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\"By presenting chapter-specific roadmaps, this book offers a behind-the-scenes chronology of the response to COVID-19 and provides a rubric for future pandemic response. Targeted at lay and scientific audiences, reflections and lessons learned grant the reader an opportunity to leverage this knowledge and improve the outcomes of future pandemics\"-- Provided by publisher.

Background Rapid diagnostic tests (RDTs) are effective tools to diagnose and inform the treatment of malaria in adults and children. The recent development of a highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum has prompted questions over whether it could improve the diagnosis of malaria in pregnancy and pregnancy outcomes in malaria endemic areas. Methods This landscape review collates studies addressing the clinical performance of the HS-RDT. Thirteen studies were identified comparing the HS-RDT and conventional RDT (co-RDT) to molecular methods to detect malaria in pregnancy. Using data from five completed studies, the association of epidemiological and pregnancy-related factors on the sensitivity of HS-RDT, and comparisons with co-RDT were investigated. The studies were conducted in 4 countries over a range of transmission intensities in largely asymptomatic women. Results Sensitivity of both RDTs varied widely (HS-RDT range 19.6 to 85.7%, co-RDT range 22.8 to 82.8% compared to molecular testing) yet HS-RDT detected individuals with similar parasite densities across all the studies including different geographies and transmission areas [geometric mean parasitaemia around 100 parasites per µL (p/µL)]. HS-RDTs were capable of detecting low-density parasitaemias and in one study detected around 30% of infections with parasite densities of 0–2 p/µL compared to the co-RDT in the same study which detected around 15%. Conclusion The HS-RDT has a slightly higher analytical sensitivity to detect malaria infections in pregnancy than co-RDT but this mostly translates to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity. The analysis presented here highlights the need for larger and more studies to evaluate incremental improvements in RDTs. The HS-RDT could be used in any situation where co-RDT are currently used for P. falciparum diagnosis, if storage conditions can be adhered to.

The coronavirus disease (COVID-19) pandemic has created an urgent need for rapid, accurate, and cost-effective diagnostic tools. In this study, an economical electrochemical immunosensor for the rapid diagnosis of COVID-19 was developed and optimized based on charge transfer resistance (Rct) values obtained by electrochemical impedance spectroscopy (EIS) from the interaction between antibodies (anti-SARS-CoV-2) immobilized as a bioreceptor and the virus (SARS-CoV-2). The sensor uses modified pencil graphite electrodes (PGE) coated with poly(4-hydroxybenzoic acid), anti-SARS-CoV-2, and silver nanoparticles. The immobilization of anti-SARS-CoV-2 antibodies was optimized at a concentration of 1:250 for 30 min, followed by blocking the surface with 0.01% bovine serum albumin for 10 min. The optimal conditions for virus detection in clinical samples were a 1:10 dilution with a response time of 20 min. The immunosensor responded linearly in the range of 0.2–2.5 × 106 particles/μL. From the relationship between the obtained signal and the concentration of the analyzed sample, the limit of detection (LOD) and limit of quantification (LOQ) obtained were 1.21 × 106 and 4.04 × 106 particles/μL, respectively. The device did not cross-react with other viruses, including Influenza A and B, HIV, and Vaccinia virus. The relative standard deviation (RSD) of the six immunosensors prepared using the shared-pool sample was 3.87. Decreases of 22.3% and 12.4% were observed in the response values of the ten immunosensors stored at 25 °C and 4.0 °C, respectively. The sensor provides timely and accurate results with high sensitivity and specificity, offering a cost-effective alternative to the existing diagnostic methods.

Background Routine testing for cancer patients not presenting COVID‐19‐related symptoms and fully vaccinated for SARS‐CoV‐2 prior to cancer treatment is controversial. Methods In this retrospective study we evaluated whether antigen‐rapid‐diagnostic‐test (Ag‐RDT) monitoring for SARS‐CoV‐2 in a large cohort of consecutive asymptomatic (absence of SARS‐CoV‐2‐related symptoms such as fever, cough, sore throat or nasal congestion) and fully vaccinated cancer patients enrolled in a short period during cancer treatment has an impact on the therapeutic path of cancer patients. Results From December 27, 2021, to February 11, 2022, 2439 cancer patients were screened through Ag‐RDT for SARS‐CoV‐2 before entering the hospital for systemic treatment. Fifty‐three patients (2.17%) tested positive, of whom 7 (13.2%) subsequently developed COVID‐related symptoms, generally mild. Cancer treatment was discontinued, as a precaution, in 49 patients (92.5%) due to the test positivity. Conclusion SARS‐CoV‐2 screening in asymptomatic and fully vaccinated cancer patients during systemic treatment appeared to be not cost‐effective: the low rate of SARS‐CoV‐2 positive patients and the low percentage of overt associated infection do not seem proportional to the direct costs (nursing work for swabs, costs of materials and patient monitoring) and indirect costs (dedicated rooms, extension of waiting times for patients and oncologists in delivering therapy as well as its discontinuation in the positive ones). It can, on the other hand, be detrimental when systemic cancer treatment is suspended as a precaution. Given the small number of patients testing positive and the rapid and favorable trend of the infection, it is recommended to always consider continuing systemic oncological treatment, especially when this impacts patient survival as in the adjuvant or neoadjuvant setting. SARS‐CoV‐2 screening in asymptomatic and fully‐vaccinated cancer patients during systemic treatment appeared to be not cost‐effective.

Background The introduction of malaria rapid diagnostic tests (RDTs) has expanded the parasitological confirmation of malaria at all levels of health systems in sub-Saharan Africa, improving case management and surveillance. However, concerns persist regarding healthcare worker adherence to RDT outcomes and the accuracy of RDT results recorded in health facility registers. Electronic RDT readers have been proposed to improve the consistency of interpretation and reporting. The HealthPulse smartphone application (Audere, Seattle, WA, USA), an RDT reader using an artificial intelligence (AI) computer vision algorithm, was assessed against a trained human panel interpreting RDT results from photographs to determine the application’s performance characteristics. Methods In 2023, the Malaria Rapid Diagnostic Test Capture and Reporting Assessment (MaCRA) was implemented in health facilities in Benin, Côte d’Ivoire, Nigeria, and Uganda. Study staff photographed malaria RDTs using the HealthPulse application after healthcare workers performed and interpreted the tests. A trained panel of external reviewers interpreted the RDT images and served as the reference standard. RDTs in the images were classified according to the manufacturer’s instructions as positive, negative or invalid (i.e., no visible control line) or labelled as uninterpretable (i.e., visibility was impeded). The performance of the HealthPulse AI algorithm was evaluated using percent accuracy, recall (i.e., sensitivity and specificity), precision (i.e., positive and negative predictive values), and F1 scores (harmonic mean of recall and precision) weighted by the number of each outcome. Logistic regression was applied to assess factors influencing recall across countries, RDT products, presence of faint lines, and anomalies. Results Of the 110,843 RDT images collected, 106,877 (96.4%) were included in the analysis. The AI algorithm demonstrated high accuracy (96.8%; 95% confidence interval (CI) 96.7%, 96.9%) compared with the panel interpretation and an overall F1 score of 96.6. Recall and precision were > 97% for positive and negative outcomes but much lower for invalid (recall: 84.8%; precision: 42.8%) and uninterpretable (recall: 0.8%; precision: 2.3%) classifications. AI performance varied by country, RDT product, the presence of faint lines and the quality of the image. When test lines were faint, the AI algorithm was significantly less likely to recall both positive results (adjusted odds ratio (aOR) 0.02; 95% CI 0.02, 0.02) and negative results (aOR 0.10; 95% CI 0.07, 0.16). Conclusions The HealthPulse AI algorithm demonstrated strong agreement with a trained panel in interpreting malaria RDT images across diverse settings. However, the reduced performance for invalid outcomes and varying performance by country, RDT product and faint lines highlight the need for further research and refinement. The HealthPulse application shows potential as a supportive tool in research, training, surveillance, and quality assurance.

After a pilot study, we tested 443 cadavers using OraQuick Ebola rapid diagnostic tests during surveillance after the 10th Ebola outbreak in the Democratic Republic of the Congo. No false negative and 2% false-positive results were reported. Quickly returning results and engaging the community enabled timely public health actions.

Background Malaria diagnosis by Rapid Diagnostic Test (RDT) is challenged by the newly emerging histidine-rich protein 2 (HRP2) gene deletion in the Plasmodium falciparum species. The alternative lactate dehydrogenase (LDH)-dependent RDTs suffer from low sensitivity, and improvement in the sensitivity of LDH RDTs is the cornerstone for detecting the (HRP2) gene deletion species. This study aimed to evaluate a novel, improved Mologic Malaria Pf LDH-dependent RDT for the diagnosis of P. falciparum malaria in partnership with the Foundation for Innovative Diagnostics (FIND), Switzerland. Methods This is a descriptive cross-sectional study evaluating the clinical performance of the improved Mologic LDH- RDT in two rural sites in Khartoum state, Sudan. Five hundred patients presenting with symptoms suggestive of malaria in the two primary care health centres were enrolled after signing informed consent. Finger-prick blood was collected for examination with microscopy, the index Mologic LDH RDT, the comparator RDT, and preparation of DBS for PCR, the reference method. Results The mean age of the study subjects was 31 years, ranging from 5 to 80 years. Out of 500 patients, 210 (42%) were positive by PCR, 200 (40%) by expert microscopy, 193 (38.6%) by index Mologic LDH RDT, and 199 (39.8%) by comparator RDT. The sensitivities of microscopy, index RDT, and comparator RDT were 95.24% (95% CI, 91.4–97.6), 91.9% (95% CI, 87.3–95.2), and 93.81% (95% CI, 89.6–96.6), respectively. All tests were nearly 100% specific for the detection of P. falciparum parasites. The concordance test showed almost perfect agreement with the reference test ( κ  = 0.929). Six samples were P. falciparum HRP2 Ag negative and were detected by Mologic LDH RDT. A limitation of this study is that there is no confirmation of HRP2 gene deletion by PCR. Conclusion The novel Mologic LDH RDT showed performance concordant with standard expert microscopy and the comparator HRP2-based RDT. The sensitivity of the Mologic LDH RDT makes it suitable for the clinical management of P. falciparum HRP2 negative malaria.

Background Accurate and efficient malaria diagnosis is critical for effective malaria control and elimination. Rapid diagnostic tests (RDTs) have been deployed over the last decade, particularly in rural and low-and-middle-income countries, as an alternative to microscopy-based diagnosis. Methods This study analysed retrospective health data from the Solomon Islands District Health Information System (DHIS2) for 2017–2019, focusing on factors affecting diagnostic test selection and positivity rates for microscopy versus RDTs. Results The national Annual Parasite Incidence (API) of malaria declined over the 3 years, with localised increases in specific health zones. The choice of malaria diagnostic test was associated with administrative division, patient age, health facility type and year. Overall, RDTs had higher malaria positivity rates than microscopy for both Plasmodium falciparum (microscopy, 6%; RDT, 11%) and Plasmodium vivax (microscopy, 10%; RDT, 14%). Conclusions RDTs were more widely used than microscopy in health facilities and had higher test positivity rates. This study highlights the factors influencing diagnostic test selection and underscores the importance of considering detection limits and potential overdiagnosis when interpreting positivity rates from different diagnostic methods.

This study was aimed at investigating risk factors for mortality in patients suffering from KPC-producing Klebsiella pneumoniae (KPC-Kp) bloodstream infections (BSIs), evaluating the impact of rapid diagnostics and ceftazidime/avibactam use. This observational retrospective study (January 2017–May 2021) included all patients with a KPC-Kp BSI. Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on both in-hospital death (IHD) and 30-day all-cause mortality, and the role of the combination of ceftazidime/avibactam plus polymyxin. One hundred and ninety-six patients met the study’s inclusion criteria. Older age, having undergone renal replacement therapy during the 30 days preceding the KPC-Kp BSI onset, having an INCREMENT-CPE score ≥ 8, and having suffered from a superimposed and/or following KPC-Kp BSI treatment candidemia were found to be the main factors associated with both mortality rates. Among protective factors, the centrality of ceftazidime/avibactam in monotherapy (IHD: OR: 0.34; CI 95%: 0.11–1.00—30-day all-cause mortality: OR: 0.18; CI 95%: 0.04–0.77) or combination (IHD: OR: 0.51; CI 95%: 0.22–1.19—30-day all-cause mortality: OR: 0.62; CI 95%: 0.21–1.84) emerged and became even more evident once the effect of ceftazidime/avibactam plus polymyxin was removed. Rapid diagnostics may be useful to adopt more effective strategies for the treatment of KPC-Kp BSI patients and implement infection control measures, even if not associated with higher patient survival. Ceftazidime/avibactam, even when used alone, represents an important option against KPC-Kp, while combined use with polymyxin might not have altered its efficacy. Patient comorbidities, severity of BSI, and complications such as candidemia were confirmed to have a significant burden on survival.

Background Rapid diagnostic tests (RDTs) based on Plasmodium falciparum histidine-rich protein 2 ( Pf HRP2-RDTs) are widely used for malaria diagnosis. However, the efficacy of Pf HRP2-RDTs is compromised by deletions and genetic variations in the pfhrp2 and pfhrp3 genes. In addition, antigen variability, including diverse protein variants and epitope profiles, can affect the sensitivity of RDTs. This study aimed to report the frequency and genetic variability of pfhrp2 and pfhrp3 deletions and to assess Pf HRP2 and Pf HRP3 protein variability by analysing their impact on RDT performance in Cubal, a rural area in western Angola. Methods Samples were collected at the Hospital Nossa Senhora da Paz in Cubal from May to July 2022. A total of 100 dried blood samples from febrile patients were confirmed positive for Plasmodium spp. by real-time PCR. The diagnosis of malaria was validated by thick blood smear microscopy and RDT targeting Pf HRP2 and pan-malarial lactate dehydrogenase. Deletions in pfhrp2 and pfhrp3 were assessed by PCR amplification of exons 1–2 and 2. Exon 2 sequences were analysed for amino acid repeats and candidate epitopes, and samples were sorted according to predicted RDT sensitivity. Results Species identification revealed that 96% were infected with P. falciparum and were included in the analyses; deletions in exon 1–2 were found in 7.29% ( pfhrp2 ) and 11.46% ( pfhrp3 ). No deletions were observed in exon 2 of pfhrp2 or pfhrp3 . Protein analysis revealed significant variability in histidine repeats between RDT sensitivity groups. In Pf HRP2, epitopes 3A4 and C1-13 were present in 100% of the samples, with the highest frequencies per isolate being observed (15 and 18 times per isolate, respectively). Conclusions The low prevalence of deletions in pfhrp2 and the absence of double deletions in pfhrp2 / 3 , together with the good performance of Pf HRP2-RDT suggest that these tests are a suitable diagnostic tool in Cubal. However, continued monitoring of pfhrp2 and pfhrp3 deletions is essential to ensure long-term efficacy. Pf HRP2 variability may influence RDT performance; however, further research is needed to clarify its precise impact. These findings enhance the understanding of the genetic variability and structure of Pf HRP2 and Pf HRP3, highlighting the potential of Pf HRP2-RDTs targeting the 3A4 and C1-13 epitopes for improved malaria diagnosis. Graphical abstract