Serological Evolution Research Articles

Serologic evolution and follow-up to IgG antibodies of infants born to mothers with gestational COVID

BackgroundIt is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce.MethodsThis prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother’s and infant’s antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression.Results51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers’ titers, with a positive moderate correlation (Pearson’s correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7–2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants’ antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period.ConclusionsTransplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant’s IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants.

57-Year-Old Man With Headache, Vomiting, and Gait Instability

57-Year-Old Man With Headache, Vomiting, and Gait Instability

Humoral Response Following Triple Dose of mRNA Vaccines Against SARS-CoV-2 in Hemodialysis Patients: Results After 1 Year of Follow-Up.

IntroductionCOVID-19 is associated with an increased mortality in hemodialysis patients. Therefore, achieving a long-lasting effective immune response to SARS-CoV-2 vaccines is essential. This study describes the humoral immune response in hemodialysis patients following three doses of mRNA vaccines against SARS-CoV-2, and explores the factors associated with a sustained immune response.Materials and MethodsWe analyzed the monthly serological evolution of SARS-CoV-2 anti-S(RBD) antibodies for 1 year in 178 chronic hemodialysis patients who received three doses of SARS-CoV-2 mRNA vaccines. The primary outcome was sustained effective humoral response defined as anti-S(RBD) levels > 1,000 AU/ml after 4 months from the third dose. Multivariate logistic regression analyses were used to identify features associated with a sustained humoral immune response.ResultsAfter the initial two SARS-CoV-2 mRNA vaccine doses, 77.8% of patients showed an immediate effective humoral response, decreasing to 52.5% after 4 months. Antibody levels were significantly higher in COVID-exposed patients and HBV vaccine responders. After the third dose, 97% of patients showed an effective humoral response, and remained in 91.7% after 4 months. The mean monthly rate of antibody titer decline decreased from 33 ± 14.5 to 25 ± 16.7%. Multivariate regression analysis showed that previous exposure to COVID-19 and response to HBV vaccines were associated with an effective sustained humoral immune response.ConclusionImmunization with SARS-CoV-2 mRNA vaccines elicits an effective immediate humoral immune response in hemodialysis patients, with a progressive waning in antibody levels. A third booster dose enhances the immune response with significantly higher antibody levels and more sustained humoral immune response. COVID-naïve patients and patients without previous response to HBV vaccines are likely to benefit from receiving more booster doses to maintain an effective immune response.

Two-Year Follow-Up of Trypanosoma brucei gambiense Serology after Successful Treatment of Human African Trypanosomiasis: Results of Four Different Sero-Diagnostic Tests.

Gambiense human African trypanosomiasis (gHAT), also known as gambiense sleeping sickness, is a parasitic infection caused by Trypanosoma brucei gambiense. During the last decades, gHAT incidence has been brought to an all-time low. Newly developed serological tools and drugs for its diagnosis and treatment put the WHO goal of interruption of transmission by 2030 within reach. However, further research is needed to efficiently adapt these new advances to new control strategies. We assessed the serological evolution of cured gHAT patients over a two-year period using four different tests: the rapid diagnostic test (RDT) HAT Sero K-SeT, ELISA/T.b. gambiense, Trypanosoma brucei gambiense inhibition ELISA (iELISA), and the immune trypanolysis test. High seropositive rates were observed in all the tests, although sero-reversion rates were different in each test: ELISA/T.b. gambiense was the test most likely to become negative two years after treatment, whereas RDT HAT Sero-K-SeT was the least likely. iELISA and trypanolysis showed intermediate and comparable probabilities to become negative. Stage 1 patients were also noted to be more likely to become negative than Stage 2 patients in all four serological tests. Our results confirm previous findings that trypanosome-specific antibody concentrations in blood may persist for up to two years, implying that HAT control programs should continue to take the history of past HAT episodes into consideration.

Immune treatment in COVID-19.

Current immune treatment directed to avoid viral replication relies mainly in convalescent plasma and monoclonal antibodies (mAbs). No clinical benefit for convalescent plasma has been reported in a meta-analysis and systematic review compared to standard of care. MAbs are recombinant proteins capable to bind with SARS-CoV-2 preventing its entrance into cells. Several mAbs have shown reduction in viral load and/ or progression of the disease such as casirivimab-imdevimab, bamlanivimab-etesevimab and sotrovimab. After the apparition of Omicron variant, it has been reported that sotrovimab retained its activity whereas the other two combinations exhibited loss of neutralizing activity. Several aspects as the target population, timing and doses, serological patient status and evolution of variants still require attention, monitorization and further studies for knowledge gaps.

High Incidence of Asymptomatic Phase I IgG Seroconversion After an Acute Q Fever Episode: Implications for Chronic Q Fever Diagnosis.

The aim of this study was to describe the natural history of acute Q fever, including its clinical and serological evolution and progression to chronic Q fever. Observational cohort study (January 2011-September 2020) performed at Valme University Hospital (Seville, Spain). Inclusion criteria: (1) patients aged ≥18 years; (2) acute Q fever diagnosis, defined as suggestive symptoms in the presence of phase II immunoglobulin G (IgG) titer >1:256; (3) at least 6 months' follow-up after the acute Q fever episode. The incidence of seroconversion to a chronic Q fever serological pattern, defined as phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis, was assessed. During the study period, 117 patients were included. Thirty-four (29%) patients showed phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis. All patients with classic serological criteria for chronic Q fever diagnosis remained asymptomatic despite no specific treatment, with a median (quartile 1-quartile 3 [Q1-Q3]) follow-up of 26.5 (14-44) months in this subgroup. No cases of Q fever endocarditis nor other persistent focalized infection forms were observed during the study period. A significant proportion of acute Q fever patients develop classic serological criteria for chronic Q fever diagnosis in the absence of additional data of chronic Q fever. Consequently, phase I IgG cutoff titers >1:800 should not be used as a criterion to consider such a diagnosis. The incidence of persistent focalized infection forms after acute Q fever is extremely low and does not justify the use of prophylaxis strategies.

Trypanocidal therapy among children infected by Trypanosoma cruzi. Serological and electrocardiographic changes over a mean twenty-five-years follow-up period

This study compared the serological and electrocardiographic evolution among patients with chronic T. cruzi infection treated during childhood or left untreated. A retrospective cohort study was conducted during a mean follow-up period of 25 years in 82 patients: half of them underwent treatment (nifurtimox 8, benznidazole 33) before being 15 years old, whereas the other half remained untreated. During the follow-up, negative seroconversion occurred in 92.7% of the treated children, while all the untreated ones remained positive for conventional serology. At baseline, 2 patients from each group had electrocardiographic abnormalities. During the study period, 4/41 (9.75%) and 9/41 (21.95%) of treated and untreated patients displayed an altered electrocardiogram, respectively. In multivariate analyses, the probability of developing electrocardiographic abnormalities was significantly reduced among treated patients (OR = 0.18, 95% CI = 0.04-0.79; p = 0.023). Electrocardiographic abnormalities attributable to Chagas cardiomyopathy were seen in 3 patients from the untreated group (complete right bundle branch block + left anterior fascicular block, frequent ventricular extrasystole, and left anterior fascicular block). The remarkable seronegativization seen in Benznidazole and Nifurtimox recipients underlines the parasiticidal effect of both compounds. Such demonstration along with the fact that CCC-related alterations were only present in the untreated group, reinforces the view of trypanocidal treatment in chronically T. cruzi-infected children as decreasing the risk for cardiomyopathy development.

Blood-based immunological monitoring after heart transplant. Current status and future prospects.

The development of effective immunosuppressive strategies has been a key to successful outcomes in heart transplantation. Immunosuppression however is a double-edged sword with consequences of rejection when underutilized and risk for infection, malignancy, and drug toxicity when used in excess. The search for non-invasive blood-based monitoring not only to assess allograft rejection but also to monitor overall state of immunosuppression remains very attractive, potentially reducing cost and complications and allowing more frequent testing to assess response to anti-rejection therapy. This review outlines the current status of blood-based immunological monitoring after heart transplantation including serological monitoring, biomarkers, and evolution of molecular technologies.

Serological Evolution of VDRL Test after Penicillin Treatment of Non-Pregnant Patients with Early Syphilis Without HIV Infection: Identifying an Efficient Serological Follow-Up Scheme

Serological Evolution of VDRL Test after Penicillin Treatment of Non-Pregnant Patients with Early Syphilis Without HIV Infection: Identifying an Efficient Serological Follow-Up Scheme

The Epidemiological and Clinical Characteristics of the Epidemic of Syphilis in Barcelona

BackgroundSince 2000, substantial increases in syphilis have been reported in metropolitan areas of Western countries, with increases noted among men who have sex with men (MSM). Clinical manifestations of syphilis might be influenced by concomitant VIH infection and previous episodes of syphilis. The objectives of this study were to describe the epidemiological and clinical characteristics of the cases of syphilis diagnosed in Barcelona. MethodsRetrospective study of cases with early syphilis diagnosed in the referral STI Unit of Barcelona from January 2003 to December 2013. Revision of medical records with structured collection of epidemiological and clinical data. Univariate and multivariate statistical analyses comparing the characteristics of MSM cases with and without VIH infection and with and without previous syphilis. ResultsA total of 1702 cases of syphilis (37% primary, 48% secondary and 14% early latent) were diagnosed, 93% of them in MSM. Among MSM 40% were coinfected with VIH, VIH-positive cases were associated with a previous syphilis (aOR, 5.2 [95% CI, 3.32–8.24]) and with unprotected anal intercourse (aOR, 1.75 [95%CI, 1.17–2.63]). Cases with a history of syphilis presented less often with primary syphilis compared to those without it (27.5% vs 40%) (aOR, 0.58 [95% CI, 0.44-0.77]). One year after treatment, the clinical and serological evolution were similar between VIH-positive and VIH-negative cases. ConclusionThe epidemic of syphilis in Barcelona disproportionately affects MSM and is closelly linked to VIH infection. The presentation of syphilis is influenced by VIH infection and by previous history of syphilis, without significant differences in their evolution after one year of treatment.

Las características epidemiológicas y clínicas de la epidemia de sífilis en Barcelona

BackgroundSince 2000, substantial increases in syphilis have been reported in metropolitan areas of Western countries, with increases noted among men who have sex with men (MSM). Clinical manifestations of syphilis might be influenced by concomitant VIH infection and previous episodes of syphilis. The objectives of this study were to describe the epidemiological and clinical characteristics of the cases of syphilis diagnosed in Barcelona. MethodsRetrospective study of cases with early syphilis diagnosed in the referral STI Unit of Barcelona from January 2003 to December 2013. Revision of medical records with structured collection of epidemiological and clinical data. Univariate and multivariate statistical analyses comparing the characteristics of MSM cases with and without VIH infection and with and without previous syphilis. ResultsA total of 1702 cases of syphilis (37% primary, 48% secondary and 14% early latent) were diagnosed, 93% of them in MSM. Among MSM 40% were coinfected with VIH, VIH-positive cases were associated with a previous syphilis (aOR, 5.2 [95% CI, 3.32-8.24]) and with unprotected anal intercourse (aOR, 1.75 [95%CI, 1.17-2.63]). Cases with a history of syphilis presented less often with primary syphilis compared to those without it (27.5% vs. 40%) (aOR, 0.58 [95% CI, 0.44-0.77]). One year after treatment, the clinical and serological evolution were similar between VIH-positive and VIH-negative cases. ConclusionThe epidemic of syphilis in Barcelona disproportionately affects MSM and is closelly linked to VIH infection. The presentation of syphilis is influenced by VIH infection and by previous history of syphilis, without significant differences in their evolution after one year of treatment.

Serological evolution in early syphilis

IntroductionThe evolution of syphilis after treatment could be affected by different factors, for example HIV. In consequence, HIV positive patients are sometimes treated with more doses of penicillin (PBG).The aim of the study is to describe and compare the serological evolution by different factors in patients with early syphilis in Barcelona. MethodsThe serological control was made over the following year. A time analysis was performed through the study of Kaplan–Meier curves. ResultsThe serological control was made in 208 patients, 42.5% of whom were HIV-positive. In a Kaplan–Meier curve the median of days needed to observe the cure was 99 [97–105] without differences depending on HIV, previous syphilis, stage or RPR titters. A better evolution was observed in patients treated with doxycycline p=0.02. ConclusionsThe serological evolution is similar in HIV-negative and HIV-positive patients treated according to current recommendations, observing the cure at 3 month after treatment.

Antiplatelet Antibody Testing in Immune Thrombocytopenia and Evans Syndrome: Longitudinal Serologic Evolution and Relation to Clinical Features

Introduction: Antiplatelet antibody (APA) testing is considered an adjunct laboratory test in the diagnosis of immune thrombocytopenia (ITP). While it is not routinely obtained owing to inconsistent sensitivity and specificity in prior studies (Neunert et al, 2011), the definition of ITP used in these studies was not standardized. Additionally, potential clinical utility of this testing beyond diagnosis has been suggested, such as correlations between certain serologic patterns and response to IVIG (Peng et al, 2014). In consideration of these prior findings, we undertook a retrospective analysis of APA testing [glycoprotein-specific testing done by the commercial PakAuto assay (Immucor, Brookfield, WI), a monoclonal antibody immobilization of platelet antigens (MAIPA) assay, with all testing performed by the same laboratory] utilizing standardized ITP and Evans syndrome (ES) diagnostic criteria for patient inclusion. We examined serologic evolution over time and relation of antibody positivity to disease severity and response to therapies.Methods: Data collected for analysis included dates and results of APA testing (including disease status and platelet count at time of testing), patient demographics, and disease characteristics. Satisfaction of the 2011 American Society of Hematology (ASH) ITP diagnostic criteria were required for ITP patient inclusion and standard definitions of disease severity and response to treatment from the ASH guidelines were used in analysis. Logistic regression was used to model the probability of disease severity (non-severe, severe, or refractory) and treatment response (to corticosteroids or IVIG) based on serologic findings. Longitudinal serologic evolution in patients with multiple APA assays were analyzed.Results: A total of 214 APA assays from 115 ITP patients and 12 ES patients were collected; results from eluate testing (direct assay) only were used in analysis. Baseline patient characteristics are listed in Table 1. Of 7 possible positive test serologic patterns, only 4 were seen (Figure 1); antibodies against both GPIIb/IIIa and GPIb/IX were required for the presence of antibodies against GPIa/IIa. A multinomial logistic regression model including disease severity, age, sex, duration of disease, and platelet count at time of APA assay found a statistically significant predictive relationship between an increasing number of positive antibodies and disease severity [relative to non-severe ITP, relative risk ratio for severe ITP and refractory ITP was 1.89 (P=0.001) and 2.38 (P=0.004), respectively, per one additional positive antibody, Figure 2]. Multiple logistic regression models including antibody positivity to each platelet glycoprotein (GPIIb/IIIa, GPIb/IX, or GPIa/IIa), age, sex, disease duration and splenectomy status found a significant predictive relation between presence of anti-GPIa/IIa and non-response to corticosteroid treatment (odds ratio, 0.082, P=0.008). No significant relation was found between an antibody and non-response to IVIG. Fifty patients had multiple (2 to 5) APA assays performed over months to years. In evaluation of serologic evolution over time, all 7 patients who entered clinical remission also converted from a positive to a negative serology; 22 patients had stable serologic findings over time; 5 patients had a reduction in number of positive antibodies; and 18 patients demonstrated evidence for epitope spreading, with an increase in the number of positive antibodies (Figure 3). The sensitivity of a positive APA assay for the presence of active ITP was 91%. The sensitivity and specificity of a negative APA assay for remission in a patient with previously confirmed ITP (N=40 assays in patients with clinical remission in the study) were 88% and 91%, respectively.Conclusions: The MAIPA-based direct APA assay is sensitive for the presence of active ITP in patients satisfying 2011 ASH diagnostic criteria. To our knowledge, this is the first study demonstrating that a higher number of positive glycoprotein-specific antibodies may predict for more severe disease as defined by 2011 ASH disease severity criteria. Anti-GPIa/IIa antibodies only occur in the setting of pre-existing positivity for both anti-GPIIb/IIIa and anti-GPIb/IX antibodies, possibly due to a distinctive sequence of epitope spreading. Serologic testing typically turns negative when a patient enters clinical remission. [Display omitted] DisclosuresAl-Samkari:Agios: Consultancy. Kuter:Novartis: Consultancy; Pfizer: Consultancy; Syntimmune: Consultancy; Argenx: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; ONO: Consultancy; Amgen Inc.: Consultancy; Bioverativ: Consultancy, Research Funding; Principia: Research Funding; Rigel: Consultancy, Research Funding; BMS: Research Funding; Protalex: Research Funding.

La evolución serológica en sífilis precoz

IntroductionThe evolution of syphilis after treatment could be affected by different factors, for example HIV. In consequence, HIV positive patients are sometimes treated with more doses of penicillin (PBG).The aim of the study is to describe and compare the serological evolution by different factors in patients with early syphilis in Barcelona. MethodsThe serological control was made over the following year. A time analysis was performed through the study of Kaplan- Meier curves. ResultsThe serological control was made in 208 patients, 42.5% of whom were HIV-positive. In a Kaplan-Meier curve the median of days needed to observe the cure was 99 [97-105] without differences depending on HIV, previous syphilis, stage or RPR titters. A better evolution was observed in patients treated with doxycycline P=.02. ConclusionsThe serological evolution is similar in HIV-negative and HIV-positive patients treated according to current recommendations, observing the cure at 3 month after treatment.

Discrimination of patients with different serological evolution of HIV and co-infection with HCV using metabolic fingerprinting based on Fourier transform infrared.

Human immunodeficiency virus (HIV) is a retrovirus that weakens the immune system and permits opportunistic diseases such as hepatitis C (HCV) to enter the body. These diseases induce metabolic disorders in the patients and it is therefore logical to approach them from a holistic, functional perspective, studying the metabolome comprehensively to identify metabolic signatures associated with certain disease states. The metabolomics strategy here proposed involves metabolic fingerprinting using Fourier transform infrared spectroscopy and chemometric tools on 72 plasma samples (subdivided into 63 training and 9 test samples) to differentiate between healthy subjects and patients with different disease stages. Several options, relating to the variable selection method used in linear discriminant analysis and the number of categories being considered, were explored to optimize discrimination ability. A total of 18 bands enabled differentiation between control subjects, HIV patients and the group that encompassed patients with acquired immune deficiency syndrome (AIDS), AIDS/HCV and HIV/HCV, providing overall classification and internal prediction rates of 97.67% and 93.65%, respectively. Only 9 bands were required to further discriminate between AIDS, AIDS/HCV and HIV/HCV, with 99.20% (training) and 89.66% (cross-validation) correct classifications. The simplicity and effectiveness of the classification methodology proposed was reinforced by the satisfactory results obtained in external prediction.

Evaluation of an automated quantitative latex immunoturbidimetric non-treponemal assay for diagnosis and follow-up of syphilis: a prospective cohort study.

Purpose. We evaluated the Sekure rapid plasma reagin (RPR-S) (Sekisui Diagnostics) automated quantitative latex immunoturbidimetric assay performed on the SK500 clinical chemistry system for clinical appropriateness.Methodology. Syphilis-infected individuals and controls were recruited into a prospective cohort study conducted at a sexually transmitted infection clinic in Antwerp, Belgium. Sera collected at diagnosis (baseline) and at 3, 6, 9 and 12 months post-treatment were tested with RPR-S and Macro-Vue RPR card (RPR-C) (Becton Dickinson) assays; RPR-C was considered the reference test. IgG/IgM enzyme immunoassay and Treponema pallidum polA serum PCR results were consulted by discordancy at baseline. Categorical analyses were performed and correlations were assessed with (non)-linear regression. Post-treatment longitudinal serological evolution was evaluated.Results. A total of 463 samples from 120 new syphilis cases from a variety of clinical stages and 30 syphilis-negative controls were tested. Initially, there was a weak correlation between quantitative RPR-C/S (r=0.15). In 70 samples there was a strong suspicion of hook effect. Of these, 57/70 sera were retested with an extra dilution step, resulting in an average 12-fold increase in quantitative RPR-S results. After the extra dilution, the overall qualitative RPR-C/S agreement was 78.89 %, (κ-coefficient: 0.484). Of the 92 discordant samples, 9 were from the baseline visit (RPR-C titre: 1-8), which could have led to possible missed diagnoses using the RPR-S.Conclusions. The sensitivity and accuracy of the RPR-S test requires improvement before it can be used to diagnose syphilis and evaluate treatment efficacy in clinical practice.

Serological evolution in women with positive antiphospholipid antibodies.

To explore the clinical and serological course of fertile women with positive antiphospholipid (aPL), and the factors and therapeutic implications associated with aPL negativization. Retrospective study including 105 women with a positive aPL serology between 1995 and 2013 attending the obstetric autoimmune pathology clinic of a tertiary facility. Patients were classified into the following 3 groups: patients with primary antiphospholipid syndrome (pAPS, 49), patients with a positive serology for aPL, not meeting clinical criteria (42), and patients with systemic lupus erythematosus and a positive aPL serology (14). They were also classified according to the serological aPL evolution: persistently negative aPL, transiently positive serology, and persistently positive serology according to established criteria. After a mean follow-up of 114.4 ± 37.2 months, 59% of patients had persistently negative antibodies, while 25.7% of patients presented persistently positive aPL serology. Multivariate analysis confirmed that smoking (OR = 4; 95% CI: 1.45-11.08; p = 0.008) was an independent risk factor for positive persistence. Persistent positivity as well as a higher antibody load was associated with higher risk for further pregnancy morbidity. In 29 patients, with persistently negative serology who were asymptomatic, treatment with low-dose aspirin was discontinued. No clinical events related to APS were reported after treatment withdrawal, during the 40.95 months of follow-up. A significant proportion of fertile women with aPL antibodies became negative during follow-up. Tobacco use and the number of positive antibodies are associated with persistently positive serology. Patients with persistently positive aPL serology suffer more obstetric complications. Treatment withdrawal might be safe in selected patients.

Course of Chronic Trypanosoma cruzi Infection after Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies.

BackgroundChagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia).ObjectivesTo summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection.MethodsElectronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies.Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration’s tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion.Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2.The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162).ResultsOut of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10–20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%.The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high.Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs earlier in children compared to adults.ConclusionsWe acknowledge that there is a dynamic pattern of response based on parasitological, molecular and serological tests in subjects chronically infected with T. cruzi after treatment. Our findings suggest a trypanocidal effect in the long-term follow-up.Further research is needed to explore potential sources of heterogeneity and to conduct reliable subgroup analysis.

Acute Q fever and the risk of developing endocarditis

ObjectivesAssess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever. Patients and methodsRetrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered. ResultsEighty patients were recruited, 20% of whom had phase I IgG antibody levels≥1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase I IgG antibodies. ConclusionsThe early increase in phase I IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment.

Fiebre Q aguda: riesgo de desarrollo de endocarditis

ObjectivesAssess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever. Patients and methodsRetrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered. ResultsEighty patients were recruited, 20% of whom had phase i IgG antibody levels ≥ 1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase i IgG antibodies. ConclusionsThe early increase in phase i IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment.