Should SARS-CoV-2 serological testing be used in the decision to deliver a COVID-19 vaccine booster? A pro-con assessment.

Anti-SARS-CoV-2 vaccination has saved millions of lives in the past few years. To maintain a high level of protection, particularly in at-risk populations, booster doses are recommended to counter the waning of circulating antibody levels over time and the continuous emergence of immune escape variants of concern (VOCs). As anti-spike serology is now widely available, it may be considered a useful tool to identify individuals needing an additional vaccine dose, i.e., to screen certain populations to identify those whose plasma antibody levels are too low to provide protection. However, no recommendations are currently available on this topic. We reviewed the relevant supporting and opposing arguments, including areas of uncertainty, and concluded that in most populations, spike serology should not be used to decide about the administration of a booster dose. The main counterarguments are as follows: correlates of protection are imperfectly characterised, essentially owing to the emergence of VOCs; spike serology has an intrinsic inability to comprehensively reflect the whole immune memory; and booster vaccines are now VOC-adapted, while the commonly available commercial serological assays explore antibodies against the original virus.

Epidemiology and Clinical Outcomes of Bacterial Meningitis in Children and Adults in Low- and Middle-Income Countries.

Purpose of Review: Despite the availability of effective vaccines against the three primary pathogens (Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries. Recent Findings: Bacterial meningitis represents a significant public health challenge for national and global health systems. Since vaccine-preventable meningitis remains highly prevalent in low-income and middle-income countries, the World Health Organization (WHO) recently developed a global roadmap to defeating meningitis by 2030 and ameliorating its associated neurological sequelae. Summary: There is a need for a global approach to surveillance and prevention of bacterial meningitis. Increasing vaccination coverage with conjugate vaccines against pneumococcus and meningococcus with optimal immunization schedules are high-value healthcare interventions. Additionally, overcoming diagnostic challenges and the early institution of empirical antibiotic therapy and, when feasible, adjunctive steroid therapy constitutes the pillars of reducing the disease burden of bacterial meningitis in resource-limited settings.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.

Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019.

Background: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Objective: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. Methods: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Results: Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90 days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). Conclusion: In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients.

Epidemiological trends of cryptococcosis in the US The epidemiology and outcomes of cryptococcosis across the United States have not been recently examined. This study analyzed an insured population from 2017 to 2019 and revealed a relatively stable incidence of cryptococcosis among people with HIV, while concurrently demonstrating a slightly increased incidence among individuals without HIV. Notably, mortality rates were highest among non-HIV-infected and non-transplant patients.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Positive Toxoplasma IgG Serology Is Associated with Increased Overall Mortality - A Propensity Score-Matched Analysis.

Toxoplasma gondii is a prevalent parasitic disease with significant morbidity and mortality in immunocompromised populations. We lack long-term outcomes for latent infections. We aimed to elucidate the relationship between latent T. gondii infection and mortality risk. We queried TriNetX, a international multicenter network, to validate mortality risk differences among patients with positive or negative toxoplasma IgG through propensity score matching (PSM). We excluded patients with toxoplasmosis disease by International Classification of Diseases codes or polymerase chain reaction testing. We found 28,138 patients with available toxoplasma IgG serology. Seropositive patients were older and had a male preponderance. More seropositive patients identified as Hispanic, Latino, or Black persons. Patients who were positive for T. gondii IgG serology were slightly more likely to have underlying heart failure, a transplanted organ or tissue, malignant neoplasms of lymphoid or hematopoietic tissues, and diseases of the nervous system than seronegative controls. After PSM of patients with positive (N = 6,475) and negative (N = 6,475) toxoplasma IgG serologies, toxoplasmosis-positive patients were more likely to have long-term drug use but less likely to suffer from behavioral disorders. The overall PSM 1- and 5-year mortality was higher among patients with a positive toxoplasma IgG serology. The risk of schizophrenia was increased at 5 years. We found a prevalence of toxoplasma IgG positivity of 0.03% during the last 3 years. Latent T. gondii associates with a higher overall mortality risk. The study of social determinants of health and follow-up studies are necessary to corroborate the findings and find possible causal mechanisms.

El comodín de la historia universal: las enfermedades infecciosas / The wild card of world history: infectious diseases

La migración de las poblaciones, a través de las diferentes etapas de la historia y su incursión en diversos ecosistemas del planeta, ha permitido irremediablemente una interacción dinámica con animales, plantas, insectos y con el mundo microbiológico. En esta trayectoria algunos microorganismos establecieron relaciones simbióticas con los seres humanos mediante la negociación de compromisos celulares y moleculares, eventualmente esculpiendo al genoma humano. Sin embargo, en muchas otras instancias, ciertos microorganismos han actuado como agentes de selección natural, ocasionando enfermedad y muerte. De esta forma, el establecimiento de las sociedades actuales se debe en gran medida al impacto que las enfermedades infecciosas tuvieron en la conformación de las poblaciones a través de los milenios. Las epidemias ocasionadas por esas enfermedades han influenciado aspectos políticos, económicos y sociales al menos por cuatro transiciones epidemiológicas: el Neolítico con la aparición de los primeros asentamientos humanos, la Edad Media -particularmente con el impacto de la plaga bubónica en Europa y Asia-, la época de exploración y colonialismo europeo y la actual era de globalización. La historia de la humanidad estaría inexorablemente ligada a la coexistencia con los agentes infecciosos

Throughout the history of mankind, population migration has played an important role in determining a dynamic interplay of humans with other animals, plants, insects, and microbial agents in different ecological niches. In this journey, some microbes have negotiated symbiotic relationships with humans by achieving molecular and cellular compromises, ultimately sculpting the human genome. In other cases, many microbial agents have acted as pathogens and therefore becoming forces of natural selection throughout different human societies by leading to morbidity, dysfunction, or death. In this manner, the establishment of modern societies is in many ways the result of the burden of disease associated with infectious pathogens throughout millennia. Throughout the history of mankind, epidemics of infectious diseases have influenced political, economic and social aspects of human societies at least through the occurrence of four epidemiologic transitions: a) the Neolithic period with the establishment of the first human villages with enough population density enabling the spread of infectious agents; b) the middle-ages with the spread of bubonic plague causing important demographic changes; c) the worldwide exploration of European with colonization in new territories; and d) the current era of globalization. In summary, there is an inextricable link between humanity's journey and microorganisms resulting in either beneficial or antagonistic interactions

La Lepra: una enfermedad vigente / Leprosy: an ongoing disease

El libro resalta que la lepra continúa siendo una enfermedad presente en Colombia y que aún constituye un problema de salud pública importante por los costos sociales, económicos y de sufrimiento humano que conlleva. Sabiendo que la literatura sobre el tema es escasa en nuestro medio, este libro surge como una herramienta de consulta creada para médicos y otros profesionales de salud, con la certeza de que es preciso mejorar la oportunidad del diagnóstico. Siendo fundamental que, durante su proceso formativo, todos los profesionales de la salud adquieran conocimientos sobre dicha enfermedad, que cada día se hace más visible por sus secuelas y diagnóstico tardío.

The book highlights the fact that leprosy continues to be a disease present in Colombia and that it is still a major public health problem due to the social, economic and human suffering costs it entails. Knowing that the literature on the subject is scarce in our country, this book is intended as a reference tool for doctors and other health professionals, in the knowledge that it is necessary to improve the timeliness of diagnosis. It is essential that, during their training process, all health professionals acquire knowledge about this disease, which is becoming more and more visible every day due to its sequelae and late diagnosis.

Aerobic actinomycetes that masquerade as pulmonary tuberculosis

Background: There is an increasing recognition of organisms in the order Actinomycetales including Nocardia sp. causing lung infections that mimic pulmonary tuberculosis or fungal pneumonias. Methods: We retrospectively evaluated a cohort of patients in the southeastern United States in whom a presumptive diagnosis of pulmonary tuberculosis was initially entertained but who eventually were found to have infection caused by Rhodococcus sp. or Tsukamurella sp. Results: Among a cohort of 52 individuals diagnosed as case suspects for pulmonary tuberculosis, we identified six patients who were infected with either Rhodococcus sp. or Tsukamurella sp. Of these six patients, two had co-infection with Mycobacterium tuberculosis. Conclusions: Infection with aerobic actinomycetes may mimic pulmonary tuberculosis or may cause concomitant disease in patients with pulmonary tuberculosis.

The global burden of neglected tropical diseases

The neglected tropical diseases (NTDs) consist of a group of chronic, debilitating, and poverty-promoting parasitic, bacterial, and viral and fungal infections that are widespread among people in poor rural or peri-urban communities living in tropical or subtropical areas. However, due to population mobility, diseases such as Chagas disease can be diagnosed anywhere on the globe. The NTDs are disabling, disfiguring and deadly diseases impacting more than one billion people worldwide. They also impair physical and cognitive development, cause adverse pregnancy outcomes, and limit adult productivity in the workforce. The global burden of disease associated with the NTDs is comparable to other infectious diseases such as that of malaria or tuberculosis. Controlling or eliminating NTDs represents an affordable opportunity to improve the health of poor communities, which may ultimately promote social development.

Achievements and challenges in controlling Chagas disease

American trypanosomiasis or Chagas disease continues to endanger the lives of many million people in Latin America, and through travel and population migration there is a risk of congenital cases in nonendemic settings. Substantial improvements in the transmission of the disease have been achieved through vector control and blood-bank screening. However, vector-borne transmission remains the main mode of acquisition of infection in many settings coupled with congenital transmission and food-borne and accidental exposure through transplantation or laboratory exposure. The main sites of affection include the heart and gastrointestinal tract. Antiparasitic treatment of indeterminate forms is successful in many cases by delaying the risk of progression of cardiomyopathy, but treatment of chronic chagasic cardiomyopathy remains mainly supportive. The BENEFIT trial that will be completed by late 2011 or early 2012 will provide evidence for or against treating chronic symptomatic forms. Control or eliminating Chagas disease transmission coupled with decreasing the associated burden of disease in Latin America will promote better health and social and economic development among the most impoverished populations in the region.

Leprosy: a modern assessment of an ancient neglected disease

Leprosy or Hansen's disease is a chronic mycobacterial infectious disease caused by Mycobacterium leprae and affects mainly peripheral nerves and skin as well as upper respiratory mucosae. This infection is a conjoined bacteriological and immunological disease. Target cells of infection are macrophages, histiocytes in the skin, and the nonmyelinating and myelinating Schwann cells in the peripheral nerves leading to axonal dysfunction and demyelination leading to functional impairment and deformity. Leprosy reactions represent the most important determinant of nerve impairment if untreated and unrecognized. Control of leprosy transmission remains a challenge despite substantial improvements through the use of multidrug therapy in many settings. Most importantly, although many patients have been microbiologically cured through the efforts of the World Health Organization, many are left with significant disability that has recently been estimated to be ~20% of those treated (~15 million individuals) in the last decades. Further efforts are needed to elucidate the epidemiology and risk factors for disability among those with multibacillary forms.

Are leprosy reactions autoinflammatory diseases?

There are two types of leprosy reactions: reversal reactions or type 1 and erythema nodosum leprosum or type 2. Deformity and disability associated with leprosy are frequently the result of uncontrolled or untreated reactions. Although there is current availability of glucocorticoids as the mainstay of therapy, much needs to be learned about the etiology, risk factors, and pathogenesis of leprosy reactions. There is some evidence that leprosy reactions may represent, particularly, erythema nodosum leprosum autoinflammatory disease due to the aberrant activation of the innate immune system. The role for herpesviruses influencing autophagy in macrophages needs to be evaluated in the pathogenesis of leprosy reactions.

Inmunizaciones y equidad en el Plan Regional del Sistema Mesoamericano de Salud Pública / Immunization and equity in the Regional Initiative of the Mesoamerican Health Initiative

Las cifras nacionales de inmunización indican altas coberturas de vacunación en Mesoamérica, sin embargo, hay evidencia creciente de que los grupos más vulnerables no son alcanzados por los programas de vacunación. La planeación de este proyecto se llevó a cabo entre junio y diciembre de 2009. La ejecución del proyecto se llevará a cabo en la población objetivo seleccionada a partir de junio de 2011. Está integrada por niños menores de cinco años y mujeres en edad fértil de las poblaciones más vulnerables en los países de Mesoamérica, identificadas geográficamente por un bajo índice de desarrollo humano o por la alta prevalencia de pobreza en el ámbito municipal, o a través del uso de métodos participativos para definir pobreza y vulnerabilidad en contextos locales. El Grupo de Trabajo ha definido tres líneas de acción para las intervenciones de enfermedades prevenibles por vacunación, para lograr una mejor cobertura efectiva en poblaciones vulnerables: 1) estudios piloto de coberturas para vacíos de conocimiento, 2) fortalecimiento de las políticas de vacunación, 3) ejecución de prácticas basadas en evidencia. El fortalecimiento de los sistemas de salud bajo la óptica de equidad en salud es el objetivo regional central del Grupo de Trabajo en inmunizaciones enfocado en un aumento de la cobertura efectiva.

National immunization rates indicate high vaccine coverage in Mesoamerica, but there is growing evidence that the most vulnerable groups are not being reached by immunization programs. Therefore, there is likely low effective vaccine coverage in the region, leading to persistent and growing health inequity. The planning phase of this project was from June to December 2009. The project will be conducted in the target populations which includes children under five, pregnant women, and women of child-bearing age from the most vulnerable populations within countries of the Mesoamerican region, as indicated geographically by a low human development index (HDI) and/or high prevalence of poverty at the municipal level and through the use of participatory methods to define poverty and vulnerability in local contexts. We defined three lines of action for vaccine-preventable disease interventions: 1) pilot projects to fill gaps in knowledge; 2) strengthening immunization policy; and 3) implementation of evidence-based practices. Health system strengthening through health equity is the central regional objective of the immunization workgroup. We hope to have a transformational impact on health systems so as to improve effective coverage, including vaccine and other integrated primary healthcare services.

Prevalence of untreated schistosomiasis among Sudanese refugees: "The Lost Boys of Sudan" in the United States

Background. The increase in global travelling also brings infections from endemic to non-endemic regions where diagnosis and treatment may be delayed. Methods. From 2005 to 2008, 104 Sudanese refugees were evaluated to determine the prevalence of untreated schistosomiasis at the Tropical Medicine Clinic at Emory University in Atlanta, GA. Sera from 87 patients were screened using FAST-ELISA and antigen-specific immunoblots. Results. Of the 87 patients screened, 44.8% were positive for schistosomiasis antibodies, including Schistosoma mansoni and S. haematobium. Conclusion. Our study emphasizes the need for single-dose presumptive treatment of praziquantel among sub-Saharan refugees and long-term travelers.