Nipah virus (NiV) is a highly pathogenic and re-emerging virus that requires containment in biosafety level 4 (BSL-4) laboratories. The limited accessibility of these high-security facilities poses major obstacles to investigating immunopathogenesis and developing effective antiviral treatments. Reverse genetics allows manipulation of viral genomes without the need to handle the wild-type virus and has become instrumental in understanding NiV pathogenesis and advancing therapeutic research. These tools have proven vital for other high-containment viruses, notably during the SARS-CoV-2 pandemic, and have been adapted effectively for NiV. Reverse genetics-derived systems were used to evaluate the drug candidates in the preclinical studies of NiV, with several candidates in the development pipeline. This narrative review summarizes established reverse genetics and pseudotyping methodologies for NiV, highlighting their contributions to understanding viral pathogenesis and accelerating vaccine and therapeutic development.
Danielle R. Miyazawa Ferreira, Giovanna Pais G. Esteves, Melissa Caroline G. Prestes
et al.
Introdução: Profissionais de saúde têm alta exposição ao SARS-CoV-2, portanto, o Ministério da Saúde (MS) preconiza uma dose de reforço anual da vacina para profissionais vacinados com esquema completo para COVID-19. Porém, ainda não está claro o tempo de proteção da vacina para os diversos profissionais. Objetivo: Avaliar o perfil de adoecimento de profissionais de saúde com o decorrer do tempo após a vacinação para COVID-19. Método: Coorte retrospectiva que analisou profissionais de saúde com sintomas respiratórios atendidos em um ambulatório de um hospital terciário, entre janeiro de 2020 e dezembro de 2021. A amostra incluiu profissionais com esquema vacinal completo ou incompleto para COVID-19 e que apresentaram testes de detecção viral positivos (PCR ou antígeno) para SARS-CoV-2 na evolução, até 31 de dezembro de 2023. O trabalho foi aprovado pelo comitê de ética (parecer: 4.084.024). Resultados: De 2.312 profissionais atendidos, 1.013 foram incluídos, sendo 71,2% mulheres. A mediana de idade foi 44 anos (20 - 88). Receberam esquema vacinal completo 92,3%. Os profissionais com idade maior ou igual a 60 anos tiveram mais esquema incompleto, em comparação com aqueles com idade inferior a 60 anos. Do total, 67,6% negaram ter comorbidades, 9,9% apresentam hipertensão arterial, 7,0% obesidade e 3,9% asma. 453 pacientes positivaram após a segunda dose e 634 após a terceira. A mediana de tempo para adoecer após a terceira dose foi de 207 dias em profissionais com mais de 60 anos e de 161 dias para o grupo com menos de 60 anos. A mediana para a positividade após a segunda dose da vacina foi de 139 dias (primeiro e terceiro quartil em 94 e 196 dias, respectivamente). Após a terceira dose, a mediana para positividade foi 176 dias (primeiro quartil em 95 e terceiro em 281 dias). Portanto, com 3 doses houve aumento de tempo de proteção de 37 dias em relação a 2 doses. Considerando os pacientes que tomaram a terceira dose em um período de até 281 dias, a vacina foi 70% mais protetora em homens com comorbidades, sendo que mulheres com comorbidades tiveram 2,5 vezes mais chance de adoecer em comparação aos homens. Conclusão: Os profissionais de saúde apresentaram elevada adesão ao esquema vacinal completo. O tempo de positividade após a vacinação corroborou com a recomendação de doses com intervalo de 6 meses. No entanto, é importante continuar monitorando e analisando esses profissionais para melhor compreensão da eficácia das vacinas e implementação de políticas de vacinação direcionadas aos grupos especiais.
Pedro Emmanuel Alvarenga Americano do Brasil, Vinicius Lins Costa Melo
Introdução: A COVID-19 já não é uma emergência de saúde global, mas continua a ser uma questão de saúde presente em todo o mundo, e o desafio dos cuidados hospitalares da COVID-19 permanece. Instrumentos prognósticos para a progressão da COVID-19 para estado crítico podem auxiliar na tomada de decisões para pacientes hospitalizados com COVID-19, como manter hospitalizados os pacientes com maior risco de se tornarem críticos. Objetivo: Desenvolver e validar um instrumento para prever a progressão de condição crítica em pacientes hospitalizados com COVID-19 em uma população durante o curso da pandemia. Metodologia: Estudo observacional com seguimento. Os participantes foram internados em unidades não críticas para tratamento, entre janeiro e abril de 2021 e entre setembro de 2021 e fevereiro de 2022 e recrutados sequencialmente de 2 unidades de internação em Niterói/RJ. Foram incluídos adultos, com resultado de RT-PCR positivo, histórico de exposição ou achados de imagem clínica ou radiológica compatíveis com COVID-19. O desfecho foi definido como transferência para terapia intensiva ou óbito. Preditores como dados demográficos, clínicos, comorbidades, testes laboratoriais e de imagem foram coletados à internação. Um modelo de regressão “Random forest” (dentre modelos alternativos) foi desenvolvido e validado para estimar o risco de progressão. Resultados: A prevalência geral do desfecho foi de 41,8% em 301 participantes. A maioria dos pacientes estudados não foi imunizada contra a COVID-19. As comorbidades mais prevalentes foram hipertensão arterial sistêmica e diabetes mellitus. Após o desenvolvimento do modelo e validação cruzada, foram mantidos os seguintes oito preditores: D-dímero, Uréia, Índice de comorbidade de Charlson, oximetria de pulso, frequência respiratória, desidrogenase láctica, RDW e escore radiológico RALE. O intercepto e a inclinação corrigidas pelo viés foram de -0,0004 e 1,079, respectivamente, e o erro médio de previsão foi de 0,028. A área sob curva ROC foi de 0,795 e a variância explicada foi de 0,289. Conclusão: O modelo prognóstico foi considerado bom o suficiente para ser recomendado para uso clínico em pacientes internados. Foi desenvolvido uma calculadora que permite o usuário fazer previsões (QR code). O benefício clínico e o desempenho em diferentes cenários ainda não são conhecidos. Palavras chaves: COVID-19, Prognóstico, Estado Terminal. Palavras-chave: COVID-19, Prognóstico, Estado Terminal, Mortalidade, Modelos de previsão. Conflitos de interesse: Os autores informam que não há conflito de interesses. Ética e financiamentos: O registro e aprovação do Comitê de Ética do INI-Fiocruz pode ser acessado em https://plataformabrasil.saude.gov.br/login.jsf com número CAAE 39520820.7.0000.5262. Não houve financiamento específico para este projeto.
Scrub typhus is a poorly studied but life-threatening disease caused by the intracellular bacteriumOrientia tsutsugamushi(Ot). Cellular and humoral immunity inOt-infected patients is not long-lasting, waning as early as one-year post-infection; however, its underlying mechanisms remain unclear. To date, no studies have examined germinal center (GC) or B cell responses inOt-infected humans or experimental animals. This study was aimed at evaluating humoral immune responses at acute stages of severeOtinfection and possible mechanisms underlying B cell dysfunction. Following inoculation withOtKarp, a clinically dominant strain known to cause lethal infection in C57BL/6 mice, we measured antigen-specific antibody titers, revealing IgG2c as the dominant isotype induced by infection. Splenic GC responses were evaluated by immunohistology, co-staining for B cells (B220), T cells (CD3), and GCs (GL-7). Organized GCs were evident at day 4 post-infection (D4), but they were nearly absent at D8, accompanied by scattered T cells throughout splenic tissues. Flow cytometry revealed comparable numbers of GC B cells and T follicular helper (Tfh) cells at D4 and D8, indicating that GC collapse was not due to excessive death of these cell subtypes at D8. B cell RNAseq analysis revealed significant differences in expression of genes associated with B cell adhesion and co-stimulation at D8 versus D4. The significant downregulation ofS1PR2(a GC-specific adhesion gene) was most evident at D8, correlating with disrupted GC formation. Signaling pathway analysis uncovered downregulation of 71% of B cell activation genes at D8, suggesting attenuation of B cell activation during severe infection. This is the first study showing the disruption of B/T cell microenvironment and dysregulation of B cell responses duringOtinfection, which may help understand the transient immunity associated with scrub typhus.
Mostafa Naseri-Nezhad, Mahla Asadian, Mohammad Khalifeh Gholi
et al.
Abstract Background Immigration is considered as a risk factor of tuberculosis (TB). Qom province receives millions of pilgrims and significant numbers of immigrants each year. Most of the immigrants to Qom, arrive from neighboring TB-endemic countries. This study aimed to identify the current circulating Mycobacterium tuberculosis genotypes in Qom province using 24-locus MIRU-VNTR genotyping. Methods Eighty six M. tuberculosis isolates were collected during 2018–2022 from patients referring to Qom TB reference laboratory. The DNA of isolates was extracted and followed by 24 loci MIRU-VNTR genotyping which performed using the web tools available on MIRU-VNTRplus. Results Of 86 isolates, 39 (45.3%) were of Delhi/CAS genotype, 24 (27.9%) of NEW-1, 6 (7%) of LAM, 6 (7%) of Beijing, 2 (2.3%) of UgandaII, 2 (2.3%) of EAI, 1 of S (1.2%) and 6 (7%) did not match with profiles present in MIRUVNTRplus database. Conclusions About half of the isolates belong to Afghan immigrants; which warns health policy makers about the future situation of TB in Qom. Also, the similarity of Afghan and Iranian genotypes provides evidence that immigrants partake in the circulation of M. tuberculosis. This study underpin the studies about the circulating M. tuberculosis genotypes, their geographical distribution, the association of TB risk factors with these genotypes and the impact of immigration on the situation of TB in Qom province.
Cham-mill Kim, Victor Zhao, Maeve Brito De Mello
et al.
ABSTRACT: Objectives: Although the World Health Organization recommends ‘frequent’ screening of sexually transmitted infections (STI) for people who use pre-exposure prophylaxis for HIV, there is no evidence for optimal frequency. Methods: We searched five databases and used random-effects meta-analysis to calculate pooled estimates of STI test positivity. We narratively synthesized data on secondary outcomes, including adherence to recommended STI screening frequency and changes in STI epidemiology. Results: Of 7477 studies, we included 38 for the meta-analysis and 11 for secondary outcomes. With 2-3 monthly STI screening, the pooled positivity was 0.20 (95% confidence interval [CI]: 0.15-0.25) for chlamydia, 0.17 (95% CI: 0.12-0.22) for gonorrhea, and 0.07 (95% CI: 0.05-0.08) for syphilis. For chlamydia and gonorrhea, the positivity was approximately 50% and 75% lower, respectively, in studies that screened 4-6 monthly vs 2-3 monthly. There was no significant difference in the positivity for syphilis in studies that screened 4-6 monthly compared to 2-3 monthly. Adherence of clients to recommended screening frequency varied significantly (39-94%) depending on population and country. Modeling studies suggest more frequent STI screening could reduce incidence. Conclusion: Although more frequent STI screening could reduce delayed diagnoses and incidence, there remain significant knowledge gaps regarding the optimal STI screening frequency.
Hannah K. Brosnan, Karen W. Yeh, Padma S. Jones
et al.
In Los Angeles County, California, USA, public health surveillance identified 118 mpox cases among persons experiencing homelessness (PEH) during July–September 2022. Age and sex were similar for mpox case-patients among PEH and in the general population. Seventy-one (60%) PEH mpox case-patients were living with HIV, 35 (49%) of them virally suppressed. Hospitalization was required for 21% of case-patients because of severe disease. Sexual contact was likely the primary mode of transmission; 84% of patients reported sexual contact <3 weeks before symptom onset. PEH case-patients lived in shelters, encampments, cars, or on the street, or stayed briefly with friends or family (couch surfed). Some case-patients stayed at multiple locations during the 3-week incubation period. Public health follow-up and contact tracing detected no secondary mpox cases among PEH in congregate shelters or encampments. Equitable efforts should continue to identify, treat, and prevent mpox among PEH, who often experience severe disease.
We report the rapid emergence of severe acute respiratory syndrome coronavirus 2 lineages B.1.619 and B.1.620 in South Korea. The surge in frequency in a relatively short time emphasizes the need for ongoing monitoring for new lineages to track potential increases in transmissibility and disease severity and reductions in vaccine efficacy.
Laura Vaughan, Darlene Veruttipong, Jonathan G. Shaw
et al.
Abstract Background COVID-19 studies are primarily from the inpatient setting, skewing towards severe disease. Race and comorbidities predict hospitalization, however, ambulatory presentation of milder COVID-19 disease and characteristics associated with progression to severe disease is not well-understood. Methods We conducted a retrospective chart review including all COVID-19 positive cases from Stanford Health Care (SHC) in March 2020 to assess demographics, comorbidities and symptoms in relationship to: 1) their access point of testing (outpatient, inpatient, and emergency room (ER)) and 2) development of severe disease. Results Two hundred fifty-seven patients tested positive: 127 (49%), 96 (37%), and 34 (13%) at outpatient, ER and inpatient, respectively. Overall, 61% were age < 55; age > 75 was rarer in outpatient setting (11%) than ER (14%) or inpatient (24%). Most patients presented with cough (86%), fever/chills (76%), or fatigue (63%). 65% of inpatients reported shortness of breath compared to 30–32% of outpatients and ER patients. Ethnic/minority patients had a significantly higher risk of developing severe disease (Asian OR = 4.8 [1.6–14.2], Hispanic OR = 3.6 [1.1–11.9]). Medicare-insured patients were marginally more likely (OR = 4.0 [0.9–17.8]). Other factors associated with developing severe disease included kidney disease (OR = 6.1 [1.0–38.1]), cardiovascular disease (OR = 4.7 [1.0–22.1], shortness of breath (OR = 5.4 [2.3–12.6]) and GI symptoms (OR = 3.3 [1.4–7.7]; hypertension without concomitant CVD or kidney disease was marginally significant (OR = 2.3 [0.8–6.5]). Conclusions Early widespread symptomatic testing for COVID-19 in Silicon Valley included many less severely ill patients. Thorough manual review of symptomatology reconfirms the heterogeneity of COVID-19 symptoms, and challenges in using clinical characteristics to predict decline. We re-demonstrate that socio-demographics are consistently associated with severity.
Ahmad Safapour, Arash Alghasi, Farhad Abolnezhadian
Introduction: Immune thrombocytopenic purpura (ITP) is known as the most important cause of sudden drop in platelet count among children. The acute form of unexpected drop in platelet count in children calls for treatment with medications such as corticosteroids, intravenous immunoglobulin (IVIg), and Rho(D) immunoglobulin (anti-DIG). Most of the previous studies have accordingly compared short-term therapeutic outcomes of steroids with those of IVIg. In some cases, IVIg has led to better results. However, there are few studies on the long-term treatment effects of both medicine categories. Objectives: This study was aimed to evaluate the therapeutic effects and recurrence rate (RR) of corticosteroids, IVIg, or both in the long-term to find the best and most effective treatment for these patients. Patients and Methods: A total of 188 children diagnosed with acute ITP were admitted to the hematology departments of Shafa and Baghaei hospitals of Ahvaz, Khuzestan, Iran. The therapeutic consequences and RRs of corticosteroids, IVIg, or both were compared within one year. Results: Comparing treatments employing corticosteroids and IVIg in children having acute ITP in terms of the long-term treatment outcomes showed no statistically significant difference. In addition, the findings revealed that 34% of the patients had experienced recurrence within one year with no remarkable difference between both drug groups. Conclusion: The long-term therapeutic outcomes in both medicine categories were not significantly different. Therefore, given the world’s current economic conditions and inadequate supply of all medicines, it seems more rational to use the least expensive drugs.
Specialties of internal medicine, Infectious and parasitic diseases
Rossely Paulo, Miguel Brito, Pedro Van-Dunem
et al.
The prevalence of Loa loa, Onchocerca volvulus and Wuchereria bancrofti infections in an under-surveyed area of Bengo Province, Angola, was determined by surveying 22 communities with a combination of clinical, serological and DNA diagnostics. Additional information was collected on participants' duration of residency, access to mass drug administration, knowledge of insect vectors and use of bednets. A total of 1616 individuals (38.1% male: 61.9% female), with an average age of 43 years, were examined. For L. loa, 6.2% (n = 100/16616) individuals were found to have eyeworm, based on the rapid assessment procedure for loiasis (RAPLOA) surveys, and 11.5% (n =178/1543) based on nested PCR analyses of venous blood. L. loa prevalences in long-term residents (>10 years) and older individuals (>60 years) were significantly higher, and older men with eyeworm were better informed about Chrysops vectors. For O. volvulus, 4.7% (n = 74/1567) individuals were found to be positive by enzyme-linked immunosorbent assay (Ov 16 ELISA), with only three individuals reporting to have ever taken ivermectin. For W. bancrofti, no infections were found using the antigen-based immunochromatographic test (ICT) and real-time PCR analysis; however, 27 individuals presented with lymphatic filariasis (LF) related clinical conditions (lymphoedema = 11, hydrocoele = 14, both = 2). Just under half (45.5%) of the participants owned a bednet, with the majority (71.1%) sleeping under it the night before. Our approach of using combination diagnostics reveals the age-prevalence of loiasis alongside low endemicity of onchocerciasis and LF. Future research foci should be on identifying opportunities for more cost-effective ways to eliminate onchocerciasis and to develop innovative surveillance modalities for clinical LF for individual disease management and disability prevention.
Abstract Cefiderocol, formerly S-649266, is a first in its class, an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many β-lactamases, including extended spectrum β-lactamases such as CTX-M, and carbapenemases such as KPC, NDM, VIM, IMP, OXA-23, OXA-48-like, OXA-51-like and OXA-58. Cefiderocol’s spectrum of activity encompasses both lactose-fermenting and non-fermenting Gram-negative pathogens, including carbapenem-resistant Enterobacterales. Cefiderocol recently received US Food and Drug Administration approval for the treatment of complicated urinary tract infections, including pyelonephritis, and is currently being evaluated in phase III trials for nosocomial pneumonia and infections caused by carbapenem-resistant Gram-negative pathogens. The purpose of this article is to review existing data on the mechanism of action, microbiology, pharmacokinetics, pharmacodynamics, efficacy, and safety of cefiderocol to assist clinicians in determining its place in therapy.