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BMC Infectious Diseases Nov 2023Parasitological investigation of bone marrow, splenic or lymph node aspirations is the gold standard for the diagnosis of visceral leishmaniasis (VL). However, this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parasitological investigation of bone marrow, splenic or lymph node aspirations is the gold standard for the diagnosis of visceral leishmaniasis (VL). However, this invasive test requires skilled clinical and laboratory staff and adequate facilities, and sensitivity varies depending on the tissue used. The direct agglutination test (DAT) is a serological test that does not need specialised staff, with just minimal training required. While previous meta-analysis has shown DAT to have high sensitivity and specificity when using parasitology as the reference test for diagnosis, meta-analysis of DAT compared to other diagnostic techniques, such as PCR and ELISA, that are increasingly used in clinical and research settings, has not been done.
METHODS
We conducted a systematic review to determine the diagnostic performance of DAT compared to all available tests for the laboratory diagnosis of human VL. We searched electronic databases including Medline, Embase, Global Health, Scopus, WoS Science Citation Index, Wiley Cochrane Central Register of Controlled Trials, Africa-Wide Information, LILACS and WHO Global Index. Three independent reviewers screened reports and extracted data from eligible studies. A meta-analysis estimated the diagnostic sensitivity and specificity of DAT.
RESULTS
Of 987 titles screened, 358 were selected for full data extraction and 78 were included in the analysis, reporting on 32,822 participants from 19 countries. Studies included were conducted between 1987-2020. Meta-analysis of studies using serum and DAT compared to any other test showed pooled sensitivity of 95% (95%CrI 90-98%) and pooled specificity of 95% (95%CrI 88-98%). Results were similar for freeze-dried DAT and liquid DAT when analysed separately. Sensitivity was lower for HIV-positive patients (90%, CrI 59-98%) and specificity was lower for symptomatic patients (70%, CrI 43-89%). When comparing different geographical regions, the lowest median sensitivity (89%, CrI 67-97%) was in Western Asia (five studies).
CONCLUSIONS
This systematic review and meta-analysis demonstrates high estimated pooled sensitivity and specificity of DAT for diagnosis of VL, although sensitivity and specificity were lower for different patient groups and geographical locations. This review highlights the lack of standardisation of DAT methods and preparations, and the lack of data from some important geographical locations. Future well-reported studies could provide better evidence to inform test implementation for different patient populations and use cases.
PROSPERO REGISTRATION
CRD42021240830.
Topics: Humans; Leishmaniasis, Visceral; Agglutination Tests; Serologic Tests; Sensitivity and Specificity; HIV Seropositivity
PubMed: 37946107
DOI: 10.1186/s12879-023-08772-1 -
Frontiers in Cellular and Infection... 2020Toxoplasmosis is a widely distributed zoonotic infection caused by the obligate intracellular apicomplexan parasite . It is mainly transmitted through the ingestion of... (Review)
Review
Toxoplasmosis is a widely distributed zoonotic infection caused by the obligate intracellular apicomplexan parasite . It is mainly transmitted through the ingestion of oocysts shed by an infected cat acting as its definitive host. The key to effective control and treatment of toxoplasmosis is prompt and accurate detection of infection. Several laboratory diagnostic methods have been established, including the most commonly used serological assays such as the dye test (DT), direct or modified agglutination test (DAT/MAT), indirect hemagglutination test (IHA), latex agglutination test (LAT), indirect immunofluorescent test (IFAT), enzyme-linked immunosorbent assays (ELISA), immunochromatographic tests (ICT), and the western blot. Nonetheless, creating specific and reliable approaches for serodiagnosis of infection, and differentiating between acute and chronic phases of infection remains a challenge. This review provides information on the current trends in the serodiagnosis of human toxoplasmosis. It highlights the advantages of the use of recombinant proteins for serological testing and provides insight into the possible future direction of these methods.
Topics: Agglutination Tests; Animals; Antibodies, Protozoan; Cats; Enzyme-Linked Immunosorbent Assay; Humans; Serologic Tests; Toxoplasma; Toxoplasmosis, Animal
PubMed: 32457848
DOI: 10.3389/fcimb.2020.00204 -
Transactions of the Royal Society of... Jan 2011Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most... (Review)
Review
Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most severe form. Since clinical features of visceral leishmaniasis (VL) mimic several other common diseases, accurate diagnosis is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rK39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL.
Topics: Agglutination Tests; Animals; Antigens, Protozoan; Enzyme-Linked Immunosorbent Assay; Humans; Leishmaniasis, Visceral; Polymerase Chain Reaction; Sensitivity and Specificity; Serologic Tests
PubMed: 21074233
DOI: 10.1016/j.trstmh.2010.09.006 -
PLoS Neglected Tropical Diseases Mar 2018Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is endemic in Europe with Mediterranean countries reporting endemic status alongside a worrying...
BACKGROUND
Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is endemic in Europe with Mediterranean countries reporting endemic status alongside a worrying northward spread. Serological diagnosis, including immunochromatographic test based on the recombinant antigen rK39 (rK39-ICT) and a direct agglutination test (DAT) based on the whole parasite antigen, have been validated in regions with high VL burden, such as eastern Africa and the Indian subcontinent. To date, no studies using a large set of patients have performed an assessment of both methods within Europe.
METHODOLOGY/PRINCIPAL FINDINGS
We selected a range of clinical serum samples from patients with confirmed VL (including HIV co-infection), Chagas disease, malaria, other parasitic infections and negative samples (n = 743; years 2009-2015) to test the performance of rK39-ICT rapid test (Kalazar Detect Rapid Test; InBios International, Inc., USA) and DAT (ITM-DAT/VLG; Institute of Tropical Medicine Antwerp, Belgium). An in-house immunofluorescence antibody test (IFAT), was included for comparison. Estimated sensitivities for rK39-ICT and DAT in HIV-negative VL patients were 83.1% [75.1-91.2] and 84.2% [76.3-92.1], respectively. Sensitivity was reduced to 67.3% [52.7-82.0] for rK39 and increased to 91.3% [82.1-100.0] for DAT in HIV/VL co-infected patients. The in-house IFAT was more sensitive in HIV-negative VL patients, 84.2% [76.3-92.1] than in HIV/VL patients, 79.4% [73.3-96.2]. DAT gave 32 false positives in sera from HIV-negative VL suspects, compared to 0 and 2 for rK39 and IFAT, respectively, but correctly detected more HIV/VL patients (42/46) than rK39 (31/46) and IFAT (39/46).
CONCLUSIONS/SIGNIFICANCE
Though rK39-ICT and DAT exhibited acceptable sensitivity and specificity a combination with other tests is required for highly sensitive diagnosis of VL cases in Spain. Important variation in the performance of the tests were seen in patients co-infected with HIV or with other parasitic infections. This study can help inform the choice of serological test to be used when screening or diagnosing VL in a European Mediterranean setting.
Topics: Adult; Agglutination Tests; Antibodies, Protozoan; Chromatography, Affinity; Endemic Diseases; Female; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Middle Aged; Predictive Value of Tests; Reagent Kits, Diagnostic; Sensitivity and Specificity; Spain; Young Adult
PubMed: 29494596
DOI: 10.1371/journal.pntd.0006277 -
Zoonoses and Public Health Jun 2022Despite public concern on the role of free-roaming cats as reservoirs of zoonotic agents, little is known about the influence of urban and peri-urban landscapes on the...
Despite public concern on the role of free-roaming cats as reservoirs of zoonotic agents, little is known about the influence of urban and peri-urban landscapes on the exposure risk. We evaluated the seroprevalence of three zoonotic agents (Chlamydia felis, Coxiella burnetii and Toxoplasma gondii) in domestic cats (Felis catus). Two hundred and ninety-one free-roaming cats were trapped in Murcia municipality (Southeast Spain), and their sera were tested for specific antibodies against T. gondii using a modified agglutination test (MAT), and for C. felis, C. burnetii and feline immunodeficiency virus (FIV) antibodies with ELISA technique. Pathogen seroprevalence at 95% CI was calculated for each sex and age category (up to and over 12 months) and compared with a chi-squared test. The role of human population density and urban landscape characteristics on the risk of pathogen exposure in the cat population was explored using generalized linear models. Seropositivity against a single pathogen was found in 60% of the cats, while 19% was seropositive for two or three pathogens. Seroprevalence of C. felis was 8% (CI : 5-11), 37% (CI : 31-42) for C. burnetii and 42% (CI : 36-47) for T. gondii. In addition to these three pathogens, FIV seropositivity was low (1%, CI : -0.1 to 2) and adult cats were more likely to be seropositive to C. burnetii than young individuals (OR: 2.3, CI : 1.2-4.2). No sex or age class differences in seroprevalence were observed for the rest of the pathogens. Seropositivity was correlated with water surface areas for C. felis, and not with crop areas. Coxiella burnetii seropositivity was correlated with the percentage of urban areas (continuous with only buildings and discontinuous, that include buildings, parks, and pedestrian and urban green areas), human population size and peri-urban areas with shrubs, and not correlated with other agricultural landscapes (orchards and crop areas). However, the seroprevalence of T. gondii was only associated with agricultural landscapes such as orchards. The detection of hotspot areas of high pathogen exposure risk is the basis for municipal services to implement surveillance and risk factor control campaigns in specific-risk areas, including (a) efficient health management of urban cat colonies by geographical location, population census and health status monitoring of the components of each cat colony, (b) improvement of hygiene and sanitary conditions at the feeding points of the cat colony and (c) free-roaming cat trapping for health monitoring and, in the long term, to know the evolution of the health status of their populations.
Topics: Agglutination Tests; Animals; Antibodies, Protozoan; Cat Diseases; Cats; Chlamydia; Risk Factors; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis, Animal
PubMed: 35129882
DOI: 10.1111/zph.12919 -
The Tohoku Journal of Experimental... Apr 2023The incidence of Brucella canis (B. canis) in humans is unknown in Northern Cyprus. In this study, we investigated the prevalence of B. canis and Brucella abortus (B....
The incidence of Brucella canis (B. canis) in humans is unknown in Northern Cyprus. In this study, we investigated the prevalence of B. canis and Brucella abortus (B. abortus) infection in human sera and evaluated the results obtained by agglutination-based techniques using standardized antigens made from B. canis comparatively. All of the subjects were negative in terms of Rose-Bengal plate test. Undiluted serum samples were initially screened by rapid slide agglutination test (RSAT), and those which were found positive were retested in the dilution of 1/25-1/200. Confirmation of the positive results was performed by using 2-mercaptoethanol standard agglutination test (SAT). The test antigen was prepared from the less mucoid M (-) variant of B. canis, and 1/1,048 titered dog antiserum was used as positive control. In 225 serum samples, 3.6% (8/225) was positive by B. canis M (-) RSAT, 4.4 % (10/225) was positive by B. canis M (-) indirect enzyme-linked immunosorbent assay (iELISA). 5.3% (12/225) was positive by B. abortus S99 RSAT and 9.8% (22/225) was positive by B. abortus S99 iELISA. Nine samples were positive by both B. abortus S99 RSAT and B. abortus S99 iELISA. Seven samples were positive by both B. canis M (-) RSAT and B. canis M (-) iELISA. One patient was positive by all methods. It is important to evaluate patient samples with RSAT and iELISA. Until the notification system gives better results to the Ministry of Health, in order to reach the real data for Northern Cyprus, multicenter prevalence determination studies should be done for future.
Topics: Humans; Animals; Dogs; Brucella canis; Brucella abortus; Brucellosis; Cyprus; Antigens, Bacterial; Antibodies, Bacterial; Enzyme-Linked Immunosorbent Assay; Agglutination Tests
PubMed: 36384858
DOI: 10.1620/tjem.2022.J096 -
Journal of Infection in Developing... Jun 2014The worldwide gold standard of diagnosing of enteric fever depends on the isolation of Salmonella enterica serovar Typhi from a patient's bone marrow and/or blood... (Comparative Study)
Comparative Study Review
The worldwide gold standard of diagnosing of enteric fever depends on the isolation of Salmonella enterica serovar Typhi from a patient's bone marrow and/or blood culture. In Libya clinicians are heavily dependent on the Widal test for diagnosis of enteric fever which has been used without determining the locally appropriate threshold titer, because the laboratories lack the skilled, experienced personnel and appropriate facilities to detect and serotype Salmonella isolates. To improve the diagnosis process, clinical management and reliability of public health measures, there is an urgent need for the effective training of laboratory technicians and to provide resources to culture Salmonella species according to published guidelines. Clinicians should understand the limitations of Widal test and recognize that it cannot be expected to give a reliable diagnosis.
Topics: Agglutination Tests; Antibodies, Bacterial; Bacteriological Techniques; Developing Countries; Diagnostic Errors; Humans; Libya; Reproducibility of Results; Salmonella typhi; Typhoid Fever
PubMed: 24916864
DOI: 10.3855/jidc.3700 -
The Cochrane Database of Systematic... Jun 2014The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available.
OBJECTIVES
To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas.
SEARCH METHODS
We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits.
SELECTION CRITERIA
This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards.
MAIN RESULTS
Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and rKE16 ICT) recruiting 4271 participants (2605 with VL) were included. We carried out a meta-analysis for the rK39 ICT (including 18 studies; 3622 participants) and the latex agglutination test (six studies; 1374 participants). The results showed considerable heterogeneity. For the rK39 ICT, the overall sensitivity was 91.9% (95% confidence interval (95% CI) 84.8 to 96.5) and the specificity 92.4% (95% CI 85.6 to 96.8). The sensitivity was lower in East Africa (85.3%; 95% CI 74.5 to 93.2) than in the Indian subcontinent (97.0%; 95% CI 90.0 to 99.5). For the latex agglutination test, overall sensitivity was 63.6% (95% CI 40.9 to 85.6) and specificity 92.9% (95% CI 76.7 to 99.2).
AUTHORS' CONCLUSIONS
The rK39 ICT shows high sensitivity and specificity for the diagnosis of visceral leishmaniasis in patients with febrile splenomegaly and no previous history of the disease, but the sensitivity is notably lower in east Africa than in the Indian subcontinent. Other rapid tests lack accuracy, validation, or both.
Topics: Africa, Eastern; Agglutination Tests; Antigens, Protozoan; Asymptomatic Infections; Biomarkers; Chromatography, Affinity; Clinical Trials, Phase III as Topic; Humans; India; Latex Fixation Tests; Leishmaniasis, Visceral; Nepal; Protozoan Proteins; Sensitivity and Specificity
PubMed: 24947503
DOI: 10.1002/14651858.CD009135.pub2 -
Indian Journal of Medical Microbiology 2014Leptospirosis is a potentially fatal bacterial disease that mimics many diseases; therefore, laboratory confirmation is pivotal. Though microscopic agglutination test...
BACKGROUND AND OBJECTIVES
Leptospirosis is a potentially fatal bacterial disease that mimics many diseases; therefore, laboratory confirmation is pivotal. Though microscopic agglutination test (MAT) is accepted as World Health Organisation (WHO) reference test, it has got many pitfalls such as being hazardous, tedious, cumbersome and expensive. Counterimmunoelectrophoresis (CIE) is popularly used for diagnosing many infectious diseases but rarely for Leptospirosis. The aim of this study is to find suitability of CIE for the routine laboratory diagnostic purposes.
MATERIALS AND METHODS
Repeat sampling (paired sera) was possible from 401 subjects of which 181 were in-patients of Salem Government General and Private Hospitals and the remaining 220 MAT negative healthy College students gave their consent for the study. All the 802 sera samples were collected from January 2009 to November 2012 and subjected to the present study. After carrying out MAT and CIE on the suspected and control samples, a comparative evaluation was conducted. McNemars test method was used to find out the significant difference between the two tests in the early diagnosis.
RESULT
The sensitivity, specificity, Positive Predictive value (PPV), Negative Predictive value (NPV) and Efficiency test for CIE were 96.80%, 89.28%, 95.23%, 92.59% and 94.47%, respectively. The corresponding values for MAT were 95.90%, 89.83%, 95.08%, 91.37% and 93.92%, respectively. There was no significant difference between MAT and CIE at 95% and 99% confidence intervals according to McNemars test. P value in the early stage of illness was greater for CIE than MAT when Polymerase Chain Reaction (PCR) was used as Gold Standard of diagnosis.
INTERPRETATION AND CONCLUSION
It was concluded that the CIE could be advantageous over MAT due to its safety, rapidity, simplicity, economic and easy for large number of samples. It can answer little earlier than MAT and found as reliable as that of MAT. Since both the tests had shown similar efficacies in the later stage of the illness, the importance could be given to CIE due to early diagnosis.
Topics: Adolescent; Agglutination Tests; Child; Child, Preschool; Clinical Laboratory Techniques; Counterimmunoelectrophoresis; Female; Humans; Infant; Leptospirosis; Male; Predictive Value of Tests; Sensitivity and Specificity
PubMed: 24399383
DOI: 10.4103/0255-0857.124291 -
Turkish Journal of Medical Sciences Feb 2018Background/aim: It was aimed to evaluate the results of Rose Bengal (RB), ELISA total tests (IgM and IgG), and the Brucella Coombs gel test (BCGT), which are used as... (Comparative Study)
Comparative Study
Background/aim: It was aimed to evaluate the results of Rose Bengal (RB), ELISA total tests (IgM and IgG), and the Brucella Coombs gel test (BCGT), which are used as screening tests, with the combined results of a tube agglutination test (standard Wright test: SWT) and a tube agglutination test with antihuman globulin (AHG TAT). Materials and methods: Samples from 97 patients prediagnosed with brucellosis (age ≥18 years) were screened with RB, ELISA, and BCGT. SWT < 160 samples and RB-negative but ELISA- or BCGT-positive samples were tested by AHG TAT. SWT ≥ 160 or AHG TAT ≥ 160 was taken as reference. Results: Thirty-two of 56 RB-positive samples and one RB-negative but ELISA- and BCGT-positive sample were found to be ≥160 with SWT or AHG TAT. Sensitivity, specificity, accuracy, and agreement (kappa) values according to SWT ≥ 160 or AHG TAT ≥ 160 positivity were as follows, respectively: RB 96.9%, 62.5%, 74.2%, and 0.509; ELISA total 100%, 60.9%, 74.2%, and 0.515; BCGT test 97%, 70.3%, 79.4%, and 0.594. Conclusion: Sensitivities of the screening tests are similar, but positivities should be confirmed by more specific tests. Positive samples from screening tests should be tested with AHG if the SWT value is <160.
Topics: Adolescent; Adult; Agglutination; Agglutination Tests; Antibodies, Bacterial; Brucella; Brucellosis; Clinical Laboratory Techniques; Coombs Test; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Immunoglobulin M; Male; Rose Bengal; Sensitivity and Specificity
PubMed: 29479956
DOI: 10.3906/sag-1707-122