and alternative screening tools and strategies in HIV-positive inpatients and to compare the diagnostic accuracy of the WHO Xpert algorithm with Xpert confirmatory testing for all HIV-positive inpatients iii. To determine the performance of WHO screening criteria and alternative screening tools and strategies to guide LF-LAM testing in HIV-positive inpatients and to compare the performance of the WHO AlereLAM algorithm with AlereLAM and Fujifilm SILVAMP TB-LAM (FujiLAM; a novel LF-LAM test) confirmatory testing in all HIV-positive inpatients. iv. To develop and validate novel clinical prediction models (CPMs) for tuberculosis screening in outpatient PLHIV and to determine the clinical utility of these CPMs and WHO-recommended screening tools Methods We conducted a systematic review and individual participant data (IPD) meta-analysis. We updated a search of PubMed (MEDLINE), Embase, Cochrane Library, and conference 2 abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to August 2, 2019 (objectives i and iv) and March 1, 2020 (objectives ii and iii). We also screened reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional studies, observational studies, and randomized trials that enrolled adult and adolescent (age ≥10 years) PLHIV irrespective of symptoms and signs of tuberculosis. We also included studies that enrolled outpatient PLHIV with a positive W4SS (objective iv only). We extracted study-level data using a standardized data extraction form, and we requested IPD from study authors. The reference standards were culture (objectives i, ii, and iv) and culture or Xpert (objective iii). For screening tools and strategies, we also used separate reference standards of Xpert (objective i and ii), AlereLAM (objective iii), and FujiLAM (objective iii). We selected these confirmatory tests as reference standards since these tests are the most likely confirmatory tests used in practice. We obtained pooled proportion estimates with a random-effects model, assessed diagnostic accuracy (i.e., sensitivity and specificity) by fitting random-effects bivariate models, and assessed diagnostic yield (i.e., proportion of total tuberculosis cases with a positive confirmatory test) descriptively. For CPMs, we first used logistic regression, allowing for non-linear relations, to develop an extended CPM (using backwards selection of C-reactive protein [CRP] and other predictors) and a CRP-only CPM (which only included CRP along with spline transformations); we then used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility (i.e., decision curve analysis) of both CPMs and other screening strategies. Decision curve analysis plots net benefit across a range of risk thresholds. This systematic review has been registered with PROSPERO, CRD42020155895. Results i. We obtained data for 22 of 25 studies (n= 15,666 participants; 4,347 on antiretroviral therapy [ART]). W4SS sensitivity was 82% (95% CI 72, 89) and specificity was 42% (29, 57). CRP (≥10 mg/L) had similar sensitivity (77% [61, 88]), but higher specificity (74% [61, 83]; n=3571). Cough (lasting ≥2 weeks), haemoglobin (< 8 g/dL), body mass index (

BACKGROUND: Progress in achieving maternal health goals and the rates of reductions in deaths from individual conditions have varied over time and across countries. Assessing whether research priorities in maternal health align with the main causes of mortality, and those factors responsible for inequitable health outcomes, such as health system performance, may help direct future research. The study thus investigated whether the research done in low- and middle-income countries (LMICs) matched the principal causes of maternal deaths in these settings. METHODS: Systematic mapping was done of maternal health interventional research in LMICs from 2000 to 2012. Articles were included on health systems strengthening, health promotion; and on five tracer conditions (haemorrhage, hypertension, malaria, HIV and other sexually transmitted infections (STIs)). Following review of 35,078 titles and abstracts in duplicate, data were extracted from 2292 full-text publications. RESULTS: Over time, the number of publications rose several-fold, especially in 2004-2007, and the range of methods used broadened considerably. More than half the studies were done in sub-Saharan Africa (55.4 %), mostly addressing HIV and malaria. This region had low numbers of publications per hypertension and haemorrhage deaths, though South Asia had even fewer. The proportion of studies set in East Asia Pacific dropped steadily over the period, and in Latin America from 2008 to 2012. By 2008-2012, 39.1 % of articles included health systems components and 30.2 % health promotion. Only 5.4 % of studies assessed maternal STI interventions, diminishing with time. More than a third of haemorrhage research included health systems or health promotion components, double that of HIV research. CONCLUSION: Several mismatches were noted between research publications, and the burden and causes of maternal deaths. This is especially true for South Asia; haemorrhage and hypertension in sub-Saharan Africa; and for STIs worldwide. The large rise in research outputs and range of methods employed indicates a major expansion in the number of researchers and their skills. This bodes well for maternal health if variations in research priorities across settings and topics are corrected.

Despite access to antiretroviral therapy, mortality from cryptococcal meningitis (CM) is high among persons with advanced HIV infection in sub-Saharan Africa. Cryptococcal antigen (CrAg) is present several weeks to months before the onset of symptoms of meningitis and can be screened to prevent life threatening meningitis. Recently, the World Health Organisation recommended that a new rapid CrAg lateral flow ‘‘dipstick’’ assay (LFA) is to be used to screen HIV-infected persons with CD4 counts of less than 100 cells/µL. In this paper, we describe two cases of cryptococcosis with differing outcomes. In the first case, the new CrAg LFA was used as part of a screen and preemptive treatment strategy to prevent CM. In the second case, our patient had no access to the CrAg LFA and subsequently developed life threatening meningitis. To the best of our knowledge, this is the first case report of cryptococcosis diagnosed using this novel assay.