Effectiveness of spatially targeted interventions for control of HIV, tuberculosis, leprosy and malaria: a systematic review.

BACKGROUND: As infectious diseases approach global elimination targets, spatial targeting is increasingly important to identify community hotspots of transmission and effectively target interventions. We aimed to synthesise relevant evidence to define best practice approaches and identify policy and research gaps. OBJECTIVE: To systematically appraise evidence for the effectiveness of spatially targeted community public health interventions for HIV, tuberculosis (TB), leprosy and malaria. DESIGN: Systematic review. DATA SOURCES: We searched Medline, Embase, Global Health, Web of Science and Cochrane Database of Systematic Reviews between 1 January 1993 and 22 March 2021. STUDY SELECTION: The studies had to include HIV or TB or leprosy or malaria and spatial hotspot definition, and community interventions. DATA EXTRACTION AND SYNTHESIS: A data extraction tool was used. For each study, we summarised approaches to identifying hotpots, intervention design and effectiveness of the intervention. RESULTS: Ten studies, including one cluster randomised trial and nine with alternative designs (before-after, comparator area), satisfied our inclusion criteria. Spatially targeted interventions for HIV (one USA study), TB (three USA) and leprosy (two Brazil, one Federated States of Micronesia) each used household location and disease density to define hotspots followed by community-based screening. Malaria studies (one each from India, Indonesia and Kenya) used household location and disease density for hotspot identification followed by complex interventions typically combining community screening, larviciding of stagnant water bodies, indoor residual spraying and mass drug administration. Evidence of effect was mixed. CONCLUSIONS: Studies investigating spatially targeted interventions were few in number, and mostly underpowered or otherwise limited methodologically, affecting interpretation of intervention impact. Applying advanced epidemiological methodologies supporting more robust hotspot identification and larger or more intensive interventions would strengthen the evidence-base for this increasingly important approach. PROSPERO REGISTRATION NUMBER: CRD42019130133.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS:We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38­52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63­87), increasing to 89% (80­94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05­3·08) but not after 30 days (1·25, 0·84­2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16­8·84). INTERPRETATION:In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients