Vertical transmission of zika virus and its outcomes:a Bayesian synthesis of prospective studies

BACKGROUND: Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure.METHODS: This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available.FINDINGS: The estimated mean risk of vertical transmission was 47% (95% credible interval 26 to 76) following maternal infection in the first trimester, 28% (15 to 46) in the second, and 25% (13 to 47) in the third. 9% (4 to 17) of deliveries following infections in the first trimester had symptoms consistent with congenital Zika syndrome, 3% (1 to 7) in the second, and 1% (0 to 3) in the third. We estimated that in infections during the first, second, and third trimester, respectively, 13% (2 to 27), 3% (-5 to 14), and 0% (-7 to 11) of pregnancies had adverse outcomes attributable to Zika virus infection. Diagnostic sensitivity of markers of congenital infection was lowest in the first trimester (42% [18 to 72]), but increased to 85% (51 to 99) in trimester two, and 80% (42 to 99) in trimester three. There was substantial between-study variation in the risks of vertical transmission and congenital Zika syndrome.INTERPRETATION: This preliminary analysis recovers the causal effects of Zika virus from disparate study designs. Higher transmission in the first trimester is unusual with congenital infections but accords with laboratory evidence of decreasing susceptibility of placental cells to infection during pregnancy.FUNDING: European Union Horizon 2020 programme

Researching Zika in pregnancy:lessons for global preparedness

Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015\u201316 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies

Recomanacions per a la prevenció i el control de la tuberculosi pediàtrica a Catalunya

Tuberculosi pediàtrica; Diagnòstic de malalties; TractamentsTuberculosis pediátrica; Diagnóstico de enfermedades; TratamientosPediatric tuberculosis; Disease diagnosis; TreatmentsLa finalitat d’aquest document és revisar, des d’una perspectiva multidisciplinària, els reptes en el diagnòstic i el tractament de la TB pediàtrica, l’optimització de la realització dels estudis de contactes, la integració del cribratge de la infecció tuberculosa en el Programa de seguiment del nen sa de l’atenció primària (AP) i el model d’organització assistencial, amb l’objectiu de realitzar recomanacions pràctiques que contribueixin a millorar les respostes que cal articular per a la prevenció i el control de la TB pediàtrica al territori

Tuberculosis infection in children visiting friends and relatives in countries with high incidence of tuberculosis : A study protocol

Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals

Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis.

CAPRISA, 2018.Abstract available in pdf

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities

Eosinophilia prevalence and related factors in travel and immigrants of the network +REDIVI

[ES] Algunas enfermedades infecciosas han adquirido más relevancia por el aumento de los movimientos poblacionales. La eosinofilia es un hallazgo frecuente en inmigrantes y en viajeros. Una de las causas más frecuentes de eosinofilia es la infección por helmintos y algunos protozoos intestinales. El objetivo de este trabajo es describir las características epidemiológicas de los casos con eosinofilia y su asociación con la presencia de parásitos en la red de datos REDIVI. Se trata de un estudio observacional multicéntrico prospectivo, donde se incluyen los casos diagnosticados de eosinofilia registrados en la Red cooperativa para el estudio de las infecciones importadas por viajeros e inmigrantes (+REDIVI) desde enero de 2009 hasta diciembre de 2012. Se registraron en la red un total de 5.255 episodios durante el periodo de estudio, y la eosinofilia fue un hallazgo en el 8,1 al 31,3% de los casos (dependiendo del tipo migratorio). Fueron hombres el 60,2%, con una mediana de 31,0 años, inmigrantes el 72,4% y asintomáticos el 81,2%. Los parásitos más frecuentemente identificados fueron S. stercoralis (34,4%), Schistosoma sp. (11,0%) y uncinarias (8,6%). Existía asociación entre eosinofilia y presencia de parásitos para todos los helmintos (excepto para larva migrans cutánea). La sintomatología y la duración del viaje no determinaron significativamente la presencia de eosinofilia. Ante una eosinofilia en una persona que ha vivido en zonas endémicas de helmintiasis es aconsejable realizar estudios dirigidos para su diagnóstico, independientemente del tipo migratorio, la duración de la estancia o la presencia de sintomatología.[EN] The population movements during the last decades have resulted in a progressively increasing interest in certain infectious diseases. Eosinophilia is a common finding in immigrants and travellers. One of the most common causes of eosinophilia is helminth infection, and some intestinal protozoa. The aim of this paper is to describe the epidemiological characteristics of cases with eosinophilia and its association with the presence of parasites in the REDIVI data network. This is a multicentre prospective observational study that includes patients diagnosed with eosinophilia registered in the cooperative network for the study of infectious diseases in travellers and immigrants (+REDIVI) from January 2009 to December 2012. A total of 5,255 episodes were recorded in the network during the study period, and eosinophilia was observed in 8.1-31.3% of cases (depending on the immigration group). There were 60.2% men, with a median age of 31 years. There were 72.4% immigrants, and 81.2% were asymptomatic. The most commonly identified parasites were S. stercoralis (34.4%), Schistosoma sp. (11.0%), and hookworm (8.6%). The relationship between eosinophilia and parasite infection was significant for all helminths (except for cutaneous larva migrans). The symptoms and duration of the journey did not significantly determine the presence of eosinophilia. In the case of eosinophilia in a person who has lived in helminth endemic areas, it is advisable to carry out targeted studies to diagnose the infection, regardless of immigration type, length of stay, or the presence of symptoms.Peer reviewe

Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays' (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9-12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79-11.94)] and active TB [aOR (95% CI): 3.40 (1.45-7.98)]. Moreover, IGRAs' sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.This research was supported by: (i) a grant from the Instituto de Salud Carlos III (PI13/01546, PI16/01912, and PI18/00411), integrated in the Plan Nacional I+D+I and co-funded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and CERCA Programme/Generalitat de Catalunya; and (ii) a grant from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR; Barcelona, Spain) (Smoking Integrated Research Programme Call

Recomanacions per a la prevenció i el control de la tuberculosi pediàtrica a Catalunya

Tuberculosi pediàtrica; Diagnòstic de malalties; TractamentsTuberculosis pediátrica; Diagnóstico de enfermedades; TratamientosPediatric tuberculosis; Disease diagnosis; TreatmentsLa finalitat d’aquest document és revisar, des d’una perspectiva multidisciplinària, els reptes en el diagnòstic i el tractament de la TB pediàtrica, l’optimització de la realització dels estudis de contactes, la integració del cribratge de la infecció tuberculosa en el Programa de seguiment del nen sa de l’atenció primària (AP) i el model d’organització assistencial, amb l’objectiu de realitzar recomanacions pràctiques que contribueixin a millorar les respostes que cal articular per a la prevenció i el control de la TB pediàtrica al territori