BACKGROUND: In the last two decades, several rapid lateral flow immunoassays (LFIs) for the diagnosis of human leptospirosis were developed and commercialized. However, the accuracy and reliability of these LFIs are not well understood. In this study, we aimed to evaluate the accuracy of leptospirosis LFIs as well as the factors affecting the test efficiency using systematic review and meta-analysis.
RESULTS: Original articles reporting the accuracy of human leptospirosis LFIs against microagglutination tests (MAT) or immunofluorescent assays (IFA) were searched from PubMed, Embase, and Scopus, and selected as per pre-set inclusion and exclusion criteria. A total of 49 data entries extracted from 24 eligible records published between 2003 and 2023 were included for meta-analysis. A meta-analysis was performed using STATA. The quality of the included studies was assessed according to the revised QUADAS-2. Only nine studies (32.1%) were considered to have a low risk of bias and no concern for applicability. Pooled sensitivity and specificity were calculated to be 68% (95% confidence interval, CI: 57-78) and 93% (95% CI: 90-95), respectively. However, the ranges of sensitivity (3.6 - 100%) and specificity (53.5 - 100%) of individual entries are dramatically broad, possibly due to the heterogeneity found in both study designs and LFIs themselves. Subgroup analysis demonstrated that IgM detection has better sensitivity than detection of IgG alone. Moreover, the test performance seems to be unaffected by samples from different phases of infection.
CONCLUSIONS: The pooled specificity of LFIs observed is somewhat acceptable, but the pooled sensitivity is low. These results, however, must be interpreted with caution because of substantial heterogeneity. Further evaluations of the LFIs with well-standardized design and reference test will be needed for a greater understanding of the test performance. Additionally, IgM detection type should be employed when leptospirosis LFIs are developed in the future.

UNASSIGNED: Invasive meningococcal disease (IMD) is potentially fatal and associated with severe sequelae among survivors. It is preventable by several vaccines, including meningococcal vaccines targeting the most common disease-causing serogroups (A, B, C, W, Y). The meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT [Nimenrix]) is indicated from 6 weeks of age in the European Union and >50 additional countries.
UNASSIGNED: Using PubMed, Google Scholar, ClinicalTrials.gov and ad hoc searches for publications to June 2023, we review evidence of antibody persistence for up to 10 years after primary vaccination and up to 6 years after MenACWY-TT revaccination. We also review global MenACWY revaccination recommendations and real-world impact of vaccination policies, focusing on how these data can be considered alongside antibody persistence data to inform future IMD prevention strategies.
UNASSIGNED: Based on clear evidence that immunogenicity data (demonstrated antibody titers above established correlates of protection) are correlated with real-world effectiveness, long-term persistence of antibodies after MenACWY-TT vaccination suggests continuing protection against IMD. Optimal timing of primary and subsequent vaccinations is critical to maximize direct and indirect protection. Recommending bodies should carefully consider factors such as age at vaccination and long-term immune responses associated with the specific vaccine being used.

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.

Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study.
Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar.
We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country.
We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

BACKGROUND: Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT\'s sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen.
METHODS: We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool.
RESULTS: For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%).
CONCLUSIONS: Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.

UNASSIGNED: In neuroborreliosis (NB) serology might objectively differentiate ongoing from past infection when the intrathecal space is involved. The hierarchy of the parallel serum-CSF (cerebrospinal fluid) methods is seldom discussed and remains elusive in daily practice. We compared the efficacy of certain methods and assessed the prevalence of anti-Borrelia antibodies in the local population.
UNASSIGNED: We summarized standard two-tier test results in all ELISA-reactive samples of patients with suspected NB (n=152) since 2017 and tested 122 unrelated sera for anti-Borrelia antibodies from central Hungary.
UNASSIGNED: The most common central nervous system symptom was a cranial nerve palsy (27.6% of all subjects). CSF was available in 25 cases. A serum-CSF IgG-matched line immunoassay (LIA) detected intrathecal antibody production correctly in 6 of 8 samples when compared to the ELISA-based antibody-index (AI). Among the 122 random sera the prevalence of specific anti-Borrelia IgG antibodies (on LIA, not including anti-p41) were 6.8% above 30 and 10% above 60 years. Our results enable us to assume the predictive values of serological results according to the pretest probability of neuroborreliosis.
UNASSIGNED: Our results suggest that recombinant antigen-based two-tier serology from solely the sera might have sufficient positive predictive value to verify NB in young individuals with characteristic anamnestic data in our region. When parallel serum-CSF testing is warranted, AI should have priority. IgG and albumin concentrations in the both serum and the CSF, the potential time of exposure and the nature and duration of symptoms form the bare minimal set of data for conclusive testing.

The direct methods for diagnosis of bovine brucellosis have several limitations, therefore serological tests are the basis for the diagnosis of the disease. However, a meta-analysis estimating the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) on the main tests used in bovine brucellosis control programs worldwide has not been performed. This systematic review and meta-analysis aimed to estimate the DSe, DSp and thereby accuracy of serological tests individually used in the diagnosis of bovine brucellosis. The databases CABI, Cochrane Library, PubMed/MEDLINE, SciELO, Scopus and Web of Science were used to select articles. The search resulted in 5308 studies, of which 71 were selected for systematic review using quality assessment tools and 65 studies were included in the meta-analysis. For the meta-analysis, 178 assays and 11 different serological tests were considered. To estimate DSe and DSp of the tests, studies were divided according to animal selection for the studies: (1) studies that carried out a random or consecutive selection of participants (noncasecontrol studies) and (2) all studies, including casecontrol studies. Considering only the non-case-control studies to estimate the DSe, the tests that exhibited the best and worst performance were the iELISA test (indirect enzyme immunoassay - bacterial suspension as antigen - BS) (96.5%, 95% CI: 94.1-97.9%) and 2ME (2- mercaptoethanol test) (85.0%, 95% CI: 79.6-89.1%), respectively; while for DSp, the FPA (fluorescence polarization assay) (99, 7%, 95% CI: 99.5-99.8%) and PCFIA tests (protein concentration fluorescence immunoassay) (78.5%, 95% CI: 70.0-85.1%) showed better and worse performance, respectively. Overall, our results showed an overestimation in the DSe and DSp of the eleven serological tests assessed when casecontrol studies were included in the meta-analysis, which is a concern considering its impacts on the time and costs associated with populational diagnosis of the diseases, since several of these tests are routinely used in the control and eradication programs of bovine brucellosis worldwide. Furthermore, the tests that exhibited the best DSe and DSp, iELISA (BS) and FPA, respectively, are relatively easy to perform and interpret and the test which showed the best overall accuracy was FPA.

Psittacosis is a zoonotic disease caused by Chlamydia psittaci, a bacterium classified as an agent with bioterrorist potential. It has caused multiple outbreaks in exposed poultry workers around the world. Colombia has no epidemiological follow-up of the infection and a big knowledge gap.
To determine the antibodies’ frequency against C. psittaci in workers with occupational exposure to birds and to review the literature on studies conducted in Colombia.
We conducted a cross-sectional descriptive study with analytical intent on workers in contact with birds and reviewed the related literature in Colombia. IgM and IgG serum antibodies against C. psittaci were detected by microimmunofluorescence. The sociodemographic and exposure characteristics were expressed as frequencies and summary measures. Associated factors were explored by bivariate and multivariate analysis. The scientific and gray literature review was done with a structured search.
We analyzed 54 workers in contact with birds. Antibody prevalence was 31.5%. Slaughtering and evisceration by non-veterinarians was a risk factor for antibody presence. There are only four previous studies on C. psittaci in Colombia.
Here, we present the first evidence of C. psittaci circulation among workers exposed to birds in Antioquia and the second report in the country. These findings contribute to the “One Health” public health strategy.
La psitacosis es una enfermedad zoonótica causada por Chlamydia psittaci. Esta bacteria es catalogada como un agente con potencial bioterrorista y ha causado múltiples brotes en trabajadores con exposición laboral a aves en diferentes lugares del mundo. En Colombia, no se hace seguimiento epidemiológico de la infección y existe una gran brecha en el conocimiento.
Determinar la frecuencia de anticuerpos contra C. psittaci en trabajadores con exposición laboral a aves y sus factores asociados. Además, revisar la literatura en relación con los estudios sobre el tema realizados en Colombia.
Se llevó a cabo un estudio descriptivo, transversal, con intención analítica, en trabajadores en contacto con aves y se revisó la literatura científica relacionada en Colombia. Se detectaron anticuerpos IgM e IgG contra C. psittaci en suero por microinmunofluorescencia. La descripción de las características sociodemográficas y de exposición se hizo con frecuencias y medidas de resumen. Se exploraron factores asociados por análisis bivariados y multivariados. La revisión de la literatura científica y gris se hizo con búsqueda estructurada.
Se analizaron 54 trabajadores en contacto con aves y se encontró una prevalencia de anticuerpos del 31,5 %. El ejercer funciones de sacrificio y faenado de las aves sin ser médico veterinario fue un factor de riesgo para la presencia de anticuerpos. Solo se encontraron cuatro estudios previos sobre C. psittaci hechos en Colombia.
Este estudio constituye la primera evidencia de la circulación de C. psittaci en trabajadores en contacto con aves en Antioquia y el segundo reporte en el país. Estos hallazgos aportan desde la salud pública a la estrategia One Health.

Cattle brucellosis is a severe zoonosis of worldwide distribution caused by Brucella abortus and B. melitensis. In some countries with appropriate infrastructure, animal tagging and movement control, eradication was possible through efficient diagnosis and vaccination with B. abortus S19, usually combined with test-and-slaughter (T/S). Although S19 elicits anti-smooth lipopolysaccharide antibodies that may interfere in the differentiation of infected and vaccinated animals (DIVA), this issue is minimized using appropriate S19 vaccination protocols and irrelevant when high-prevalence makes mass vaccination necessary or when eradication requisites are not met. However, S19 has been broadly replaced by vaccine RB51 (a rifampin-resistant rough mutant) as it is widely accepted that is DIVA, safe and as protective as S19. These RB51 properties are critically reviewed here using the evidence accumulated in the last 35 years. Controlled experiments and field evidence shows that RB51 interferes in immunosorbent assays (iELISA, cELISA and others) and in complement fixation, issues accentuated by revaccinating animals previously immunized with RB51 or S19. Moreover, contacts with virulent brucellae elicit anti-smooth lipopolysaccharide antibodies in RB51 vaccinated animals. Thus, accepting that RB51 is truly DIVA results in extended diagnostic confusions and, when combined with T/S, unnecessary over-culling. Studies supporting the safety of RB51 are flawed and, on the contrary, there is solid evidence that RB51 is excreted in milk and abortifacient in pregnant animals, thus being released in abortions and vaginal fluids. These problems are accentuated by the RB51 virulence in humans, lack diagnostic serological tests detecting these infections and RB51 rifampicin resistance. In controlled experiments, protection by RB51 compares unfavorably with S19 and lasts less than four years with no evidence that RB51-revaccination bolsters immunity, and field studies reporting its usefulness are flawed. There is no evidence that RB51 protects cattle against B. melitensis, infection common when raised together with small ruminants. Finally, data acumulated during cattle brucellosis eradication in Spain shows that S19-T/S is far more efficacious than RB51-T/S, which does not differ from T/S alone. We conclude that the assumption that RB51 is DIVA, safe, and efficaceous results from the uncritical repetition of imperfectly examined evidence, and advise against its use.

Shigella is a major global pathogen and the etiological agent of shigellosis, a diarrheal disease that primarily affects low- and middle-income countries. Shigellosis is characterized by a complex, multistep pathogenesis during which bacteria use multiple invasion proteins to manipulate and invade the intestinal epithelium. Antibodies, especially against the O-antigen and some invasion proteins, play a protective role as titres against specific antigens inversely correlate with disease severity; however, the context of antibody action during pathogenesis remains to be elucidated, especially with Shigella being mostly an intracellular pathogen. In the absence of a correlate of protection, functional assays rebuilding salient moments of Shigella pathogenesis can improve our understanding of the role of protective antibodies in blocking infection and disease. In vitro assays are important tools to build correlates of protection. Only recently animal models to recapitulate human pathogenesis, often not in full, have been established. This review aims to discuss in vitro assays to evaluate the functionality of anti-Shigella antibodies in polyclonal sera in light of the multistep and multifaced Shigella infection process. Indeed, measurement of antibody level alone may limit the evaluation of full vaccine potential. Serum bactericidal assay (SBA), and other functional assays such as opsonophagocytic killing assays (OPKA), and adhesion/invasion inhibition assays (AIA), are instead physiologically relevant and may provide important information regarding the role played by these effector mechanisms in protective immunity. Ultimately, the review aims at providing scientists in the field with new points of view regarding the significance of functional assays of choice which may be more representative of immune-mediated protection mechanisms.