Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa

Multihost multiparasite systems are evolutionarily and ecologically dynamic, which presents substantial trans‐disciplinary challenges for elucidating their epidemiology and designing appropriate control. Evidence for hybridizations and introgressions between parasite species is gathering, in part in line with improvements in molecular diagnostics and genome sequencing. One major system where this is becoming apparent is within the Genus Schistosoma, where schistosomiasis represents a disease of considerable medical and veterinary importance, the greatest burden of which occurs in sub‐Saharan Africa. Interspecific hybridizations and introgressions bring an increased level of complexity over and above that already inherent within multihost, multiparasite systems, also representing an additional source of genetic variation that can drive evolution. This has the potential for profound implications for the control of parasitic diseases, including, but not exclusive to, widening host range, increased transmission potential and altered responses to drug therapy. Here, we present the challenging case example of haematobium group Schistosoma spp. hybrids in West Africa, a system involving multiple interacting parasites and multiple definitive hosts, in a region where zoonotic reservoirs of schistosomiasis were not previously considered to be of importance. We consider how existing mathematical model frameworks for schistosome transmission could be expanded and adapted to zoonotic hybrid systems, exploring how such model frameworks can utilize molecular and epidemiological data, as well as the complexities and challenges this presents. We also highlight the opportunities and value such mathematical models could bring to this and a range of similar multihost, multi and cross‐hybridizing parasites systems in our changing world

Pre-treatment loss to follow-up in adults with pulmonary TB in Kenya

County referral hospital in western Kenya. To ascertain the proportion of pre-treatment loss to follow-up (PTLFU) and associated patient factors in adults with pulmonary TB (PTB) in western Kenya. A retrospective data review of laboratory and treatment registers for adults with bacteriologically confirmed PTB between January 2018 to December 2021. We defined PTLFU as failure to initiate treatment within 14 days of diagnosis. We used multivariable logistic regression modelling to identify patient factors associated with PTLFU. Of 476 patients with PTB, 67.2% were male; the mean age was 36.1 years; 37.0% were HIV-positive; 5.7% had a history of anti-TB treatment; 40.6% were not traceable in the treatment register; 202 (42.4%, 95% CI 38.1–46.9) experienced PTLFU. Age ≥55 years (aOR 2.6, 95% CI 1.0–6.7) and providing only an address (aOR 34.2, 95% CI 18.7–62.5) or only a telephone contact number (aOR 22.3, 95% CI 3.5–141.1) were associated with PTLFU. Sex, HIV status, history of anti-TB treatment and place of residence were not associated with PTLFU. PTLFU contributes markedly to TB patient losses in western Kenya. Strengthening systems for documenting patient information and actively monitoring PTLFU are crucial for attrition reduction

Health worker views on pre-treatment loss to follow-up in adults with pulmonary TB in Western Kenya

SETTING: County referral hospital in Western Kenya. OBJECTIVES: To explore factors contributing to pre-treatment loss to follow-up (PTLFU) in adults with pulmonary TB and propose solutions to address PTLFU from healthcare worker (HCW) perspectives. DESIGN: This was an exploratory qualitative study using thematic analysis. RESULTS: We conducted 19 key informant interviews with HCWs representing laboratory, clinical care, management and the community. Participant age ranged from 26 to 62 years; 14 (74%) were females; and most (74%) had worked in TB care for 5 years. They reported that patients experienced stigma and had misconceptions about TB that contributed to PTLFU. HCWs were hesitant to work in the TB clinic, which contributed to suboptimal patient care, leading to PTLFU. Unclear linkage between laboratory and clinician, and limited financial resources to track patients were among the healthcare system factors that led to PTLFU. HCWs suggested having proper patient preparation, assigning resources to track patients and holding regular interdisciplinary meetings as practical solutions to address PTLFU. CONCLUSION: HCWs reported multiple factors that may influence PTLFU and recommended various solutions to address these. Knowledge of TB management, patient preparation, resources to track patients and multidisciplinary meetings will be central to addressing PTLFU

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

Use of malaria rapid diagnostic tests by community health workers in Afghanistan: cluster randomised trial

Background: The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria accurately, improving treatment of febrile illness. Methods: A cluster randomised trial in community health services was undertaken in Afghanistan. The primary outcome was the proportion of suspected malaria cases correctly treated for polymerase chain reaction (PCR)-confirmed malaria and PCR negative cases receiving no antimalarial drugs measured at the level of the patient. CHWs from 22 clusters (clinics) received standard training on clinical diagnosis and treatment of malaria; 11 clusters randomised to the intervention arm received additional training and were provided with mRDTs. CHWs enrolled cases of suspected malaria, and the mRDT results and treatments were compared to blind-read PCR diagnosis. Results: In total, 256 CHWs enrolled 2400 patients with 2154 (89.8%) evaluated. In the intervention arm, 75.3% (828/1099) were treated appropriately vs. 17.5% (185/1055) in the control arm (cluster adjusted risk ratio: 3.72, 95% confidence interval 2.40–5.77; p < 0.001). In the control arm, 85.9% (164/191) with confirmed Plasmodium vivax received chloroquine compared to 45.1% (70/155) in the intervention arm (p < 0.001). Overuse of chloroquine in the control arm resulted in 87.6% (813/928) of those with no malaria (PCR negative) being treated vs. 10.0% (95/947) in the intervention arm, p < 0.001. In the intervention arm, 71.4% (30/42) of patients with P. falciparum did not receive artemisinin-based combination therapy, partly because operational sensitivity of the RDTs was low (53.2%, 38.1–67.9). There was high concordance between recorded RDT result and CHW prescription decisions: 826/950 (87.0%) with a negative test were not prescribed an antimalarial. Co-trimoxazole was prescribed to 62.7% of malaria negative patients in the intervention arm and 15.0% in the control arm. Conclusions: While introducing mRDT reduced overuse of antimalarials, this action came with risks that need to be considered before use at scale: an appreciable proportion of malaria cases will be missed by those using current mRDTs. Higher sensitivity tests could be used to detect all cases. Overtreatment with antimalarial drugs in the control arm was replaced with increased antibiotic prescription in the intervention arm, resulting in a probable overuse of antibiotics. Trial registration: ClinicalTrials.gov, NCT01403350. Prospectively registered

Research on Implementation of Interventions in Tuberculosis Control in Low- and Middle-Income Countries: A Systematic Review

Prevention, Population and Disease management (PrePoD)Public Health and primary car

Publication and Reporting of Test Accuracy Studies Registered in ClinicalTrials.gov

Failure to publish and selective reporting are recognized problems in the biomedical literature, but their extent in the field of diagnostic testing is unknown. We aimed to identify nonpublication and discrepancies between registered records and publications among registered test accuracy studies. We identified studies evaluating a test's accuracy against a reference standard that were registered in ClinicalTrials.gov between January 2006 and December 2010. We included studies if their completion date was set before October 2011, allowing at least 18 months until publication. We searched PubMed, EMBASE, and Web of Science and contacted investigators for publications. We included 418 studies, of which 224 (54%) had been published by mid-2013. Among studies that had been completed at least 30 months before our analyses, 45% were published within 30 months after their completion. Publication rates were high in studies registered after study completion (76%) and low for studies with an unknown (rather than completed) study status (36%). After we excluded these 2 categories, study duration was the only characteristic significantly associated with publication, with lower rates in studies lasting up to 1 year (39%) compared to studies of 13-24 months (62%) or longer (67%) (P = 0.01). In the 153 published studies that had been registered before completion, 49 (32%) showed discrepancies between the registry and publication regarding inclusion criteria (n = 19), test/threshold (n = 9), and outcomes (n = 32). Failure to publish and selective reporting are prevalent in test accuracy studies. Their registration should be further promoted among researchers and journal editor