Receipt of antimalarials among children aged 6-59 months in Nigeria from 2010 to 2021.

BACKGROUND: Nigeria has the highest malaria burden globally, and anti-malarials have been commonly used to treat malaria without parasitological confirmation. In 2012, Nigeria implemented rapid diagnostic tests (RDTs) to reduce the use of anti-malarials for those without malaria and to increase the use of artemisinin-based combination therapy (ACT) for malaria treatment. This study examined changes in anti-malarial receipt among children aged 6-59 months during a 12-year period of increasing RDT availability. METHODS: A cross-sectional analysis was conducted using the Nigeria Malaria Indicator Survey (NMIS) data from 2010 (before RDT implementation in 2012), 2015, and 2021. The analysis assessed trends in prevalence of malaria by survey RDT result, and fever and anti-malarial/ACT receipt in the 2 weeks prior to the survey. A multivariable logistic regression was used to account for the complex survey design and to examine factors associated with anti-malarial receipt, stratified by survey RDT result, a proxy for recent/current malaria infection. RESULTS: In a nationally-representative, weighted sample of 22,802 children aged 6-59 months, fever prevalence remained stable over time, while confirmed malaria prevalence decreased from 51.2% in 2010 to 44.3% in 2015 and 38.5% in 2021 (trend test p < 0.0001). Anti-malarial use among these children decreased from 19% in 2010 to 10% in 2021 (trend test p < 0.0001), accompanied by an increase in ACT use (2% in 2010 to 8% in 2021; trend test p < 0.0001). Overall, among children who had experienced fever, 30.6% of survey RDT-positive and 36.1% of survey RDT-negative children had received anti-malarials. The proportion of anti-malarials obtained from the private sector increased from 61.8% in 2010 to 80.1% in 2021 for RDT-positive children; most of the anti-malarials received in 2021 were artemisinin-based combinations. Factors associated with anti-malarial receipt for both RDT-positive and RDT-negative children included geographic region, greater household wealth, higher maternal education, and older children. CONCLUSION: From 2010 to 2021 in Nigeria, both malaria prevalence and anti-malarial treatments among children aged 6-59 months decreased, as RDT availability increased. Among children who had fever in the prior 2 weeks, anti-malarial receipt was similar between children with either positive or negative survey RDT results, indicative of persistent challenges in reducing inappropriate anti-malarials uptake.

Visualizing and diagnosing spillover within randomized concurrent controlled trials through the application of diagnostic test assessment methods.

BACKGROUND: Spillover of effect, whether positive or negative, from intervention to control group patients invalidates the Stable Unit Treatment Variable Assumption (SUTVA). SUTVA is critical to valid causal inference from randomized concurrent controlled trials (RCCT). Spillover of infection prevention is an important population level effect mediating herd immunity. This herd effect, being additional to any individual level effect, is subsumed within the overall effect size (ES) estimate derived by contrast-based techniques from RCCT's. This herd effect would manifest only as increased dispersion among the control group infection incidence rates above background. METHODS AND RESULTS: The objective here is to explore aspects of spillover and how this might be visualized and diagnosed. I use, for illustration, data from 190 RCCT's abstracted in 13 Cochrane reviews of various antimicrobial versus non-antimicrobial based interventions to prevent pneumonia in ICU patients. Spillover has long been postulated in this context. Arm-based techniques enable three approaches to identify increased dispersion, not available from contrast-based techniques, which enable the diagnosis of spillover within antimicrobial versus non-antimicrobial based infection prevention RCCT's. These three approaches are benchmarking the pneumonia incidence rates versus a clinically relevant range, comparing the dispersion in pneumonia incidence among the control versus the intervention groups and thirdly, visualizing the incidence dispersion within summary receiver operator characteristic (SROC) plots. By these criteria there is harmful spillover effects to concurrent control group patients. CONCLUSIONS: Arm-based versus contrast-based techniques lead to contrary inferences from the aggregated RCCT's of antimicrobial based interventions despite similar summary ES estimates. Moreover, the inferred relationship between underlying control group risk and ES is 'flipped'.

A Real-Time Dashboard Approach to Decision Support: An Exercise in Co-Design.

Laboratory tests play an integral role in the delivery of quality health care. However, evidence indicates variations in diagnostic testing, which can lead to patient safety risks. Electronic decision support systems are often identified as key to reducing diagnostic error. However, such tools are often introduced into a clinical setting with little understanding of clinician workflow and how tools are likely to impact this. This study reports a qualitative co-design methodology and results from the first phase in the design and development of an analytics-driven, dashboard approach to supporting clinician test ordering in the Emergency Department.

Evaluating the gap in rapid diagnostic testing: insights from subnational Kenyan routine health data.

BACKGROUND: Understanding diagnostic capacities is essential to addressing healthcare provision and inequity, particularly in low-income and middle-income countries. This study used routine data to assess trends in rapid diagnostic test (RDT) reporting, supplies and unmet needs across national and 47 subnational (county) levels in Kenya. METHODS: We extracted facility-level RDT data for 19 tests (2018-2020) from the Kenya District Health Information System, linked to 13 373 geocoded facilities. Data quality was assessed for reporting completeness (ratio of reports received against those expected), reporting patterns and outliers. Supply assessment covered 12 RDTs reported by at least 50% of the reporting facilities (n=5251), with missing values imputed considering reporting trends. Supply was computed by aggregating the number of tests reported per facility. Due to data limitations, demand was indirectly estimated using healthcare-seeking rates (HIV, malaria) and using population data for venereal disease research laboratory test (VDRL), with unmet need computed as the difference between supply and demand. RESULTS: Reporting completeness was under 40% across all counties, with RDT-specific reporting ranging from 9.6% to 89.6%. Malaria RDTs showed the highest annual test volumes (6.3-8.0 million) while rheumatoid factor was the lowest (0.5-0.7 million). Demand for RDTs varied from 2.5 to 11.5 million tests, with unmet needs between 1.2 and 3.5 million. Notably, malaria testing and unmet needs were highest in Turkana County, as well as the western and coastal regions. HIV testing was concentrated in the western and central regions, with decreasing unmet needs from 2018 to 2020. VDRL testing showed high volumes and unmet needs in Nairobi and select counties, with minimal yearly variation. CONCLUSION: RDTs are crucial in enhancing diagnostic accessibility, yet their utilisation varies significantly by region. These findings underscore the need for targeted interventions to close testing gaps and improve data reporting completeness. Addressing these disparities is vital for equitably enhancing diagnostic services nationwide.

Diagnostic Performances of an in-House Immunochromatography Test Based on the Monoclonal Antibody 18B7 to Glucuronoxylomannan for Clinical Suspected Cryptococcosis: a Large-Scale Prototype Evaluation in Northern Thailand.

OBJECTIVE: Cryptococcosis predominantly presents as a meningoencephalitis in Thailand. Early and expeditious diagnosis is essential for reducing both mortality and morbidity associated with cryptococcal meningitis. We aim to define and establish the diagnostic performances between the benchmark commercially available diagnostic kit (CrAg® LFA) and the large-scale prototype of an inexpensive in-house immunochromatographic test (ICT) based on monoclonal antibody (MAb) 18B7. METHODS: We have developed the large-scale prototype for the rapid detection of cryptococcal polysaccharide antigens by utilizing a single antibody sandwich ICT format employing MAb 18B7, which is highly specific to Cryptococcus neoformans glucuronoxylomannan (GXM) antigens. An in-house MAb18B7 ICT was manufactured in accordance with industry standards under the control of the International Organization for Standardization (ISO) 13485. RESULTS: The diagnostic sensitivity, specificity, and accuracy for the in-house MAb 18B7 ICT were 99.10%, 97.61%, and 97.83%, respectively. The agreement kappa (κ) coefficient was 0.968 based on the retrospective evaluation of 580 specimens from patients living in northern Thailand with clinically suspected cryptococcosis. CONCLUSION: The data suggest that this in-house MAb 18B7 ICT will be highly beneficial for addressing the issue of cryptococcal infection in Thailand. Moreover, it is anticipated that this inexpensive ICT can play a pivotal role in various global strategies aimed at eradicating cryptococcal meningitis among individuals living with HIV by 2030.

The use of rapid diagnostic tests for chronic Chagas disease: An expert meeting report.

Chagas disease, caused by Trypanosoma cruzi, affects millions of people globally and is associated with significant underdiagnosis and undertreatment. Current diagnostic algorithms face challenges in remote regions. We aimed to review the potential of rapid diagnostic tests (RDTs) for screening or diagnosing chronic Chagas disease in endemic areas. An expert panel representing scientific and academic institutions from the Americas convened with the aim of discussing the use of RDTs. The study employed the nominal group technique, gathering insights from diverse experts during a 3-day meeting. Panel discussions covered RDT application, research protocols, and regulatory mechanisms. The results indicate that RDTs play a crucial role in surveillance and screening, although limitations in sensitivity and specificity exist. The expert group recommends standardized protocols, emphasizes the importance of cost-effectiveness assessments, and highlights the need to consider geographic validation. Despite these challenges, RDTs present a promising avenue for improving Chagas disease diagnosis in resource-limited settings. Future research and a collaborative approach are deemed essential for effective implementation.

Race and Ethnicity and Diagnostic Testing for Common Conditions in the Acute Care Setting.

Importance: Overuse of diagnostic testing is pervasive, but the extent to which it varies by race and ethnicity in the acute care setting is poorly understood. Objective: To use a previously validated diagnostic intensity index to evaluate differences in diagnostic testing rates by race and ethnicity in the acute care setting, which may serve as a surrogate for diagnostic test overuse. Design, Setting, and Participants: This was a cross-sectional study of emergency department (ED) discharges, hospital observation stays, and hospital admissions using administrative claims among EDs and acute care hospitals in Kentucky, Maryland, North Carolina, and New Jersey, from 2016 through 2018. The diagnostic intensity index pairs nonspecific principal discharge diagnoses (nausea and vomiting, abdominal pain, chest pain, and syncope) with related diagnostic tests to estimate rates of nondiagnostic testing. Adults with an acute care encounter with a principal discharge diagnosis of interest were included. Data were analyzed from January to February 2024. Exposure: Race and ethnicity (Asian, Black, Hispanic, White, other [including American Indian, multiracial, and multiethnic], and missing). Main Outcomes and Measures: Receipt of a diagnostic test. Generalized linear models with a hospital-specific indicator variable were estimated to calculate the adjusted odds ratio of receiving a test related to the principal discharge diagnosis by race and ethnicity, controlling for primary payer and zip code income quartile. Results: Of 3 683 055 encounters (1 055 575 encounters [28.7%] for Black, 300 333 encounters [8.2%] for Hispanic, and 2 140 335 encounters [58.1%] for White patients; mean [SD] age of patients with encounters, 47.3 [18.8] years; 2 233 024 encounters among females [60.6%]), most (2 969 974 encounters [80.6%]) were ED discharges. Black compared with White patients discharged from the ED with a diagnosis of interest had an adjusted odds ratio of 0.74 (95% CI, 0.72-0.75) of having related diagnostic testing. No other racial or ethnic disparities of a similar magnitude were observed in any acute care settings. Conclusions and Relevance: In this study, White patients discharged from the ED with a nonspecific diagnosis of interest were significantly more likely than Black patients to receive related diagnostic testing. The extent to which this represents diagnostic test overuse in White patients vs undertesting and missed diagnoses in Black patients deserves further study.

Contextual factors and G6PD diagnostic testing: a scoping review and evidence and gap map.

BACKGROUND: Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important consideration regarding treatment for malaria. G6PD deficiency may lead to haemolytic anaemia during malaria treatment and, therefore, determining G6PD deficiency in malaria treatment strategies is extremely important. METHODS: This report presents the results of a scoping review and evidence and gap map for consideration by the Guideline Development Group for G6PD near patient tests to support radical cure of Plasmodium vivax. This scoping review has investigated common diagnostic tests for G6PD deficiency and important contextual and additional factors for decision-making. These factors include six of the considerations recommended by the World Health Organization (WHO) handbook for guideline development as important to determining the direction and strength of a recommendation, and included 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. The aim of this scoping review is to inform the direction of future systematic reviews and evidence syntheses, which can then better inform the development of WHO recommendations regarding the use of G6PD deficiency testing as part of malaria treatment strategies. RESULTS: A comprehensive search was performed, including published, peer-reviewed literature for any article, of any study design and methodology that investigated G6PD diagnostic tests and the factors of 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. There were 1152 studies identified from the search, of which 14 were determined to be eligible for inclusion into this review. The studies contained data from over 21 unique countries that had considered G6PD diagnostic testing as part of a malaria treatment strategy. The relationship between contextual and additional factors, diagnostic tests for G6PD deficiency and study methodology is presented in an overall evidence and gap, which showed that majority of the evidence was for the contextual factors for diagnostic tests, and the 'Standard G6PD (SD Biosensor)' test. CONCLUSIONS: This scoping review has produced a dynamic evidence and gap map that is reactive to emerging evidence within the field of G6PD diagnostic testing. The evidence and gap map has provided a comprehensive depiction of all the available literature that address the contextual and additional factors important for decision-making, regarding specific G6PD diagnostic tests. The majority of data available investigating the contextual factors of interest relates to quantitative G6PD diagnostic tests. While a formal qualitative synthesis of this data as part of a systematic review is possible, the data may be too heterogenous for this to be appropriate. These results can now be used to inform future direction of WHO Guideline Development Groups for G6PD near patient tests to support radical cure of P. vivax malaria.

Field laboratory comparison of STANDARD Q Filariasis Antigen Test (QFAT) with Bioline Filariasis Test Strip (FTS) for the detection of Lymphatic Filariasis in Samoa, 2023.

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

Use of strips of rapid diagnostic tests as a source of ribonucleic acid for genomic surveillance of viruses: an example of SARS-CoV-2.

BACKGROUND: This study aimed to demonstrate that the genomic material of SARS-CoV-2 can be isolated from strips of COVID-19 rapid diagnostic test cassettes. METHOD: It was a prospective cross-sectional study involving patients admitted to treatment centers and sampling sites in the city of Conakry, Guinea. A total of 121 patients were double sampled, and 9 more patients were tested only for RDT. PCR was conducted according to the protocol of the RunMei kit. Sequencing was performed by using the illumina COVIDSeq protocol. Nine COVID-19 RDTs without nasopharyngeal swabs were in addition tested. RESULT: Among the 130 COVID-19 RDTs, forty-seven were macroscopically positive, whereas seventy-two were positive according to PCR using RDT strip, while among the 121 VTM swabs, sixty-four were positive. Among eighty-three negative COVID-19 RDTs, twenty-seven were positive by PCR using RDT strip with a geometric mean Ct value of 32.49 cycles. Compared to those of PCR using VTM, the sensitivity and specificity of PCR using RDT strip were estimated to be 100% and 85.96%, respectively, with 93.39% test accuracy. Among the fifteen COVID-19 RDT extracts eligible for sequencing, eleven had sequences identical to those obtained via the standard method, with coverage between 75 and 99.6%. CONCLUSION: These results show that COVID-19 RDTs can be used as biological material for the genomic surveillance of SARS-CoV-2.

Present outlooks on the prevalence of minimal and subclinical tuberculosis and current diagnostic tests: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is a major global health issue, particularly in its minimal and subclinical forms, which often go undetected and contribute to transmission. Accurate prevalence assessment of these forms and the effectiveness of diagnostic tests are crucial for improving TB control, especially in high-risk populations such as those with HIV. OBJECTIVES: This study aimed to determine the prevalence of minimal and subclinical TB and evaluate the positivity rates of current diagnostic tests. METHODS: We conducted a meta-analysis of studies published from January 2000 to December 2022. Prevalence rates and diagnostic test results, including sputum culture, smear microscopy, TST/IGRA, and chest X-ray, were analyzed, with pooled prevalence calculated and comparisons made between geographic regions. RESULTS: Minimal TB prevalence ranged from 0.9 % to 22.9 % in the general population, while subclinical TB prevalence was 0.05 % to 0.64 %, and 1.57 % to 14.63 % among individuals with HIV. The overall pooled prevalence of minimal TB was 7 % (95 % CI: 5-9 %), with higher rates in Asia (8 %, 95 % CI: 5-12 %) compared to Africa (6 %, 95 % CI: 4-8 %). Subclinical TB had a pooled prevalence of 0.2 % (95 % CI: 0.2-0.3 %) overall and 52 % (95 % CI: 46-58 %) among TB cases, with higher rates in Asia (60 %) compared to Africa (44 %). Diagnostic test positivity was 77 % (sputum culture), 15 % (smear microscopy), 64 % (TST/IGRA), and 53 % (chest X-ray). CONCLUSIONS: This study reveals significant variability in the prevalence of minimal and subclinical TB. The findings highlight the need for improved diagnostic methods to reduce undetected cases, especially in high-risk populations.

Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia.

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Assessment of the performance of five malaria rapid diagnostic tests in health facilities in Abidjan (Côte d'Ivoire).

Regular monitoring of malaria rapid diagnostic tests (RDTs) for the management of uncomplicated malaria in healthcare facilities is a key factor in improving diagnostic quality and ensuring better case management. This study aimed to assess the performance of five RDTs (Standard Q Malaria P.f Ag and Standard Q Malaria P.f/Pan (SD Biosensor, Korea), One Step Malaria HRP2/pLDH (P.f/Pan) (Guangzhou Wondfo Biotech Co., Ltd., China), Malaria Pf/Pan (B&O Pharm, France), and Malaria test P.f/pan (Das Labor, Germany)) in two healthcare facilities in Abidjan. This cross-sectional study was conducted between September and October 2022. Overall, 250 patients suffering from uncomplicated malaria were included with a predominance of female patients (56.6%). The mean age was 22.3 years (SD = 20.6; range, 0.17-73). Of the patients tested, forty-six (46) tested positive for thick smears, reflecting a prevalence of 18.5%. Plasmodium falciparum was the most commonly detected species (93.5%). The geometric mean parasitemia was 6,111.80 parasites/µl (SD = 80,026.93) (range: 116-412461). The sensitivity ranged from 95.24% to 95.65%, whereas the specificity ranged from 93.07 to 94.09% for all five tests evaluated. The false positive rate of the tests was less than 10%. No invalid test results were reported. Two-thirds of P. malariae cases detected by microscopy showed also positive results with all the RDTs. All five RDTs showed 100% sensitivity at low parasitemia levels (< 1,000 parasites/µl blood) including three cases of parasites < 200 parasites/µl blood. This study demonstrated the importance of monitoring the performance of RDTs in clinical samples.

Proactive home-based malaria management in rural communities of Bassar Health District in northern Togo from 2014 to 2017: PECADOM + , a pilot experiment.

BACKGROUND: Togo's National Malaria Control Programme has initiated an active home-based malaria management model for all age groups in rural areas of Bassar Health District. This report describes the model, reports its main results, and determines the factors associated with positive rapid diagnostic test results. METHODS: From 2014 to 2017, in three peripheral care units of Bassar Health District (Binaparba, Nangbani, and Baghan), community health workers visited residents' homes weekly to identify patients with malaria symptoms, perform rapid diagnostic tests in symptomatic patients, and give medication to positive cases. Univariate and multivariate logistic regression models were used to determine the factors associated with positive tests. RESULTS: The study covered 11,337 people (817 in 2014, 1804 in 2015, 2638 in 2016, and 6078 in 2017). The overall mean age was 18 years (95% CI 5-29; min-max: 0-112 years). The median age was 10 years (SD: 16.9). The proportions of people tested positive were 75.3% in Binaparba, 77.4% in Nangbani, and 56.6% in Baghan. The 5-10 age group was the most affected category (24.2% positive tests). Positive tests were more frequent during the rainy than during the dry season (62 vs. 38%) and the probability of positive test was 1.76 times higher during the rainy than during the dry season (adjusted OR = 1.74; 95% CI 1.60-1.90). A fever (37.5 °C or higher) increased significantly the probability of positive test (adjusted OR = 2.19; 95% CI 1.89-2.54). The risk of positive test was 1.89 times higher in passive than in active malaria detection (adjusted OR = 1.89; 95% CI 1.73-2.0). CONCLUSIONS: This novel experimental community and home-based malaria management in Togo suggested that active detection of malaria cases is feasible within 24 h, which allows rapid treatments before progression to often-fatal complications. This PECADOM + program will help Togo's National Malaria Control Programme reduce malaria morbidity and mortality in remote and hard-to-reach communities.

Evolution of pfhrp2 and pfhrp3 deletions in Equatorial Guinea between the pre- and post-RDT introduction.

BACKGROUND: Pfhrp2 and pfhrp3 deletions are threatening Plasmodium falciparum malaria diagnosis by rapid diagnostic tests (RDT) due to false negatives. This study assesses the changes in the frequencies of pfhrp2 and pfhrp3 deletions (pfhrp2Del and pfhrp3Del, respectively) and the genes in their flaking regions, before and after RDT introduction in Equatorial Guinea. METHODS: A total of 566 P. falciparum samples were genotyped to assess the presence of pfhrp2 and pfhrp3 deletions and their flanking genes. The specimens were collected 18 years apart from two provinces of Equatorial Guinea, North Bioko (Insular Region) and Litoral Province (Continental Region). Orthologs of pfhrp2 and pfhrp3 genes from other closely related species were used to compare sequencing data to assess pfhrp2 and pfhrp3 evolution. Additionally, population structure was studied using seven neutral microsatellites. RESULTS: This study found that pfhrp2Del and pfhrp3Del were present before the introduction of RDT; however, they increased in frequency after their use, reaching more than 15%. Haplotype networks suggested that pfhrp2Del and pfhrp3Del emerged multiple times. Exon 2 of pfhrp2 and pfhrp3 genes had high variability, but there were no significant changes in amino acid sequences. CONCLUSIONS: Baseline sampling before deploying interventions provides a valuable context to interpret changes in genetic markers linked to their efficacy, such as the dynamic of deletions affecting RDT efficacy.

Cost-effectiveness of sentinel screening of endemic diseases alongside malaria diagnosis: A case study in schistosomiasis.

BACKGROUND: In countries where malaria is endemic, the use of rapid diagnostic tests(RDTs) has become routine, especially in rural settings. Such regions are characterised by often having other co-endemic infectious diseases, at high levels of prevalence. AIM: To illustrate the potential added-value of "sentinel" screening for patients presenting for a routine diagnostic test for malaria, at healthcare facilities in Uganda. METHODS: We developed an economic model by combining two decision trees, one for malaria and a second for the co-endemic disease schistosomiasis. The integrated model was designed to inform policy strategies for the co-endemic disease in addition to malaria (i.e., whether to test opportunistically for schistosomiasis or use mass drug administration(MDA) as per usual practice).We performed the analysis on three comparators varying testing accuracy and costs. RESULTS: Sentinel screening can provide added value to the testing of patients compared with the status quo: when schistosomiasis prevalence is high then MDA is preferential; if low prevalence, treating no one is preferred. If the disease has average levels of prevalence, then a strategy involving testing is preferred. Prevalence thresholds driving the dominant strategy are dependent upon the model parameters, which are highly context specific. At average levels of prevalence for schistosomiasis and malaria for Uganda, adding a sentinel screening was cost-effective when the accuracy of test was higher than current diagnostics and when economies of scope were generated(Expected value clinical Information = 0.65$ per DALY averted, 137.91$ per correct diagnoses).Protocols using diagnostics with current accuracy levels were preferred only for levels of MDA coverage below 75%. CONCLUSION: The importance of the epidemiological setting is crucial in determining the best cost-effective strategy for detecting endemic disease. Economies of scope can make sentinel screenings cost-effective strategies in specific contexts. Blanket thresholds recommended for MDA may not always be the preferred option for endemic diseases.

Validation of an In Vitro Diagnostic Test for Endometriosis: Impact of Confounding Medical Conditions and Lesion Location.

With the aim to shorten the time for diagnosis and accelerate access to correct management, a non-invasive diagnostic test for endometriosis was developed and validated. The IVD test combines an ELISA test kit to quantify CA125 and BDNF concentrations in serum and a data treatment algorithm hosted in medical software processing results from the ELISA test and responses to six clinical variables. Serum samples and clinical variables extracted from psychometric questionnaires from 77 patients were collected from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of the excised lesions. Biomarkers serum concentrations and clinical variables were introduced to the software, which generates the qualitative diagnostic result ("positive" or "negative"). This test allowed the detection of 32% of cases with superficial endometriosis, which is an added value given the limited efficacy of existing imaging techniques. Even in the presence of various confounding medical conditions, the test maintained a specificity of 100%, supporting its suitability for use in patients with underlying medical conditions.

Examining the Association Between the COVID-19 Pandemic and the Rate of Diagnostic Tests for Breast, Cervical, and Colorectal Cancer in Manitoba, Canada.

Background: Strategies to minimize the impact of the COVID-19 pandemic led to a reduction in diagnostic testing. It is important to assess the magnitude and duration of this impact to plan ongoing care and avoid long-lasting impacts of the pandemic. Objective: We examined the association between the COVID-19 pandemic and the rate of diagnostic tests for breast, cervical, and colorectal cancer in Manitoba, Canada. Design and Participants: A population-based, cross-sectional study design with an interrupted time series analysis was used that included diagnostic tests from January 1, 2015 until August 31, 2022. Setting: Manitoba, Canada. Main Outcomes: Outcomes included mammogram, breast ultrasound, colposcopy, and colonoscopy rates per 100,000. Cumulative and percent cumulative differences between the fitted and counterfactual number of tests were estimated. Mean, median, and 90th percentile number of days from referral to colonoscopy date by referral type (elective, semiurgent, urgent) were determined. Results: In April 2020, following the declaration of the COVID-19 public health emergency, bilateral mammograms decreased by 77%, unilateral mammograms by 70%, breast ultrasounds by 53%, colposcopies by 63%, and colonoscopies by 75%. In Winnipeg (the largest urban center in the province), elective and semiurgent colonoscopies decreased by 76% and 39%, respectively. There was no decrease in urgent colonoscopies. As of August 2022, there were an estimated 7270 (10.7%) fewer bilateral mammograms, 2722 (14.8%) fewer breast ultrasounds, 836 (3.3%) fewer colposcopies, and 11 600 (13.8%) fewer colonoscopies than expected in the absence of COVID-19. As of December 2022, in Winnipeg, there were an estimated 6030 (23.9%) fewer elective colonoscopies, 313 (2.6%) fewer semiurgent colonoscopies, and 438 (27.3%) more urgent colonoscopies. Conclusions: In Manitoba, the COVID-19 pandemic was associated with sizable decreases in diagnostic tests for breast, colorectal, and cervical cancer. Two and a half years later, there remained large cumulative deficits in bilateral mammograms, breast ultrasounds, and colonoscopies.

Economic Impact of Whole Genome Sequencing and Whole Transcriptome Sequencing Versus Routine Diagnostic Molecular Testing to Stratify Patients with B-Cell Acute Lymphoblastic Leukemia.

Whole genome and whole transcriptome sequencing (WGTS) can accurately distinguish B-cell acute lymphoblastic leukemia (B-ALL) genomic subtypes. However, whether this is economically viable remains unclear. This study compared the direct costs and molecular subtype classification yield using different testing strategies for WGTS in adolescent and young adult/adult patients with B-ALL. These approaches were: (1) combined BCR::ABL1 by fluorescence in situ hybridization (FISH) + WGTS for all patients; and (2) sequential BCR::ABL1 FISH + WGTS contingent on initial BCR::ABL1 FISH test outcome. The cost of routine diagnostic testing was estimated using Medicare or hospital fees, and the additional cost of WGTS was evaluated from the health care provider perspective using time-driven activity-based costing with resource identification elicited from experts. Molecular subtype classification yield data were derived from literature sources. Parameter uncertainty was assessed through deterministic sensitivity analysis; additional scenario analyses were performed. The total per patient cost of WGTS was $4319 (all costs reported in US dollars); consumables accounted for 74% of the overall cost, primarily driven by sequencing-related consumables. The incremental cost per additional patient categorized into molecular subtype was $8498 for combined BCR::ABL1 FISH + WGTS for all patients and $5656 for initial BCR::ABL1 FISH + WGTS for select patients compared with routine diagnostic testing. A reduction in the consumable costs of WGTS or an increase in the yield of molecular subtype classification is favorable.