Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study.

BACKGROUND: Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future "screen and treat" strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests. METHODS: During active screening, venous blood samples from 1095 individuals from Côte d'Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar. RESULTS: One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1-99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5-88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7-84.2%); DCN HAT RDT 78.2% (95% CI: 75.7-80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9-80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7-100% (n = 399) and 93.0-100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity. CONCLUSIONS: Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based "screen and treat" strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT. TRIAL REGISTRATION: The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.

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.

[Biological threats to global malaria elimination II Deletion in the malaria rapid diagnostic test target Plasmodium falciparum histidine-rich protein 2/3 genes].

The global malaria epidemic is still severe. Because of simple procedures, rapid detection and accuracy results, rapid diagnostic test (RDT) has become the most important and the most widely used diagnostic tool for malaria prevention and control. However, deletions in the RDT target Plasmodium falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes may cause false-negative results of RDT, which has been included as one of the four biological threats to global malaria elimination. This article reviews the applications of RDT in the global malaria diagnosis, analyzes the threats and challenges caused by Pfhrp2/3 gene deletion, proposes methods for monitoring Pfhrp2/3 gene deletion, and summarizes the causes and countermeasures of negative RDT detections, so as to provide insights into consolidation of malaria elimination achievements in China and contributions to global malaria elimination.

Evaluation of blood based quantitative PCR as a molecular diagnostic tool for post kala-azar dermal leishmaniasis (PKDL).

BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is a consequential dermal manifestation of visceral leishmaniasis (VL), serving as a parasite reservoir. The traditional diagnostic approach, which requires an invasive skin biopsy is associated with inherent risks and necessitates skilled healthcare practitioners in sterile settings. There is a critical need for a rapid, less invasive method for Leishmania detection. The main objective of this study was to evaluate and compare the diagnostic efficacy of PCR and qPCR in detecting PKDL, utilizing both skin and blood samples and to assess the utility of blood samples for molecular diagnosis. METHODS AND RESULTS: 73 individuals exhibiting clinical symptoms of PKDL and who had tested positive for rK39 rapid diagnostic test (RDT) were enrolled in this study. For the diagnosis of PKDL, both PCR and real-time quantitative PCR (qPCR), employing SYBR Green and TaqMan assays, were performed on blood and skin matched samples. qPCR results using both TaqMan and SYBR Green assay, indicated higher parasite loads in the skin compared to blood, as evident by the Ct values. Importantly, when blood samples were used for PKDL diagnosis by qPCR, an encouraging sensitivity of 69.35% (TaqMan assay) and 79.36% (SYBR Green) were obtained, compared to 8.2% with conventional PCR. CONCLUSION: The findings of the study suggest the potential utility of blood for molecular diagnosis by qPCR, offering a less invasive alternative to skin biopsies in field setting for the early detection of parasitaemia in PKDL patients and effective management and control of the disease.

Prehospital use of point-of-care tests by community health workers: a scoping review.

Introduction: Point-of-Care Tests (POCTs) are utilized daily in resource abundant regions, however, are limited in the global south, particularly in the prehospital setting. Few studies exist on the use of non-malarial POCTs by Community Health Workers (CHWs). The purpose of this scoping review is to delineate the current diversity in and breadth of POCTs evaluated in the prehospital setting. Methods: A medical subject heading (MeSH) analysis of known key articles was done by an experienced medical librarian and scoping searches were performed in each database to capture "point of care testing" and "community health workers." This review was guided by the PRISMA Extension for scoping reviews. Results: 2735 publications were returned, 185 were nominated for full-text review, and 110 studies were confirmed to meet study criteria. Majority focused on malaria (74/110; 67%) or HIV (25/110; 23%); 9/110 (8%) described other tests administered. Results from this review demonstrate a broad geographic range with significant heterogeneity in terminology for local CHWs. Conclusion: The use of new POCTs is on the rise and may improve early risk stratification in limited resource settings. Current evidence from decades of malaria POCTs can guide future implementation strategies.

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for 7 tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the 5 best performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 best performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to Zika virus. For the detection of previous DENV infections the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

Prevalence of HIV, Hepatitis C and Hepatitis B Infection Among Detainees in a French Administrative Detention Centre.

BACKGROUND: In France, migrants constitute a significant proportion of people diagnosed with HIV, hepatitis C (HCV) and B (HBV). This study estimated the prevalence of these three viruses among detainees at a French administrative detention centre (CRA), through systematic Rapid Diagnostic Test (RDT) screening. METHODS: This prospective, single-centre, cross-sectional, pilot study included detainees at the Nîmes CRA from February to December 2022. The primary endpoint was HIV, HCV and HBV prevalence determined by RDT. Secondary outcomes were: co-infections; study acceptability, reasons for non-inclusion, causes of non-contributory samples; and concordance between serological tests and RDT. RESULTS: Among the 350 people agreeing to participate of 726 eligible, five refused the RDT, leaving 345 analysable participants for a participation rate of 47.5% (345/726). Participants were predominantly male (90%) with an average age of 31 years. The most common country of origin was Algeria (34%). Twenty (6%) had taken drugs intravenously and 240 (70%) had had unprotected sex within a median of 4.92 [1.08; 15] months. Virus prevalence was: 0% HIV; 4.64 [2.42; 6.86] % HCV; and 2.32 [1.01; 4.52] % HBV. Eleven (73%) of the RDT HCV positive cases were confirmed serologically. RDT detected one false-positive HCV case, as an anti-HCV Ac serological test was negative. Of the eight patients with positive HBV RDT, one declined the serology testing, thus 100% (7/7) of the tested RDT positive cases were confirmed by serology. CONCLUSION: The study highlighted the need to screen detainees for HIV, HCV and HBV infection and suitability of RDTs.

In vitro diagnostic methods of Chagas disease in the clinical laboratory: a scoping review.

Background: Chagas disease (CD), caused by Trypanosoma cruzi, is a global health concern with expanding geographical reach. Despite improved and accessible test methods, diagnosing CD in its various phases remains complex. The existence of clinical scenarios, including immunosuppressed patients, transplant-related CD reactivation, transfusion-associated cases, and orally transmitted acute infections, adds to the diagnostic challenge. No singular gold standard test exists for all phases, and recommendations from PAHO and the CDC advocate for the use of two serological methods for chronic CD diagnosis, while molecular methods or direct parasite detection are suggested for the acute phase. Given the complexity in the diagnostic landscape of CD, the goal of this scoping review is to characterize available diagnostic tests for CD in the clinical laboratory. Methods: A literature search in PubMed was conducted on studies related to In vitro diagnosis (IVD) in humans published in English, Spanish, or Portuguese language as of 28 August 2023, and extended backward with no predefined time frame. Studies underwent title and abstract screening, followed by full-text review. Studies included were classified based on the diagnostic method used. Test methods were grouped as serological, molecular, and other methods. Performance, availability, and regulatory status were also characterized. Results: Out of 85 studies included in the final review, 115 different tests were identified. These tests comprised 89 serological test types, 21 molecular test types, and 5 other test methods. Predominant serological tests included ELISA (38 studies, 44.70%), Rapid tests (19 studies, 22.35%), and chemiluminescence (10 studies, 11.76%). Among molecular tests, Polymerase Chain Reaction (PCR) assays were notable. Twenty-eight tests were approved globally for IVD or donor testing, all being serological methods. Molecular assays lacked approval for IVD in the United States, with only European and Colombian regulatory acceptance. Discussion and conclusion: Serological tests, specifically ELISAs, remain the most used and commercially available diagnostic methods. This makes sense considering that most Chagas disease diagnoses occur in the chronic phase and that the WHO gold standard relies on 2 serological tests to establish the diagnosis of chronic Chagas. ELISAs are feasible and relatively low-cost, with good performance with sensitivities ranging between 77.4% and 100%, and with specificities ranging between 84.2% and 100%. Molecular methods allow the detection of specific variants but rely on the parasite's presence, which limits their utility to parasitemia levels. Depending on the PCR method and the phase of the disease, the sensitivity ranged from 58.88 to 100% while the mean specificity ranged from 68.8% to 100%. Despite their performance, molecular testing remains mostly unavailable for IVD use. Only 3 molecular tests are approved for IVD, which are available only in Europe. Six commercial serological assays approved by the FDA are available for blood and organ donor screening. Currently, there are no guidelines for testing CD oral outbreaks. Although more evidence is needed on how testing methods should be used in special clinical scenarios, a comprehensive approach of clinical assessment and diagnostics tests, including not IVD methods, is required for an accurate CD diagnosis.

Circulation of yellow fever virus in Benin city, Edo state Nigeria.

Yellow fever (YF) is one of the most acute viral hemorrhagic diseases of the 18th and 19th centuries, which continues to cause severe morbidity and mortality in Africa. After 21 years of no reported cases of yellow fever in Nigeria, till 2017 where a case was confirmed in Kwara State, also in November 2018,WHO was informed of a cluster of suspected yellow fever cases and deaths in Edo state, Nigeria. The study was among all age group attending health centres in Benin City, Edo state. A total of 280 blood samples were collected from consented febrile patients and were screened for antibodies to Zika virus using rapid diagnostic test (RDT) kits. Blood samples positive to Zika virus (IgM/IgG RDT), were subjected to molecular characterization. Using the flavividae family primers, six (6) samples where confirmed positive by Hemi-nested reverse transcription PCR (hnRT-PCR) sequencing. Nucleotide sequence blast revealed the sequenceswere similar to Yellow fever virus strains. Phylogenetic analysis revealed that the yellow fever virus sequences are closely related to the African strains. Despite the safe and effective yellow fever vaccine, yellow fever virus is seen to be in circulation, hence the need for continues mass vaccination.

Comparison of SD Bioline Malaria Ag Pf/Pan and Acro Malaria P.f./P.v./Pan with Microscopy and Real Time PCR for the Diagnosis of Human Plasmodium Species.

The early diagnosis of malaria is crucial to controlling morbidity and mortality. The World Health Organization (WHO) recommends diagnosing malaria either using light microscopy or a malaria rapid diagnostic test (RDT). Most RDTs use antibodies to detect two P. falciparum histidine-rich proteins named PfHRP2 and PfHRP3. However, false-negative results are known to occur due to the poor performance of RDTs depending on the species and the deletion of the Pfhrp2 and Pfhrp3 genes. This study evaluated new malaria RDTs for the detection of the human Plasmodium species. The Acro Malaria P.f./P.v./Pan Rapid Test Cassette allows the qualitative detection of parasite antigens, such as PfHRP2 specific to Plasmodium falciparum, PvLDH specific to Plasmodium vivax, and/or panLDH Plasmodium genus lactate dehydrogenase, in the blood of infected individuals. This RDT was assessed against 229 samples collected from imported malaria cases, mainly from Africa. The samples were previously diagnosed using light microscopy and RDT (SD Malaria Ag P.f./Pan, SD Bioline Alere Abbott), then confirmed using real time PCR. The two RDTs were evaluated using a comparison with real time PCR as the reference method, and their performances were compared with each other. Compared to SD RDT, the Acro RDT showed a better sensitivity to P. falciparum (96.8% vs. 89.8%), P. vivax (78.6% vs. 64.3%), P. ovale (73.7% vs. 5.3%), and P. malariae (20.0% vs. 0%). The respective specificities of the Acro RDT and SD RDT are 90.7% vs. 95.3% to P. falciparum, 100% to P. vivax, and 100% vs. 100% to Plasmodium genus. Therefore, Acro RDT showed better performance in the identification of P. ovale and low parasitaemia of P. falciparum. In addition, Acro RDT has the advantage of detecting PvLDH-specific antigens. The Acro Malaria RDT presents the benefits of detecting a P. falciparum antigen (PfHRP2) and a P. vivax antigen (PvLDH) with high sensitivity (96.8% and 73.7%, respectively) and specificity (90.7% and 100%, respectively). Acro Malaria P.f./P.v./Pan rapid diagnostic tests could be effectively used in endemic areas, especially when microscopic examination cannot be performed.

Cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural Cambodia and Bangladesh.

Background: Multiplex lateral flow rapid diagnostic tests (LF-RDTs) may aid management of patients with acute non-malarial febrile illness (NMFI) in rural south and southeast Asia. We aimed to evaluate the cost-effectiveness in Cambodia and Bangladesh of a putative, as-yet-undeveloped LF-RDT capable of diagnosing enteric fever and dengue, as well as measuring C-reactive protein (CRP) to guide antibiotic prescription, in primary care patients with acute NMFI. Methods: A country-specific decision tree model-based cost-effectiveness analysis was conducted from a health system plus limited societal perspective considering the cost of antimicrobial resistance. Parameters were based on data from a large observational study on the regional epidemiology of acute febrile illness, published studies, and procurement price lists. Costs were expressed in US$ (value in 2022), and cost-effectiveness evaluated by comparing incremental cost-effectiveness ratios with conservative opportunity cost-based willingness-to-pay thresholds and the more widely used threshold of per capita gross domestic product (GDP). Findings: Compared to standard of care, LF-RDT-augmented clinical assessment was dominant in Cambodia, being more effective and cost-saving. The cost per disability-adjusted life year (DALY) averted in Bangladesh was US$482, slightly above the conservative opportunity cost-based willingness-to-pay threshold of US$388 and considerably lower than the GDP-based threshold of US$2687. The intervention remained dominant in Cambodia and well below the GDP-based threshold in Bangladesh when antimicrobial resistance costs were disregarded. Interpretation: These findings provide guidance for academic, industry, and policymaker stakeholders involved in acute NMFI diagnostics. While definitive conclusions cannot be made in the absence of established thresholds, our results suggest that similar results are highly likely in some target settings and possible in others. Funding: Wellcome Trust, UK Government, Royal Australasian College of Physicians, and Rotary Foundation.

Communication: Evaluation of the Humasis COVID-19 Antigen Rapid Diagnostic Test for the Diagnosis of SARS-CoV-2 Infection.

OBJECTIVE: We assessed the performance of the Humasis COVID-19 AgHS Test (Humasis, Korea), a novel antigen rapid diagnostic test (Ag-RDT) based on lateral flow immunoassay. METHODS: 85 SARS-CoV-2-positive and 155 SARS-CoV-2-negative nasopharyngeal swab specimens confirmed by rRT-PCR were tested using the Humasis and PBCheck Ag-RDTs. The analytical specificity of the Humasis Ag-RDT was evaluated using 27 strains of human respiratory pathogens. RESULTS: The overall sensitivity and specificity were 72.9% and 99.4% for the Humasis Ag-RDT and 64.7% and 100% for the PBCheck Ag-RDT, respectively. The sensitivity for specimens with Ct≤25 was 100% for both Ag-RDTs. The Humasis Ag-RDT showed no cross-reactivity with other respiratory pathogens. CONCLUSION: Our data suggests that the Humasis Ag-RDT can be a useful diagnostic tool for the detection of SARS-CoV-2 infection.

Lesson Learned from Mass Antibody Rapid Diagnostic Used in the Early COVID-19 Pandemic in Indonesia Contributors.

Introduction: Laboratory examination is extremely important in handling the COVID-19 pandemic. In the first era of the pandemic, the molecular and antigen tests were limited. Hence, at that time, it was necessary to carry out antibody Rapid Diagnostic Tests (RDT). However, many antibody RDTs were yet to obtain Food and Drug Authorization (FDA)'s approval. Purpose: Therefore, The Indonesian Association of Clinical Pathology and Medical Laboratory (PDS PatKLIn) decided to conduct a validity test of RDT antibodies to find out the quality of SARS-CoV-2 diagnosis performance based on these RDTs used. Patient and Methods: This is a descriptive observational design with diagnostic analysis. The retrospective secondary data were collected from 34 provinces in Indonesia from May to June 2020. Data analysis was carried out on the sensitivity and specificity values of each antibody RDT brand to the RT-PCR result and analyzed descriptive data. Results: The amount of secondary data of antibody RDT and RT-PCR results collected was 139,908, consisting of 59 RDT brands of which 44% were authorized by The Indonesian COVID-19 Response Acceleration Task Force (Gugus Tugas Percepatan Penanganan COVID-19 Indonesia). There were huge variations of SARS-CoV-2 antibody RDT performance between total antibody types (sensitivity 59.18%, specificity 62%), IgM RDT (sensitivity 16-100%, specificity 7-97%), and RDT IgG (sensitivity 33-96%, specificity 19-100%). Conclusion: The variations in the RDT antibodies'performance can cause errors in diagnosis leading to significant material and immaterial losses. Therefore, cooperation from various parties is needed for the pre- and post-marketing surveillance process to assess the performance and the characteristics of each RDT kit and other diagnostic methods to assist the rapid pandemic response process.

Assessment of the Performance of Lactate Dehydrogenase-Based Rapid Diagnostic Test for Malaria in Djibouti in 2022-2023.

Until 2020, Djiboutian health authorities relied on histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) to establish the diagnosis of Plasmodium falciparum. The rapid spread of P. falciparum histidine-rich protein-2 and -3 (pfhrp2/3) gene-deleted parasite strains in Djibouti has led the authorities to switch from HRP2-based RDTs to lactate dehydrogenase (LDH)-based RDTs targeting the plasmodial lactate dehydrogenase (pLDH) specific for P. falciparum and P. vivax (RapiGEN BIOCREDIT Malaria Ag Pf/Pv pLDH/pLDH) in 2021. This study was conducted with the primary objective of evaluating the diagnostic performance of this alternative RDT. Operational constraints related, in particular, to the implementation of this RDT during the COVID-19 pandemic were also considered. The performance of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT was also compared to our previously published data on the performance of two HRP2-based RDTs deployed in Djibouti in 2018-2020. The diagnosis of 350 febrile patients with suspected malaria in Djibouti city was established using two batches of RapiGEN BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT over a two-year period (2022 and 2023) and confirmed by real-time quantitative polymerase chain reaction. The sensitivity and specificity for the detection of P. falciparum were 88.2% and 100%, respectively. For P. vivax, the sensitivity was 86.7% and the specificity was 100%. Re-training and closer supervision of the technicians between 2022 and 2023 have led to an increased sensitivity to detect P. falciparum (69.8% in 2022 versus 88.2% in 2023; p < 0.01). The receiver operating characteristic curve analysis highlighted a better performance in the diagnosis of P. falciparum with pLDH-based RDTs compared with previous HRP2-based RDTs. In Djibouti, where pfhrp2-deleted strains are rapidly gaining ground, LDH-based RDTs seem to be more suitable for diagnosing P. falciparum than HRP2-based RDTs. Awareness-raising and training for technical staff have also been beneficial.

The diagnostic performance evaluation of Panbio and STANDARD Q coronavirus disease 2019 antigen tests against real-time polymerase chain reaction in southern Ethiopia.

The coronavirus disease 2019 (COVID-19) pandemic has created a public health crisis. This study aimed to evaluate the diagnostic performance of the Panbio and STANDARD Q COVID-19 antigen rapid diagnostic tests (RDTs) against the real-time polymerase chain reaction (RT-PCR) at one of the largest hospitals in southern Ethiopia. Nasopharyngeal samples, which were collected during the pandemic from individuals suspected of COVID-19 and stored at - 70 °C, were analyzed in June and July 2022. The performance of the Panbio COVID-19 antigen tests was evaluated in 200 randomly selected nasopharyngeal samples (100 positives and 100 negatives for severe acute respiratory syndrome 2 by RT-PCR). The STANDARD Q test was evaluated using 100 positive and 50 negative samples. The respective sensitivity, specificity, positive predictive value and negative predictive values were 88%, 99%, 98.9% and 89.2% for the Panbio test and 91%, 98%, 98.9% and 84.5%, for the STANDARD Q test. The kappa values were 0.87 for the Panbio and 0.86 for the STANDARD Q test. Based on the findings presented here, the RDTs could be utilized as an alternative to conventional RT-PCR when it is challenging to diagnose COVID-19 owing to a lack of time, skilled lab personnel, or suitable equipment or electricity.

Temporal Trend of the SARS-CoV-2 Omicron Variant and RSV in the Nasal Cavity and Accuracy of the Newly Developed Antigen-Detecting Rapid Diagnostic Test.

The aim of this work is to analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two-antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection.

Assessment of pre-referral treatment for malaria, diarrhea, and pneumonia by rural community health workers in Southwestern Uganda: a cross-sectional study.

BACKGROUND: Pre-referral treatment aims to stabilize the child's condition before transferring them to a higher level of healthcare. This study explored pre-referral treatment for diarrhea, malaria and pneumonia in children U5. The study aims to assess pre-referral treatment practices among community health workers (CHWs) for children aged 2 to 59 months diagnosed with malaria, diarrhea, and pneumonia. METHODS: Conducted in 2023, this study employed a quantitative retrospective analysis of secondary data gathered from March 2014 to December 2018. Among the subjects, 171 patients received pre-referral treatment, serving as the foundation for categorical data analysis, presenting proportions and 95% confidence intervals across different categories. RESULTS: In this cohort, 90 (53%) of the 177 children U5 were male, and age distribution showed 39 (23%), 70 (41%), and 62 (36%) in the 2-11 months, 12-35 months, and 36-60 months categories, respectively. Rapid Diagnostic Test (RDT) malaria results indicated a negative outcome in 83(60%) and positive in 55 (40%) of cases. Symptomatically, 45 (26%) had diarrhea, 52 (30%) exhibited fast breathing, and 109 (63%) presented with fever. Furthermore, 59 (35%) displayed danger signs, while 104 (61%) sought medical attention within 24 h. CONCLUSION: The study analyzed a sample of 171 children under 5 years old to assess various characteristics and variables related to pre-referral treatment. The findings reveal notable proportions in gender distribution, age categories, RDT results, presence of diarrhea, fast breathing, fever, danger signs, and timely medical visits. The results highlight the need to strengthen pre-referral treatment interventions and enhance iCCM programs.

The basic reproduction number (R0) of ebola virus disease: A systematic review and meta-analysis.

BACKGROUND: Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R0): the average number of new cases associated with an Ebola case in a completely susceptible population. METHODS: We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (Rt). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R0 was determined by a random-effects meta-analysis. R0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R0) × 100 %. RESULTS: The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R0 was 1.95 (95 % CI 1.74-2.15), with high heterogeneity (I2 = 99.99 %; τ2 = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R0 values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R0 was 9.38 (95 % CI 4.16-14.59) in Nigeria, 3.31 (95 % CI 2.30-4.32) in DR Congo, 2.0 (95 % CI 1.25-2.76) in Uganda, 1.83 (95 % CI 1.61-2.05) in Liberia, 1.73 (95 % CI 1.47-2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29-1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective. CONCLUSIONS: Ebola R0 varies widely across countries. Ebola has a much wider R0 range than is often claimed (1.3-2.0). It is possible for an Ebola index case to infect more than two susceptible individuals.

Comparison of the Diagnostic Performances of Five Different Tests in Diagnosing Visceral Leishmaniasis in an Endemic Region of Ethiopia.

The lack of accurate and feasible diagnostic tests poses a significant challenge to visceral leishmaniasis (VL) healthcare services in endemic areas. To date, various VL diagnostic tests have been or are being developed, and their diagnostic performances need to be assessed. In the present study, the diagnostic performances of rk39 RDT, the direct agglutination test (DAT), microscopy, loop-mediated isothermal amplification (LAMP), and miniature direct-on-blood polymerase chain reaction-nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) were assessed using quantitative polymerase chain reaction (qPCR) as the reference test in an endemic region of Ethiopia. In this study, 235 suspected VL cases and 104 non-endemic healthy controls (NEHCs) were recruited. Among the suspected VL cases, 144 (61.28%) tested positive with qPCR. The sensitivities for rk39 RDT, DAT, microscopy, LAMP assay, and mini-dbPCR-NALFIA were 88.11%, 96.50%, 76.58%, 94.33%, and 95.80%, respectively. The specificities were 83.33%, 97.96%, 100%, 97.38%, and 98.92% for rk39 RDT, DAT, microscopy, LAMP assay, and mini-dbPCR-NALFIA, respectively. In conclusion, rk39 RDT and microscopy exhibited lower sensitivities, while DAT demonstrated excellent performance. LAMP and mini-dbPCR-NALFIA showed excellent performances with feasibility for implementation in remote endemic areas, although the latter requires further evaluation in such regions.

Usefulness of the Rapid Antigen Test in Detecting SARS-CoV-2 for Infection Control in Hospitals.

BACKGROUND: We aimed at evaluating the diagnostic performance of rapid antigen test (RAT) compared to polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 and the possible transmission of infection to close contacts from patients with negative RAT and positive PCR results. MATERIALS AND METHODS: Patients/guardians urgently requiring admission to the ward on the same day had been hospitalized with RAT-negative result before the PCR results were available. We performed an epidemiologic investigation of the close contacts of those with negative RAT but positive PCR results after hospitalization. RESULTS: A total of 4,237 RATs were performed from March to August 2022. When the PCR test was used as the reference, RAT had a sensitivity of 28.8% (17/59; 95% confidence interval [CI], 17.8 - 42.1), a specificity of 100% (4,220/4,220; 95% CI, 99.9 - 100.0), a positive predictive value of 100.0% (17/17; 95% CI, 100.0 - 100.0), and a negative predictive value of 99.0% (4,178/4,220; 95% CI, 99.3 - 99.8). The epidemiologic investigation revealed that among the 32 patients with negative RAT and subsequent positive PCR results after admission into multi-patient room, two (6.3%) showed secondary coronavirus disease 2019. CONCLUSION: The secondary transmission rate from patients with negative RAT and positive PCR results was low. Our data suggest that RAT may be useful for rapid exclusion of high transmissible cases. However, further evaluation using whole genome sequencing is needed to determine the potential for transmissibility in cases showing a negative RAT but a positive PCR result.