Integrating serological and genetic data to quantify cross-species transmission: brucellosis as a case study

Epidemiological data are often fragmented, partial, and/or ambiguous and unable to yield the desired level of understanding of infectious disease dynamics to adequately inform control measures. Here, we show how the information contained in widely available serology data can be enhanced by integration with less common type-specific data, to improve the understanding of the transmission dynamics of complex multi-species pathogens and host communities. Using brucellosis in Northern Tanzania as a case-study, we developed a latent process model based on serology data obtained from the field, to reconstruct Brucella transmission dynamics. We were able to identify sheep and goats as a more likely source of human and animal infection than cattle; however, the highly cross-reactive nature of Brucella spp. meant that it was not possible to determine which Brucella species (B. abortus or B. melitensis) is responsible for human infection. We extended our model to integrate simulated serology and typing data, and show that although serology alone can identify the host source of human infection under certain restrictive conditions, the integration of even small amounts (5%) of typing data can improve understanding of complex epidemiological dynamics. We show that data integration will often be essential when more than one pathogen is present and when the distinction between exposed and infectious individuals is not clear from serology data. With increasing epidemiological complexity, serology data become less informative. However, we show how this weakness can be mitigated by integrating such data with typing data, thereby enhancing the inference from these data and improving understanding of the underlying dynamics

Detection of Leishmania infantum by PCR, serology and cellular immune response in a cohort study of Brazilian dogs

The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative response to Leishmania antigen for the detection of Leishmania infantum infection were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil. For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and ribosomal primers. The infection status and time of infection of each dog were estimated from longitudinal data. The sensitivity of PCR in parasite-positive samples was 98%. However, the overall sensitivity of PCR in post-infection samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR varied during the course of infection, being highest (78–88%) 0–135 days post-infection and declining to around 50% after 300 days. The sensitivity of PCR also varied between dogs, and was highest in sick dogs. The sensitivity of serology was similar in parasite-positive (84%), PCR-positive (86%) and post-infection (88%) samples. The sensitivity of serology varied during the course of infection, being lowest at the time of infection and high (93–100%) thereafter. Problems in determining the specificity of serology are discussed. The sensitivity and specificity of cellular responsiveness were low. These data suggest that PCR is most useful in detecting active or symptomatic infection, and that serology can be a more sensitive technique for the detection of all infected dogs

Relation between serology of meat juice and bacteriology of tonsils and feces for the detection of enteropathogenic Yersinia spp. in pigs at slaughter

The association between positive serology and culture detection of Yersinia spp. in individual pigs was determined. Pieces of diaphragm from 370 pig carcasses were collected for serological analysis, and tonsils and feces of the same carcass were collected for bacteriological analysis. Detection of anti-Yersinia antibodies in meat juice samples was done using an indirect enzyme-linked immunosorbent assay (ELISA) based on Yops (Yersinia outer proteins). Tonsils and feces were tested for the presence of enteropathogenic Yersinia spp. by direct plating on cefsulodin–irgasan–novobiocin agar plates. Of the 370 meat juice samples, 241 (65.1%) gave a positive serological reaction using a cutoff value of 20%. Enteropathogenic Yersinia spp. (Yersinia enterocolitica serotype O:3 and Yersinia pseudotuberculosis) were found in tonsils of 161 pigs and feces of 30 pigs. Recovery of enteropathogenic Yersinia from the tonsils was highly correlated with positive serotiters, whereas no correlation was found between serology and fecal excretion. Results demonstrated that serology has an acceptable sensitivity, but a relatively low specificity for the rapid detection of enteropathogenic Yersinia spp. in tonsils of pigs at slaughter

Frequency of the Congenital Transmission of Trypanosoma cruzi: A Systematic Review and Meta-Analysis

BACKGROUND: Chagas disease is caused by the parasite Trypanosoma cruzi and is endemic in much of Latin America. With increased globalisation and immigration, it is a risk in any country, partly through congenital transmission. The frequency of congenital transmission is unclear. OBJECTIVE: To assess the frequency of congenital transmission of T. cruzi. SEARCH STRATEGY: PubMed, Journals@Ovid Full Text, EMBASE, CINAHL, Fuente Academica and BIREME databases were searched using seven search terms related to Chagas disease or T. cruzi and congenital transmission. SELECTION CRITERIA: The inclusion criteria were the following: Dutch, English, French, Portuguese or Spanish language; case report, case series or observational study; original data on congenital T. cruzi infection in humans; congenital infection rate reported or it could be derived. This systematic review included 13 case reports/series and 51 observational studies. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data on study characteristics, diagnosis and congenital infection rate. The principal summary measure - the congenital transmission rate - is defined as the number of congenitally infected infants divided by the number of infants born to infected mothers. A random effects model was used. MAIN RESULTS: The pooled congenital transmission rate was 4.7% (95% confidence interval: 3.9-5.6%). Countries where T. cruzi is endemic had a higher rate of congenital transmission compared with countries where it is not endemic (5.0% versus 2.7%). CONCLUSIONS: Congenital transmission of Chagas disease is a global problem. Overall risk of congenital infection in infants born to infected mothers is about 5%. The congenital mode of transmission requires targeted screening to prevent future cases of Chagas disease.Fil: Howard, Elizabeth J.. University of Tulane; Estados UnidosFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Carlier, Yves. Université Libre de Bruxelles; BélgicaFil: Sosa-estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Buekens, Pierre. University of Tulane; Estados Unido

Syphilis serology in HIV-positive and HIV-negative Nigerians: The public health significance

Syphilis has acquired new potential for morbidity and mortality through association with increased risk for HIV infection. Case-control survey was conducted using Rapid Plasma Reagin test and confirmatory Immunochromatographic test among HIV-positive (cases) and HIV-negative (control) Nigerians. A total of 35(14.0%) of 250 HIV-positive and 5(2.0%) of 250 HIV-negative individuals studied were seropositive for syphilis, the difference was statistically significant (P<0.05). The prevalence was higher among females than males of HIV-positive (15.0% versus 12.7%) and of the HIV-negative (2.1% versus 1.9%) individuals. Syphilis seroprevalence was highest among HIV-positive individuals aged 21-30 years (20.5%) and 41-50 years old HIV-negative individuals (4.5%). Sex education, promotion of safer sexual behaviour, prompt diagnosis of STDs and provision of effective, accessible treatment are recommende

Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients

Background: Systemic sclerosis (SSc) and primary biliary cholangitis (PBC) are autoimmune diseases that may occur concomitantly and are both strongly associated with disease-specific autoantibodies. This study investigated the prevalence and fine specificity of PBC-specific serology (PBC-Ab) and associations with the SSc-subtypes and SSc-specific antibodies as well as the association with cholestatic liver enzymes. Furthermore, three different techniques for the detection of PBC-Ab were compared. Methods: Serum of 184 Belgian SSc patients with a known SSc-antibody profile, was analyzed for PBC-Ab (antimitochondrial antibodies [AMA], anti-Gp210, anti-Sp100 and anti-PML) using indirect immunofluorescence (IIF) analysis on human epithelioma-2000 (HEp-2000) cells (ANA-IIF, Immunoconcepts) and liver-kidney-stomach tissue sections (IIF-LKS) (Menarini), and a line immunoblot (LB) (Eurolmmun). Alkaline phosphatase/gamma-glutamyl transferase (ALP/GGT) were evaluated at time of first sampling (t0) and after 3 years of follow-up (t3). Results: PBC-Ab were present in 13% of patients and significantly correlated with centromere antibodies (anti-CENP-B), but not correlated with the limited cutaneous SSc subgroup (lcSSc). The most frequent reactivities were AMA (11%, with 9% AMA-M2) and Sp-100 antibodies (5%), showing a major overlap. There was no relevant association between the presence of PBC-Ab and ALP or GGT elevation at t0 nor at t3. Detection of AMA with IIF-LKS is comparable to LB. ANA-IIF screening was less sensitive compared to LB. Conclusions: A wide range of PBC-Ab is detectable in SSc in the absence of cholestatic liver enzyme elevations, even after 3 years of follow-up. However, as these antibodies may precede PBC-disease up to 10 years further prospective follow-up of our cohort will be necessary

Incidence, prevalence, and clinical course of hepatitis C following liver transplantation

Hepatitis C virus (HCV) is the agent responsible for posttransfusion hepatitis. The incidence, timing, and clinical course of HCV positive hepatitis in liver transplant recipients are unknown. Three hundred and seventeen donor-recipient liver transplant pairs were grouped on the basis of their pretransplant HCV antibody status. The biopsy findings were examined. Four distinct groups were identified on the basis of HCV serology: group I, both were negative; group II, donor was negative and recipient was positive; group III, donor was positive and recipient was negative; group IV, both were positive. The prevalence of anti-HCV positivity in recipients was 13.6%. The rate of seroconversion was 9.2%. Histologic hepatitis not ascribable to any specific cause other than non-A, non-B (NANB) hepatitis occurred in 13.8%. The incidence of histologic chronic active hepatitis was 1.6%, and none progressed to cirrhosis. The concordance rate for a positive anti-HCV serology and NANB hepatitis was 2.8%. Of the 35 patients (group II and IV) with positive anti-HCV serology pretransplant, only 17 were positive posttransplantation. Based on these data it can be concluded that posttransplant NANB hepatitis occurred in 13.8% of liver recipients. Twenty percent of these were anti-HCV positive. Progression to histologic chronic active hepatitis occurs over a period of 1-5 years in 1.6% of cases. © 1992

Longitudinal Monitoring of SARS-CoV-2 IgM and IgG Seropositivity to Detect COVID-19.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel beta-coronavirus that has recently emerged as the cause of the 2019 coronavirus pandemic (COVID-19). Polymerase chain reaction (PCR) based tests are optimal and recommended for the diagnosis of an acute SARS-CoV-2 infection. Serology tests for viral antibodies provide an important tool to diagnose previous exposure to the virus. Here we evaluate the analytical performance parameters of the Diazyme SARS-CoV-2 IgM/IgG serology assays and describe the kinetics of IgM and IgG seroconversion observed in patients with PCR-confirmed COVID-19 who were admitted to our hospital.MethodsWe validated the performance of the Diazyme assay in 235 presumed SARS-CoV-2 negative subjects to determine specificity. Subsequently, we evaluated the SARS-CoV-2 IgM and IgG seroconversion of 54 PCR-confirmed COVID-19 patients and determined sensitivity of the assay at three different timeframes.ResultSensitivity and specificity for detecting seropositivity at ≥15 days following a positive SARS-CoV-2 PCR result, was 100.0% and 98.7% when assaying for the panel of IgM and IgG. The median time to seropositivity observed for a reactive IgM and IgG result from the date of a positive PCR was 5 days (IQR: 2.75-9 days) and 4 days (IQR: 2.75-6.75 days), respectively.ConclusionsOur data demonstrate that the Diazyme IgM/IgG assays are suited for the purpose of detecting SARS-CoV-2 IgG and IgM in patients with suspected SARS-CoV-2 infections. For the first time, we report longitudinal data showing the evolution of seroconversion for both IgG and IgM in a cohort of acutely ill patients in the United States. We also demonstrate a low false positive rate in patients who were presumed to be disease free