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Surface antigenic variation is crucial for major pathogens that infect humans, e.g.Plasmodium1,Trypanosoma2,Giardia3. In order to escape the immune system, they exploit various mechanisms in order to modify or exchange the protein that is exposed on the cell surface, at the genetic, expressional, and/or epigenetic level4. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. However, those used by the fungusPneumocystis jiroveciithat causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable5, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggest that the system involves mediation of homologous recombinations during meiosis by DNA triplexes. This leads to the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression within subpopulations of cells6. The recombinations generates also constantly new mosaic genes. Dispersion of the new alleles and repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from all over the world. Our observations reveal a unique strategy of antigenic variation allowing colonization of the non-sterile niche corresponding to lungs of healthy humans. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes7. Such mirror sequences are widespread in eukaryotic genomes8, as well as in HIV virus9, but remain poorly understood so far.

In cystic fibrosis (CF), there is a predisposition to bronchial colonization by potentially pathogenic microorganisms, such as fungi. Our aims were to describe the dynamics of respiratory mycobiota in patients with CF and to evaluate the geographic, age and gender variability in its distribution.Cohort study in which 45 patients with CF from four hospitals in three Spanish cities were followed up during a 1-year period, obtaining spontaneous sputum samples every 3 to 6 months. Fungal microbiota were characterized by Internal Transcribed Spacer sequencing and Pneumocystis jirovecii was identified by nested PCR in a total of 180 samples.The presence of fungi were detected in 119 (66.11%) of the 180 samples and in 44 (97.8%) of the 45 patients: 19 were positive and 1 negative throughout all follow-ups and the remaining 25 presented alternation between positive and negative results. A total of 16 different genera were identified, with Candida spp. (50/180, 27.78%) and Pneumocystis spp. (44/180, 24.44%) being the most prevalent ones. The distribution of fungal genera was different among the evaluated centres (p 0.05), by age (non-adults aged 6-17 years vs. adults aged ≥18 years) (p 0.05) and by gender (p 0.05).A high prevalence of fungal respiratory microbiota in patients with CF was observed, whose dynamics are characterized by the existence of multiple cycles of clearance and colonization, reporting the existence of geographic, age and gender variability in the distribution of fungal genera in this disease.

Objective To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients’ prognosis. Methodology We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis. Results The study included 108 patients, and the mean age was 71.48 ± 11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p = .043), at 3 months (p = .028) and at 1 year (p = .007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p = .063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p = .041) and hospital mortality (p = .007) and 3-month mortality (p = .05). Conclusions The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.

[EN] Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in immunocompromised patients. The objective of this study was to know the P. jirovecii epidemiology in Venezuelan patients with Human Immunodeficiency Virus (HIV) infection and suspected pneumonia, through passive surveillance at a national reference laboratory during six years. Laboratory records of patients with HIV infection, who were hospitalized with acute lower respiratory tract infection (ALRTI), and presumptive clinical diagnosis of PCP, were reviewed between January 2007 and December 2012, at the Mycology Department of the Instituto Nacional de Higiene Rafael Rangel. Several respiratory specimens were received and the direct immunofluorescence assay (DIF) and nested polymerase chain reaction (nPCR) diagnostic techniques were used. One hundred and sixty-one respiratory samples were processed and P. jirovecii was detected in 76 samples by DIF and in 20 by nPCR. PCP’s frequency in Venezuelan patients with HIV is high and it has been sustained throughout time. Colonization by P. jirovecii has uncertain clinical significance, but this study provides evidence that the state of advanced immunosuppression increases the probability of colonization. DIF and nPCR are very useful techniques for PCP diagnosis, but are of limited access in many hospital centers, especially in developing countries. We recommend the use of DIF with spontaneous sputum specimens as the first diagnostic line for PCP in patients with HIV infection. The results obtained by nPCR should be interpreted with caution, taking into account the patient’s clinical symptoms., [ES] La neumonía por Pneumocystis jirovecii (PCP) es una de las infecciones oportunistas más frecuente en pacientes inmunocomprometidos. El objetivo de este trabajo fue conocer la epidemiología del P. jirovecii en pacientes venezolanos con infección por el Virus de Inmunodeficiencia Humana (VIH) y sospecha de neumonía, mediante vigilancia pasiva en un laboratorio de referencia nacional durante un período de 6 años. Se revisaron los registros de laboratorio de los pacientes con infección por el VIH hospitalizados con Infección Aguda del Tracto Respiratorio Inferior (IATRI) y diagnóstico clínico presuntivo de PCP, entre enero de 2007 a diciembre de 2012 en el Departamento de Micología del Instituto Nacional de Higiene Rafael Rangel. Se recibieron diversas muestras del tracto respiratorio y los métodos diagnósticos empleados fueron inmunofluorescencia directa (IFD) y reacción en cadena de la polimerasa anidada (nPCR). Se procesaron 161 muestras respiratorias y se detectó P. jirovecii en 76 muestras por IFD y en 20 por nPCR. La frecuencia de PCP en pacientes venezolanos con HIV es elevada y se ha mantenido en el tiempo. La colonización por P. jirovecii tiene un significado clínico incierto, pero este estudio aporta evidencia de que un estado avanzado de inmunosupresión incrementa la probabilidad de colonización. La IFD y la nPCR son técnicas muy útiles para el diagnóstico de la PCP, pero son de acceso limitado en muchos centros hospitalarios, sobre todo en países en vías de desarrollo. Recomendamos la utilización de la IFD con muestras de esputo espontáneo como primera línea de diagnóstico para la PCP en pacientes con VIH. Los resultados obtenidos por nPCR deben ser interpretados tomando en cuenta la sintomatología clínica del paciente.

[Purpose of the Review]: The aim of this work is to contribute to the knowledge of diagnosis, burden, and mortality of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in Venezuela., [Recent Findings]: Historically, PCP diagnosis has been clinical and histopathological, but diagnosis based on PCP clinical suspicion, without confirmation of laboratory detection of P. jirovecii, causes a significant negative impact on both morbidity and mortality of this disease. Risk estimation for PCP and mortality rates according to official records contrasts with the scarce epidemiological data and makes more difficult to have a real view of the impact of this disease in our country., [Summary]: This review summarizes three fundamental aspects: the meaning and usefulness of direct immunofluorescence assay (DIF) and nested PCR (nPCR) for PCP diagnosis in a developing country, risk estimation for PCP based on available national publications, and official mortality rates.

[Objectives] To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru., [Methods] A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the “well baby” outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants’ clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed., [Results] P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p, [Conclusion] Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2–3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii., This work was supported by the European Commission (grant number Era-Net LAC 2014 HID-0254).

Purpose Heart failure (HF) is a chronic, frequent and disabling condition but with a modifiable course and a large potential for improving. The aim of this study was to validate the two available clinical prediction rules for mortality at one year in patients with primo-hospitalization for decompensated HF: PREDICE and AHEAD. The secondary aim was to evaluate in our setting the changes in the clinical pattern of HF in the last decade in patients hospitalized for a first episode of the disease. Patients and methods A prospective multicenter cohort study, which included 180 patients hospitalized with "de novo" HF was conducted to validate the PREDICE score. Calibration and discrimination measurements were calculated for the PREDICE model and the PREDICE score (using the validation cohort of the PREDICE) and the AHEAD score (using both the development and the validation cohort of the PREDICE). Results For the PREDICE models, the area under the curve (AUC) was 0.68 (95% confidence interval [CI]: 0.57-0.79) and the calibration slope 0.65 (95% CI: 0.21-1.20). For the PREDICE score AUC was 0.59 (95% CI: 0.47-0.71) and slope 0.42 (95% CI: -0.20-1.17). For the AHEAD score the AUC was 0.68 (95% CI: 0.62-0.73) and slope 1.38 (95% CI: 0.62-0.73) when used the development cohort of PREDICE and the AUC was 0.58 (95% CI: 0.49-0.67), and slope 0.68 (95% CI: -0.06 to 1.47) when used its validation cohort. Conclusion The present study shows that the two risk scores available for patients with primo-hospitalization for decompensated HF (PREDICE and AHEAD) are not currently valid for predicting mortality at one-year. In our setting the clinical spectrum of hospitalized patients with new-onset HF has been modified over time. The study underscores the need to validate the prognostic models before clinical implementation.

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic.

We conducted a pilot study of patients with cystic fibrosis (CF) to assess intra-family transmission of P. jirovecii and compare it with data on other prevalent pathogens such as P. aeruginosa and S. pneumoniae, in which respiratory transmission has already been documented. Oral swab samples from 10 patients with CF and 15 household members were collected at baseline and 2 weeks later. P. aeruginosa and S. pneumoniae were assessed using standardized culture methods and PCR, and P. jirovecii was assessed using real and nested PCR, genotyping the positive samples by direct sequencing. P. aeruginosa cultures were positive for 7/10 (70%) of patients with CF at baseline and was identified by PCR in 8/10 (80%) of cases at baseline and 2 weeks later. S. pneumoniae cultures were negative for all patients, but the microorganism was identified by PCR in two cases. P. jirovecii was detected by real time and nested PCR in 5/10 (50%) of the patients at the two time points. In the household members, P. aeruginosa and P. jirovecii were identified in 7/15 (46.7%), and S. pneumoniae was identified in 8/15 (53,3%). The concordance of positive or negative pairs of patients with CF and their household members was 33.3% (5/15) for P. aeruginosa, 46.7% (7/15) for S. pneumonia and 93.3% (14/15) for P. jirovecii. The concordance for P. jirovecii genotypes among five pairs with available genotype was 100%. This study suggests for the first time the possible transmission of Pneumocystis in the home of patients with CF, indicating that patients and their household members are reservoirs and possible sources of infection., The study was supported, in part, by the Red Iberoamericana sobre Pneumocystosis in the framework of The Ibero-American Programme for Science, Technology and Development (grant CYTED 212RT0450).

Twenty-years ago, considering the host specificity of Pneumocystis species, the human-derived Pneumocystis, Pneumocystis carinii formae specialis hominis, was renamed Pneumocystis jirovecii. Pneumocystis carinii formae specialis carinii was finally renamed Pneumocystis carinii and kept for the species derived from Rattus norvegicus. P. jirovecii is now widely used by most authors. The PCP acronym that initially referred to “Pneumocystis cariniipneumonia” was contemporaneously redefined to stand for Pneumocystispneumonia in order to avoid changing the acronym of the name of the disease that clinicians have used for several decades. Using analysis of multidata bases on PubMed, we have noted a recent acceleration in the use of PJP for Pneumocystis jiroveciipneumonia, which may be grammatically correct but not in accordance with retaining PCP, which was proposed in the early 2000s. Through this reminder, in order to standardize the literature on P. jirovecii, we plead for the use of only one acronym, PCP. Lay Summary Through this reminder on Pneumocystis nomenclature, we plead for the use of only one acronym, PCP, the retention of which was proposed in the early 2000s, and which currently stands for Pneumocystispneumonia.

[Purpose of the Review]: The aim of this work is to contribute to the knowledge of the epidemiology of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in Venezuela, by an updated review of the information currently available., [Recent Findings]: The PCP epidemiology in Venezuela is not formally known. There is no national surveillance program for mycosis, and systemic mycoses are not mandatory notification diseases. Efforts made to record the disease in our country have not been sufficient; therefore, there is a sub-registry. All the information carried out prevents comparisons with other reports due to the variations in study designs, heterogeneity of the studied patients, and diagnostic methods., [Summary]: This review summarizes the current knowledge about PCP epidemiology in Venezuela based on available national publications. The contributions of these studies are very valuable, since they reflect the need for systematic PCP study, not only in AIDS patients, but in cancer and COPD patients.

[ES] Antecedentes: La primoinfección por Pneumocystis jirovecii ocurre de forma asintomática antes de los 6 meses de edad, lo que sugiere que la infección se adquiere muy precozmente en la vida. Se ha descrito también la presencia de neumonía por Pneumocystis en recién nacidos, lo que indica la necesidad de estudiar la colonización en el binomio madre-hijo. Objetivos: Evaluar la prevalencia de colonización de Pneumocystis en gestantes y explorar la potencial transmisión transplacentaria. Métodos: Estudio transversal que incluyó a mujeres gestantes mayores de 18 años con 37 o más semanas de gestación y negativas para el VIH que acudieron al Hospital Cayetano Heredia en los años 2016-2017. Se obtuvo información clínica y demográfica de la gestante y del recién nacido. Se tomaron muestras de lavado orofaríngeo/hisopado nasal de la gestante, de placenta y de aspirado nasofaríngeo/hisopado nasal del recién nacido. Todas las muestras respiratorias fueron analizadas mediante PCR anidada. En el caso de las muestras de placenta solo fueron analizadas aquellas procedentes de mujeres con resultados positivos de PCR para Pneumocystis en las muestras respiratorias. Resultados: De las 92 gestantes incluidas en el estudio cinco presentaban colonización por Pneumocystis (5,43%). Se evaluaron las muestras de 87 recién nacidos y las placentas de las cinco madres con PCR positiva, no encontrándose ADN de Pneumocystis en ninguna de ellas. Conclusiones: Aunque el 5,43% de las mujeres gestantes estuvieran colonizadas por Pneumocystis no pudo determinarse el rol de esta colonización en la transmisión a sus recién nacidos, ya que en ninguno de ellos se demostró la presencia de Pneumocystis., [EN] Background: Pneumocystis jirovecii primary infection occurs asymptomatically before 6 months of age, suggesting that the infection is acquired very early in life. Furthermore, Pneumocystis pneumonia has been described in newborns, which emphasizes the importance of studying Pneumocystis colonization in mother-infant pairs. Aims: To evaluate the prevalence of Pneumocystis colonization among pregnant women and to determine the potential transplacental transmission. Methods: A cross-sectional study was carried out on HIV-negative women over 18 years-old, and 37 or more weeks of pregnancy attending Hospital Cayetano Heredia Maternity unit during 2016-2017. Clinical and demographical information was collected on them and their newborns. Oropharyngeal washes, nasal swabs, and placenta samples were collected from women, as well as a nasopharyngeal aspirate and nasal swab from newborns. All respiratory samples were analysed by nested-PCR for the detection of Pneumocystis. Placenta samples from women with a positive PCR result in their respiratory samples were also analysed by nested-PCR. Results: Of the 92 pregnant women included, five of them (5.43%) were colonized by Pneumocystis. Pneumocystis DNA was not found in any of the 87 available newborn samples or in the placentas of the five women who had a positive result by PCR in their upper respiratory samples. Conclusions: It was found that 5.43% of the pregnant women were colonized by Pneumocystis, there was no evidence of any role of this colonization in the transmission to their newborns, since none of them tested positive for Pneumocystis., Este trabajo se realizó en el marco de la Red Iberoamericana sobre Pneumocystosis (212RT0450) del Programa para el Desarrollo de la Ciencia y la Tecnología en Iberoamérica (CYTED) y fue financiado por CONCYTEC, Perú, en el contexto del proyecto ERANet-LAC (HID0254 ELAC2014), 7.° Programa Marco de la Unión Europea.

Pneumocystis jirovecii and microsporidia species are recognized as opportunistic infectious pathogens in AIDS patients. Coinfection of both in one patient has been rarely reported. The aim of the present study was to investigate the coinfection of P. jirovecii and microsporidia in different tissues from AIDS deceased patients. Post mortem histological finding of P. jirovecii and microsporidia was demonstrated by means of the Grocott's methenamine silver and Brown Brenn staining, respectively. Molecular technique was used for identification and characterization of both fungi. Out of the 514 autopsied cases P. jirovecii and microsporidia species were identified in 53 (10.3%) and 62 (12.1%) cases respectively. A total of five cases (0.97%) coinfected with Pneumocystis and microsporidia were recovered from all analyzed autopsies. Coinfection of Pneumocystis and microsporidia is very challenging and raises interesting issues about host-parasite relationship. The early diagnosis of both pathogens must be crucial to establish correct and early treatments, improve the patient's evolution, reducing the risk of death., This work was supported by the ‘Red Iberoamericana sobre Pneumocystosis’ (212RT0450) in the framework of The Ibero-American Programme for Science, Technology and Development (CYTED).

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.

Enrique Calderón,1 María Eloísa Calderón-Seoane,2 Rafael García-Hernández,1 Luis Miguel Torres1 1Pain Unit, Anesthesiology Department, Puerta del Mar University Hospital, 2Health Center North-Algeciras, Cadiz, Spain Objectives: Chronic neuropathic pain and chronic complex regional pain syndrome (CRPS), in particular, are debilitating and difficult-to-treat conditions that have a strong impact on patient’s quality of life. The aim of this study was to evaluate the effectiveness of 5% lidocaine-medicated plaster as add-on therapy in patients with chronic peripheral neuropathic pain conditions, including CRPS.Patients and methods: This was a single-center, prospective, observational study set in a specialized pain unit of a tertiary hospital in Spain. A total of 56 patients with long-standing peripheral neuropathic pain, ten of them with CRPS, received 5% lidocaine-medicated plaster as add-on analgesic therapy for 6months.Results: After 6months of treatment, a ≥50% reduction in pain intensity was attained by 75% of patients, as measured by numeric rating scale (NRS) for pain. The average NRS score was reduced by 61% (4.7 points), from a baseline mean score of 7.8 to an end point mean score of 3.1. Marked improvements were also observed in the CRPS group: six out of ten patients achieved a ≥50% reduction in NRS score, and the average NRS score for patients with CRPS was reduced by 51% (4.0 points), from a baseline mean score of 7.9 to an end point mean score of 3.9. The improvements in pain intensity were partially translated into a decrease in disability index and in anxiety levels.Conclusion: 5% Lidocaine-medicated plaster may be useful as add-on therapy for a number of peripheral neuropathic pain conditions, including CRPS. Keywords: peripheral neuropathic pain, complex regional pain syndrome, topical lidocaine, analgesic therapy, chronic pain

The possible presence of Pneumocystis in a bronchoscopy unit of a tertiary-hospital was examined by detecting Pneumocystis-specific DNA by polymerase chain reaction in prospectively obtained samples of oropharyngeal wash from seven healthcare workers (HCWs) and air from three areas of the unit at different time points (baseline, days +15,+30,+60,+90 after initiation of the study). Positive samples were genotyped at two genetic loci: the mitochondrial large subunit ribosomal RNA (mtLSUrRNA) fragment by direct sequencing and the gene for dihydropteroate synthase (DHPS) by restriction fragment-length polymorphism. Pneumocystis DNA was identified in 13/24 samples from HCWs, in 4/14 air samples and also in two patients with Pneumocystis pneumonia (PcP) and another with a Pneumocystis-associated disease subjected to bronchoscopy on days +15 and +60 after initiation of the study. The HCWs harbored a high rate of mtLSU-rRNA genotypes 1 and 3 and samples from air and patients with only genotype 3. DHPS mutations related to sulpha resistance were detected in three samples from HCWs and in one from air; 65% of the positive samples showed genotypic concordance. The study demonstrates that HCWs of bronchoscopy units represent a new dynamic reservoir and a possible source of infection for human Pneumocystis species, including DHPS genotypes related to sulpha resistance that could be transmitted within hospitals to immunosuppressed hosts in whom a PcP can develop. The results provide the first evidence of the risk of Pneumocystis transmission in the bronchoscopy units and arguments to improve prevention and control of this infection in nosocomial setting.

[Background] Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity., [Methods] A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology., [Results] From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p, [Conclusions] This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings., Quique Bassat had during the duration of the study a fellowship from the program Miguel Servet of the ISCIII (Plan Nacional de I+D+I 2008-2011, grant number: CP11/00269). Lola Madrid had a fellowship from the program Río Hortega of the ISCIII (CM13/00260). Rosauro Varo has a fellowship from the program Rio Hortega of the ISCIII (CD16/00024). CISM receives financial support from the Spanish Agency for International Cooperation. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution., This project has received funding from the Marie Curie International Research Staff Exchange Scheme within the 7th European Community Framework Program under grant agreement No 612583-DEANN. Part of this work was done during an internship of L.D. as invited professor at the Universidad de Valencia. Support from CONACYT (grant 454938) is gratefully acknowledged. This work was supported by grants to A.M. from the Spanish Ministry of Science and Competitivity (projects SAF 2012-31187, SAF2013-49788-EXP, SAF2015-65878-R), Carlos III Institute of Health (projects PIE14/00045, AC 15/00022 and AC15/00042), Generalitat Valenciana (project PrometeoII/2014/065) and cofinanced by FEDER.