Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Respiratory syncytial virus: A new era.

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain.

Unresolved issues in the diagnosis of catheter related candidemia: A position paper.

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper.

COVID-19: On the threshold of the fifth year. The situation in Spain.

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection.

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Recommendations for the prevention of healthcare-associated infections in nursing homes.

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similarities with a nosocomium as they are places where many patients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person responsible for implementing these projects. The document includes measures to be implemented and ways of quantifying the reality of different problems and of monitoring the impact of the measures established.

Advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in Spain. How and when is it justified to maintain it?

We address the advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organization on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respecting the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respiratory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of severe COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections.

Sexually transmitted infections in Spain: Current status.

Sexually Transmitted Infections (STI) are a major public health problem. The problems inherent to their diagnosis, treatment and prevention have to do not only with their nature, but also with organizational issues and overlapping competencies of the different health authorities in Spain. The real situation of STI in Spain, at present, is poorly known. For this reason, the Scientific Committee on COVID and Emerging Pathogens of the Illustrious Official College of Physicians of Madrid (ICOMEM) has formulated a series of questions on this subject which were distributed, not only among the members of the Committee, but also among experts outside it. The central health authorities provide very high and increasing figures for gonococcal infection, syphilis, Chlamydia trachomatis infection and lymphogranuloma venereum (LGV). Both HIV infection and Monkeypox are two important STI caused by viruses in our environment, to which it should be added, mainly, Herpes simplex virus (HSV) and Human papillomavirus (HPV) infections. Emerging microorganisms such as Mycoplasma genitalium pose not only pathogenic challenges but also therapeutic problems, as in the case of N. gonohrroeae. The pathways that patients with suspected STI follow until they are adequately diagnosed and treated are not well known in Spain. Experts understand that this problem is fundamentally managed in public health institutions, and that Primary Care and Hospital Emergency Services, together with some institutions that deal monographically with this problem, are the recipients of most of these patients. One of the most serious difficulties of STI lies in the availability of the microbiological tests necessary for their diagnosis, particularly in this era of outsourcing of microbiology services. Added to this is the increased cost of implementing the latest generation of molecular techniques and the difficulties of transporting samples. It is clear that STI are not diseases to which the entire population is equally exposed and it is necessary to have a better knowledge of the risk groups where to focus the necessary interventions adapted to their characteristics. It should not be forgotten that STI are also a problem in the pediatric age group and that their presence can be a marker of sexual abuse with all that this implies in terms of health care and medicolegal activity. Finally, STI are infections that are associated with a high cost of care for which we have very little information. The possibility of expanding the automatic performance of laboratory tests for STI surveillance through laboratory routines is encountering ethical and legal problems that are not always easy to solve. Spain has created a ministerial area of specific attention to STI and there are plans to improve the diagnosis, treatment and prevention of these problems, but we still lack the necessary evidence on their impact. We cannot forget that these are diseases that transcend the individual and constitute a Public Health problem.

Positron Emission Tomography-Computed Tomography and Magnetic Resonance Imaging Assessments in a Mouse Model of Implant-Related Bone and Joint Staphylococcus aureus Infection.

Osteomyelitis is an infection of the bone, associated with an inflammatory process. Imaging plays an important role in establishing the diagnosis and the most appropriate patient management. However, data are lacking regarding the use of preclinical molecular imaging techniques to assess osteomyelitis progression in experimental models. This study aimed to compare structural and molecular imaging to assess disease progression in a mouse model of implant-related bone and joint infections caused by Staphylococcus aureus. In SWISS mice, the right femur was implanted with a resorbable filament impregnated with S. aureus (infected group, n = 10) or sterile culture medium (uninfected group, n = 6). Eight animals (5 infected, 3 uninfected) were analyzed with magnetic resonance imaging (MRI) at 1, 2, and 3 weeks postintervention, and 8 mice were analyzed with [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) at 48 h and at 1, 2, and 3 weeks postintervention. In infected animals, CT showed bone lesion progression, mainly in the distal epiphysis, although some uninfected animals presented evident bone sequestra at 3 weeks. MRI showed a lesion in the articular area that persisted for 3 weeks in infected animals. This lesion was smaller and less evident in the uninfected group. At 48 h postintervention, FDG-PET showed higher joint uptake in the infected group than in the uninfected group (P = 0.025). Over time, the difference between groups increased. These results indicate that FDG-PET imaging was much more sensitive than MRI and CT for differentiating between infection and inflammation at early stages. FDG-PET clearly distinguished between infection and postsurgical bone healing (in uninfected animals) from 48 h to 3 weeks after implantation. IMPORTANCE Our results encourage future investigations on the utility of the model for testing different therapeutic procedures for osteomyelitis.

Infection control in long term care institutions for the elderly: A reflection document on the situation in Spain.

A progressively increasing percentage of the elderly live during the last years of their lives in nursing homes. Although these institutions are intended to mimic life at home as much as possible, they have characteristics that make them quite similar to a "nosocomiun", i.e. an establishment for the treatment of the sick. The very coexistence among the elderly, the fact of sharing caregivers and the very significant exposure to third parties, together with the frequent predisposing diseases to infection in this population, make infection frequent among residents and also easily transmissible. This leads us to ask what can be done to prevent infection in this environment and more specifically what is the state of the art of the matter in a Western European nation such as ours. The Board of Trustees of the Health Sciences Foundation has asked itself a series of questions on the subject of infection prevention in Nursing Homes, the structure of procedures, the legislation available, compliance with the measures indicated, the best indicators of the processes and therefore, the need to promote in Spain a document of recommendations to avoid infections in this poplation whose morbidity and mortality need not be highlighted. To this end, a multidisciplinary group of experts in different aspects of this problem has been convened and asked the proposed questions. The questions were discussed by the group as a whole and led to a series of conclusions agreed upon by the participants. The results of the meeting are reported below.

Impact of the COVID-19 pandemic on the mental health of the general population and health care workers.

The Health Sciences Foundation has assembled a multidisciplinary group around a series of questions about the impact of the COVID-19 pandemic on the mental health of the general population and specific groups within that population, particularly healthcare workers. In the general population, the most prevalent mental disorders have been anxiety, sleep disorders and affective disorders, primarily depression. There has been a considerable increase in suicidal behavior, especially in young women and men over 70 years of age. There has been an increase in alcohol abuse and nicotine, cannabis and cocaine use. In contrast, the use of synthetic stimulants during periods of confinement has decreased. With regard to non-substance addictions, gambling was very limited, pornography consumption increased significantly and there was an increase in compulsive shopping and the use of video games. Particularly vulnerable groups include adolescents and patients with autism spectrum disorders. Healthcare workers suffered an increase in depression, anxiety and post-traumatic stress, especially those who were exposed during the early stages of the pandemic. Female sex, being a nurse, proximity to patients with COVID-19, working in a rural environment and having previous psychiatric or organic illnesses were some of the most frequently repeated factors in various studies in this population group. The media have shown a good degree of knowledge about these problems and have dealt with them frequently and from the point of view of ethics, crisis situations, such as the one experienced, have triggered not only physical but also moral claudications.

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain. The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation. There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults. The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain. These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper.

Cytomegalovirus reactivation in patients diagnosed with severe COVID-19: A point prevalence study in a general hospital.

OBJECTIVE: To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital. METHODS: Point prevalence study in all hospitalized patients with severe COVID-19 (admitted either to general wards or ICU). Determination of the presence of CMV DNA in circulating blood. COVID-19 was confirmed in patients with compatible clinical manifestations, usually with pneumonia and a positive nasopharyngeal PCR test. RESULTS: We included 140 hospitalized patients with COVID-19 who consented to participate. A total of 16 patients (11.42%), had circulating CMV-DNA in peripheral blood at the time of the study. Patients with positive CMV viral load were mainly ICU patients (11/37 -29,7%) and only 5/103 cases (4,85%) were hospitalized into general wards. The accumulated doses of corticosteroids (prednisone equivalents) in the study day were (median and IQR) 987.50 mg (396.87-2,454.68) and 187.50 mg (75.00-818.12) respectively in CMV positive and negative patients (p < 0.001). A significant proportion of CMV positive patients were discovered because of the study and were clinically unsuspected by their physicians. The coinfected COVID-CMV positive population had a higher risk of accumulated secondary nosocomially-acquired infections and a worse prognosis. CONCLUSIONS: CMV reactivation should be systematically searched in patients in COVID-19 cases admitted to the ICU.

Insights for COVID-19 in 2023.

Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.

Impact and control of the COVID pandemic in an elite sports club: Real Madrid.

The incidence and risk factors for poor outcome in patients with COVID are well known, as are the protective measures in high-risk populations. In contrast, the epidemiological and clinical behavior of this disease in the population of elite athletes who are the paradigm of good health is poorly understood. Data on COVID in athletes are scarce and have focused preferentially on the consequences on sports performance of confinement measures and on the pathophysiological risks of infected athletes. Real Madrid is a large elite sports institution with facilities in the City of Madrid where 600 athletes train daily. The incidence of COVID during a study period of 671 days of observation in athletes, professional or amateur, working in the institution has been 0,74 per 1,000 days of exposure. The disease has been asymptomatic or oligosymptomatic in all athletes and did not require any hospital admissions. The different teams did not have to suspend any of its sportive commitments for COVID during the study period and there was no evidence of outbreaks of internal transmission between members of the different teams.

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.

Unresolved issues in the epidemiology and diagnosis of bacteremia: an opinion paper.

Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently. In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak. The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory. We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus.

Monkeypox in humans: a new outbreak.

Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an Orthopoxvirus (MPVX) that was isolated in monkeys in 1958 and proved capable of passing to humans in 1970. It remained contained in Africa, causing isolated episodes of infection, until 2003 when an outbreak occurred in the United States following importation of animals from that continent. Since then, anecdotal cases have continued to be reported outside Africa, usually very clearly linked to travelers to those countries, but in May 2022, a broad outbreak of this disease has begun, now affecting several continents, with the emergence of human cases of MPVX (H-MPVX) infection mainly among Men that have Sex with Men (MSM). The disease has an incubation time ranging from 5 to 15 days and is characterized by the presence of pustules, fever, malaise and headache. The presence of significant regional lymphadenopathy is a differential feature with episodes of classical smallpox. Proctitis and pharyngitis, with minimal skin lesions, may be another form of presentation. Diagnosis can be confirmed by PCR testing of lesions or by demonstration of MPVX in other body fluids or tissues, although in the appropriate epidemiologic setting the clinical picture is highly suggestive of the disease. Effective drug treatment has been developed as part of programs to protect against potential bioterrorist agents and smallpox vaccinees are known to have high protection against monkeypox. New vaccines are available, but neither the drugs nor the vaccines are yet freely available on the market. The prognosis of the disease appears, at least in adults in developed countries, to be good, with very low mortality figures and much less aggressive behavior than that described in classical smallpox. Isolation measures, essential for the control of the outbreak, have been published by the health authorities.