RESUMEN

In many regions of New Zealand liver fluke is endemic, infecting most grazing ruminants, including cattle, sheep, and deer. Restricting the economic losses and welfare costs associated with liver fluke relies on accurately identifying those animals with a production limiting infection. This has proven a difficult goal and although several antemortem quantitative tests are available, including faecal egg counts (FEC), serum ELISA and copro-antigen ELISA, none can be considered a gold standard test of liver fluke infection. The accepted gold standard test for fascioliasis is the total fluke count, which is both laborious and can only be completed at post-mortem. This study aimed to compare the performance of four liver fluke diagnostic tests, against the results of a gold standard total fluke count test. Two groups of cattle were selected, 29 culled mixed age beef cows (MAC) and ten 30-month-old steers. The cattle were blood sampled and faecal sampled prior to slaughter and their whole livers recovered post slaughter at the abattoir. Liveweight was also recorded at slaughter. After collection, each liver was weighed, scored for gross pathology, then serum, faeces and livers were frozen at -20 °C for later analysis. Faecal egg counts and F. hepatica copro-antigen ELISA tests were completed on the faecal samples and total fluke counts were completed on the livers. Fasciola hepatica antibody concentration in serum samples were quantified using a commercial ELISA test. Poisson regression models were built to model the association between each diagnostic test and the total fluke count, and a linear regression model was built to examine the relationship between each diagnostic test and live weight at slaughter. The median fluke count was significantly higher in MAC than steers (p = 0.01), and F. hepatica eggs were present in 100% steers and 66% MAC. There was a significant effect of copro-antigen ELISA value on total fluke count (p < 0.0001), with a coproantigen ELISA value = 20.1 predicting 10 flukes and a value = 44.8 predicting 30 flukes. There was also a significant effect of FEC on total fluke count (p = 0.002) but the R-squared value for this model was lower. There was no association between liver fibrosis score or antibody ELISA test and total fluke count (p = 0.95, p = 0.73, respectively). There was a significant effect of total fluke count (p = 0.03) on liveweight at slaughter, with liveweight falling 20.4 kg for each unit increase in loge (total fluke count). There was no effect of FEC (p = 0.11), antibody ELISA (p = 0.55) or copro-antigen ELISA value (p = 0.16) on liveweight at slaughter. Taken together, these results show that the coproantigen ELISA test is the better test for estimating the true liver fluke burden and that the number of flukes in the liver has a negative effect on cattle live weights at slaughter.

Asunto(s)

Enfermedades de los Bovinos , Ensayo de Inmunoadsorción Enzimática , Fasciola hepatica , Fascioliasis , Heces , Recuento de Huevos de Parásitos , Animales , Bovinos , Fascioliasis/veterinaria , Fascioliasis/diagnóstico , Fascioliasis/parasitología , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/parasitología , Heces/parasitología , Fasciola hepatica/aislamiento & purificación , Fasciola hepatica/inmunología , Recuento de Huevos de Parásitos/veterinaria , Nueva Zelanda , Masculino , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Sensibilidad y Especificidad , Hígado/parasitología , Pruebas Diagnósticas de Rutina/veterinaria , Pruebas Diagnósticas de Rutina/métodos , Anticuerpos Antihelmínticos/sangre

RESUMEN

Background: Plasmodium vivax malaria has been one of the most troublesome diseases in the Democratic People's Republic of Korea (DPRK). Given that a majority of malaria cases are concentrated near the demilitarized zone, concerted elimination efforts from both the Republic of Korea (ROK) and DPRK are essential for a malaria-free Korean Peninsula. This study assessed the impact of rapid diagnostic tests (RDTs) and tafenoquine on malaria incidence in DPRK. Methods: We patterned the current model structure from the previously developed Plasmodium vivax malaria dynamic transmission model for ROK. Model parameters were adjusted using demographic and climate data from malaria-risk areas in DPRK, and the model was calibrated to annual malaria incidences from 2014 to 2018 in DPRK, as reported by the World Health Organization. Subsequently, we estimated the preventable malaria cases over a decade after introducing RDTs and tafenoquine compared to using microscopy alone and primaquine, respectively. Sensitivity analysis was performed to account for uncertainty in model parameters. Results: When comparing RDTs to microscopy, a one-day reduction in diagnostic time due to the introduction of RDTs led to a reduction in malaria incidence by 26,235 cases (65.6%) over the next decade. With a two-day reduction, incidences decreased by 33,635 (84.1%). When comparing a single dose of tafenoquine with a 14-day primaquine regimen, the former prevented 1,222 (77.5%) relapse cases and 4,530 (11.3%) total cases over the years. Conclusion: The continuous and simultaneous implementation of RDTs and tafenoquine emerges as a potent strategy to considerably reduce malaria in DPRK.

Asunto(s)

Antimaláricos , Malaria Vivax , Malaria Vivax/epidemiología , Malaria Vivax/prevención & control , Humanos , Antimaláricos/uso terapéutico , Incidencia , República Popular Democrática de Corea/epidemiología , Plasmodium vivax/efectos de los fármacos , Aminoquinolinas/uso terapéutico , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Adulto , Masculino , Persona de Mediana Edad

RESUMEN

The summary receiver operating characteristic (SROC) curve has been recommended as one important meta-analytical summary to represent the accuracy of a diagnostic test in the presence of heterogeneous cutoff values. However, selective publication of diagnostic studies for meta-analysis can induce publication bias (PB) on the estimate of the SROC curve. Several sensitivity analysis methods have been developed to quantify PB on the SROC curve, and all these methods utilize parametric selection functions to model the selective publication mechanism. The main contribution of this article is to propose a new sensitivity analysis approach that derives the worst-case bounds for the SROC curve by adopting nonparametric selection functions under minimal assumptions. The estimation procedures of the worst-case bounds use the Monte Carlo method to approximate the bias on the SROC curves along with the corresponding area under the curves, and then the maximum and minimum values of PB under a range of marginal selection probabilities are optimized by nonlinear programming. We apply the proposed method to real-world meta-analyses to show that the worst-case bounds of the SROC curves can provide useful insights for discussing the robustness of meta-analytical findings on diagnostic test accuracy.

Asunto(s)

Metaanálisis como Asunto , Método de Montecarlo , Sesgo de Publicación , Curva ROC , Sesgo de Publicación/estadística & datos numéricos , Humanos , Simulación por Computador , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Modelos Estadísticos , Estadísticas no Paramétricas , Interpretación Estadística de Datos

RESUMEN

BACKGROUND: To evaluate diagnostic tests for low prevalence conditions, classification accuracy metrics such as sensitivity, specificity, and positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are advantageous because they are prevalence-independent and thus estimable in studies enriched for the condition. However, classification accuracy goals are often chosen without a clear understanding of whether they are clinically meaningful. Pennello (2021) proposed a risk stratification framework for determining classification accuracy goals. A software application is needed to determine the goals and provide data analysis. METHODS: We introduce DxGoals, a freely available, R-Shiny software application for determining, visualizing, and analyzing classification accuracy goals for diagnostic tests. Given prevalence p for the target condition and specification that a test's positive and negative predictive values PPVand NPV=1-cNPV should satisfy PPV>PPV* and cNPV

Asunto(s)

Teorema de Bayes , Pruebas Diagnósticas de Rutina , Sensibilidad y Especificidad , Programas Informáticos , Humanos , Pruebas Diagnósticas de Rutina/normas , Pruebas Diagnósticas de Rutina/métodos , Valor Predictivo de las Pruebas

RESUMEN

BACKGROUND: Malaria is the parasitic disease with the highest morbimortality worldwide. The World Health Organization (WHO) estimates that there were approximately 249 million cases in 2022, of which 3.4% were in Angola. Diagnosis is based on parasite identification by microscopy examination, antigen detection, and/or molecular tests, such as polymerase chain reaction (PCR). This study aimed to evaluate the usefulness of real-time PCR as a diagnostic method for malaria in an endemic area (Cubal, Angola). METHODS: A cross-sectional study was carried out at the Hospital Nossa Senhora da Paz in Cubal, Angola, including 200 patients who consulted for febrile syndrome between May and July 2022. From each patient, a capillary blood sample was obtained by finger prick for malaria field diagnosis [microscopy and rapid diagnostic test (RDT)] and venous blood sample for real-time PCR performed at the Hospital Universitario Vall d'Hebron in Barcelona, Spain. Any participant with a positive result from at least one of these three methods was diagnosed with malaria. RESULTS: Of the 200 participants included, 54% were female and the median age was 7 years. Malaria was diagnosed by at least one of the three techniques (microscopy, RDT, and/or real-time PCR) in 58% of the participants, with RDT having the highest percentage of positivity (49%), followed by real-time PCR (39.5%) and microscopy (33.5%). Of the 61 discordant samples, 4 were only positive by microscopy, 13 by real-time PCR, and 26 by RDT. Plasmodium falciparum was the most frequent species detected (90.63%), followed by P. malariae (17.19%) and P. ovale (9.38%). Coinfections were detected in ten participants (15.63%): six (60%) were caused by P. falciparum and P. malariae, three (30%) by P. falciparum and P. ovale, and one (10%) triple infection with these three species. In addition, it was observed that P. falciparum and P. malariae coinfection significantly increased the parasite density of the latter. CONCLUSIONS: RDT was the technique with the highest positivity rate, followed by real-time PCR and microscopy. The results of the real-time PCR may have been underestimated due to suboptimal storage conditions during the transportation of the DNA eluates. However, real-time PCR techniques have an important role in the surveillance of circulating Plasmodium species, given the epidemiological importance of the increase in non-falciparum species in the country, and can provide an estimate of the intensity of infection.

Asunto(s)

Fiebre , Malaria , Plasmodium , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Angola/epidemiología , Femenino , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Masculino , Estudios Transversales , Malaria/diagnóstico , Malaria/parasitología , Malaria/epidemiología , Niño , Fiebre/parasitología , Preescolar , Plasmodium/aislamiento & purificación , Plasmodium/genética , Plasmodium/clasificación , Adolescente , Adulto , Microscopía/métodos , Adulto Joven , Lactante , Sensibilidad y Especificidad , Persona de Mediana Edad , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Pruebas Diagnósticas de Rutina/métodos

RESUMEN

BACKGROUND: Reactive case detection (RCD) aims to reduce malaria transmission stemming from asymptomatic carriers. Symptomatic individuals diagnosed with malaria at a health centre are followed to their households, where members of the index case and neighbouring households are tested and treated for malaria. An RCD programme was tested in the Ashanti region of Ghana in order to study diagnostic accuracy in the hospital and household settings, assess the prevalence of subclinical infections and possible clustering in index case households, and identify operational challenges for future RCD programmes. Currently, transmission in this region is high, but reactive interventions might become an option once transmission is reduced. METHODS: 264 febrile individuals were enrolled at the Mankranso Government Hospital and tested for malaria using rapid diagnostic tests (RDT). From the pool of RDT-positive febrile index cases, 14 successful RCD follow-ups were conducted, and 233 individuals were enrolled from the index case, neighbour, and control households. The sensitivity of diagnostic tools for clinical and subclinical cases was compared, including RDT, expert microscopy by World Health Organization-certified microscopists, field microscopy, and qPCR. RESULTS: Poor diagnosis and low receptivity to RCD-style follow-ups were major limitations to a successful and effective RCD programme. Field microscopy detected only 49% of clinical infections compared to RDT. 54% of individuals did not agree to a follow-up, and 66% of attempted follow-ups failed. The system effectiveness of RCD, calculated as the product of correctly diagnosed index cases, successful follow-ups, and proportion of asymptomatic infections detected by RDT, was very low at 4.0%. CONCLUSIONS: Due to low system effectiveness and the endemic nature of the disease setting in which asymptomatic prevalence is high and infections are not clustered around index case households, RCD is currently not a feasible option for malaria control in this region. The operational challenges identified through this study may help inform future reactive intervention programme designs once transmission is reduced.

Asunto(s)

Infecciones Asintomáticas , Pruebas Diagnósticas de Rutina , Malaria Falciparum , Ghana/epidemiología , Humanos , Malaria Falciparum/diagnóstico , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Infecciones Asintomáticas/epidemiología , Femenino , Masculino , Preescolar , Niño , Adolescente , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Adulto , Adulto Joven , Lactante , Persona de Mediana Edad , Plasmodium falciparum/aislamiento & purificación , Prevalencia , Sensibilidad y Especificidad , Anciano

RESUMEN

OBJECTIVE: To perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa. DESIGN: A systematic review of study methods. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022. ELIGIBILITY CRITERIA: Primary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa. DATA EXTRACTION AND SYNTHESIS: Studies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings. RESULTS: Our search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs' potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers. CONCLUSION: Impact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs' effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation. PROSPERO REGISTRATION NUMBER: CRD42018083816.

Asunto(s)

Pruebas Diagnósticas de Rutina , Malaria , Humanos , África del Sur del Sahara , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Prueba de Diagnóstico Rápido

RESUMEN

BACKGROUND: Accurate diagnosis and timely treatment are crucial in combating malaria. METHODS: A total of 449 samples were screened for Plasmodium falciparum infection by expert microscopy, qPCR, and three RDTs, namely Rapigen Biocredit Malaria Ag Pf (detecting HRP2 and pLDH on separate bands), Abbott NxTek Eliminate Malaria Ag Pf (detecting HRP2), and SD Bioline Malaria Ag Pf (detecting HRP2). hrp2/3 deletion typing was done by digital PCR. RESULTS: 45.7% (205/449) individuals tested positive by qPCR for P. falciparum with a mean parasite density of 12.5 parasites/µL. Using qPCR as reference, the sensitivity of microscopy was 28.3% (58/205), the Biocredit RDT was 52.2% (107/205), the NxTek RDT was 49.3% (101/205), and the Bioline RDT was 39.5% (81/205). When only samples with densities > 20 parasites/µL were included (n = 89), sensitivity of 62.9% (56/89) by microscopy, 88.8% (79/89) by Biocredit, 88.8% (79/89) by NxTek, and 78.7% (70/89) by Bioline were obtained. All three RDTs demonstrated specificities > 95%. The limits of detection (95% probability that a sample tested positive) was 4393 parasites/µL (microscopy), 56 parasites/µL (Biocredit, considering either HRP2 or pLDH), 84 parasites/µL (NxTek), and 331 parasites/µL (Bioline). None of the three qPCR-confirmed P. falciparum positive samples, identified solely through the pLDH target, or eight samples negative for all RDTs but qPCR-positive at densities > 20 parasites/µL carried hrp2/3 deletions. CONCLUSION: The Biocredit and NxTek RDTs demonstrated comparable diagnostic efficacies. All three RDTs performed better than microscopy.

Asunto(s)

Pruebas Diagnósticas de Rutina , Malaria Falciparum , Plasmodium falciparum , Sensibilidad y Especificidad , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Humanos , Plasmodium falciparum/aislamiento & purificación , Plasmodium falciparum/genética , Ghana , Pruebas Diagnósticas de Rutina/métodos , Preescolar , Adolescente , Adulto , Niño , Adulto Joven , Femenino , Persona de Mediana Edad , Masculino , Microscopía/métodos , Lactante , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Anciano , Anciano de 80 o más Años , Prueba de Diagnóstico Rápido

RESUMEN

OBJECTIVE: Cryptococcosis predominantly presents as a meningoencephalitis in Thailand. Early and expeditious diagnosis is essential for reducing both mortality and morbidity associated with cryptococcal meningitis. We aim to define and establish the diagnostic performances between the benchmark commercially available diagnostic kit (CrAg® LFA) and the large-scale prototype of an inexpensive in-house immunochromatographic test (ICT) based on monoclonal antibody (MAb) 18B7. METHODS: We have developed the large-scale prototype for the rapid detection of cryptococcal polysaccharide antigens by utilizing a single antibody sandwich ICT format employing MAb 18B7, which is highly specific to Cryptococcus neoformans glucuronoxylomannan (GXM) antigens. An in-house MAb18B7 ICT was manufactured in accordance with industry standards under the control of the International Organization for Standardization (ISO) 13485. RESULTS: The diagnostic sensitivity, specificity, and accuracy for the in-house MAb 18B7 ICT were 99.10%, 97.61%, and 97.83%, respectively. The agreement kappa (κ) coefficient was 0.968 based on the retrospective evaluation of 580 specimens from patients living in northern Thailand with clinically suspected cryptococcosis. CONCLUSION: The data suggest that this in-house MAb 18B7 ICT will be highly beneficial for addressing the issue of cryptococcal infection in Thailand. Moreover, it is anticipated that this inexpensive ICT can play a pivotal role in various global strategies aimed at eradicating cryptococcal meningitis among individuals living with HIV by 2030.

Asunto(s)

Anticuerpos Monoclonales , Antígenos Fúngicos , Cromatografía de Afinidad , Criptococosis , Cryptococcus neoformans , Sensibilidad y Especificidad , Humanos , Tailandia , Anticuerpos Monoclonales/inmunología , Cromatografía de Afinidad/métodos , Criptococosis/diagnóstico , Cryptococcus neoformans/inmunología , Cryptococcus neoformans/aislamiento & purificación , Antígenos Fúngicos/análisis , Antígenos Fúngicos/inmunología , Estudios Retrospectivos , Anticuerpos Antifúngicos/sangre , Polisacáridos/análisis , Polisacáridos/inmunología , Masculino , Femenino , Adulto , Pruebas Diagnósticas de Rutina/métodos , Persona de Mediana Edad , Anciano , Adulto Joven

RESUMEN

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Asunto(s)

Manejo de Caso , Malaria Falciparum , Zambia/epidemiología , Humanos , Preescolar , Adolescente , Niño , Masculino , Lactante , Femenino , Manejo de Caso/estadística & datos numéricos , Malaria Falciparum/epidemiología , Adulto , Adulto Joven , Persona de Mediana Edad , Recién Nacido , Anciano , Prevalencia , Calidad de la Atención de Salud/estadística & datos numéricos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos

RESUMEN

BACKGROUND: Spillover of effect, whether positive or negative, from intervention to control group patients invalidates the Stable Unit Treatment Variable Assumption (SUTVA). SUTVA is critical to valid causal inference from randomized concurrent controlled trials (RCCT). Spillover of infection prevention is an important population level effect mediating herd immunity. This herd effect, being additional to any individual level effect, is subsumed within the overall effect size (ES) estimate derived by contrast-based techniques from RCCT's. This herd effect would manifest only as increased dispersion among the control group infection incidence rates above background. METHODS AND RESULTS: The objective here is to explore aspects of spillover and how this might be visualized and diagnosed. I use, for illustration, data from 190 RCCT's abstracted in 13 Cochrane reviews of various antimicrobial versus non-antimicrobial based interventions to prevent pneumonia in ICU patients. Spillover has long been postulated in this context. Arm-based techniques enable three approaches to identify increased dispersion, not available from contrast-based techniques, which enable the diagnosis of spillover within antimicrobial versus non-antimicrobial based infection prevention RCCT's. These three approaches are benchmarking the pneumonia incidence rates versus a clinically relevant range, comparing the dispersion in pneumonia incidence among the control versus the intervention groups and thirdly, visualizing the incidence dispersion within summary receiver operator characteristic (SROC) plots. By these criteria there is harmful spillover effects to concurrent control group patients. CONCLUSIONS: Arm-based versus contrast-based techniques lead to contrary inferences from the aggregated RCCT's of antimicrobial based interventions despite similar summary ES estimates. Moreover, the inferred relationship between underlying control group risk and ES is 'flipped'.

Asunto(s)

Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Neumonía/diagnóstico , Incidencia , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos

RESUMEN

BACKGROUND: Tuberculosis (TB) is a major global health issue, particularly in its minimal and subclinical forms, which often go undetected and contribute to transmission. Accurate prevalence assessment of these forms and the effectiveness of diagnostic tests are crucial for improving TB control, especially in high-risk populations such as those with HIV. OBJECTIVES: This study aimed to determine the prevalence of minimal and subclinical TB and evaluate the positivity rates of current diagnostic tests. METHODS: We conducted a meta-analysis of studies published from January 2000 to December 2022. Prevalence rates and diagnostic test results, including sputum culture, smear microscopy, TST/IGRA, and chest X-ray, were analyzed, with pooled prevalence calculated and comparisons made between geographic regions. RESULTS: Minimal TB prevalence ranged from 0.9 % to 22.9 % in the general population, while subclinical TB prevalence was 0.05 % to 0.64 %, and 1.57 % to 14.63 % among individuals with HIV. The overall pooled prevalence of minimal TB was 7 % (95 % CI: 5-9 %), with higher rates in Asia (8 %, 95 % CI: 5-12 %) compared to Africa (6 %, 95 % CI: 4-8 %). Subclinical TB had a pooled prevalence of 0.2 % (95 % CI: 0.2-0.3 %) overall and 52 % (95 % CI: 46-58 %) among TB cases, with higher rates in Asia (60 %) compared to Africa (44 %). Diagnostic test positivity was 77 % (sputum culture), 15 % (smear microscopy), 64 % (TST/IGRA), and 53 % (chest X-ray). CONCLUSIONS: This study reveals significant variability in the prevalence of minimal and subclinical TB. The findings highlight the need for improved diagnostic methods to reduce undetected cases, especially in high-risk populations.

Asunto(s)

Pruebas Diagnósticas de Rutina , Tuberculosis , Humanos , África/epidemiología , Asia/epidemiología , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Salud Global/estadística & datos numéricos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Prevalencia , Esputo/microbiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/inmunología , Tuberculosis/prevención & control

RESUMEN

Importance: Overuse of diagnostic testing is pervasive, but the extent to which it varies by race and ethnicity in the acute care setting is poorly understood. Objective: To use a previously validated diagnostic intensity index to evaluate differences in diagnostic testing rates by race and ethnicity in the acute care setting, which may serve as a surrogate for diagnostic test overuse. Design, Setting, and Participants: This was a cross-sectional study of emergency department (ED) discharges, hospital observation stays, and hospital admissions using administrative claims among EDs and acute care hospitals in Kentucky, Maryland, North Carolina, and New Jersey, from 2016 through 2018. The diagnostic intensity index pairs nonspecific principal discharge diagnoses (nausea and vomiting, abdominal pain, chest pain, and syncope) with related diagnostic tests to estimate rates of nondiagnostic testing. Adults with an acute care encounter with a principal discharge diagnosis of interest were included. Data were analyzed from January to February 2024. Exposure: Race and ethnicity (Asian, Black, Hispanic, White, other [including American Indian, multiracial, and multiethnic], and missing). Main Outcomes and Measures: Receipt of a diagnostic test. Generalized linear models with a hospital-specific indicator variable were estimated to calculate the adjusted odds ratio of receiving a test related to the principal discharge diagnosis by race and ethnicity, controlling for primary payer and zip code income quartile. Results: Of 3 683 055 encounters (1 055 575 encounters [28.7%] for Black, 300 333 encounters [8.2%] for Hispanic, and 2 140 335 encounters [58.1%] for White patients; mean [SD] age of patients with encounters, 47.3 [18.8] years; 2 233 024 encounters among females [60.6%]), most (2 969 974 encounters [80.6%]) were ED discharges. Black compared with White patients discharged from the ED with a diagnosis of interest had an adjusted odds ratio of 0.74 (95% CI, 0.72-0.75) of having related diagnostic testing. No other racial or ethnic disparities of a similar magnitude were observed in any acute care settings. Conclusions and Relevance: In this study, White patients discharged from the ED with a nonspecific diagnosis of interest were significantly more likely than Black patients to receive related diagnostic testing. The extent to which this represents diagnostic test overuse in White patients vs undertesting and missed diagnoses in Black patients deserves further study.

Asunto(s)

Etnicidad , Grupos Raciales , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Transversales , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Maryland , New Jersey , North Carolina , Grupos Raciales/estadística & datos numéricos , Estados Unidos , Kentucky

RESUMEN

Chagas disease, caused by Trypanosoma cruzi, affects millions of people globally and is associated with significant underdiagnosis and undertreatment. Current diagnostic algorithms face challenges in remote regions. We aimed to review the potential of rapid diagnostic tests (RDTs) for screening or diagnosing chronic Chagas disease in endemic areas. An expert panel representing scientific and academic institutions from the Americas convened with the aim of discussing the use of RDTs. The study employed the nominal group technique, gathering insights from diverse experts during a 3-day meeting. Panel discussions covered RDT application, research protocols, and regulatory mechanisms. The results indicate that RDTs play a crucial role in surveillance and screening, although limitations in sensitivity and specificity exist. The expert group recommends standardized protocols, emphasizes the importance of cost-effectiveness assessments, and highlights the need to consider geographic validation. Despite these challenges, RDTs present a promising avenue for improving Chagas disease diagnosis in resource-limited settings. Future research and a collaborative approach are deemed essential for effective implementation.

Asunto(s)

Enfermedad de Chagas , Pruebas Diagnósticas de Rutina , Trypanosoma cruzi , Enfermedad de Chagas/diagnóstico , Humanos , Pruebas Diagnósticas de Rutina/métodos , Trypanosoma cruzi/aislamiento & purificación , Enfermedad Crónica , Sensibilidad y Especificidad , Prueba de Diagnóstico Rápido

RESUMEN

PURPOSE OF REVIEW: Cephalosporins are one of the most prescribed antibiotics worldwide and are implicated in a wide range of hypersensitivity reactions (HSR). This review summarizes recent updates in cephalosporin hypersensitivity with a focus on diagnostic testing. RECENT FINDINGS: Reported testing strategies to evaluate different immediate and delayed cephalosporin HSR have included skin testing, in vitro testing, and diagnostic drug challenges. However, the diagnostic performance of in vivo and in vitro tests remains unclear across different hypersensitivity endotypes; adequately powered studies investigating the true positive and negative predictive value of these diagnostic modalities are needed using the reference standard of drug challenges to define cephalosporin hypersensitivity. Refinement of diagnostic testing should be guided by growth in our understanding of cephalosporin antigenic determinants. This growth will be crucial in driving further clarification of cross-reactivity between cephalosporins, and potentially delineating streamlined evaluation processes resulting in reduced unnecessary antibiotic avoidance.

Asunto(s)

Antibacterianos , Cefalosporinas , Hipersensibilidad a las Drogas , Pruebas Cutáneas , Humanos , Cefalosporinas/efectos adversos , Cefalosporinas/inmunología , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Antibacterianos/efectos adversos , Antibacterianos/inmunología , Reacciones Cruzadas/inmunología , Pruebas Diagnósticas de Rutina

RESUMEN

Regular monitoring of malaria rapid diagnostic tests (RDTs) for the management of uncomplicated malaria in healthcare facilities is a key factor in improving diagnostic quality and ensuring better case management. This study aimed to assess the performance of five RDTs (Standard Q Malaria P.f Ag and Standard Q Malaria P.f/Pan (SD Biosensor, Korea), One Step Malaria HRP2/pLDH (P.f/Pan) (Guangzhou Wondfo Biotech Co., Ltd., China), Malaria Pf/Pan (B&O Pharm, France), and Malaria test P.f/pan (Das Labor, Germany)) in two healthcare facilities in Abidjan. This cross-sectional study was conducted between September and October 2022. Overall, 250 patients suffering from uncomplicated malaria were included with a predominance of female patients (56.6%). The mean age was 22.3 years (SD = 20.6; range, 0.17-73). Of the patients tested, forty-six (46) tested positive for thick smears, reflecting a prevalence of 18.5%. Plasmodium falciparum was the most commonly detected species (93.5%). The geometric mean parasitemia was 6,111.80 parasites/µl (SD = 80,026.93) (range: 116-412461). The sensitivity ranged from 95.24% to 95.65%, whereas the specificity ranged from 93.07 to 94.09% for all five tests evaluated. The false positive rate of the tests was less than 10%. No invalid test results were reported. Two-thirds of P. malariae cases detected by microscopy showed also positive results with all the RDTs. All five RDTs showed 100% sensitivity at low parasitemia levels (< 1,000 parasites/µl blood) including three cases of parasites < 200 parasites/µl blood. This study demonstrated the importance of monitoring the performance of RDTs in clinical samples.

Asunto(s)

Pruebas Diagnósticas de Rutina , Malaria , Humanos , Côte d'Ivoire/epidemiología , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Masculino , Estudios Transversales , Preescolar , Niño , Malaria/diagnóstico , Lactante , Pruebas Diagnósticas de Rutina/métodos , Anciano , Sensibilidad y Especificidad , Instituciones de Salud , Prueba de Diagnóstico Rápido

RESUMEN

BACKGROUND: Rapid diagnostic tests (RDTs) provide quick, easy, and convenient early diagnosis of malaria ensuring better case management particularly in resource-constrained settings. Nevertheless, the efficiency of HRP2-based RDT can be compromised by Plasmodium falciparum histidine-rich protein 2/3 gene deletion and genetic diversity. This study explored the genetic diversity of PfHRP2/3 in uncomplicated malaria cases from Ethiopia. METHODS: A cross-sectional study was conducted from June 2022 to March 2023 at Metehara, Zenzelema and Kolla Shele health centres, Ethiopia. Finger-prick blood samples were collected for RDT testing and microscopic examination. For molecular analysis, parasite genomic DNA was extracted from venous blood. Plasmodium falciparum was confirmed using VarATS real time PCR. Additionally, PfHRP2/3 was amplified, and DNA amplicons were sequenced using Oxford Nanopore technology. RESULTS: PfHRP2/3 sequences revealed small variations in the frequency and number of amino acid repeat types per isolate across the three health centres. Twelve and eight types of amino acid repeats were identified for PfHRP2 and PfHRP3, respectively, which had been previously characterized. Repeat type 1, 4 and 7 were present in both PfHRP2 and PfHRP3 amino acid sequences. Type 2 and 7 repeats were commonly dispersed in PfHRP2, while repeat types 16 and 17 were found only in PfHRP3. A novel 17 V repeat type variant, which has never been reported in Ethiopia, was identified in six PfHRP3 amino acid sequences. The majority of the isolates, as determined by the Baker's logistic regression model, belonged to group C, of which 86% of them were sensitive to PfHRP2-based RDT. Likewise, PfHRP2-based RDT detected 100% of the isolates in group A (product of type 2 × type 7 repeats ≥ 100) and 85.7% in group B (product of types 2 × type 7 repeats 50-99) at a parasitaemia level > 250 parasite/µl. CONCLUSION: This study highlights the significant diversity observed in PfHRP2 and PfHRP3 among clinical isolates of Plasmodium falciparum in Ethiopia. This emphasizes the necessity for monitoring of PfHRP2- based RDT efficacy and their repeat type distribution using a large sample size and isolates from various ecological settings.

Asunto(s)

Antígenos de Protozoos , Pruebas Diagnósticas de Rutina , Malaria Falciparum , Plasmodium falciparum , Proteínas Protozoarias , Etiopía , Proteínas Protozoarias/genética , Antígenos de Protozoos/genética , Estudios Transversales , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Humanos , Adulto , Femenino , Adulto Joven , Adolescente , Masculino , Persona de Mediana Edad , Niño , Preescolar , Variación Genética , Lactante

RESUMEN

Strongyloides stercoralis in humans often presents as a chronic asymptomatic infection. Diagnosis can be challenging due to the limited sensitivity of faecal-based parasitological techniques. A prototype lateral flow rapid diagnostic test (RDT) for the detection of specific antibodies against Strongyloides stercoralis (SsRapid) was evaluated using 143 samples from the serum bank of the Swiss Tropical and Public Health Institute. Group 1 (n = 30) comprised serum samples from larvae-positive individuals; the RDT's diagnostic sensitivity was 97 % (29/30). Group II comprised serum samples from patients with other parasitic infections (n = 86) and Swiss blood donors (n = 27); the RDT's diagnostic specificity for this group was 90 % (102/113). The RDT showed good diagnostic performance and is a promising point-of-care test for detecting human Strongyloides stercoralis infection.

Asunto(s)

Anticuerpos Antihelmínticos , Sensibilidad y Especificidad , Strongyloides stercoralis , Estrongiloidiasis , Strongyloides stercoralis/inmunología , Strongyloides stercoralis/aislamiento & purificación , Estrongiloidiasis/diagnóstico , Animales , Humanos , Anticuerpos Antihelmínticos/sangre , Pruebas Diagnósticas de Rutina/métodos , Suiza , Prueba de Diagnóstico Rápido

RESUMEN

BACKGROUND: Nigeria has the highest malaria burden globally, and anti-malarials have been commonly used to treat malaria without parasitological confirmation. In 2012, Nigeria implemented rapid diagnostic tests (RDTs) to reduce the use of anti-malarials for those without malaria and to increase the use of artemisinin-based combination therapy (ACT) for malaria treatment. This study examined changes in anti-malarial receipt among children aged 6-59 months during a 12-year period of increasing RDT availability. METHODS: A cross-sectional analysis was conducted using the Nigeria Malaria Indicator Survey (NMIS) data from 2010 (before RDT implementation in 2012), 2015, and 2021. The analysis assessed trends in prevalence of malaria by survey RDT result, and fever and anti-malarial/ACT receipt in the 2 weeks prior to the survey. A multivariable logistic regression was used to account for the complex survey design and to examine factors associated with anti-malarial receipt, stratified by survey RDT result, a proxy for recent/current malaria infection. RESULTS: In a nationally-representative, weighted sample of 22,802 children aged 6-59 months, fever prevalence remained stable over time, while confirmed malaria prevalence decreased from 51.2% in 2010 to 44.3% in 2015 and 38.5% in 2021 (trend test p < 0.0001). Anti-malarial use among these children decreased from 19% in 2010 to 10% in 2021 (trend test p < 0.0001), accompanied by an increase in ACT use (2% in 2010 to 8% in 2021; trend test p < 0.0001). Overall, among children who had experienced fever, 30.6% of survey RDT-positive and 36.1% of survey RDT-negative children had received anti-malarials. The proportion of anti-malarials obtained from the private sector increased from 61.8% in 2010 to 80.1% in 2021 for RDT-positive children; most of the anti-malarials received in 2021 were artemisinin-based combinations. Factors associated with anti-malarial receipt for both RDT-positive and RDT-negative children included geographic region, greater household wealth, higher maternal education, and older children. CONCLUSION: From 2010 to 2021 in Nigeria, both malaria prevalence and anti-malarial treatments among children aged 6-59 months decreased, as RDT availability increased. Among children who had fever in the prior 2 weeks, anti-malarial receipt was similar between children with either positive or negative survey RDT results, indicative of persistent challenges in reducing inappropriate anti-malarials uptake.

Asunto(s)

Antimaláricos , Pruebas Diagnósticas de Rutina , Malaria , Antimaláricos/uso terapéutico , Nigeria/epidemiología , Humanos , Lactante , Preescolar , Estudios Transversales , Femenino , Masculino , Malaria/tratamiento farmacológico , Malaria/epidemiología , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Prevalencia , Artemisininas/uso terapéutico

RESUMEN

BACKGROUND: Understanding diagnostic capacities is essential to addressing healthcare provision and inequity, particularly in low-income and middle-income countries. This study used routine data to assess trends in rapid diagnostic test (RDT) reporting, supplies and unmet needs across national and 47 subnational (county) levels in Kenya. METHODS: We extracted facility-level RDT data for 19 tests (2018-2020) from the Kenya District Health Information System, linked to 13 373 geocoded facilities. Data quality was assessed for reporting completeness (ratio of reports received against those expected), reporting patterns and outliers. Supply assessment covered 12 RDTs reported by at least 50% of the reporting facilities (n=5251), with missing values imputed considering reporting trends. Supply was computed by aggregating the number of tests reported per facility. Due to data limitations, demand was indirectly estimated using healthcare-seeking rates (HIV, malaria) and using population data for venereal disease research laboratory test (VDRL), with unmet need computed as the difference between supply and demand. RESULTS: Reporting completeness was under 40% across all counties, with RDT-specific reporting ranging from 9.6% to 89.6%. Malaria RDTs showed the highest annual test volumes (6.3-8.0 million) while rheumatoid factor was the lowest (0.5-0.7 million). Demand for RDTs varied from 2.5 to 11.5 million tests, with unmet needs between 1.2 and 3.5 million. Notably, malaria testing and unmet needs were highest in Turkana County, as well as the western and coastal regions. HIV testing was concentrated in the western and central regions, with decreasing unmet needs from 2018 to 2020. VDRL testing showed high volumes and unmet needs in Nairobi and select counties, with minimal yearly variation. CONCLUSION: RDTs are crucial in enhancing diagnostic accessibility, yet their utilisation varies significantly by region. These findings underscore the need for targeted interventions to close testing gaps and improve data reporting completeness. Addressing these disparities is vital for equitably enhancing diagnostic services nationwide.

Asunto(s)

Pruebas Diagnósticas de Rutina , Kenia , Humanos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Malaria/diagnóstico , Necesidades y Demandas de Servicios de Salud