Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L-1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). METHODS: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal-external cross-validation to evaluate performance. RESULTS: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L-1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L-1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively. CONCLUSIONS: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L-1 cut-off or in a CPM depends on available resources.

Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis.

BACKGROUND: WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria followed by AlereLAM if screen positive) with AlereLAM and FujiLAM (a novel LF-LAM test) testing in all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were (1) AlereLAM or FujiLAM for screening tests/strategies and (2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM testing in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively. FINDINGS: We obtained data from all 5 identified studies (n = 3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/µL) had high sensitivities but low specificities; cough (≥2 weeks), hemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 88% and 96%, respectively. In 2 studies that collected sputum and non-sputum samples for Xpert and/or culture, diagnostic yield of sputum Xpert was 40-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 61%, 81%, and 92% of all cases, respectively. INTERPRETATION: WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis. FUNDING: None.

Tuberculosis screening among HIV-positive inpatients: a systematic review and individual participant data meta-analysis.

BACKGROUND: Since 2011, WHO has recommended that HIV-positive inpatients be routinely screened for tuberculosis with the WHO four-symptom screen (W4SS) and, if screened positive, receive a molecular WHO-recommended rapid diagnostic test (eg, Xpert MTB/RIF [Xpert] assay). To inform updated WHO tuberculosis screening guidelines, we conducted a systematic review and individual participant data meta-analysis to assess the performance of W4SS and alternative screening tests to guide Xpert testing and compare the diagnostic accuracy of the WHO Xpert algorithm (ie, W4SS followed by Xpert) with Xpert for all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011, to March 1, 2020, for studies of adult and adolescent HIV-positive inpatients enrolled regardless of tuberculosis signs and symptoms. The separate reference standards were culture and Xpert. Xpert was selected since it is most likely to be the confirmatory test used in practice. We assessed the proportion of inpatients eligible for Xpert testing using the WHO algorithm; assessed the accuracy of W4SS and alternative screening tests or strategies to guide diagnostic testing; and compared the accuracy of the WHO Xpert algorithm (W4SS followed by Xpert) with Xpert for all. We obtained pooled proportion estimates with a random-effects model, assessed diagnostic accuracy by fitting random-effects bivariate models, and assessed diagnostic yield descriptively. This systematic review has been registered on PROSPERO (CRD42020155895). FINDINGS: Of 6162 potentially eligible publications, six were eligible and we obtained data for all of the six publications (n=3660 participants). The pooled proportion of inpatients eligible for an Xpert was 90% (95% CI 89-91; n=3658). Among screening tests to guide diagnostic testing, W4SS and C-reactive protein (≥5 mg/L) had highest sensitivities (≥96%) but low specificities (≤12%); cough (≥2 weeks), haemoglobin concentration (<8 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had higher specificities (61-90%) but suboptimal sensitivities (12-57%). The WHO Xpert algorithm (W4SS followed by Xpert) had a sensitivity of 76% (95% CI 67-84) and specificity of 93% (88-96; n=637). Xpert for all had similar accuracy to the WHO Xpert algorithm: sensitivity was 78% (95% CI 69-85) and specificity was 93% (87-96; n=639). In two cohorts that had sputum and non-sputum samples collected for culture or Xpert, diagnostic yield of sputum Xpert was 41-70% and 61-64% for urine Xpert. INTERPRETATION: The W4SS and other potential screening tests to guide Xpert testing have suboptimal accuracy in HIV-positive inpatients. On the basis of these findings, WHO now strongly recommends molecular rapid diagnostic testing in all medical HIV-positive inpatients in settings where tuberculosis prevalence is higher than 10%. FUNDING: World Health Organization.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

All-cause and cause-specific mortality in psoriasis: A systematic review and meta-analysis.

BACKGROUND: An overview of mortality risk associated with psoriasis is lacking. OBJECTIVE: To perform a systematic review and meta-analysis of mortality risk in psoriasis. METHODS: We included studies reporting all-cause or cause-specific mortality risk estimates in psoriasis patients compared with general population or subjects free of psoriasis. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: We included 12 studies. The pooled RRs for all-cause mortality were 1.21 (95% CI 1.14-1.28) in psoriasis, 1.13 (95% CI 1.09-1.16) in mild psoriasis, and 1.52 (95% CI 1.35-1.71) in severe psoriasis. The pooled RRs for cardiovascular mortality were 1.15 (95% CI 1.09-1.21) in psoriasis, 1.05 (95% CI 0.92-1.20) in mild psoriasis, and 1.38 (95% CI 1.09-1.74) in severe psoriasis. For noncardiovascular causes, mortality risk from liver disease, kidney disease, and infection was significantly increased in psoriasis, regardless of disease severity. The mortality risk in liver and kidney disease was the highest. There was also a significantly increased mortality risk associated with neoplasms in severe psoriasis patients and chronic lower respiratory disease in all and mild psoriasis patients. LIMITATIONS: Although associations were consistent, their magnitude was heterogenous. CONCLUSION: Psoriasis is associated with an increased risk for mortality from all causes (in a dose-response manner with disease severity) and from several specific causes.

Intake of folate and other nutrients related to one-carbon metabolism and risk of cutaneous melanoma among US women and men.

BACKGROUND: Nutrients involved in one-carbon metabolism - folate, vitamins B6 and B12, methionine, choline, and betaine - have been inversely associated with multiple cancer sites and may be related to skin cancer. However, there is a lack of research on the association between intake of these nutrients and cutaneous melanoma risk. The aim of this study was to examine the associations between intake of one-carbon metabolism nutrients and cutaneous melanoma risk in two large prospective cohorts. METHODS: The cohorts included 75,311 white women and 48,523 white men. Nutrient intake was assessed repeatedly by food frequency questionnaires and self-reported supplement use. We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and then pooled HRs using a random-effects model. RESULTS: Over 24-26 years of follow-up, we documented 1328 melanoma cases (648 men and 680 women). Higher intake of folate from food only, but not total folate, was associated with increased melanoma risk (pooled HR for top versus bottom quintile: 1.36; 95% CI: 1.13-1.64; P for trend = 0.001). The association was significant in men, but attenuated in women. Higher intake of vitamins B6 and B12, choline, betaine, and methionine were not associated with melanoma risk, although there was modest increasing trend of risk for vitamin B6 from food only (pooled HR for top versus bottom quintile: 1.18; 95% CI: 0.99-1.41; P for trend = 0.03). CONCLUSIONS: We found some evidence that higher intake of folate from food only was associated with a modest increased risk of cutaneous melanoma. However, since other factors related to dietary folate intake may account for the observed association, our findings warrant further investigation.

Red meat and processed meat intake and risk for cutaneous melanoma in white women and men: Two prospective cohort studies.

BACKGROUND: Red and processed meat consumption has been associated with increased risk for several cancers, but the association with cutaneous melanoma risk has been inconclusive. OBJECTIVE: To investigate the association between red and processed meat intake and melanoma risk. METHODS: Dietary information was assessed by using food frequency questionnaires in 2 prospective cohorts: 75,263 women from the Nurses' Health Study (1984-2010) and 48,523 men from the Health Professionals Follow-up Study (1986-2010). Melanoma cases were confirmed by reviewing pathology records. Pooled multivariable hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS: A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P = .002 for trend); the pooled hazard ratios (95% confidence intervals) of the 2 cohorts were 1.00 (reference), 1.00 (0.87-1.14), 0.98 (0.86-1.13), 0.89 (0.77-1.02), and 0.81 (0.70-0.95) for increasing quintiles of intake. LIMITATIONS: Findings might have limited generalizability, considering that the cohorts were limited to white health professionals. CONCLUSION: Red and processed meat intake was inversely associated with melanoma risk in these 2 cohorts.

Mapping of research on maternal health interventions in low- and middle-income countries: a review of 2292 publications between 2000 and 2012.

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.

Perspectives on the methods of a large systematic mapping of maternal health interventions.

BACKGROUND: Mapping studies describe a broad body of literature, and differ from classical systematic reviews, which assess more narrowly-defined questions and evaluate the quality of the studies included in the review. While the steps involved in mapping studies have been described previously, a detailed qualitative account of the methodology could inform the design of future mapping studies. OBJECTIVES: Describe the perspectives of a large research team on the methods used and collaborative experiences in a study that mapped the literature published on maternal health interventions in low- and middle-income countries (2292 full text articles included, after screening 35,048 titles and abstracts in duplicate). METHODS: Fifteen members of the mapping team, drawn from eight countries, provided their experiences and perspectives of the study in response to a list of questions and probes. The responses were collated and analysed thematically following a grounded theory approach. RESULTS: The objectives of the mapping evolved over time, posing difficulties in ensuring a uniform understanding of the purpose of the mapping among the team members. Ambiguity of some study variables and modifications in data extraction codes were the main threats to the quality of data extraction. The desire for obtaining detailed information on a few topics needed to be weighed against the benefits of collecting more superficial data on a wider range of topics. Team members acquired skills in systematic review methodology and software, and a broad knowledge of maternal health literature. Participation in analysis and dissemination was lower than during the screening of articles for eligibility and data coding. Though all respondents believed the workload involved was high, study outputs were viewed as novel and important contributions to evidence. Overall, most believed there was a favourable balance between the amount of work done and the project's outputs. CONCLUSIONS: A large mapping of literature is feasible with a committed team aiming to build their research capacity, and with a limited, simplified set of data extraction codes. In the team's view, the balance between the time spent on the review, and the outputs and skills acquired was favourable. Assessments of the value of a mapping need, however, to take into account the limitations inherent in such exercises, especially the exclusion of grey literature and of assessments of the quality of the studies identified.

Local and foreign authorship of maternal health interventional research in low- and middle-income countries: systematic mapping of publications 2000-2012.

BACKGROUND: Researchers in low- and middle-income countries (LMICs) are under-represented in scientific literature. Mapping of authorship of articles can provide an assessment of data ownership and research capacity in LMICs over time and identify variations between different settings. METHODS: Systematic mapping of maternal health interventional research in LMICs from 2000 to 2012, comparing country of study and of affiliation of first authors. Studies on health systems or promotion; community-based activities; and haemorrhage, hypertension, HIV/STIs and malaria were included. Following review of 35,078 titles and abstracts, 2292 full-text publications were included. Data ownership was measured by the proportion of articles with an LMIC lead author (author affiliated with an LMIC institution). RESULTS: The total number of papers led by an LMIC author rose from 45.0/year in 2000-2003 to 98.0/year in 2004-2007, but increased only slightly thereafter to 113.1/year in 2008-2012. In the same periods, the proportion of papers led by a local author was 58.4 %, 60.8 % and 60.1 %, respectively. Data ownership varies markedly between countries. A quarter of countries led more than 75 % of their research; while in 10 countries, under 25 % of publications had a local first author. Researchers at LMIC institutions led 56.6 % (1297) of all papers, but only 26.8 % of systematic reviews (65/243), 29.9 % of modelling studies (44/147), and 33.2 % of articles in journals with an Impact Factor ≥5 (61/184). Sub-Saharan Africa authors led 54.2 % (538/993) of studies in the region, while 73.4 % did in Latin America and the Caribbean (223/304). Authors affiliated with United States (561) and United Kingdom (207) institutions together account for a third of publications. Around two thirds of USAID and European Union funded studies had high-income country leads, twice as many as that of Wellcome Trust and Rockefeller Foundation. CONCLUSIONS: There are marked gaps in data ownership and these have not diminished over time. Increased locally-led publications, however, does suggest a growing capacity in LMIC institutions to analyse and articulate research findings. Differences in author attribution between funders might signal important variations in funders' expectations of authorship and discrepancies in how funders understand collaboration. More stringent authorship oversight and reconsideration of authorship guidelines could facilitate growth in LMIC leadership. Left unaddressed, deficiencies in research ownership will continue to hinder alignment between the research undertaken and knowledge needs of LMICs.

A systematic mapping of funders of maternal health intervention research 2000-2012.

BACKGROUND: The priorities of research funding bodies govern the research agenda, which has important implications for the provision of evidence to inform policy. This study examines the research funding landscape for maternal health interventions in low- and middle-income countries (LMICs). METHODS: This review draws on a database of 2340 academic papers collected through a large-scale systematic mapping of research on maternal health interventions in LMICs published from 2000-2012. The names of funders acknowledged on each paper were extracted and categorised into groups. It was noted whether support took a specific form, such as staff fellowships or drugs. Variations between funder types across regions and topics of research were assessed. RESULTS: Funding sources were only reported in 1572 (67%) of articles reviewed. A high number of different funders (685) were acknowledged, but only a few dominated funding of published research. Bilateral funders, national research agencies and private foundations were most prominent, while private companies were most commonly acknowledged for support 'in kind'. The intervention topics and geographic regions of research funded by the various funder types had much in common, with HIV being the most common topic and sub-Saharan Africa being the most common region for all types of funder. Publication outputs rose substantially for several funder types over the period, with the largest increase among bilateral funders. CONCLUSIONS: A considerable number of organisations provide funding for maternal health research, but a handful account for most funding acknowledgements. Broadly speaking, these organisations address similar topics and regions. This suggests little coordination between funding agencies, risking duplication and neglect of some areas of maternal health research, and limiting the ability of organisations to develop the specialised skills required for systematically addressing a research topic. Greater transparency in reporting of funding is required, as the role of funders in the research process is often unclear.

Systematic review of facility-based sexual and reproductive health services for female sex workers in Africa.

BACKGROUND: Several biological, behavioural, and structural risk factors place female sex workers (FSWs) at heightened risk of HIV, sexually transmitted infections (STIs), and other adverse sexual and reproductive health (SRH) outcomes. FSW projects in many settings have demonstrated effective ways of altering this risk, improving the health and wellbeing of these women. Yet the optimum delivery model of FSW projects in Africa is unclear. This systematic review describes intervention packages, service-delivery models, and extent of government involvement in these services in Africa. METHODS: On 22 November 2012, we searched Web of Science and MEDLINE, without date restrictions, for studies describing clinical and non-clinical facility-based SRH prevention and care services for FSWs in low- and middle-income countries in Africa. We also identified articles in key non-indexed journals and on websites of international organizations. A single reviewer screened titles and abstracts, and extracted data from articles using standardised tools. RESULTS: We located 149 articles, which described 54 projects. Most were localised and small-scale; focused on research activities (rather than on large-scale service delivery); operated with little coordination, either nationally or regionally; and had scanty government support (instead a range of international donors generally funded services). Almost all sites only addressed HIV prevention and STIs. Most services distributed male condoms, but only 10% provided female condoms. HIV services mainly encompassed HIV counselling and testing; few offered HIV care and treatment such as CD4 testing or antiretroviral therapy (ART). While STI services were more comprehensive, periodic presumptive treatment was only provided in 11 instances. Services often ignored broader SRH needs such as family planning, cervical cancer screening, and gender-based violence services. CONCLUSIONS: Sex work programmes in Africa have limited coverage and a narrow scope of services and are poorly coordinated with broader HIV and SRH services. To improve FSWs' health and reduce onward HIV transmission, access to ART needs to be addressed urgently. Nevertheless, HIV prevention should remain the mainstay of services. Service delivery models that integrate broader SRH services and address structural risk factors are much needed. Government-led FSW services of high quality and scale would markedly reduce SRH vulnerabilities of FSWs in Africa.

Community empowerment and involvement of female sex workers in targeted sexual and reproductive health interventions in Africa: a systematic review.

BACKGROUND: Female sex workers (FSWs) experience high levels of sexual and reproductive health (SRH) morbidity, violence and discrimination. Successful SRH interventions for FSWs in India and elsewhere have long prioritised community mobilisation and structural interventions, yet little is known about similar approaches in African settings. We systematically reviewed community empowerment processes within FSW SRH projects in Africa, and assessed them using a framework developed by Ashodaya, an Indian sex worker organisation. METHODS: In November 2012 we searched Medline and Web of Science for studies of FSW health services in Africa, and consulted experts and websites of international organisations. Titles and abstracts were screened to identify studies describing relevant services, using a broad definition of empowerment. Data were extracted on service-delivery models and degree of FSW involvement, and analysed with reference to a four-stage framework developed by Ashodaya. This conceptualises community empowerment as progressing from (1) initial engagement with the sex worker community, to (2) community involvement in targeted activities, to (3) ownership, and finally, (4) sustainability of action beyond the community. RESULTS: Of 5413 articles screened, 129 were included, describing 42 projects. Targeted services in FSW 'hotspots' were generally isolated and limited in coverage and scope, mostly offering only free condoms and STI treatment. Many services were provided as part of research activities and offered via a clinic with associated community outreach. Empowerment processes were usually limited to peer-education (stage 2 of framework). Community mobilisation as an activity in its own right was rarely documented and while most projects successfully engaged communities, few progressed to involvement, community ownership or sustainability. Only a few interventions had evolved to facilitate collective action through formal democratic structures (stage 3). These reported improved sexual negotiating power and community solidarity, and positive behavioural and clinical outcomes. Sustainability of many projects was weakened by disunity within transient communities, variable commitment of programmers, low human resource capacity and general resource limitations. CONCLUSIONS: Most FSW SRH projects in Africa implemented participatory processes consistent with only the earliest stages of community empowerment, although isolated projects demonstrate proof of concept for successful empowerment interventions in African settings.

When smear and molecular diagnostics fail: identification of tuberculosis in advanced HIV infection using the newly developed urine lipoarabinomannan lateral-flow assay.

In HIV infection, progression of immunodeficiency is associated with increased risk of paucibacillary and disseminated forms of tuberculosis (TB). As a result, the clinical presentation may be atypical and the conventional diagnostic assays often unreliable, resulting in significant treatment delays. Here, we report a case of HIV-associated immune reconstitution inflammatory syndrome and TB meningitis. Although the smear and molecular assays were negative, Mycobacterium tuberculosis was identified in our patient using the new Determine-lipoarabinomannan (LAM) lateral-flow urine 'dip-stick' assay. This case report illustrates the clinical value of this assay for the diagnosis of TB in a subgroup of HIV-infected patients with advanced immunodeficiency. Also, although two recent studies have evaluated the use of the Determine TB-LAM assay in clinical settings, to the best of our knowledge, this is the first case report of TB diagnosed using this novel assay.

Diagnosis of Cryptococcosis and Prevention of Cryptococcal Meningitis Using a Novel Point-of-Care Lateral Flow Assay.

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.