Use Of Rapid Diagnostic Tests Research Articles

Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $0.03 and $0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

Rapid diagnostic tests and antimicrobial stewardship programs for the management of bloodstream infection: What is their relative contribution to improving clinical outcomes? A systematic review and network meta-analysis.

Evidence about the clinical impact of rapid diagnostic tests (RDT) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BC) embedded within antimicrobial stewardship programs (ASP) is unknown. We performed network meta-analyses (NMA) using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS) and time to optimal therapy (TOT). Eighty-eight papers were selected, including 25,682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The NMA showed a significant reduction in mortality associated with the use of RDT + ASP vs BC alone (OR 0.72, 95%CI 0.59, 0.87) and with the use of RDT + ASP vs BC + ASP (OR 0.78 95%CI 0.63, 0.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP vs BC alone (0.91, 95%CI 0.84, 0.98) while no difference in LOS was shown between any other groups. A reduced TOT was shown when RDT + ASP was compared to BC alone (-29 h, 95%CI -35, -23), BC + ASP (-18 h, 95%CI -27, -10) and to RDT alone (-12 h, 95%CI -20, -3). The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC.

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria

BackgroundThe increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria.MethodsBetween March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke.ResultsThe determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker’s knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients’ demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money.ConclusionsThis evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers’ use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia.

A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

Evaluation of the Performance of Rapid Diagnostic Tests for Malaria Diagnosis and Mapping of Different Plasmodium Species in Mali.

The first-line diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT) that detect the Histidin Rich Protein 2 (HRP2) antigen specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold standard, aimed to describe the distribution of the Plasmodium species in each administrative region of Mali and to assess the performance of RDTs. We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs in 41 sites distributed in 9 regions of Mali. DNA extracted from the RDT nitrocellulose strip was assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with P. falciparum-, P. malariae-, P. vivax-, or P. ovale-specific qPCRs. Of the 1496 RDTs, 258 (18.6%) were positive for Plasmodium spp., of which 96.9% were P. falciparum. The P. vivax prevalence reached 21.1% in the north. RDT displayed acceptable diagnostic indices; the lower CI95% bounds of Youden indices were all ≥0.50, except in the north (Youden index 0.66 (95% CI [0.44-0.82]) and 0.63 (95% CI [0.33-0.83]. Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. We recommend the use of RDTs detecting P. vivax-specific antigens in the north.

Rapid Detection of M. tuberculosis and Its Resistance to Rifampicin and Isoniazid with the mfloDx™ MDR-TB test.

Rapid detection of tuberculosis (TB) and its resistance are essential for the prompt initiation of correct drug therapy and for stopping the spread of drug-resistant TB. There is an urgent need for increased use of rapid diagnostic tests to control the threat of increased TB and multidrug-resistant TB (MDR-TB). EMPE Diagnostics has developed a multiplex molecular diagnostic platform called mfloDx™ by combining nucleotide-specific padlock probe-dependent rolling circle amplification with sensitive lateral flow biosensors, providing visual signals, similar to a COVID-19 test. The first test kit of this platform, mfloDx™ MDR-TB can identify Mycobacterium tuberculosis (MTB) complex and its clinically significant mutations in the rpoB and katG genes and in the inhA promotor contributing resistance to rifampicin (RIF) and isoniazid (INH), causing MDR-TB. We have evaluated the performance of the mfloDx™ MDR-TB test on 210 sputum samples (110 from suspected TB cases and 100 from TB-negative controls) received from a tertiary care center in India. The clinical sensitivity for detecting MTB compared to acid-fast microscopy and mycobacteria growth indicator tube (MGIT) cultures was 86.4% and 84.9%, respectively. All the 100 control samples were negative indicating excellent specificity. In smear-positive sputum samples, the mfloDx™ MDR-TB test showed a sensitivity of 92.5% and 86.4% against MGIT culture and Xpert MTB/RIF, respectively. The clinical sensitivity for the detection of RIF and INH resistance in comparison with MGIT drug susceptibility testing was 100% and 84.6%, respectively, while the clinical specificity was 100%. From the above evaluation, we find mfloDx™ MDR-TB to be a rapid and efficient test to detect TB and its multidrug resistance in 3 h at a low cost making it suitable for resource-limited laboratories.

Primary Care Antibiotic Prescribing and Infection-Related Hospitalisation.

Inappropriate prescribing of antibiotics has been widely recognised as a leading cause of antimicrobial resistance, which in turn has become one of the most significant threats to global health. Given that most antibiotic prescriptions are issued in primary care settings, investigating the associations between primary care prescribing of antibiotics and subsequent infection-related hospitalisations affords a valuable opportunity to understand the long-term health implications of primary care antibiotic intervention. A narrative review of the scientific literature studying associations between primary care antibiotic prescribing and subsequent infection-related hospitalisation was conducted. The Web of Science database was used to retrieve 252 potentially relevant studies, with 23 of these studies included in this review (stratified by patient age and infection type). The majority of studies (n = 18) were published in the United Kingdom, while the remainder were conducted in Germany, Spain, Denmark, New Zealand, and the United States. While some of the reviewed studies demonstrated that appropriate and timely antibiotic prescribing in primary care could help reduce the need for hospitalisation, excessive antibiotic prescribing can lead to antimicrobial resistance, subsequently increasing the risk of infection-related hospitalisation. Few studies reported no association between primary care antibiotic prescriptions and subsequent infection-related hospitalisation. Overall, the disparate results in the extant literature attest to the conflicting factors influencing the decision-making regarding antibiotic prescribing and highlight the necessity of adopting a more patient-focussed perspective in stewardship programmes and the need for increased use of rapid diagnostic testing in primary care.

Improving testing capacity for COVID-19: experiences and lessons from Senegal, Uganda, Nigeria, and the Democratic Republic of Congo.

African countries leveraged testing capacities to enhance public health action in response to the COVID-19 pandemic. This paper describes experiences and lessons learned during the improvement of testing capacity throughout the COVID-19 response in Senegal, Uganda, Nigeria, and the Democratic Republic of the Congo (DRC). The four countries' testing strategies were studied using a mixed-methods approach. Desk research on COVID-19 testing strategies was conducted and complemented by interviewing key informants. The findings were synthesized to demonstrate learning outcomes across the four countries. The four countries demonstrated severely limited testing capacities at the onset of the pandemic. These countries decentralized COVID-19 testing services by leveraging preexisting laboratory systems such as PCR and GeneXpert used for the diagnosis of tuberculosis (TB) to address this gap and the related inequities, engaging the private sector, establishing new laboratories, and using rapid diagnostic tests (RDTs) to expand testing capacity and reduce the turnaround time (TAT). The use of digital platforms improved the TAT. Testing supplies were sourced through partners, although access to global markets was challenging. Case detection remains suboptimal due to high costs, restrictive testing strategies, testing access challenges, and misinformation, which hinder the demand for testing. The TAT for PCR remained a challenge, while RDT use was underreported, although Senegal manufactured RDTs locally. Key findings indicate that regionally coordinated procurement and manufacturing mechanisms are required, that testing modalities must be simplified for improved access, and that the risk-based testing strategy limits comprehensive understanding of the disease burden. Although testing capacities improved significantly during the pandemic, case detection and access to testing remained suboptimal. The four countries could benefit from further simplification of testing modalities and cost reduction. Local manufacturing and pooled procurement mechanisms for diagnostics are needed for optimal pandemic preparedness and response.

Diagnostic value of rapid test for malaria among febrile neonates in a tertiary hospital in North-East Nigeria: a prospective cross-sectional study

ObjectiveThe WHO recommends testing using microscopy or rapid diagnostic test (RDT) before treatment for malaria. However, the use of RDT to diagnose neonatal malaria has not been widely validated with...

Adherence to national malaria treatment guidelines in private drug outlets: a cross-sectional survey in the malaria-endemic Kisumu County, Kenya

BackgroundMalaria prevalence in Kenya is 6%, with a three-fold higher prevalence in western Kenya. Adherence to malaria treatment guidelines improves care for suspected malaria cases and can reduce unnecessary anti-malarial use. Data on adherence to guidelines in retail drug outlets (DOs) is limited, yet approximately 50% of people with fever access treatment first in these outlets. This study assessed adherence to the national malaria treatment guidelines among DOs in a high transmission area of Western Kenya.MethodsIn a cross-sectional survey of DOs in Kisumu Central and Seme sub-counties in 2021, DO staff were interviewed using structured questionnaires to assess outlet characteristics (location, testing services), staff demographics (age, sex, training), and health system context (supervision, inspection). Mystery shoppers (research assistants disguised as clients) observed malaria management practices and recorded observations on a standardized tool. Adherence was defined as dispensing artemether-lumefantrine (AL) to patients with a confirmed positive test, accompanied by appropriate medication counseling. Logistic regression was used to test for association between adherence to guidelines and DO-related factors.ResultsNone of the 70 DOs assessed had a copy of the guidelines, and 60 (85.7%) were in an urban setting. Staff adhered to the guidelines in 14 (20%) outlets. The odds of adherence were higher among staff who had a bachelor’s degree {odds ratio (OR) 6.0, 95% confidence interval (95% CI) 1.66–21.74}, those trained on malaria rapid diagnostic test (RDT) {OR 4.4, 95% CI 1.29–15.04}, and those who asked about patient’s symptoms {OR 3.6, 95% CI 1.08–12.25}. DOs that had higher odds of adherence included those with functional thermometers {OR 5.3, 95% CI 1.46–19.14}, those recently inspected (within three months) by Pharmacy and Poisons Board (PPB) {OR 9.4, 95% CI 2.55–34.67}, and those with all basic infrastructure {OR 3.9, 95% CI 1.01–15.00}. On logistic regression analysis, recent PPB inspection {adjusted OR (AOR) 4.6, 95% CI 1.03–20.77} and malaria RDT-trained staff (aOR 4.5, 95% CI 1.02–19.84) were independently associated with adherence.ConclusionMost outlets didn’t adhere to malaria guidelines. Regular interaction with regulatory bodies could improve adherence. Ministry of Health should enhance private sector engagement and train DOs on RDT use.

A-381 Laboratory-based Reflexive Algorithm for Identification of Falciparum and Non-Falciparum-Species and its Clinical Utility in the Diagnosis of Malaria in Southern Ghana

Abstract Background Malaria presents a public health menace to millions of people in LMICs, killingmore than 600 000 people with the highest number in children living in sub-Saharan Africa.Laboratory testing provides the basis for &amp;gt;70% of clinical decisions, although their accessibilityand affordability are limited in LMICs and results in syndromic diagnosis and self-medication.The National Malaria Control Program guidelines specify that healthcare facilities perform RapidDiagnostic Testing (RDT) or microscopy for the diagnosis of malaria. This “one size fits all”approach has the unfortunate potential of resulting in a higher number of false positives and falsenegatives. Although Plasmodium falciparum is the predominant species in Ghana, emergingevidence suggests that non-falciparum species (P. vivax, P. ovale, P. malariae, and P. knowlesi)contribute to morbidity and mortality, and complicates the diagnosis and treatment for a subset ofpatients. The rationale for this study is the development of a reflexive, stratified diagnosticapproach that combines the use of RDTs and Microscopy/NAAT for the identification offalciparum and non-falciparum species in malaria endemic areas. Method Venous blood was collected from participants and five different RDTs on the Ghanaianmarket were used to screen the blood for the presence of malaria parasites along with microscopyand the LAMP method. The diagnostic performance of the RDTs was evaluated by utilizingmicroscopy as the gold standard. For microscopy, a volume of 6 µL and 2 µL of the blood sampleswere pipetted onto labeled frosted- end slides for the preparation of thick and thin blood films,respectively. Lastly, DNA was extracted from venous blood (QIAamp DNA Mini Kit, Qiagen,Germantown, MD, USA) and analyzed using a modified version of the Nested Malaria PCR assaythat can identify the five species of the Plasmodium parasite including P. knowlesi. Results Preliminary data from results from 71 participants showed an overall sensitivity of 90%for the identification of Plasmodium infection among all the RDTs examined in this investigation.The Wondfo® One Step Malaria HRP2/pLDH (P.f/Pan) test was the only RDT that passed theWHO recommended specificity of 90% when compared to microscopy. The WHO recommends aminimum sensitivity of 95%; however, none of the five RDTs utilized in this study met thisrequirement. Conclusion Although microscopy remains the gold standard for the identification of Plasmodiumspp for malaria diagnosis, it is becoming increasing popular for most healthcare facilities in LMICsto use RDTs for screening of the huge patient numbers that present with febrile illness. From ourpreliminary results, we have shown that positive cases by RDTRs are usually confirmed positiveby microscopy while most RDT negatives are false negatives by microscopy. Our combinatorialapproach with the molecular testing assay using LAMP increases the specificity of the testingprocess that guides treatment for malaria patients.

Reducing antimicrobial overuse through targeted therapy for patients with community-acquired pneumonia: a study protocol for a cluster-randomized factorial controlled trial (CARE-CAP)

BackgroundCommunity-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients.MethodsWe will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay.DiscussionOur study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP.Trial registrationClinicalTrials.gov NCT05568654. Registered on October 4, 2022.

Challenges in the Management of Invasive Fungal Infections in the Middle East: Expert Opinion to Optimize Management Using a Multidisciplinary Approach.

Invasive fungal infection (IFI) is a significant global healthcare concern among critically ill and immunocompromised patients. In Middle Eastern countries, IFI has been steadily increasing among hospitalized patients in the past two decades. Diagnosis of IFI at an early stage is crucial for efficient management. Invasive fungal infection management is complex and requires the involvement of physicians from different specialties. There are several challenges associated with IFI management in the countries in the Middle East. This review aims to understand the key challenges associated with IFI management in the Middle East, encompassing epidemiology, diagnosis, therapeutic options, and optimizing a multidisciplinary approach. In addition, this review aims to incorporate expert opinions from multidisciplinary fields for optimizing IFI management in different Middle Eastern countries by addressing key decision points throughout the patient's journey. Lack of epidemiological data on fungal infections, slow and poorly sensitive conventional culture-based diagnostic tests, limited availability of biomarker testing, lack of awareness of clinical symptoms of the disease, limited knowledge on fungal infections, lack of local practice guidelines, and complicated disease management are the major challenges associated with IFI diagnosis and management in the Middle Eastern countries. Implementation of a multidisciplinary approach, antifungal stewardship, improved knowledge of fungal infections, the use of rapid diagnostic tests, and enhanced epidemiological research are warranted to lower the IFI burden in the Middle East.

Plasmodium falciparum with pfhrp2/3 Deletion Not Detected in a 2018-2021 Malaria Longitudinal Cohort Study in Kinshasa Province, Democratic Republic of the Congo.

Histidine-rich protein 2- (HRP2-) based rapid diagnostic tests (RDTs) are widely used to detect Plasmodium falciparum in sub-Saharan Africa. Reports of parasites with pfhrp2 and/or pfhrp3 (pfhrp2/3) gene deletions in Africa raise concerns about the long-term viability of HRP2-based RDTs. We evaluated changes in pfhrp2/3 deletion prevalence over time using a 2018-2021 longitudinal study of 1,635 enrolled individuals in Kinshasa Province, Democratic Republic of the Congo (DRC). Samples collected during biannual household visits with ≥ 100 parasites/µL by quantitative real-time polymerase chain reaction were genotyped using a multiplex real-time PCR assay. Among 2,726 P. falciparum PCR-positive samples collected from 993 participants during the study period, 1,267 (46.5%) were genotyped. No pfhrp2/3 deletions or mixed pfhrp2/3-intact and -deleted infections were identified in our study. Pfhrp2/3-deleted parasites were not detected in Kinshasa Province; ongoing use of HRP2-based RDTs is appropriate.

A COMPARATIVE STUDY OF RAPID SARS COV 2 ANTIGEN DETECTION TEST &amp; REAL TIME PCR TEST FOR DIAGNOSIS OF COVID-19 IN TERTIARY CARE INSTITUTE AT KOTA, SOUTH-EAST RAJASTHAN, INDIA

Background:The 2019 (Covid19) pandemic of coronavirus disease was caused by SARS Cov 2 Virus. The emergence of the disease was started from the Wuhan city of China in December 20191. This infection causes asymptomatic and mild diseases more than severe pneumonia. A Rapid Lateral flow immunoassays using monoclonal anti-SARS CoV- 2 antibodies, targeting SARS-CoV-2 antigens, can be used as complementary screening tests if their accuracy comes comparable to that of gold standard real-time RT-PCR assays. Objective:The present study has been conducted retrospectively on the data of patients who underwent for Covid 19 diagnosis by RAT at the Microbiology Department Central Laboratory, Maharao Bhim Singh Hospital Nayapura Kota. Material and Method: Respiratory samples from suspected 5219 COVID-19 patients, mainly nasopharyngeal and throat swabs were collected. COVID-19 Ag Confirmit™ kit (Alpine biomedicals) is a rapidchromatographic immunoassay for the detection ofSARS-CoV-2 nucleoprotein (N) antigen in respiratoryspecimens. Multiplex Real-time RT-PCR kit (TRIVITRON healthcare) was used, whichtargets envelope gene (E), and Orf1ab gene of SARS-CoV-2 genome and RPP30 Human gene as internal control, was used for SARS-CoV-2RNA detection. Descriptive statistics were used to describe the usefulness of rapid diagnostic tests. For that online MedCalcs Diagnostic test evaluation statistical tool10. Result: Among all 5219 samples (n=5219) tested by RT-PCR 785 (15.4%) samples were positive and 4434 (84.95%) were negative. Samples tested by RAT 813 (15.57%) samples were positive &amp; 4406 (84.42%) were negative, in our study we found discordant results in 36 samples. The sensitivity and specificity of the COVID-19 Ag Confirmit™ kit (Alpine biomedicals) were 99.49% and 99.28% respectively. Discussion: Out of 785 RT-PCR-positive samples in our study, the 4 false negative results were tested for SARS-CoV-2 antigen seven days after disease onset. The RT-PCR result of these samples had relatively high Ct-values. Without the present population prevalence of COVID-19, the positive and negative predictive values (PPV and NPV) of the assay could not be accurately calculated. Conclusions: There is comparable Sensitivity and Specificity between Rapid assay for SARS-CoV-2 antigen detection (COVID-19 Ag Confirmit™ kit) and real-time RT-PCR assay.

Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

Expanding the scope of the infectious diseases pharmacist in HCT: Beyond antimicrobial stewardship.

Infectious disease (ID) pharmacists and antimicrobial stewardship (AMS) programs are integral to the infection management of hematopoietic cell transplant (HCT) recipients demonstrating effective implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN), allergy assessments, and use of rapid diagnostic testing. The HCT procedure is complex, dynamic, and a high risk for infectious complications. Therefore, there is an important role for an ID and AMS pharmacist to collaborate with the primary treating team, with ongoing care, involving the optimal individual patient prophylactic, pre-emptive and treatment management of infections in this high-risk population. This review highlights key factors for consideration of ID/AMS Pharmacists in relation to HCT, including important aspects in the evaluation of infection risk prior to transplant, risk from donor sources, length of, and changes in immunosuppression, and potential drug-drug interactions from other essential supportive care therapies.

Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda

BackgroundHistorically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda.MethodsA prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul’s Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables.ResultsOf the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2–93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001).ConclusionMalaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Rapid Diagnostic Test Value and Implementation in Antimicrobial Stewardship Across Low-to-Middle and High-Income Countries: A Mixed-Methods Review.

Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

Use of rapid diagnostic tests for the detection of ancient malaria infections in dental pulp from the sixth century in Versailles, France

BackgroundPaleomicrobiological data have clarified that Plasmodium spp. was circulating in the past in southern European populations, which are now devoid of malaria. The aim of this study was to evaluate the efficacy of immunodetection and, more particularly, rapid diagnostic tests (RDT), in order to further assess Plasmodium infections in ancient northern European populations.MethodsA commercially available RDT, PALUTOP® + 4 OPTIMA, which is routinely used to detect malaria, was used to detect Plasmodium antigens from proteins recovered from ancient specimens extracted from 39 dental pulp samples. These samples were collected from 39 individuals who were buried in the sixth century, near the site of the current Palace of Versailles in France. Positive and negative controls were also used. Antigens detected were quantified using chemiluminescence imaging system analysis.ResultsPlasmodium antigens were detected in 14/39 (35.9%) individuals, including Plasmodium vivax antigens in 11 individuals and Plasmodium falciparum antigens co-detected in two individuals, while Pan-Plasmodium antigens were detected in three individuals. Controls all yielded expected results.ConclusionsThe data reported here showed that RDTs are a suitable tool for detecting Plasmodium spp. antigens in ancient dental pulp samples, and demonstrated the existence of malaria in Versailles, France, in the sixth century. Plasmodium vivax, which is regarded as being responsible for an attenuated form of malaria and less deadly forms, was the most prevalent species. This illustrates, for the first time in ancient populations, co-infection with P. falciparum, bringing into question the climate-driven ecosystems prevailing at that time in the Versailles area.