An evaluation of the diagnostic performance characteristics of the Yellow Fever IgM immunochromatographic rapid diagnostic test kit from SD Biosensor in Ghana

Yellow fever is endemic in Ghana and outbreaks occur periodically. The prodromal signs due to Yellow Fever Virus (YFV) infection are non-specific, making clinical signs unreliable as the sole criteria for diagnosis. Accurate laboratory confirmation of suspected yellow fever cases is therefore vital in surveillance programs. Reporting of ELISA IgM testing results by laboratories can delay due to late arrival of samples from the collection sites as well as limited availability of ELISA kits. In this study, the diagnostic performance characteristics of a rapid immunochromatographic Standard Q Yellow Fever IgM test kit (SD Biosensor) was evaluated for the rapid diagnosis of Yellow Fever infection in Ghana. A panel of 275 sera, comprising 81 confirmed YFV positives and 194 negatives were re-tested in this study using the Standard Q Yellow Fever IgM test kit. Using the CDC/WHO Yellow Fever IgM capture ELISA as a benchmark, the sensitivity, specificity and accuracy of the Standard Q Yellow Fever test kit were 96.3%, 97.9% and 97.5%, respectively. The false positivity rate was 5.1% and there was no cross-reactivity when the Standard Q Yellow Fever test kit was tested against dengue, malaria and hepatitis B and C positive samples. In addition, inter-reader variability and invalid rate were both zero. The results indicate that the diagnostic performance of the Standard Q Yellow Fever IgM test kit on serum or plasma is comparable to the serum IgM detection by ELISA and can be used as a point of care rapid diagnostic test kit for YFV infection in endemic areas.

Evaluation of an Antigen Detection Rapid Diagnostic Test for Detection of SARS-CoV-2 in Clinical Samples

Antigen detection rapid diagnostic tests have been developed for first-line large-scale screening given their rapidity, simplicity, and accuracy. This study evaluates the diagnostic performance of an antigen detection rapid diagnostic test (BLOK BioScience, London, UK) detecting SARS-CoV-2 nucleocapsid protein. Serially diluted SARS-CoV-2 isolate and 110 NPS from COVID-19 patients were tested to determine the test’s sensitivity, and other viral isolates and 20 NPS from non-infected individuals were, for specificity, also tested. Ten clinical samples from COVID-19 patients with SARS-CoV-2 variants, including alpha, beta, gamma, delta, and eta variants, were collected to evaluate the test’s potential application in detecting emerging variants. Overall sensitivity was 92%, and stratifying into viral loads yielded 100% for Ct < 25 samples including SARS-CoV-2 variants, but 11.11% for Ct ≥ 30 samples. The analytical sensitivity of log10 TCID50/mL 2.0 was identified for SARS-CoV-2. Ninety-seven percent specificity with only SARS-CoV cross-reactivity lead to the Youden index of 0.89. The rapid diagnostic test has a high sensitivity for detecting SARS-CoV-2 in high viral load samples, possibly including emerging SARS-CoV-2 variants, but reduced sensitivity in low viral load samples suggests its optimized usage as a complementary testing method to other tests, including RT-PCR or a point-of-care test for large-scale screening, particularly for pandemic areas or airport border infection control.

Uji Diagnostik Filariasis Menggunakan Rapid Diagnostic Test (RDT) Brugia malayi terhadap Pemeriksaan Mikroskopis di Desa Buntoi Kabupaten Gunung Mas, Provinsi Kalimantan Tengah

Gunung Mas Regency, Central Kalimantan Province is one of the endemic filariasis areas with Microfilaria rate of 3.4%. One of the efforts made to control this problem is Mass Drug Administration once a year for 5 years. Currently, the Rapid Diagnostic Test (RDT) method is being developed, a quick and easy diagnostic technique to detect the presence of parasites in the patient's body. This study aims to determine the results of the filariasis diagnostic test using the Brugia malayi RDT on the microscopic examination in Buntoi Village, Gunung Mas Regency, Central Kalimantan Province. This research is a descriptive study with a cross-sectional approach with the research subjects all residents of Buntoi Village with inclusion and exclusion criteria totaling 161 samples. Collecting data was carried out by examination and interviews with questionnaires. Data analysis by calculating the microfilaria rate, sensitivity and specificity and calculating the frequency distribution of research variables. Data is presented in percentage form and displayed in tabular form. The results of the diagnostic study of B. malayi RDT and the microscopic examination were the same, i.e all were negative and no microfilariae were found. The diagnostic test for filariasis RDT Brugia malayi on microscopic examination (SDJ) obtained 0% sensitivity, 100% specificity, 0% Positive Predictive Value and 100% Negative Predictive Value. The level of public knowledge about filariasis includes 61% good category, knowledge of MDA 40% good category and knowledge about prevention of filariasis in good category 53%.

A Novel Point-of-Care Rapid Diagnostic Test for Screening Individuals for Antibody Deficiencies

Purpose No rapid diagnostic test exists to screen individuals for primary antibody deficiencies (PAD) at or near the point of care. In settings at risk for polio where live oral polio vaccine is utilized, undiagnosed PAD patients and cases with delayed diagnosis constitute a potential reservoir for neurovirulent polioviruses, undermining polio eradication. This research aimed to develop a rapid screening test suited for use in resource-limited settings to identify individuals with low immunoglobulin G (IgG) levels, enabling early diagnosis and appropriate treatment. Methods Three prototype tests distinguishing low and normal IgG levels were evaluated with a blinded panel of serum/plasma specimens from 32 healthy controls and 86 primary immunodeficiency-confirmed patients with agammaglobulinemia, common variable immunodeficiency, and hyper-IgM syndrome, including 57 not receiving IgG therapy. Prototype tests were compared to laboratory reference and clinical case definition. Results The leading prototype correctly identified 32 of 32 healthy controls. Among primary antibody deficiency patients not receiving IgG treatment, 17 of 19 agammaglobulinemia, 7 of 24 common variable immunodeficiency, and 5 of 14 hyper-IgM were correctly identified by the prototype, with 67% agreement with the reference assay. Conclusion The Rapid IgG Screen (RIgGS) test can differentiate between low IgG levels associated with agammaglobulinemia and normal IgG antibody levels. Differentiating CVID and hyper IgM was challenging due to the wide range in IgG levels and influence of high IgM. This test can facilitate the identification of patients with primary antibody deficiencies and support polio surveillance initiatives.

Safety and efficacy of intermittent presumptive treatment with sulfadoxine-pyrimethamine using rapid diagnostic test screening and treatment with dihydroartemisinin-piperaquine at the first antenatal care visit (IPTp-SP+): study protocol for a randomized controlled trial

Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed. Methods This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday. Discussion A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites. Trial registration Pan African Clinical Trials Registry 201905721140808. Registered retrospectively on 11 May 2019

Diagnostic Performance and Comparison of Ultrasensitive and Conventional Rapid Diagnostic Test, Thick Blood Smear and Quantitative PCR for Detection of Low-Density Plasmodium Falciparum Infections During a Controlled Human Malaria Infection Study in Equatorial Guinea

BackgroundProgress towards malaria elimination has stagnated, partly because infections persisting at low parasite densities comprise a large reservoir contributing to ongoing malaria transmission and are difficult to detect. We compared the performance of an ultrasensitive rapid diagnostic test (uRDT) designed to detect low density infections to a conventional RDT (cRDT), expert microscopy using Giemsa-stained thick blood smears (TBS), and quantitative polymerase chain reaction (qPCR) during a controlled human malaria infection (CHMI) study conducted in malaria exposed adults (NCT03590340). MethodsBlood samples were collected from healthy Equatoguineans aged 18-35 years beginning on day 8 after CHMI with 3.2x103 cryopreserved, infectious Plasmodium falciparum (Pf) sporozoites (PfSPZ Challenge, strain NF54) administered by direct venous inoculation. qPCR (18s ribosomal DNA), uRDT (AlereTM Malaria Ag P.f.), cRDT (Carestart Malaria Pf/PAN (PfHRP2/pLDH)), and TBS were performed daily until the volunteer became TBS positive and treatment was administered. qPCR was the reference for the presence of Pf parasites. Results279 samples were collected from 24 participants; 123 were positive by qPCR. TBS detected 24/123 (19.5% sensitivity [95% CI 13.1% – 27.8%]), uRDT 21/123 (17.1% sensitivity [95% CI 11.1% – 25.1%], cRDT 10/123 (8.1% sensitivity [95% CI 4.2% – 14.8%]; all were 100% specific. qPCR was the most sensitive test (p<0.001); TBS and uRDT were more sensitive than cRDT (TBS vs. cRDT p=0.015; uRDT vs. cRDT p=0.053), detecting parasitemias as low as 3.7 parasites/mL (p/mL) (TBS and uRDT) compared to 5.6 p/mL (cRDT) based on TBS density measurements. TBS, uRDT and cRDT did not detect any of the 70/123 samples positive by qPCR below 5.86 p/mL, the qPCR density corresponding to 3.7 p/mL by TBS. The median prepatent periods in days (ranges) were 14.5 (10-20), 18.0 (15-28), 18.0 (15-20) and 18.0 (16-24) for qPCR, TBS, uRDT and cRDT, respectively; qPCR detected parasitemia significantly earlier (3.5 days) than the other tests.ConclusionsTBS and uRDT had similar sensitivities, both were more sensitive than cRDT, and neither matched qPCR for detecting low density parasitemia. uRDT could be considered an alternative to TBS in selected applications such as CHMI or field diagnosis where qualitative, dichotomous results for malaria infection might be sufficient.

Optimization of Case Definitions for Sensitivity as a Preventive Strategy—A Modelling Exemplified with Rapid Diagnostic Test-Based Prevention of Sexual HIV Transmission

In clinical studies, case definitions are usually designed to optimally match the desired clinical state, because lacking specificity is associated with a risk of bias regarding the study outcome. In preventive medicine, however, high sensitivity is sometimes considered as more critical in order not to overlook infectious individuals, because the latter may be associated with ongoing spread of a transmittable disease. Accordingly, this work was focused on a theoretical model on how the sensitivity of case definitions can be optimized by adding clinical symptoms to diagnostic results for preventive purposes, if the associated reduction in specificity is considered as acceptable. The model was exemplified with an analysis on whether and in how far exposure risk can be reduced by the inclusion of observable symptoms during seroconversion syndrome in case of rapid diagnostic test-based prevention of sexual HIV transmission. The approach provided a high level of safety (negative predictive values close to 1) for the price of a considerably number of false positives (positive predictive values < 0.01 for some subpopulations). When applying such a sensitivity-optimized screening as a “diagnostics as prevention” strategy, the advantages of excellent negative predictive values need to be cautiously balanced against potential undesirable consequences of low positive predictive values.

69. Implementation of a Pharmacist-Driven Blood Culture Communication Process in a Non-Profit Community Hospital

Background Rapid diagnostic testing allows for faster identification of culture results and quicker time to targeted antimicrobial therapy. For this to be effective, however, the clinician needs to understand its capabilities and limitations. Pharmacists are well-positioned to assist providers in interpreting rapid diagnostic test results and in the selection of optimal antimicrobial therapy. This study aims to determine if implementing a process in which pharmacists communicate positive blood culture and rapid diagnostic test results improves time to optimal antimicrobial therapy in a community-based hospital. Methods In November 2020, Mercy Medical Center implemented a new process in which positive blood culture and rapid diagnostic test results are communicated to a pharmacist instead of a nurse on the patient care unit. The pharmacist is responsible for interpreting the results, assessing patient information, and providing the culture results along with drug therapy recommendations to the appropriate licensed independent practitioner. This study was a single-center, pre-post, quasi-experimental study (Pre: November 2019-March 2020; Post: November 2020-March 2021). The electronic medical record was used to identify admitted patients 18 years and older with positive blood cultures in which treatment was provided. Time from culture positivity to optimal antimicrobial therapy was collected and compared pre-post intervention. Secondary outcomes included hospital length of stay and mortality. Results A total of 480 patients were identified during the study period, of which 247 met inclusion criteria (n = 125 in 2019-2020; n = 122 in 2020-2021) with comparable baseline characteristics. There was no statistical difference in time to appropriate therapy between the groups (p = 0.796). Time to optimal therapy was 6.12 hours shorter in the post-intervention cohort (p = 0.0492). No difference was found for both secondary outcomes of hospital length of stay and inpatient mortality (p = 0.2958, p = 0.096, respectively). Conclusion A pharmacist-led blood culture communication process improved the care of hospitalized patients in a non-academic, community-based hospital by shortening time to optimal antimicrobial therapy. Disclosures All Authors: No reported disclosures