Use Of Rapid Diagnostic Tests Research Articles

The use of dried tube specimens of Plasmodium falciparum in an external quality assessment programme to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centres in Togo

BackgroundThe use of rapid diagnostic tests (RDTs) to diagnose malaria is common in sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs; however, its application in National Quality Management programmes has been limited.MethodsA Plasmodium falciparum strain was grown in culture and harvested to create DTS of varying parasite density (0, 100, 200, 500 and 1000 parasites/µL). Using the dried tube specimens as quality control material, a proficiency testing (PT) programme was carried out in 80 representative health centres in Togo. Health worker competency for performing malaria RDTs was assessed using five blinded DTS samples, and the DTS were tested in the same manner as a patient sample would be tested by multiple testers per health centre.ResultsAll the DTS with 100 parasites/µl and 50% of DTS with 200 parasites/µl were classified as non-reactive during the pre-PT quality control step. Therefore, data from these parasite densities were not analysed as part of the PT dataset. PT scores across all 80 facilities and 235 testers was 100% for 0 parasites/µl, 63% for 500 parasites/µl and 93% for 1000 parasites/µl. Overall, 59% of the 80 healthcare centres that participated in the PT programme received a score of 80% or higher on a set of 0, 500 and 1000 parasites/ µl DTS samples. Sixty percent of health workers at these centres recorded correct test results for all three samples.ConclusionsThe use of DTS for a malaria PT programme was the first of its kind ever conducted in Togo. The ease of use and stability of the DTS illustrates that this type of samples can be considered for the assessment of staff competency. The implementation of quality management systems, refresher training and expanded PT at remote testing facilities are essential elements to improve the quality of malaria diagnosis.

New drugs and treatment recommendations - what are the consequences at the TB-laboratory?

Aims & objectives: Resistance to TB drugs is a severe obstacle to effective TB control globally. Timely detection of multidrug-resistant TB (MDR-TB) is crucial to avoid poor cure rates and further development and transmission of increasingly drug-resistant strains of M. tuberculosis. Molecular rapid tests are recommended by WHO for the early detection of mutations associated with drug-resistance. When resistance to rifampicin and/or isoniazid is detected, additional DST should be performed for additional drugs. Optimally all drugs used in the therapy of MDR-TB should be tested, and regimens include only drugs to which the patient's isolate has documented susceptibility. The recent introduction of new anti-TB drugs made more effective and shorter treatment of MDR-TB possible. An example is the WHO recommended all-oral bedaquiline-containing MDR-TB regimen (WHO TB treatment handbook 2020) which contains bedaquiline, levofloxacin/moxifloxacin, clofazimine, ethionamide, ethambutol, isoniazid (high dose) and pyrazinamide for 4 months followed by 5 months of treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol and pyrazinamide. The use of rapid diagnostic tests and more effective MDR-TB treatment regimens has the potential to improve treatment outcomes and reduce transmission of MDR-TB. Results: The introduction of new drugs and WHO recommendations for the therapy of MDR-TB put increased demands on TB-laboratories around the world to update their diagnostics algorithms to make sure they reflect new treatment regimens. If possible, DST should be performed for all drugs used in modern MDR-TB therapy. It is a challenge for TB laboratories to introduce DST for several compounds not earlier tested. On the other hand, DST of obsolete drugs such as the second line injectables, and especially kanamycin and capreomycin which are no longer recommended for use should be discontinued. Standardized protocols with critical concentrations for solid or liquid culture-based assays are needed to enable a successful re-focusing of DST at clinical TB laboratories. The possible added value of MIC determinations, as an alternative to just testing a single critical drug concentration, should be considered especially for the new drugs where we have more limited experience. Irrespectively of the method, there is a strong need for relevant drug-susceptible and drug-resistant control strains to ensure high quality when a new DST method is introduced. It is also of importance to develop and implement QC/EQA methods for all drugs tested. The need for knowledge transfer and training should not be neglected. Conclusions: Extended DST is initially a task of the NRL. In high drug-resistant TB burden areas, there might be a subsequent need for decentralization. To meet the demands of rapid detection of drug resistance there is a need for increased use of molecular tests. Such tests promise to be increasingly useful, but they can not be initiated for new drugs until we have a sufficient understanding of which genetic markers need to be examined to predict clinically relevant drug resistance in a reliable way. Research is ongoing to determine this for the new drugs and I expect to see such tests developed in the not so far future.

Evaluation of Histidine-Rich Proteins 2 and 3 Gene Deletions in Plasmodium falciparum in Endemic Areas of the Brazilian Amazon.

Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the pfhrp2 and pfhrp3 gene deletion in P. falciparum in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for P. falciparum infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (msp2). The pfhrp2 and pfhrp3 genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 P. falciparum isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed pfhrp2 gene deletion and 94.9% (94/99) showed pfhrp3 gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed pfhrp2 gene deletion and 98.3% (59/60) showed pfhrp3 gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of pfhrp2 and pfhrp3 gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of pfhrp2/pfhrp3 deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving P. falciparum malaria elimination.

Diagnostic performance of HRP2-only malaria rapid diagnostic test in Ghanaian pregnant women with asymptomatic peripheral blood infection: the case of First Response® test kit

Background: The use of malaria rapid diagnostic test(RDT) enables targeted treatment that mitigates against the development of parasite drug resistance. With detection thresholds at ≥200 parasites/μL, their diagnostic performance in pregnant women may be challenging as asymptomatic infections with low parasite densities are common. Few data exist on the performance of histidine-rich protein-2 (HRP2) RDTs in Ghanaian pregnant women considering commonly occurring low parasite densities. Objective: The study sought to contribute more knowledge on test performance on First Response® test kit to guide the continuous evaluation of HRP2 RDTs in pregnancy. Methods: As part of an antimalarial drug trial in pregnancy, First Response® RDT results were compared to microscopy of peripheral blood slides in 1664 women. The diagnostic performance indicators were computed as proportions with 95% confidence intervals. The risk of having a positive RDT result was computed for age, gravidity and parasite density using binomial regression methods. Results: Parasitaemia prevalence by microscopy was 5.71%(n =95/1664) while that by RDT was 21.57%(n = 359/1664). Sensitivity was 82.11% (n=78/95), specificity was 82.09% (n=1288/1569), positive predictive value was 21.73% (n=78/359), and the likelihood ratio for a positive test was 4.58. False-negative RDT results were recorded for low parasite densities as well as densities ≥ 200/ μL while false-positive results were recorded in 281of 1664 tests. Primigravidae and younger aged women were more likely to have positive RDT results compared to multigravidae and women aged ≥ 30 yr. Conclusion: The moderate sensitivity, specificity and other diagnostic parameters reported suggest the First Response® malaria RDT is useful for detecting peripheral parasitaemia in pregnant women but the use of HRP2-only RDTs is limited by the existence of parasites with HRP2 gene deletion. The use of RDTs based on combined antigens continues to be recommended. Further research is needed on RDT performance in pregnant women with declining malaria transmission.

Acceptability of rapid diagnostic tests among patients and their contacts in the Philippines is sustained beyond the completion of treatment

Background Diagnosis of leprosy currently requires individuals suspecting themselves to be affected to present for expert clinical exams. Clinic attendance can be impacted by a variety of logistical and psychological factors, but rapid diagnostic tests (RDT) could potentially be used as a screening tool to provide triaged referrals. Methods In 2015, 200 newly diagnosed, predominantly multibacillary (MB), leprosy patients attending Cebu Skin Clinic, Philippines, were interviewed with regard to their perception of how leprosy had impacted their lives and their level of acceptance of an immunologic, lateral flow-based RDT as a tool for leprosy control. Six hundred household contacts (HC) of some index cases were also asked to respond to a questionnaire. Each participant provided responses from multiple choice options and the same surveys were repeated on a regular basis to a sub-set of the cohort over the ensuing 4 years. Results At the time of diagnosis many patients (73.0%) and their HC (66.5%) reported that their lives had already been adversely affected by leprosy. RDT were perceived positively by both groups with the majority (87% patients and 71% HC) considering the tool as ‘very important’. No patients, and only 0.8% HHC, considered that tests would be of no benefit. In general, patients preferred an extensive RDT monitoring schedule following their diagnosis and indicated a preference that testing be confined among HHC rather than being extended to their larger community. Annual follow-up of a sub-set of participants (131 patients and 170 HC) indicated a retained enthusiasm for testing and, importantly, a marked decrease in those that would not like testing among community contacts, with an increase from 58.5% to 89.4% indicating that they would like testing among their respective HC. Importantly, the perceived impact of leprosy on the lives of both patients and HC declined during the monitoring period that occurred concomitantly with a progressive increase in the number of HC stating that they would definitely submit to testing. Conclusion Our data demonstrate an enthusiasm for regular use of RDT among these particular patients and their HC. Due to their ease of use and point of care applicability RDT could be accepted within high-risk target populations to provide an entry point to inform the early detection of leprosy.

Malaria risk assessment based on the use of insecticide treated nets in Nsukka Local Government Area, Enugu State, Nigeria

Background: Malaria remains a global pressing issue despite several interventions to reduce the disease. One of the key interventions is the use of insecticide treated nets (ITNs) to control malaria. This study sought to assess malaria prevalence and its risk based on the use of ITN in peri-urban communities in Enugu State, South-Eastern Nigeria. Methods & Materials: This was a cross-sectional study conducted in Nsukka, Obimo and Edem communities of Nsukka Local Government Area. A total of 317 participants from 125 randomly selected households were screened for malaria using rapid diagnostic test (RDT) and confirmed with microscopy. Socio-demographic data related to ITN were collected using structured questionnaires and field observation. Bivariate and multivariable logistic regression analyses determined socio-demographic and ITN characteristics associated with malaria. Results: Malaria prevalence among participants was 23.7% (RDT) and 14.5% (microscopy). Prevalence of malaria differed significantly among the age group (p < 0.01), with 5–15 years having the highest prevalence both by RDT (6.9%) and microscopy (5.4%). Severity of malaria cases revealed 54.3%, 30.4% and 15.3% for moderate, low and severe parasitemia respectively. Of the 125 households surveyed, less than half (44.0%) possessed at least one ITN with only a few (18.2%) in good condition. Members of households without ITN were 1.32 more likely to have malaria using RDT (0.23–3.81, p = 0.09). Not using ITN (aOR = 1.5, CI = 0.45–3.62) and the use of damaged ITN (aOR = 3.81, CI = 1.24–9.71) were significantly associated with having malaria by use of RDT. Conclusion: Malaria prevalence was high among the study participants particularly the older children. Most of the ITNs used by households were damaged. Participants who did not have ITN were more at risk of being affected with malaria. There is need for regular provision of ITNs to risk populations and increased community sensitization on the use of ITN to prevent human-mosquito contact.

Cost-effectiveness of rapid diagnostic tests, compared to microscopic tests, for the diagnosis and treatment of gestational malaria in Colombia from an institutional perspective

BackgroundGestational malaria is associated with negative outcomes in maternal and gestational health; timely diagnosis is crucial to avoid complications. However, the limited infrastructure, equipment, test reagents, and trained staff make it difficult to use thick blood smear tests in rural areas, where rapid testing could be a viable alternative. The purpose of this study was to estimate the cost-effectiveness of rapid tests type III (Plasmodium falciparum/Plasmodium spp P.f/pan) versus microscopic tests for the diagnosis and treatment of gestational malaria in Colombia.MethodsCost-effectiveness analyses of gestational malaria diagnosis from an institutional perspective using a decision tree. Standard costing was performed for the identification, measurement and assessment phases, with data from Colombian tariff manuals. The data was collected from Health Situation Analysis, SIVIGILA and meta-analysis. Average and incremental cost-effectiveness ratio were estimated. The uncertainty was assessed through probabilistic sensitivity analysis.ResultsThe cost of rapid diagnostic tests in 3,000 pregnant women with malaria was US$66,936 and 1,182 disability adjusted life years (DALYs) were estimated. The cost using thick blood smear tests was US$50,838 and 1,023 DALYs, for an incremental cost-effectiveness of US$ 101.2. The probabilistic sensitivity analysis of rapid diagnostic tests determined that they are highly cost-effective in 70% of the cases, even below the US$1,200 threshold; also, they showed an incremental net monetary benefit of $150,000 when payer’s willingness is US$1,000.ConclusionThe use of rapid diagnostic tests for timely diagnosis and treatment of gestational malaria is a highly cost-effective strategy in Colombia, with uncertainty analyses supporting the robustness of this conclusion and the increased net monetary benefit that the health system would obtain. This strategy may help in preventing the negative effects on maternal health and the neonate at a low cost.

Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania

BackgroundHistidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania.MethodsA community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes.ResultsOf all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes.ConclusionsThis study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future.

Navigating the Diagnostics of COVID-19

Introduction/ObjectiveThe recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Hubei province, China in December 2019 and has spread worldwide at an alarming rate. With millions of individuals infected and over two hundred thousand deaths, the necessity to develop fast and efficient diagnostic methods is of high importance. Diagnostic modalities rely on a combination of epidemiology, clinical presentation, laboratory examination, and appropriate imaging to diagnose and distinguish SARS-CoV-2 from other pulmonary infections. The purpose of this paper is to report on currently available diagnostic screening methods for patients infected with SARS-CoV-2 to guide frontline healthcare workers involved with COVID-19 patient care.MethodsAn electronic literature search was performed for peer-reviewed articles published from January 1, 2020, until April 26, 2020. Articles were then reviewed and included based on the applicability to the topic.ResultsThe preferred diagnostic approach is reverse transcription of the virus’ RNA followed by PCR amplification (RT-PCR). This method recognizes the gene-specific primers to target various viral protein genes, such as the envelope protein gene or the nucleocapsid protein gene, which enables this test to be both sensitive and specific toward SARS-CoV-2. However, this method has been proven to be time-consuming taking hours-to-days for the results. In order to improve the speed and efficiency of diagnostics, newer rapid diagnostic serological tests are being developed for testing SARS-CoV-2, each with its own unique advantages and disadvantages. They could potentially be used as triage tests to rapidly identify patients who are very likely to have COVID-19 in combination with other accurate diagnostic methods.ConclusionTherefore, a combination of diagnostic testing used in a timely manner may be beneficial for the rapid and accurate detection of SARS-CoV-2. This was evident in cases where despite initial negative RT-PCR tests for various patients, who later demonstrate chest CT scans with various degrees of consolidation and ground-glass opacity. Thus establishing the need for radiology diagnosis to be complementary to RT-PCR for COVID-19 patients. Hopefully, the continuous development and use of rapid diagnostic tests and the implementation of public health measures will help control the spread of the disease.

Self-diagnosis and self-treatment of Plasmodium spp. infection by travellers (1989–2019): A systematic review and meta-analysis

BackgroundStandby emergency self-treatment (SBET) is often recommended as an anti-malaria strategy for travellers to low-risk endemic areas. This self-treatment enables competent malaria therapy, if medical assistance is unavailable. The World Health Organization (WHO) recommends performing reliable diagnostic tests before starting antimalarial treatment. For the self-diagnosis of malaria in travellers, rapid diagnostic tests (RDT) can be used to confirm the infection before SBET is used. The aim of this research is to assess the use of RDT and/or SBET in travellers. MethodsWe searched the databases (PubMed, Scopus, Embase, CINAHL) using terms and synonyms for ‘self-diagnosis’ and ‘self-treatment’ combined with ‘malaria’ and ‘travel’. Articles in English, French and German were included. Potential articles were screened and extracted by two authors (KU and PS). Only original articles and case reports documenting the self-use of RDT and/or SBET in travellers were included. Data were extracted using a standardised approach. We defined ‘correct use’ of RDT and SBET. Data on number and performance of RDT and SBET use, as well as malaria verification were collected in an Excel table. Five meta-analyses were performed using a random effects model and calculating pooled proportions. This systematic review was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42018108874). ResultsThe research resulted in 867 articles of possible relevance on RDT and 955 articles on SBET. After screening, a total of 4 articles on RDT use and 17 articles for SBET use in travellers were included in the systematic review. Most of the RDT were performed and interpreted properly by the travellers (pooled proportion 88%, 95% confidence interval (CI) from 64% to 97%), whereby the proportion of correct performance was increased after a pre-travel test run (97%). Major problems in the implementation such as pricking finger, placing blood drop, identifying lines and interpreting results could be discovered. We found data on 1025 SBET uses in studies of travellers to high-risk African countries. In these studies, the pooled proportion of SBET uses was 6% (95% CI from 2% to 13%). We found 545 SBET uses in studies of travellers to countries of mixed malaria risk. In these studies, the pooled proportion of SBET uses was 2% (95% CI from 1% to 7%). Furthermore, the evaluation showed a high proportion of correct SBET use (pooled proportion 69%, 95% CI from 35% to 90%). As a cause for incorrect use, errors in dosage (under- or overdose), disregard of minimal incubation period (< 7 days since first possible malaria exposure) and absence of fever were identified. Four cases of post-SBET severe adverse events were documented. In a third of travellers who used SBET, a Plasmodium spp. infection could be detected (pooled proportion 31%, 95% CI from 16% to 51%). ConclusionsThis systematic review and meta-analysis showed that the majority of travellers were able to use RDT and SBET correctly. Standardised pre-travel instructions and specific training are indicated to increase the proportions of correct RDT and SBET use. With improved and user-friendly technology, RDT may become an integral part of SBET malaria recommendations for travellers. Combined use of RDT and SBET could be an appropriate strategy for selected subgroups of travellers to low-risk, remote malaria areas. Future research should focus on combined RDT and SBET strategies.

Évaluation de la phase pilote de l’utilisation des tests de diagnostic rapide du paludisme au niveau communautaire, au Burkina Faso

Evaluation of the Pilot Phase of the Use of Rapid Malaria Diagnostic Tests at the Community Level in Burkina Faso : Introduction: According to the World Health Organization (WHO) guidelines, treatment for malaria should be carried out after diagnostic confirmation. At the community level, diagnostic confirmation by rapid diagnostic tests (RDTs) and treatment of malaria cases should be ensured by Community-Based Health Workers (ASBCs). This formative evaluation thus aimed to measure the level and quality of implementation of the pilot phase of the use of RDTs for malaria case confirmation at the community level in Burkina Faso from 2013 to 2015. Materials and methods: A multiple case study with multiple levels of analysis was conducted using a concurrent mixed approach in three health districts (Sapone, Nouna and Kaya). The quantitative approach consisted of administering a questionnaire to different groups of stakeholders (ASBCs, beneficiaries and health workers). The qualitative approach combined document review, individual interviews and focus groups with various key informants. The analysis of quantitative data was carried out using Stata version 15 and Excel 2007 software. A thematic content analysis was carried out using Nvivo 10.0 software for the qualitative data. A triangulation of the different quantitative and qualitative data was performed to deepen the analysis and validate some of our results. Results: The pilot phase of the use of RDTs for malaria at the community level was an intervention that was well accepted by the populations. The different components and activities of the intervention have been implemented. All ASBCs were trained in the use of RDTs. The integration of the supervision of ASBCs into the overall supervision of community activities was a positive aspect of the intervention. However, there were some difficulties in the implementation of each component of the intervention: not all the health and social promotion centres (CSPSs) in the three districts implemented this strategy to the same degree of adherence. In fact, difficulties were noted during the evaluation, such as the lack of RDTs and the existence of outdated stocks at the ASBCs, as well as the lack of security equipment. In addition, the monitoring of the intervention was limited by the poor quality of reporting of the activities carried out, due to the low level of education of most of the ASBCs and the weakness of supervision. Conclusion: The evaluation of the implementation of case confirmation by community-based RDTs in the health districts of Kaya, Nouna, and Sapone, shows that not all components were implemented with a high degree of adherence to the initial plan. The occurrence of a series of moderating factors that were not adequately supervised could partly explain this performance.

Management of Gram-Negative Bloodstream Infections in the Era of Rapid Diagnostic Testing: Impact With and Without Antibiotic Stewardship.

BackgroundVerigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI.MethodsThis was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression.ResultsEight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P < .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9–67.7) hours vs 24.9 (12.4–55.2) hours vs 26.5 (10.3–66.5) hours (P = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04–1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01–1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult.ConclusionsWith the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.

Usefulness of rapid diagnostic test in the diagnosis of asymptomatic malaria in HIV infected children on cotrimoxazole prophylaxis in Benin City, Nigeria

Background: Rapid diagnostic test (mRDT) is a useful tool in demonstrating parasitologically proven malaria. Its efficacy is however hampered when parasite density is low. Prophylactic use of cotrimoxazoleas in cases of HIV infected children can cause reduction in parasite count. It is doubtful if mRDT will retain its diagnostic usefulness among such individuals.Objectives: The study sought to evaluate the diagnostic value of mRDT in HIV infected children on cotrimoxazole prophylaxis in Benin City.Methods: In the prospective, cross sectional and descriptive study, we assessed malaria parasitaemia using standard methods in microscopy and parasite density and malaria antigenaemia using Care Start Pf (monoclonal antibodies specific to histidine rich protein – 2 antigen) in 221 each of HIV infected subjects on cotrimoxazole managed in a specialist clinic and HIV negative controls all seen at the University of Benin Teaching Hospital between April and June 2016.Results: Malaria antigenaemia rate MAr (20.8%) was lower than malaria parasitaemia rate MPr (24.4%) in subjects. MAr (20.8) and MPr (24.4%) in subjects were higher than MAr (18.10%) and MPr (17.7%) in controls. Mean (SEM) parasite count in subjects of was low (50.88 + 2.24 per μl). Using microscopy as gold standard the sensitivity, specificity, PPV and NPV of mRDT in subjects were 77.8%, 97.6%, 91.3% and 93.1%. Corresponding values in controls were 100.0%, 99.5%, 97.5% and 100.0%.Youden indices for subjects and controls were 0.75 and 0.99.Conclusions/Recommendations: Sensitivity of mRDT in HIV infected children on cotrimoxazole prophylaxis for opportunistic infections (OI) is reduced. However the indices of specificity, PPV and NPV are high enough to retain its value in the evaluation of HIV infected children for asymptomatic malaria and perhaps the clinical disease.&#x0D; Keywords: mRDT, Utility, HIVinfected Children, Cotrimoxazoleprophylaxis, Benin City

Navigating the Diagnostics of COVID-19.

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Hubei province, China, in December 2019 and has spread worldwide at an alarming rate. With over eight million individuals infected and exceeding 400,000 deaths globally, the necessity to develop fast and efficient diagnostic methods is of high importance. This paper reports on currently available diagnostic screening methods for patients infected with SARS-CoV-2 to guide frontline healthcare workers involved with the diagnosis of 2019 novel coronavirus disease (COVID-19) patient. An electronic literature search was performed for peer-reviewed articles published from January 1, 2020, until June 19, 2020. Published articles were then reviewed and included based on the applicability to the topic. The preferred diagnostic approach is the reverse transcription (RT) of the virus’ ribonucleic acid (RNA) followed by polymerase chain reaction (PCR) amplification (RT-PCR). However, this method has been proven to be time-consuming. In improving the speed and efficiency of diagnostics, newer rapid diagnostic serological tests are in development for testing SARS-CoV-2, each with its unique advantages and disadvantages. They could potentially be used as triage tests to rapidly identify patients who are very likely to have COVID-19 in combination with other accurate diagnostic methods, such as diagnostic imaging. A combination of the disease history, clinical manifestations, laboratory diagnostic testing, and diagnostic imaging is crucial for making an accurate and useful diagnosis for COVID-19. Hopefully, the continuous development and use of rapid diagnostic tests and the implementation of public health measures will help control the spread of the disease.

Performance of rapid tests in the management of dengue fever imported cases in Lazio, Italy 2014-2019

BackgroundIn Italy, dengue virus is the most frequent agent of imported viral infections. The use of rapid diagnostic tests (RDTs) may be of help as a preliminary user-friendly quick assay to facilitate dengue diagnosis, as ordinary laboratory diagnosis of dengue fever may require special efforts in terms of tools availability, interpretation of results, and skilled personnel. The performance of RDTs, however, may vary according to different epidemiological and laboratory background. MethodsWe reviewed five years of laboratory records of two dengue RDT results (Colorimetric SD-Bioline Dengue-Duo-RDT and Fluorimetric SD-Biosensor-STANDARD-F-Dengue-RDT), able to detect viral NS1 antigen and specific IgM and IgG. Diagnostic parameters were calculated using as reference the results of molecular (RT-PCR) and serological (immunofluorescence, IFA) tests. Overall performance, calculated considering the final case definition, was included in the accuracy assessment of RDTs. ResultsThe combined use of NS1 and IgM/IgG RDT for the detection of acute dengue cases resulted in an overall sensitivity and specificity of 87.2% and 97.9% for Colorimetric RDT, 96.2% and 96.2% for Fluorimetric RDT. NS1 was the most reliable marker of acute infection, while IgM resulted falsely positive in nine samples, including sera derived from 2 Zika and 4 non-arbovirus infected patients. ConclusionsThe inclusion of RDT in the diagnostic algorithm is of undeniable help in the prompt management and surveillance of dengue infection in non-endemic areas. Confirmatory tests are, however, necessary to rule in or rule out dengue fever diagnosis.

Evaluating the implementation of rapid diagnostic tests in a malaria elimination setting

BackgroundIt was recommended that malaria rapid diagnostic tests (RDTs) should be available in all epidemiological situations. But evidence was limited on the implementation of RDTs and its effectiveness in malaria elimination settings. This study examined the implementation of RDTs and how it affected the diagnosis of imported malaria patients in Jiangsu Province, China.MethodsTo scale up RDTs, this study developed an intervention package with four major elements covering the supply of RDT test, the training on RDTs, the monitoring and management of RDT use, and the advocacy of RDTs. By using a pretest-posttest control group design, we implemented the interventions in 4 cities in Jiangsu Province with the rest nine cities as controlled areas, from January 2017 to January 2018. Difference-in-Difference approach was used to evaluate the impact of the scale-up of RDTs on the identification of malaria cases. Three binary outcome measures were included to indicate delayed malaria diagnosis, malaria cases with confirmed malaria diagnosis at township-level institutions, and severe malaria cases, respectively. Linear probability regression was performed with time and group fixed effects and the interaction term between time and group.ResultsIntervention areas received sufficient RDT test supply, regular professional training programs, monthly tracking and management of RDT supply and use, and health education to targeted population. The implementation of interventions was associated with 10.8% (P = 0.021) fewer patients with delayed diagnosis. But intervention areas did not see a higher likelihood of having confirmed diagnosis from township-level institutions (coefficient = -0.038, P = 0.185) or reduced severe malaria cases (coef. = 0.040, P = 0.592).ConclusionsThe comprehensive package of RDT implementation in this study is promising in scaling up RDT use and improving access to care among malaria patients, especially in malaria elimination settings.

Improving the Quality of Hospital Antibiotic Use: Impact on Multidrug-Resistant Bacterial Infections in Children.

Antimicrobial resistance (AMR) is considered a rapidly growing global public health emergency. Neonates and children are among patients for whom antibiotics are largely prescribed and for whom the risk of AMR development is high. The phenomenon of increasing AMR has led to the need to develop measures aimed at the rational and effective use of the available drugs also in children and antimicrobial stewardship (AS), which is one of the measures that in adults has showed the highest efficacy in reducing antibiotic abuse and misuse, appears as an attractive approach. The aim of this manuscript is to analyze the basic principles and strategies of pediatric AS. To this end, we searched in PubMed articles published in years 2000 to 2019 containing “antimicrobial resistance,” “antibiotic use,” “antimicrobial stewardship,” and “children” or “pediatric” as keywords. Our review showed that the balance between multi-resistant organisms and new antimicrobials is extremely precarious. The AS tools are the most important weapon at our disposal to stem the phenomenon. Careful monitoring of prescriptions, continuous training of prescribing physicians and collaboration with highly qualified multidisciplinary staff, creation of local and national guidelines, use of rapid diagnostic tests, technological means of support, and research activities by testing new broad-spectrum antibiotics are mandatory. However, all of these measures must be supported by adequate investment by national and international health organizations. Only by making AS daily practice, through the use of financial resources and dedicated staff, we can fight AMR to ensure safe and effective care for our young patients.

Modelling the cost-effectiveness of introducing subsidised malaria rapid diagnostic tests in the private retail sector in sub-Saharan Africa

BackgroundOver the last 10 years, there has been a huge shift in malaria diagnosis in public health facilities, due to widespread deployment of rapid diagnostic tests (RDTs), which are accurate,...

Diagnostic Performance of Three Rapid Diagnostic Test Kits for Malaria Parasite Plasmodium falciparum.

Malaria is a potent burden on public healthcare worldwide due to requiring rapid diagnosis and treatment. Nowadays, prompt diagnosis with rapid diagnostic tests (RDTs) has been widely accepted as an effective diagnostic technique in malaria-endemic countries, primarily due to their easy operation, fast output, and straightforward interpretation. The global availability and use of RDTs have gradually grown over recent decades as field-applicable diagnostic tests for the reliable confirmation of malaria infection and proper case management. This study was conducted to evaluate diagnostic performance of 3 commercially available malaria RDT kits : BIOCREDITTM Malaria Ag Pf(pLDH), Malaria Ag Pf(pLDH/pHRPII), and Malaria Ag Pf/Pv(pLDH/pLDH) (where pLDH and pHRPII stand for plasmodium lactate dehydrogenase and histidine-rich protein 2, respectively) for the specific detection of Plasmodium falciparum. A total of 1,129 blood samples including 95 blood samples, confirmed as vivax malaria infection by microscopic examinations and a nested-PCR method, were tested for falciparum malaria infection. The overall sensitivity and specificity of Malaria Ag Pf(pLDH/pHRPII), Malaria Ag Pf/Pv(pLDH/pLDH), and Pf(pLDH) for P. falciparum were 99.0% and 100%, 95.8% and 100%, and 100% and 100%, respectively. It is proposed that the 3 RDT kits perform reliable level of diagnostic accuracy of detection for P. falciparum parasites.

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone

BackgroundMalaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone.MethodsBlood samples from 534 febrile individuals reporting to a hospital in Bo, Sierra Leone, were tested using three methods: a commercial RDT, microscopy, and a Multiplex Malaria Sample Ready (MMSR) PCR designed to detect a universal malaria marker and species-specific markers for Plasmodium falciparum and Plasmodium vivax. A separate PCR assay was used to identify species of Plasmodium in samples in which MMSR detected malaria, but was unable to identify the species.ResultsMMSR detected the presence of any malaria marker in 50.2% of all tested samples with P. falciparum identified in 48.7% of the samples. Plasmodium vivax was not detected. Testing of MMSR P. falciparum-negative/universal malaria-positive specimens with a panel of species-specific PCRs revealed the presence of Plasmodium malariae (n = 2) and Plasmodium ovale (n = 2). The commercial RDT detected P. falciparum in 24.6% of all samples while microscopy was able to detect malaria in 12.8% of tested specimens.ConclusionsWider application of PCR for detection of malaria parasites may help to fill gaps existing as a result of use of microscopy and RDTs. Due to its high sensitivity and specificity, species coverage, room temperature stability and relative low complexity, the MMSR assay may be useful for detection of malaria and epidemiological studies especially in low-resource settings.