Trop. Med. Infect. Dis., Volume 7, Issue 3 (March 2022) – 17 articles

Introduction: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. Methods: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. Results: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO₂)/fraction of inspired oxygen (FiO₂) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO₂/FiO₂ ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. Conclusions: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir. Full article

The “bench to bedside” (BTB) paradigm of translational medicine (TM) assumes that medical progress emanates from basic science discoveries transforming clinical therapeutic models. However, a recent report found that most published medical research is false due, among other factors, to small samples, inherent bias and inappropriate statistical applications. Translation-blocking factors include the validity (or lack thereof) of the underlying pathophysiological constructs and related therapeutic paradigms and adherence to faulty traditional beliefs. Empirical discoveries have also led to major therapeutic advances, but scientific dogma has retrospectively retranslated these into the BTB paradigm. A review of the history of intravenous (I.V.) and oral therapy for cholera and NDDs illustrates some fallacies of the BTB model and highlights pitfalls blocking translational and transformative progress, and retro-translational factors, including programmatic modifications of therapeutic advances contradicting therapeutic paradigms and medical economic factors promoting more expensive and profitable medical applications inaccessible to resource-limited environments. Full article

Nuh, Haryana, is one of India’s least developed districts. To improve TB case notifications, ZMQ carried out an active case-finding (ACF) intervention conducted by community health workers (MIRAs) using a digital TB storytelling platform to create TB awareness in the community. The combined storytelling and ACF intervention were conducted house-to-house or in community group settings. Steps included (A) the development of digital TB awareness-raising stories using a participatory approach called Story Labs; (B) the implementation of the intervention; and (C) process, outcome, and impact evaluation of these activities. Six digital stories were created and used during ACF in which 19,345 people were screened and 255 people were diagnosed with TB. Of 731 participants surveyed, the stories were well received and resulted in an increase in TB knowledge. ACF activities resulted in a 56% increase in bacteriologically confirmed TB and an 8% decrease in all forms of TB compared to baseline. All form notifications may have been impacted by COVID-19 lockdowns. Digital TB storytelling can improve TB awareness and knowledge, particularly for low-literacy populations. The use of these tools may benefit ACF campaigns and improve TB case finding. Full article

Tuberculosis (TB), caused by bacilli from the Mycobacterium tuberculosis complex, remains a serious global public health problem, representing one of the main causes of death from infectious diseases. About one quarter of the world’s population is infected with Mtb and has a latent TB infection (LTBI). According to the World Health Organization (WHO), an LTBI is characterized by a lasting immune response to Mtb antigens without any TB symptoms. Current LTBI diagnoses and treatments are based on this simplified definition, although an LTBI involves a broad range of conditions, including when Mtb remains in the body in a persistent form and the immune response cannot be detected. The study of LTBIs has progressed in recent years; however, many biological and medical aspects of an LTBI are still under discussion. This review focuses on an LTBI as a broad spectrum of states, both of the human body, and of Mtb cells. The problems of phenotypic insusceptibility, diagnoses, chemoprophylaxis, and the necessity of treatment are discussed. We emphasize the complexity of an LTBI diagnosis and its treatment due to its ambiguous nature. We consider alternative ways of differentiating an LTBI from active TB, as well as predicting TB reactivation based on using mycobacterial “latency antigens” for interferon gamma release assay (IGRA) tests and the transcriptomic analysis of human blood cells. Full article

Malignant syphilis (MS) is a rare form of secondary syphilis with grotesque skin lesions, systemic manifestation and life-threatening complications. This article presents a case of MS in an immunocompetent 41-year-old female, who initially manifested with a generalized nonpruritic erythematous rash and systemic symptoms. She was mistreated for generalized impetigo and hepatitis attributed to chronic alcoholism. After partial recovery and a 3-month latent period, she developed infiltrated plaques with crusts on the trunk, head and neck; pharyngitis and laryngeal lesions; generalized lymphadenopathy and nonspecific systemic symptoms. Serologic tests confirmed syphilis, and cerebrospinal fluid analyses indicated the presence of anti-treponemal antibodies. Urine drug screening was positive for cannabinoids. The polymerase chain reaction from skin biopsy samples identified T. pallidum, confirmed with Warthin-Starry staining. Immunohistochemical analysis was uncharacteristic. Tertiary syphilis, neurosyphilis, ocular syphilis and otosyphilis were excluded. However, the patient was treated for neurosyphilis with benzylpenicillin (18 million IU intravenously daily, 14 days) and corticosteroids. No Jarisch-Herxheimer reaction occurred. Ten months after treatment, residual scars were visible, and 1 year later, she attempted suicide. Since MS can resemble other diseases, it should be suspected in a mentally ill patient with chronic drug abuse, systemic nonspecific manifestations and dermatological abnormalities, including the head and neck region. Full article

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease commonly diagnosed in the Volga Federal District (VFD). HFRS is caused by Puumala orthohantavirus (PUUV), and this virus is usually detected in bank voles as its natural host (Myodes glareolus). The PUUV genome is composed of the single-stranded, negative-sense RNA containing three segments. The goal of the current study is to identify genome variants of PUUV strains circulating in bank voles captured in the Udmurt Republic (UR) and Ulyanovsk region (ULR). The comparative and phylogenetic analysis of PUUV strains revealed that strains from Varaksino site UR are closely related to strains previously identified in the Pre-Kama area of the Republic of Tatarstan (RT), whilst strains from Kurlan and Mullovka sites ULR are similar to strains from the Trans-Kama area of the RT. It was also found that Barysh ULR strains form a separate distinct group phylogenetically equidistant from Varaksino and Kurlan–Mullovka groups. The identified groups of strains can be considered as separate sub-lineages in the PUUV Russian genetic lineage. In addition, the genomes of the strains from the UR, most likely, were formed as a result of reassortment. Full article

The study of the spatial differentiation of COVID-19 in cities and its driving mechanism is helpful to reveal the spatial distribution pattern, transmission mechanism and diffusion model, and evolution mechanism of the epidemic and can lay the foundation for constructing the spatial dynamics model of the epidemic and provide theoretical basis for the policy design, spatial planning and implementation of epidemic prevention and control and social governance. Geodetector (Origin version, Beijing, China) is a great tool for analysis of spatial differentiation and its influencing factors, and it provides decision support for differentiated policy design and its implementation in executing the city-specific policies. Using factor detection and interaction analysis of Geodetector, 15 indicators of economic, social, ecological, and environmental dimensions were integrated, and 143 cities were selected for the empirical research in China. The research shows that, first of all, risks of both infection and death show positive spatial autocorrelation, but the geographical distribution of local spatial autocorrelation differs significantly between the two. Secondly, the inequalities in urban economic, social, and residential environments interact with COVID-19 spatial heterogeneity, with stronger explanatory power especially when multidimensional inequalities are superimposed. Thirdly, the spatial distribution and spread of COVID-19 are highly spatially heterogeneous and correlated due to the complex influence of multiple factors, with factors such as Area of Urban Construction Land, GDP, Industrial Smoke and Dust Emission, and Expenditure having the strongest influence, the factors such as Area of Green, Number of Hospital Beds and Parks, and Industrial NOx Emissions having unignorable influence, while the factors such as Number of Free Parks and Industrial Enterprises, Per-GDP, and Population Density play an indirect role mainly by means of interaction. Fourthly, the factor interaction effect from the infected person’s perspective mainly shows a nonlinear enhancement effect, that is, the joint influence of the two factors is greater than the sum of their direct influences; but from the perspective of the dead, it mainly shows a two-factor enhancement effect, that is, the joint influence of the two factors is greater than the maximum of their direct influences but less than their sum. Fifthly, some suggestions are put forward from the perspectives of building a healthy, resilient, safe, and smart city, providing valuable reference and decision basis for city governments to carry out differentiated policy design. Full article

During the COVID-19 pandemic, an excess of all-cause mortality has been recorded in several countries, including Peru. Most excess deaths were likely attributable to COVID-19. In this study, we compared the excess all-cause mortality and COVID-19 mortality in 25 Peruvian regions to determine whether most of the excess deaths in 2020 were attributable to COVID-19. Excess deaths were calculated as the difference between the number of observed deaths from all causes during the COVID-19 pandemic (in 2020) and the number of expected deaths in 2020 based on a historical from recent years (2017–2019). Death data were retrieved from the Sistema Informatico Nacional de Defunciones (SINADEF) at the Ministry of Health of Peru from January 2017 to December 2020. Population counts were obtained from projections from Peru’s Instituto Nacional de Estadística e Informática (INEI). All-cause excess mortality and COVID-19 mortality were calculated by region per 100,000 population. Spearman’s test and linear and multiple regression models were used to estimate the correlation between excess all-cause mortality and COVID-19 mortality per 100,000 population. Excess all-cause death rates varied widely among regions (range: 115.1 to 519.8 per 100,000 population), and COVID-19 mortality ranged between 83.8 and 464.6 per 100,000 population. There was a correlation between the all-cause excess mortality and COVID-19 mortality (r = 0.90; p = 0.00001; y = 0.8729x + 90.808; R² = 0.84). Adjusted for confounding factors (mean age in the region, gender balance, and number of intensive care unit (ICU) beds), the all-cause excess mortality rate was correlated with COVID-19 mortality rate (β = 0.921; p = 0.0001). These findings suggest that most of the excess deaths in Peru are related to COVID-19. Therefore, these findings can help decision-makers to understand the high COVID-19 mortality rates in Peru. Full article

Mounting evidence indicates that new arrhythmic events frequently occur during and after coronavirus disease (COVID-19), posing additional mortality risk in older-aged and critically ill patients. However, the underlying mechanisms and cardio pathological substrates of COVID-related arrhythmias have not been clarified yet. Here, we report findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and genes in the atrioventricular node (AV-node) of a cardiac conduction system, pointing to its direct infection as a possible arrhythmogenic factor. Full article

Background: Widespread and rapidly emerging multidrug-resistant uropathogens, particularly carbapenem-resistant pathogens, are a public health concern that impairs the determination of empirical therapy. This study aims to evaluate the antimicrobial susceptibility profile and factors associated with catheter-associated urinary tract infection (CA-UTI). Method: This retrospective study was carried out on a total of 779 urine cultures over a 3-year period. Antimicrobial sensitivity tests were performed using the standard Kirby–Bauer disk diffusion method. Results: The prevalence of CA-UTI in our study was 12.7%; a total of 47% of cultures had multi-drug-resistant (MDR) uropathogens, and 13% of the cultures showed extended-spectrum beta-lactamase (ESBL)-producing pathogens. Elderly patients, intensive care unit admissions, and associated comorbidities were correlated with higher rates of CA-UTI caused by multidrug-resistant uropathogens (p < 0.021, 95% CI: 0.893–2.010), (p < 0.008, 95% CI: 1.124–5.600), (p < 0.006, 95% CI: 0.953–2.617). Latex catheters and prolonged catheterization time were associated with increased risk of CA-UTI (p < 0.0001, 95% CI: 0.743–1.929, p = 0.012, 95% CI: 0.644–4.195). Patients with MDR uropathogens had prolonged hospital stays, i.e., 49% in more than 2 weeks (p < 0.04, 95% CI: 0.117–3.084). E. coli was the most common pathogen (26.3%), followed by Acinetobacter baumannii (24.3%). Acinetobacter baumannii showed the highest MDR pattern (88.5%), followed by Pseudomonas aeruginosa (68%). Acinetobacter baumannii and Klebsiella pneumoniae were associated with prolonged hospital stays (>2 w at 73.1 and 69%, respectively). Higher antimicrobial resistance against ceftriaxone (85.7%), meropenem (54.3%), ertapenem (50%), ciprofloxacin (58.5%), amikacin (27%), tigecycline (7.6%), and colistin (4.6%), was revealed in the study. Conclusion: Aside from the higher antimicrobial resistance against cephalosporins and fluoroquinolones, the findings of this study revealed that carbapenems are facing increased rates of antimicrobial resistance and are associated with substantial morbidity, prolonged hospitalization times, and increased healthcare expenses. Full article

Central nervous system (CNS) infections constitute a life-threatening condition, especially in children. Treatment limitations exist for drug-resistant CNS bacterial infections. Inadequate CNS penetration and intravenous (IV) antibiotic treatment failure represent a major clinical challenge. However, patients with antibiotic-resistant bacterial CNS infections may benefit from intrathecal (IT) or intraventricular (IVT) colistin. The authors aimed to assess the safety and effectiveness of IT/IVT colistin therapy in the pediatric population, with or without other antibiotics, for the treatment of antibiotic-resistant CNS infections. A comprehensive literature search was conducted using the electronic databases of PubMed, Ovid, and Embase for relevant articles using the following terms: “Colistin”, “CNS infection”, and “Outcome”, as well as their combinations. The retrieved articles were filtered by age (Child), language (English), route of administration (IT/IVT), and species (Humans). The present systematic review comprised 20 articles that included 31 children (19; 61.2% were boys) with multidrug-resistant CNS infection. Their ages ranged from less than one month to 18 years (median: 9 months). Acinetobacter baumannii was the main causative organism in 22 patients (70.9%), and infection occurred mainly after neurosurgical interventions (83.8%). An external ventricular drain was inserted to administer colistin into the ventricular system in 29 cases (93.5%). The median duration for colistin therapy was 18 days. Twenty-three patients (74%) recovered, while five patients (16%) had residual disability, and three patients (10%) died. The authors concluded that IT/IVT colistin therapy is safe and effective as either the primary or adjunct treatment for antibiotic-resistant cases with CNS infection. Full article

Erythema nodosum leprosum (ENL) is an acute immune complex-mediated condition of the dermis, subcutaneous tissue, and other tissues seen in patients with multibacillary (MB) leprosy, causing severe impairment to patients’ quality of life. To date, there is no standard diagnostic criteria for ENL. We aimed to study the diagnostic value and accuracy of Neutrophil-to-Lymphocyte ratio (NLR), Lymphocyte-to-Monocyte ratio (LMR), and Platelet-to-Lymphocyte ratio (PLR) in diagnosing ENL. This is an analytic retrospective study with a cross-sectional design that describes the distribution and clinical characteristics of all newly diagnosed MB patients of Dr. Soetomo General Hospital Surabaya in the years 2018–2020. NLR, LMR, and PLR were calculated for all patients, and a receiver operating characteristic curve (ROC) was generated to identify the cut-off points. Among a total of 182 patients with MB leprosy, 22 cases (12.09%) were reported with ENL. WBC, neutrophils, monocytes, and thrombocytes showed a positive correlation with the incidence of ENL, but not lymphocytes. The NLR cut-off point for the diagnosis of ENL was 4.99 (sensitivity 86.4%, specificity 82.5%, accuracy 82.97), while that of PLR was 237.46 (sensitivity 63.6%, specificity 73.1%, accuracy 71.98%). LMR had poor sensitivity and specificity levels of 50% and 28.7%, with cut-off point of 2.28 and accuracy of 31.32%. These results suggest that NLR and PLR could be potential biomarkers for the diagnosis of ENL. Full article

Influenza is one of the most common respiratory virus infections. We analyzed hemagglutinin (HA) and neuraminidase (NA) gene segments of viruses isolated from influenza patients who visited Evercare Hospital Dhaka, Bangladesh, in early 2020 immediately before the coronavirus disease 2019 (COVID-19) pandemic. All of them were influenza virus type A (IAV) H1N1pdm. Sequence analysis of the HA segments of the virus strains isolated from the clinical specimens and the subsequent phylogenic analyses of the obtained sequences revealed that all of the H1N1pdm recent subclades 6B.1A5A + 187V/A, 6B.1A5A + 156K, and 6B.1A5A + 156K with K209M were already present in Bangladesh in January 2020. Molecular clock analysis results suggested that the subclade 6B.1A5A + 156K emerged in Denmark, Australia, or the United States in July 2019, while subclades 6B.1A5A + 187V/A and 6B.1A5A + 156K with K209M emerged in East Asia in April and September 2019, respectively. On the other hand, sequence analysis of NA segments showed that the viruses lacked the H275Y mutation that confers oseltamivir resistance. Since the number of influenza cases in Bangladesh is usually small between November and January, these results indicated that the IAV H1N1pdm had spread extremely rapidly without acquiring oseltamivir resistance during a time of active international flow of people before the COVID-19 pandemic. Full article

COVID-19 has proved to be a serious, and consequential disease that has affected millions of people globally. Previously, the adverse effects of proton pump inhibitors (PPI) have been observed with increasing the risk of pneumonia and COVID-19. This meta-analysis aims to address the relationship between the use of PPI and the severity of COVID-19 infection. We conducted a systemic literature search from PUBMED, Science Direct, and Cinahl from December 2019 to January 2022. Published and unpublished randomized control trials and cohort studies were included. Review Manager was used for all statistical analyses. In total, 14 studies were included in this systemic review and meta-analysis. Outcomes of interest include: (1) susceptibility of COVID-19 infection and (2) severity of COVID-19 (defined as the composite of poor outcomes: ICU admission, need for oxygen therapy, need for a ventilator, or death), and (3) mortality due to COVID-19. PPI use was marginally associated with a nominal but statistically significant increase in the risk of COVID-19 infection (OR 1.05 [1.01, 1.09]; I² 97%, p = 0.007). PPI use also increased the risk of the composite poor outcome (OR 1.84 [1.71, 1.99]; I² 98%, p < 0.00001) and mortality (OR 1.12 [1.00, 1.25]; I² 84%, p = 0.05) in patients with COVID-19. Full article

Since 2008, Bangladesh has had a school-based deworming programme to combat soil-transmitted helminth (STH) infection among school-aged children (SACs). Existing programmes have trouble reaching SACs, especially those out-of-school (OSCs). This study evaluated deworming coverage among school going children (SGCs) and OSCs in two Nilphamari sub-districts. It also evaluated community knowledge on STH control and deworming coverage in both areas for all SACs. Saidpur (intervention) and Kishoregonj (control) sub-districts, in Nilphamari, were surveyed in December 2019. The survey included SACs and their parents. Among SGCs, the intervention group (89.0%) had higher deworming coverage than the control group (75.5%). In the intervention group, 59.9% of OSCs received the deworming tablet versus 24.6% in the control group. Community involvement activities including door-to-door visits, courtyard gatherings, and miking benefited both SACs and their primary caregivers. SACs living in the intervention region, awareness of the last pill distribution date, and caregivers observing BRAC workers in action, were linked to SAC deworming coverage. Re-strategizing the deworming programme to include the OSCs is vital and suggests timely action. Building community awareness and periodic epidemiological assessment can further facilitate an improved drug intake. Full article