Assessment of the predictive value of plasma calprotectin in the evolution of SARS-Cov-2 primo-infection.

BACKGROUND: The COVID-19 epidemic still calls for anticipation aimed at preventing the overloading of critical care services. With this in mind, the predictive value of easily accessible biomarkers is to be assessed. OBJECTIVE: Secretion of calprotectin is stimulated during an inflammatory process, especially in the cytokine storm. We tried to determine whether early plasma concentration of calprotectin in patients with primary SARS-CoV-2 infection could predict an adverse outcome in cases of COVID-19. METHODS: We included 308 patients with a primary diagnosis of SARS-CoV-2 confirmed by PCR. Heparinized tube samples, collected within the first 24 h of hospitalization, were used for biomarker assays, in which plasma calprotectin was included. Data from the patients' medical records and severity groups established subsequent to diagnosis at the end of hospitalization were collected. RESULTS: Early plasma calprotectin concentration is significantly associated with progression to a severe form of COVID-19 in patients with primary infection (Relative Risk: 2.2 [1.6-2.7]). In multivariate analysis, however, it does not appear to provide additional information compared to other parameters (age, GFR, CRP…). CONCLUSION: Our study shows that while an early single blood test for calprotectin could help to predict the progression of a primary SARS-CoV-2 infection, it is not superior to the other parameters currently used in emergency medicine. However, it paves the way for future considerations, such as the interest of this biomarker for high-risk infected patients (immunocompromised individuals…). Finally, the usefulness of early serial measurements of plasma calprotectin to assess progression towards severity of COVID-19 requires further assessment.

Severe acute herpes virus type 2 primo-infection and its association with anti-type 1 interferon autoantibodies.

Herpes simplex virus type 2 (HSV-2) is a common cause of infection, which is usually self-limited and asymptomatic. A 71-year-old patient with HSV-2 primo-infection developed acute hepatitis and secondary hemophagocytic lymphohistiocytosis. The patient had high levels of autoantibodies against type I interferon (IFN) (> 1000 ng/mL), neutralizing high concentration (10 ng/mL) of both IFN-α and IFN-ω but not IFN-ß. Anti-IFN-I auto-antibodies are rarely observed in healthy individuals; however, their prevalence increases in individuals over 70 years of age and have been identified as a cause of some severe viral diseases, including critical COVID-19. Considering the function of IFN-I in innate immunity, the pathological role of these autoantibodies in severe viral diseases following primo-infections in elderly patient appears crucial.

Post-Transplantation Cytomegalovirus Infection Interplays With the Development of Anastomotic Biliary Strictures After Liver Transplantation.

Background: Anastomotic biliary stricture (ABS) remains the most frequent complication after liver transplantation (LT). This study aimed to identify new anastomotic biliary stricture risk factors, with a specific focus on postoperative events. Additionally, ABS management and impact on patient and graft survival were assessed. Methods: All consecutive patients who underwent LT with duct-to-duct anastomosis between 2010 and 2019 were included. All patients who died within 90 days after LT due to non-ABS-related causes were excluded. Results: Among 240 patients, 65 (27.1%) developed ABS after a median time of 142 days (range, 13-1265). Median follow-up was 49 months (7-126). Upon multivariable analysis, donor BMI (OR=0.509, p = 0.037), post-LT CMV primoinfection (OR = 5.244, p < 0.001) or reactivation (OR = 2.421, p = 0.015) and the occurrence of post-LT anastomotic biliary fistula (OR = 2.691, p = 0.021) were associated with ABS. Anastomotic technical difficulty did not independently impact the risk of ABS (OR = 1.923, p = 0.051). First-line ABS treatment was systematically endoscopic (100%), and required a median of 2 (range, 1-11) procedures per patient. Repeat LT was not required in patients developing ABS. The occurrence of ABS was not associated with overall patient survival (p = 0.912) nor graft survival (p = 0.521). Conclusion: The risk of developing ABS after LT seems driven by the occurrence of postoperative events such as CMV infection and anastomotic fistula. In this regard, the role of CMV prophylaxis warrants further investigations.

Primoinfección por Toxoplasma gondii en gestantes de Atención Primaria de Salud en La Habana / Primoinfection by Toxoplasma gondii in pregnant women in Primary Health Care in Havana

Introducción: La primoinfección por Toxoplasma gondii adquirida durante el embarazo puede causar manifestaciones clínicas graves en el producto de la gestación, hecho tratable y prevenible. Objetivo: Describir evidencias serológicas de primoinfección por T. gondii en gestantes de Atención Primaria de Salud (APS) en La Habana. Metodología: Se realizó una descripción retrospectiva de resultados serológicos de embarazadas pesquisadas en APS, La Habana, desde 2005 a 2011. Se procesaron 1820 sueros en el Laboratorio Nacional de Referencia de Parasitología del Instituto Pedro Kourí (LNRP-IPK) a través de inmunofluorescencia indirecta (IFI), VIDAS TOXO IgM y Toxo IgG Avidity. A las muestras con títulos de anticuerpos ≥ 1/128 por IFI, se les determinó IgM; si eran positivas, se precisó la avidez de IgG. Resultados: Hubo 1151 (63,2 por ciento) sueros negativos. La mayoría eran gestantes entre 16 y 35 años con un promedio de positividad de 34,1 por ciento, sin diferencias significativas entre los municipios de procedencia. Prevalecieron los títulos de IgG anti-Toxoplasma 1/16-1/64, en gestantes de más de 35 años hubo 120/209 (57,4 por ciento), resultado significativo al compararlo con el grupo menor de 16 años (4/14; 28,5 por ciento). En 58 mujeres aparecieron títulos de IgG ≥ 1/128 (3,1 por ciento), y predominaron las menores de 16 años (2/14; 14,2 por ciento). El 17,2 por ciento de las embarazadas resultó IgG e IgM positivas, aspecto relevante en La Habana Vieja (6,8 por ciento). Se encontraron cifras bajas de avidez en 5/10 (índice < 0,200 IgG), que representó el 0,2 por ciento del total de las gestantes estudiadas. Conclusión: En embarazadas de algunas áreas de salud en La Habana, hubo evidencias de primoinfección por T. gondii(AU)

Introduction: Primoinfection by Toxoplasma gondii acquired during pregnancy can cause severe clinical manifestations in the newborn parameters; it is a treatable and preventable event, though. Objective: To describe serological evidence of primoinfection by T. gondii in pregnant women in Primary Health Care (PHC) in Havana. Methods: A retrospective descriptive study of serological results of pregnant women screened in the PHC, Havana, from 2005 to 2011 was conducted. A total of 1820 sera were processed at the National Reference Laboratory of Parasitology of Pedro Kourí Institute (LNRP-IPK) through indirect immunofluorescence assay (IFA), VIDAS TOXO IgM and Toxo IgG Avidity. Samples with antibody titers ≥ 1/128 by IFA were tested for IgM; if positive, IgG avidity was determined. Results: 1151 sera (63.2%) yielded negative results. Most were pregnant women between 16 and 35 years of age with an average positivity of 34.1 percent, without significant distinction between municipalities of origin. Anti-Toxoplasma IgG titers prevailed 1/16-1/64. In pregnant women over 35 years of age, titers were 120/209 (57.4 percent), a significant result when compared with the group under 16 years of age (4/14; 28.5 percent). IgG titers ≥ 1/128 (3.1 percent) appeared in 5858 women, and those under 16 years of age predominated (2/14; 14.2 percent). IgG and IgM were positive in 17.2 percent of pregnant women, a relevant aspect in Old Havana (6.8 percent). Low levels of avidity were found in 5/10 (index < 0.200 IgG), which represented 0.2 percent of the total number of pregnant women studied. Conclusion: In pregnant women in some health areas in Havana, primoinfection by T. gondii was confirmed(AU)

A case report of isolated primary herpes-simplex virus neuroretinitis in an immunocompetent adult.

BACKGROUND: Herpes simplex virus (specifically HSV-1 and HSV-2) are greatly prevalent viruses that can cause conjunctivitis, keratitis and other rarer ocular disorders such as acute retinal necrosis syndrome or neuroretinitis. We report a case of an isolated unilateral neuroretinitis with primary HSV infection in an immunocompetent adult without other related clinical features. CASE PRESENTATION: A 60-year-old immunocompetent woman presented with sudden painless central vision loss in her left eye (best corrected visual acuity was 20/200) showing optic disc edema, submacular fluid and a delayed development of a macular star. The macular optical coherence tomography (OCT) showed a serous retinal detachment. Arterial hypertension or exposure to ionizing radiation were ruled out and the microbiological blood test battery was only positive for immunoglobulin M (IgM) for HSV-1 which allowed etiological treatment with oral valacyclovir. Complete resolution and good visual results were found within 3 months. CONCLUSIONS: The present case of isolated neuroretinitis as a primary HSV infection in an immunocompetent patient was resolved with good functional results after valacyclovir treatment. Presence of HSV IgM in absence of other laboratory results could be enough evidence to start HSV treatment in immunocompetent patients with a macular star, as an isolated lesion, after ruling out other non-infectious causes, such as arterial hypertension or exposure to ionizing radiation. Rare infectious agents in immunocompetent patients must be considered in the differential diagnosis of neuroretinitis, even if there are no other typical symptoms or signs that could suggest the disease.

No benefit of longer eradication therapy of Pseudomonas aeruginosa primoinfections in pediatric cystic fibrosis.

OBJECTIVE: Patients with cystic fibrosis are more susceptible than members of the general population to lung infections. Infections with Pseudomonas aeruginosa require particular attention, because they may accelerate the deterioration of lung function if not adequately treated. This study assessed the eradication rate of P. aeruginosa primoinfections, with a protocol of inhaled tobramycin and oral ciprofloxacin over a 3 months' period. RESULTS: Retrospective single-center study from June 1st, 2007 to December 31st, 2015. Inclusion of 28 pediatric patients (11 females, 17 males), with a total of 49 primoinfections. Overall success rate of 67.3%, which is similar or even inferior to figures published in the literature.

Prévention et prise en charge de l'infection herpétique au cours de la grossesse et de l'accouchement : recommandations pour la pratique clinique ­ texte des recommandations (texte court).

OBJECTIVE: Identify measures to diagnose, prevent and treat genital herpes infection during pregnancy and childbirth and neonatal infection. METHODS: Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines. RESULTS: Genital herpes lesion is most often due to HSV2 (LE2). The risk of HSV seroconversion during pregnancy is 1 to 5% (LE2). Genital herpes ulceration during pregnancy in a woman with history of genital herpes corresponds with a recurrence. In this situation, there is no need for virologic confirmation (grade B). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type specific IgG (Professional consensus). In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) can be administered (grade C). The risk of neonatal herpes is estimated between 25% and 44% in case of initial episode (LE2) and 1% in case of recurrence (LE3) at the time of delivery. Antiviral prophylaxis should be offered for women with first episode genital herpes or recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (grade B). In case of a history of genital herpes without episode of recurrence during pregnancy, it is not recommended routinely offer a prophylactic treatment (professional consensus). A cesarean section should be performed if there is a suspicion of first episode genital herpes at the onset of labor (grade B), in the event of premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and vaginal delivery will be all the more considered in case of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE 3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous acyclovir (60mg/kgs/day 3 times daily) (grade A) prior to the results of HSV PCR (professional consensus). The duration of the treatment depends on the clinical form (professional consensus) CONCLUSION: There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes, the risk of recurrence term and the cesarean rate performed to decrease the risk of neonatal herpes.

Severe infectious mononucleosis in immunocompetent adults.

OBJECTIVES: To determine the risk factors for severe infectious mononucleosis (IM) occurrence in immunocompetent adults. METHODS: We performed a multicenter, retrospective case series including immunocompetent adults presenting with confirmed IM between 2001 and 2011. Severe presentations were compared with uncomplicated presentations using Stata® 9 software. The significance level was set at 5%. RESULTS: In univariate analysis, age over 30 years (n=13 or 41.9% vs. n=5 or 12.8%; P=0.006), prior use of non-steroidal anti-inflammatory drugs (NSAIDs) (n=7 or 87.5% vs. n=1 or 12.5%; P=0.009), and smoking (n=13 or 68.4% vs. n=6 or 31.6%; P=0.013) were associated with severe IM onset. In multivariate analysis, only age over 30 years (OR=3.55; P=0.05) and prior use of NSAIDs (OR=15; P=0.05) remained associated with severe IM onset, without reaching significance level (P=0.05). CONCLUSION: Our study confirmed that age over 30 years is a risk factor for severe IM onset. Prior use of NSAIDs also seems to be correlated with severe presentations. This new data needs to be confirmed in a prospective study.

[Results of tuberculosis screening in children with household contact]. / Résultats du dépistage de la tuberculose chez les enfants contacts de parents tuberculeux.

INTRODUCTION: Tuberculosis screening in children is important to identify and treat latent tuberculosis infection and thus avoid progression to disease. METHODS: It is a prospective study realized in 83 children between November 2009 and January 2013 who consulted after a household contact for tuberculosis in the pediatric department B of Abderrahmen Mami hospital of Ariana. RESULTS: The mean age of the children was 4.8 years (3 months-15 years). A latent tuberculosis infection was diagnosed in 31.3% of children, 10.8% had tuberculosis and 57.8% were considered healthy. Fifty-seven children (68.7%) had a close daytime contact with the index and 57.8% slept in the same bedroom of the contaminator. The identified risk factors were the diagnosis delay of the index of more than 30 days (P=0.023), presence of cavitations on the chest X-ray of the index (P=0.029) and a close daytime contact (P=0.004). CONCLUSION: Our study showed a high rate of contamination in children with a household contact. Efforts are needed to shorten the time to diagnosis of adults' tuberculosis.

[Primary infection and pulmonary tuberculosis]. / La primo-infection et la tuberculose pulmonaire.

Tuberculosis is a major public health problem worldwide. Indeed, a third of the world population is infected with Mycobacterium tuberculosis and more than 8 million new cases of tuberculosis each year. Pulmonary tuberculosis is the most common location. Its diagnosis is difficult and often established with a delay causing a spread of infection. The diagnosis of tuberculosis infection is mainly based on immunological tests represented by the tuberculin skin test and detection of gamma interferon, while the diagnosis of pulmonary tuberculosis is suspected on epidemiological context, lasting general and respiratory symptoms, contrasting usually with normal lung examination, and a chest radiography showing suggestive lesions. The radioclinical feature may be atypical in patients with extreme ages and in case of immunodeficiency. Confirmation of tuberculosis is bacteriological. Conventional bacteriological methods remain the reference. Innovative tests using the technique of molecular biology have improved the diagnosis of tuberculosis in terms of sensitivity and especially speed. However, those techniques are of limited use.

Rapid and sustained autologous neutralizing response leading to early spontaneous recovery after HCV infection.

After HCV infection, the association between the humoral response and viral sequence evolution remains unclear. We investigated the mechanisms leading to early HCV clearance and spontaneous recovery in two patients. The early evolution of the HCV envelope glycoproteins, and the infectivity spectrum of variants were explored using retroviral pseudoparticles bearing HCV envelopes. Ability of the autologous neutralizing response to control these variants was analyzed. For the first case, the maximum neutralizing activity was for serum collected between two and three months post ALT peak, this activity was still detectable after 30 months. For the second case, autologous neutralizing activity against the variant isolated at the ALT peak was detected in every serum collected between 4 days and 13 months after. The neutralizing response was sustained beyond the time at which the virus was cleared. This raise interesting questions about the role of such antibodies in case of re-exposure.

Dengue hemorrágico en un lactante después de primoinfección / Dengue hemorrhagic fever in an infant after primoinfection

Introducción. El dengue es una enfermedad infecciosa causada por un flavivirus y transmitida por un vector. Puede originar cuadros febriles inespecíficos, fiebre hemorrágica por dengue (FHD) o, incluso, síndrome de choque. El tratamiento se basa en el control hemodinámico y control del balance hídrico. Caso clínico. Paciente femenino de 4 meses, inicia con fiebre y desarrolla síntomas y signos, primero de FHD y posteriormente síndrome de choque. Se corroboró el diagnóstico serológico de primoinfección por dengue. No existió evidencia de infección previa en la madre. Con tratamiento de soporte mejora y posteriormente se egresa asintomática. Conclusiones. Según algunas teorías, la FHD en lactantes se asocia a anticuerpos no neutralizantes, transmitidos de manera pasiva por una madre previamente infectada, que ocasionan en el lactante una reacción severa ante una primoinfección. En este caso, otros factores independientes del huésped, como virulencia del virus infectante, pudieran ser los responsables.

Background. Dengue fever is an infectious disease caused by a flavivirus and transmitted by a vector. It causes dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). When one of these last two appears, treatment consists of intensive fluid balance control. Case report. A 4-month-old female infant presented fever. She was admitted and later showed signs and symptoms of DHF followed by DSS. Serological diagnosis was confirmed, and appropriate treatment offered. The mother does not have evidence of prior infection. Discussion. One theory proposes that DHF occurs in infants when passively transferred maternal antibodies from a previous infection cause an enhanced immune response when the infant is infected by a different type of dengue virus. This theory does not explain the occurrence of DHF in our report. Factors not dependent on the host, such as virological factors, may be responsible.

Case report: cytomegalovirus primoinfection may be associated with severe outcome in burns.

We report two cases of severe cytomegalovirus (CMV) primoinfection in seriously burned patients. The infection may have contributed to both patients' fatal outcome. This underlines the importance of research in viral aetiology, especially with regard to CMV, when immunodeficient patients - as burn patients are - develop unexplained fever. We propose a monitoring and a prevention strategy for CMV in the most severely burned patients. The prevention strategy involves the use of skin allografts and blood products in seronegative patients. CMV infection should not be underestimated in severely burned patients.