Trop. Med. Infect. Dis., Volume 9, Issue 9 (September 2024) – 35 articles

Vibrio cholerae, a Gram-negative bacterium, is widely known as the cause of cholera, an acute diarrheal disease. While only certain strains are capable of causing cholera, non-O1/non-O139 V. cholerae strains (NOVC) can lead to non-pathogenic colonization or mild illnesses such as gastroenteritis. In immunocompromised patients, however, NOVC can cause severe infections, including rare cases of bacteremia, especially in those with underlying conditions like liver disease, hematologic disorders, and malignancies. This case report presents a rare instance of NOVC bacteremia in a 71-year-old patient with advanced lung cancer, illustrating the clinical presentation, diagnostic challenges, and treatment interventions required. The patient presented with fever, asthenia, and confusion, and was found to have bacteremia caused by NOVC, confirmed through blood cultures and molecular analysis. Treatment with intravenous ceftriaxone and ciprofloxacin led to a rapid clinical improvement and resolution of the infection. This case, along with an overview of similar incidents, underscores the importance of considering NOVC in differential diagnoses for immunocompromised patients presenting with fever, and highlights the necessity of timely diagnosis and targeted antimicrobial therapy to achieve favorable outcomes. Full article

Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin’s peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin’s peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs. Full article

WHO promotes the implementation of a comprehensive strategy to control and eliminate schistosomiasis through preventive chemotherapy, snail control, clean water supply, improved sanitation, behaviour change interventions, and environmental management. The transmission of schistosomiasis involves infected definitive hosts (humans or animals) excreting eggs that hatch (miracidia), which infect freshwater snail vectors (also referred to as intermediate snail hosts) living in marshlands, ponds, lakes, rivers, or irrigation canals. Infective larvae (cercariae) develop within the snail, which, when released, may infect humans and/or animals in contact with the water. Snail control aims to interrupt the transmission cycle of the disease by removing the vector snails and, by so doing, indirectly improves the impact of the preventive chemotherapy by reducing reinfection. Snail control was, for many years, the only strategy for the prevention of schistosomiasis before preventive chemotherapy became the primary intervention. Snails can be controlled through various methods: environmental control, biological control, and chemical control. The chemical control of snails has proven to be the most effective method to interrupt the transmission of schistosomiasis. The current review aims to describe the vector snails of human schistosomiasis, present the chemicals and strategies for the control of snails, the challenges with the implementation, and the future needs. Snail control can play a key role in reducing schistosomiasis transmission and, thus, complements other interventions for disease control. There is a need to develop new molluscicide products or new formulations and methods of applications for existing molluscicides that would target snail vectors more specifically. Full article

Schistosomiasis is a parasitosis caused by trematodes of the genus Schistosoma. Humans are infected when coming into contact with freshwater containing the parasites’ infective stages, which are amplified through freshwater-dwelling snails acting as intermediate hosts. Schistosomiasis has posed significant problems for troops exposed to freshwater in endemic regions ever since the Napoleonic wars. Schistosomiasis has substantial differences in clinical presentation, depending on the type of parasite, intensity of infection and reinfection, clinical form, and disease stage. It can remain undiagnosed for long periods of time, with well-known long-term morbidity and mortality risks. The diagnosis of schistosomiasis depends on its stage and relays on several tests, all with limitations in sensitivity and specificity. The diagnostic gold standard is the detection of eggs in urine, feces, or tissue biopsies, but this can raise problems in patients such as military personnel, in which the worm burden is usually low. Praziquantel is the drug of choice for schistosomiasis. Currently, there is no available commercial vaccine against any Schistosoma parasite. Avoiding freshwater exposure is the best prevention. Herein, we review the clinical presentation, diagnosis, treatment, and prevention of schistosomiasis in the military. This information may decrease the impact of schistosomiasis on this particular professional group. Full article

During population-based HIV impact assessments (PHIAs), some participants who self-reported testing HIV-positive (PSRP) tested negative in one or more subsequent survey HIV tests. These unexpected discrepancies between their self-reported results and the survey results draw into question the validity of either the self-reported status or the test results. We analyzed PSRP with negative test results aged 15–59 years old using data collected from 2015 to 2021 in 13 countries, assessing prevalence, self-report status, survey HIV status, viral load, rapid tests and confirmatory tests, and answers to follow-up questions (such as years on treatment). Across these surveys, 19,026 participants were PSRP, and 256 (1.3%) of these were concluded to be HIV-negative after additional survey-based testing and review. PSRP determined to be HIV-negative trended higher in countries with a higher HIV prevalence, but their number was small enough that accepting self-reported HIV-positive status without testing would not have significantly affected the prevalence estimates for HIV or viral load suppression. Additionally, using more detailed information for Uganda, we examined 107 PSRP with any negative test results and found no significant correlation with years on treatment or age. Using these details, we examined support for the possible reasons for these discrepancies beyond misdiagnosis and false reporting. These findings suggest that those conducting surveys would benefit from a nuanced understanding of HIV testing among PSRP to conduct surveys ethically and produce high-quality results. Full article

Visceral leishmaniasis (VL) is a neglected tropical disease that is potentially fatal when untreated. Current diagnostic methods have limitations that contribute to ongoing transmission and poor prognosis. Thus, new tests are needed to provide quick, accurate diagnoses and evaluate clinical progression and treatment efficacy. The monokine induced by interferon-gamma (MIG) and interferon-gamma-inducible protein 10 (IP-10) has been associated with the host susceptibility to VL with potential diagnostic and prognostic purposes. We performed a systematic review using four search databases (Scopus, PubMed, Web of Science, and MEDLINE) to identify studies assessing MIG and IP-10 as potential biomarkers in patients with VL across various clinical conditions. A total of 13 studies were potentially eligible and included in this review. The articles, in general, reveal that the chemokines MIG and IP-10 are elevated in response to infection by Leishmania spp., acting on the host’s resistance to the development of the disease. They are associated with asymptomatic conditions and after VL treatment, and this relationship can be observed in both immunocompetent and immunocompromised individuals. Consequently, these chemokines hold relevance in the diagnoses and appropriate management of individuals with VL. Full article

Miltefosine, an orally administered drug, is an important component of the therapeutic arsenal against visceral and mucosal forms of leishmaniasis. However, data regarding the safety and tolerability of miltefosine treatment for cutaneous leishmaniasis (CL) are relatively limited. The aim of this study was to evaluate the tolerability, safety, and adverse events (AEs) of miltefosine treatment in patients with CL. In this cohort study, we reviewed the medical records of all miltefosine-treated patients between 1 January 2016 and 31 December 2022, at Israel Defense Forces military dermatology clinics and the dermatology and Tropical Medicine Clinics at Chaim Sheba Medical Center, Ramat-Gan, Israel. A total of 68 patients (54 males, 79%) with a median age of 30.3 ± 15.6 years (range: 18–88) were included in this study. Leishmania species were identified as L. major (n = 37, 54.4%), L. tropica (n = 12, 17.6%), L. braziliensis (n = 18, 26.5%), and L. infantum (n = 1, 1.5%) using polymerase chain reaction (PCR). Miltefosine tablets were administered orally at a dose of 50 mg, three times daily, for 28 days. Overall, 44 patients (65%) completed the 28-day treatment, and the remaining patients required dose reduction or early discontinuation of treatment. AEs (of any degree) were common, reported in 91% of patients. Both previously reported and previously unreported AEs were documented. Gastrointestinal symptoms (66.1%) and malaise (23.5%) typically occurred during the first two weeks of treatment and tended to subside. Other AEs, including acute renal failure (20.6%), sudden and severe pleuritic chest pain (7.6%), acne exacerbation (11.8%), suppuration of CL lesions (17.8%), and AEs related to the male genitourinary system (39.6% of males), typically occurred towards the end of treatment. The latter included testicular pain, epididymitis, diminution or complete absence of ejaculate, inability to orgasm, and impotence. Severe AEs necessitated treatment discontinuation (29.4%) or hospitalization (10.3%). URTI-like symptoms, arthritis, cutaneous eruption, pruritus, and laboratory abnormalities were also observed. Overall, the cure rate (for all patients combined) evaluated 3 months after the completion of treatment was 60%. The tolerability of miltefosine treatment for CL is low. Close clinical and laboratory monitoring is required during treatment, as severe AEs are not uncommon. As new insights regarding its toxicities emerge, further studies are required to define the role of miltefosine in the treatment of CL. Full article

Poultry carcasses may be reservoirs for the zoonotic transmission of antimicrobial-resistant bacteria to humans and pose a major public health hazard. During the isolation of Salmonella from poultry and other foods, many of the presumptive typical Salmonella colonies on xylose lysine deoxycholate (XLD) agar were found to lack the invA gene, which is the specific target gene for Salmonella spp. Therefore, the current study aimed to estimate the prevalence and antimicrobial resistance profiles of extensively drug-resistant invA-negative non-Salmonella isolates recovered from native Egyptian chicken carcasses as presumptive Salmonella colonies on XLD agar. The non-Salmonella isolates were detected in 84% (126/150) of the examined native Egyptian chicken carcasses and classified into five genera, with prevalence rates of 64% (96/150), 14% (21/150), 6.7% (10/150), 3.3% (5/150), and 1.3% (2/150) for Proteus, Citrobacter, Shigella, Pseudomonas, and Edwardsiella, respectively. One hundred and ninety-five invA-negative, non-verified presumptive Salmonella isolates were recovered and classified at the species level into Proteus mirabilis (132/195; 67.7%), Proteus vulgaris (11/195; 5.6%), Citrobacter freundii (26/195; 13.3%), Shigella flexneri (8/195; 4.1%), Shigella sonnei (6/195; 3.1%), Shigella dysenteriae (3/195; 1.5%), Pseudomonas fluorescens (6/195; 3.1%), and Edwardsiella tarda (3/195; 1.5%). All (195/195; 100%) of these isolates showed resistance against cefaclor and fosfomycin. Additionally, these isolates showed high resistance rates of 98%, 92.8%, 89.7%, 89.2%, 89.2%, 86.7%, 80%, 78.5%, 74.4%, and 73.9% against cephalothin, azithromycin, vancomycin, nalidixic acid, tetracycline, sulfamethoxazole/trimethoprim, cefepime, gentamicin, cefotaxime, and ciprofloxacin, respectively. Interestingly, all (195/195; 100%) of the identified isolates were resistant to at least five antibiotics and exhibited an average MAR (multiple antibiotic resistance) index of 0.783. Furthermore, 73.9% of the examined isolates were classified as extensively drug-resistant, with an MAR index equal to 0.830. The high prevalence of extensively drug-resistant foodborne Proteus, Citrobacter, Shigella, Pseudomonas, and Edwardsiella isolated from native chicken carcasses poses a great hazard to public health and necessitates more monitoring and concern about the overuse and misuse of antibiotics in humans and animals. This study also recommends the strict implementation of GHP (good hygienic practices) and GMP (good manufacturing practices) in the chicken meat supply chain to protect consumer health. Full article

Malaria and Typhoid fever are prevalent diseases in tropical regions, and both are exacerbated by unclear protocols, drug resistance, and environmental factors. Prompt and accurate diagnosis is crucial to improve accessibility and reduce mortality rates. Traditional diagnosis methods cannot effectively capture the complexities of these diseases due to the presence of similar symptoms. Although machine learning (ML) models offer accurate predictions, they operate as “black boxes” with non-interpretable decision-making processes, making it challenging for healthcare providers to comprehend how the conclusions are reached. This study employs explainable AI (XAI) models such as Local Interpretable Model-agnostic Explanations (LIME), and Large Language Models (LLMs) like GPT to clarify diagnostic results for healthcare workers, building trust and transparency in medical diagnostics by describing which symptoms had the greatest impact on the model’s decisions and providing clear, understandable explanations. The models were implemented on Google Colab and Visual Studio Code because of their rich libraries and extensions. Results showed that the Random Forest model outperformed the other tested models; in addition, important features were identified with the LIME plots while ChatGPT 3.5 had a comparative advantage over other LLMs. The study integrates RF, LIME, and GPT in building a mobile app to enhance the interpretability and transparency in malaria and typhoid diagnosis system. Despite its promising results, the system’s performance is constrained by the quality of the dataset. Additionally, while LIME and GPT improve transparency, they may introduce complexities in real-time deployment due to computational demands and the need for internet service to maintain relevance and accuracy. The findings suggest that AI-driven diagnostic systems can significantly enhance healthcare delivery in environments with limited resources, and future works can explore the applicability of this framework to other medical conditions and datasets. Full article

Background: Experimental models of neurocysticercosis (NCC) are helpful for an improved understanding of the pathophysiological mechanisms of human diseases and for testing novel therapeutic approaches. Controlling inflammation without reducing the effectiveness of anthelmintics is an important challenge in treating neurocysticercosis. This study investigates the effects of currently used drugs (Albendazole and Dexamethasone) in treating murine extraparenchymal NCC. Methods: Twenty-two rats were inoculated with Taenia crassiceps in the subarachnoid space. The animals underwent magnetic resonance imaging to ascertain the success of infection 3 months after inoculation. The infected animals were randomly assigned to one of the three groups (five rats each): control (no treatment), Albendazole (ABZ), or Albendazole + Dexamethasone (ABZ + DXM) for 14 days. The animals were subsequently euthanised for morphological assessment 2 weeks after the end of treatment. Results: Macroscopically integrated cysts were found in all animals. The ABZ + DXM animals demonstrated lower ventricular sizes, lymphocyte infiltration rates, and immunopositivity for IL-6, with statistical differences in lymphocytes within the arachnoid region. Conclusions: This experimental model, which has previously shown similarities to human infections, is also helpful in reproducing the morphological changes upon treatment with Albendazole and Dexamethasone. Full article

Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb) bacteria, is one of the world’s deadliest infectious diseases. Despite being the world’s oldest pandemic, tuberculosis is very much a challenge of the modern era. In high-incidence settings, all people are at risk, irrespective of whether they have common vulnerabilities to the disease warranting the current WHO recommendations for community-wide tuberculosis active case finding in these settings. Despite good evidence of effectiveness in reducing tuberculosis transmission, uptake of this strategy has been lacking in the communities that would derive greatest benefit. We consider the various complexities in eliminating tuberculosis from the first principles of the disease, including diagnostic and other challenges that must be navigated under an elimination agenda. We make the case that community-wide tuberculosis active case finding is the best strategy currently available to drive elimination forward in high-incidence settings and that no time should be lost in its implementation. Recognizing that high-incidence communities vary in their epidemiology and spatiosocial characteristics, tuberculosis research and funding must now shift towards radically supporting local implementation and operational research in communities. This “preparing of the ground” for scaling up to community-wide intervention centers the local knowledge and local experience of community epidemiology to optimize implementation practices and accelerate reductions in community-level tuberculosis transmission. Full article

Cytopenias or coagulation deficiencies can occur in people living with HIV (PLWH). The severity of these disorders is influenced by the low levels of CD4+ lymphocytes, viral load, and the stage of viral infection. The aim of our retrospective observational study was to determine the frequency of cytopenias and coagulation deficiencies in PLWH as well as the need for replacement therapy with blood products. We sought to determine whether there is an association between severe anemia or thrombocytopenia (requiring replacement therapy) and CD4+T lymphocyte levels. All 29 patients were critically ill, with 27 out of 29 (93%) in advanced stages of HIV disease and 23 out of 29 (79%) having CD4+ lymphocyte counts below 200 cells/microL. Most patients were either late presenters (45%) or had been lost to follow-up (41%). In addition to HIV infection, various conditions that could alter hematologic parameters were associated, including co-infections with hepatitis viruses, tuberculosis at various sites, malignant diseases, sepsis, SARS-CoV-2 infection, or other opportunistic infections. No significant correlation was found between severe anemia or severe thrombocytopenia or coagulation deficiencies and the CD4+T lymphocyte count. Our data suggest that these hematological disorders in patients with advanced HIV infection are more likely to be associated comorbidities rather than the HIV infection per se. Full article

Healthcare settings, especially intensive care units, can provide an ideal environment for the transmission of pathogens and the onset of outbreaks. Many factors can contribute to the onset of an epidemic in a neonatal intensive care unit (NICU), including neonates’ vulnerability to healthcare-associated infections, especially for those born preterm; facility design; frequent invasive procedures; and frequent contact with healthcare personnel. Outbreaks in NICUs are one of the most relevant problems because they are often caused by multidrug-resistant organisms associated with increased mortality and morbidity. The prompt identification of an outbreak, the subsequent investigation to identify the source of infection, the risk factors, the reinforcement of routine infection control measures, and the implementation of additional control measures are essential elements to contain an epidemic. Full article

(1) Background: The World Health Organisation (WHO) categorises moxifloxacin and levofloxacin as Group A drugs, which should be prioritised in the treatment of rifampicin-resistant tuberculosis. We compare their relative efficacy and safety using data from the STREAM trial; (2) Methods: Marginal structural models were used to balance differences in the baseline characteristics of participants receiving the STREAM control regimen containing either moxifloxacin or levofloxacin as this was not a randomised comparison. The difference in proportions between regimens was estimated for favourable outcome, any grade 3/4 adverse event, QTcF increase to ≥500 ms, QTcF increase from baseline by at least 60 ms, and any grade 3/4 adverse event excluding QT events, using weighted analyses; (3) Results: In efficacy analyses (n = 123), the weighted risk difference (moxifloxacin—levofloxacin, wRD) for a favourable outcome was −0.045 (−0.213, 0.123), p = 0.60. Similarly, estimates from the safety analyses (n = 127) showed no evidence of a difference between the fluoroquinolones, other than a suggestion of fewer QTcF increases from baseline on levofloxacin (wRD 0.160 (−0.026, 0.346), p = 0.091); (4) Conclusions: In this small dataset, we found no statistically significant difference in key efficacy or safety outcomes between the moxifloxacin- and levofloxacin-containing regimens; there was a suggestion that QTcF increases from baseline were fewer on levofloxacin. Full article

Point-of-care testing (PoCT), an alternative to laboratory-based testing, may be useful in the clinical care of critically ill children in resource-limited settings. We evaluated the clinical utility of PoCT in the care of 193 Malawian children treated for World Health Organization-defined cerebral malaria (CM) between March 2019 and May 2023. We assessed the frequency of abnormal PoCT results and the clinical interventions performed in response to these abnormalities. We determined the association between abnormal PoCT results and patient outcomes. Overall, 52.1% of all PoCT results were abnormal. Of the children with abnormal results, clinical interventions occurred in 16.9%. Interventions most commonly followed abnormal results for PoCT glucose (100.0% of the patients had treatment for hypoglycemia), potassium (32.1%), lactate (22.0%), and creatinine (16.3%). Patients with hypoglycemia, hyperlactatemia, and hypocalcemia had a higher mortality risk than children with normal values. Future studies are needed to determine whether obtaining laboratory values using PoCT and the clinical response to these interventions modify outcomes in critically ill African children with CM. Full article

Like many countries, Ukraine faces challenges with diagnosing tuberculosis (TB) in children due to the paucibacillary nature of the disease and difficulty obtaining respiratory samples. To improve diagnostic efficiency, stool testing is being integrated into routine pediatric TB services. This started with a pilot introduction at 12 regional TB facilities, where stool was collected for children with a preliminary diagnosis of TB, based on clinical and/or radiological or laboratory findings, in addition to routine testing. For 168 children, a stool test was conducted between November 2021 and September 2022, with samples submitted in all 12 pilot regions. For 132 children, other samples were available in addition to stool. Mycobacterium tuberculosis (MTB) was bacteriologically confirmed in 37 children (in stool for 18 children). For 7 of the 18 children with MTB in stool, stool was the only sample in which MTB was detected. Rifampicin resistance was detected in seven children (in stool for three). This noninvasive TB diagnostic sample is especially beneficial for young children who cannot produce sputum. Early detection of TB and its drug-resistant strains in children will allow medical workers to provide safer and more effective treatment and save more lives. Based on the pilot implementation, Ukraine’s national TB program began implementing stool testing throughout the country. Full article

Leishmaniasis is a complex disease caused by different species of Leishmania. To date, no vaccine for humans or ideal therapy has been developed owing to the limited efficacy and toxicity of available drugs, as well as the emergence of resistant strains. Therefore, it is necessary to identify novel therapeutic targets and discover therapeutic options for leishmaniasis. In this study, we evaluated the impact of deleting the lipid droplet protein kinase (LDK) enzyme in Leishmania infantum using an untargeted metabolomics approach performed using liquid chromatography and high-resolution mass spectrometry. LDK is involved in lipid droplet biogenesis in trypanosomatids. Thirty-nine lipid metabolites altered in the stationary and logarithmic growth phases were noted and classified into five classes: (1) sterols, (2) fatty and conjugated acids, (3) ceramides, (4) glycerophosphocholine and its derivatives, and (5) glycerophosphoethanolamine and its derivatives. Our data demonstrated that glycerophosphocholine and its derivatives were the most affected after LDK deletion, suggesting that the absence of this enzyme promotes the remodeling of lipid composition in L. infantum, thus contributing to a better understanding of the function of LDK in this parasite. Full article

Background: Almost the entire country of Burkina Faso was endemic to onchocerciasis. Onchocerciasis control efforts thus brought the prevalence of O. volvulus to a level where the disease was no longer a public health problem in 2002. A resurgence of onchocerciasis cases has been observed in two regions (Cascades and the Southwest) located around several river basins in 2010–2011. In accordance with WHO guidelines for the management of resurgent cases, community-directed treatment with ivermectin (CDTI) was implemented in the affected areas. The aim of this study was to determine the effects of this intervention on parasitological indices of onchocerciasis, depending on the distance between villages and rivers. Methodology: We conducted a paired pre-post study using aggregated village-level data from two cross-sectional surveys conducted in each region. A Wilcoxon signed-rank test was used to compare the standardized microfilarodermia prevalence and community microfilarial load (CMFL). Results: A total of 43 villages in 6 health districts, in the Southwest (18) and Cascades (25) regions were included in the study. The key findings were that standardized microfilaria prevalence and CMFL decreased significantly after the implementation of CDTI in both regions (p < 0.0001). The median standardized microfilaria prevalence was 2.8 [interquartile range (IQR): 0.2–6.6] before CDTI and 0.72 [IQR: 0.0–2.17] after CDTI. The results showed also a decline in standardized microfilaria prevalence and CMFL in all villages, regardless of the distance separating the village from the streams. However, the results were not statistically significant for the villages located 5 km or more from streams (p = 0.0816 and 0.0542 for standardized microfilaria prevalence and CMFL, respectively). Conclusion: Our results thus show that the implementation of effective CDTI could stop the transmission of O. volvulus in these two regions. The main challenge for stopping transmission could be the migration of populations to neighboring countries and migration of the vector from one country to another, as Burkina Faso shares some river basins with neighboring countries. Full article

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO₂/FiO₂ (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% (p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine (p = 0.04) and PF ratio (p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion’s benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients. Full article

The order Bunyavirales belongs to the class of Ellioviricetes and is classified into fourteen families. Some species of the order Bunyavirales pose potential threats to human health. The continuously increasing research reveals that various viruses within this order achieve immune evasion in the host through suppressing interferon (IFN) response. As the types and nodes of the interferon response pathway are continually updated or enriched, the IFN suppression mechanisms and target points of different virus species within this order are also constantly enriched and exhibit variations. For instance, Puumala virus (PUUV) and Tula virus (TULV) can inhibit IFN response through their functional NSs inhibiting downstream factor IRF3 activity. Nevertheless, the IFN suppression mechanisms of Dabie bandavirus (DBV) and Guertu virus (GTV) are mostly mediated by viral inclusion bodies (IBs) or filamentous structures (FSs). Currently, there are no effective drugs against several viruses belonging to this order that pose significant threats to society and human health. While the discovery, development, and application of antiviral drugs constitute a lengthy process, our focus on key targets in the IFN response suppression process of the virus leads to potential antiviral strategies, which provide references for both basic research and practical applications. Full article

A high incidence of diphtheria cases in children in East Java province, Indonesia, has been observed since the beginning of this century. Despite many efforts, the outbreaks continue. This study aims to explain the high incidence of diphtheria in children in East Java province since 2013. This cross-sectional surveillance report-based study used data from 38 districts in East Java since 1 January 2013. Collected data included demographics, clinical information, additional examinations, immunization history, and close contact management. Over eleven years, there were 4009 diphtheria patients, of whom 2921 (72.86%) were under 18 years of age. Boys (59.77%) outnumbered girls, and the most common age category was >60–144 months (51.66%). Most cases had incomplete or zero immunization (76.16%). Tonsillopharyngeal diphtheria was the most common type (69.60%). The five top districts with the most cases were Surabaya, Sidoarjo, Kabupaten Blitar, Kota Malang, and Kabupaten Malang. The eleven-year case fatality rate (CFR) was 2.36% (69/2921). This study shows that diphtheria cases in children and adolescents in East Java have consistently been high, and low immunization coverage might still be the leading cause. There has also been a shift in the district distribution. Diphtheria outbreaks require complete and sustainable efforts, not just outbreak response immunizations. Full article

Leptospirosis is a disease caused by the bacteria of the Leptospira genus, which can usually be acquired by humans through contact with urine from infected animals; it is also possible for this urine to contaminate soils and bodies of water. The disease can have deadly consequences in some extreme cases. Fortunately, until now, patients with leptospirosis have responded adequately to treatment with doxycycline and azithromycin, and no cases of antibiotic resistance have been reported. However, with the extensive use of such medications, more bacteria, such as Staphylococci and Enterococci, are becoming resistant. The purpose of this study is to determine the presence of genes related to antibiotic resistance in the Leptospira genus using bioinformatic tools, which have not been undertaken in the past. Whole genomes from the 69 described Leptospira species were downloaded from NCBI’s GeneBank and analyzed using CARD (The Comprehensive Antibiotic Resistant Database) and RAST (Rapid Annotations using Subsystem Technology). After a detailed genomic search, 12 genes associated with four mechanisms were found: resistance to beta-lactamases, vancomycin, aminoglycoside adenylyltransferases, as well as multiple drug efflux pumps. Some of these genes are highly polymorphic among different species, and some of them are present in multiple copies in the same species. In conclusion, this study provides evidence of the presence of genes related to antibiotic resistance in the genomes of some species of the genus Leptospira, and it is the starting point for future experimental evaluation to determine whether these genes are transcriptionally active in some species and serovars. Full article

This study aimed to identify the factors associated with all-cause in-hospital mortality in laboratory-confirmed dengue cases from 2020 to mid-2024. A nationwide retrospective cohort study was conducted in Mexico and data from 18,436 participants were analyzed. Risk ratios (RRs) and 95% confidence intervals (CIs), estimated using generalized linear regression models, were used to evaluate the factors associated with all-cause in-hospital mortality risk. The overall case–fatality rate was 17.5 per 1000. In the multiple model, compared to dengue virus (DENV) 1 infections, DENV-2 (RR = 1.81, 95% CI 1.15–2.86) and DENV-3 (RR = 1.87, 95% CI 1.19–2.92) were associated with increased mortality risk. Patient characteristics, such as increasing age (RR = 1.02, 95% CI 1.01–1.03), type 2 diabetes mellitus (RR = 2.07, 95% CI 1.45–2.96), and chronic kidney disease (RR = 3.35, 95% CI 2.03–5.51), were also associated with an increased risk of a fatal outcome. We documented the influence of both the virus and individual susceptibility on mortality risk, underscoring the need for a comprehensive public health strategy for dengue. Full article

West Nile Virus (WNV) poses a significant global public health threat as a mosquito-borne pathogen. While laboratory mouse models have historically played a crucial role in understanding virus biology, recent research has focused on utilizing immunocompromised models to study arboviruses like dengue and Zika viruses, particularly their interactions with Aedes aegypti mosquitoes. However, there has been a shortage of suitable mouse models for investigating WNV and St. Louis encephalitis virus interactions with their primary vectors, Culex spp. mosquitoes. Here, we establish the AG129 mouse (IFN α/β/γ R^−/−) as an effective vertebrate model for examining mosquito–WNV interactions. Following intraperitoneal injection, AG129 mice exhibited transient viremia lasting several days, peaking on the second or third day post-infection, which is sufficient to infect Culex quinquefasciatus mosquitoes during a blood meal. We also observed WNV replication in the midgut and dissemination to other tissues, including the fat body, in infected mosquitoes. Notably, infectious virions were present in the saliva of a viremic AG129 mouse 16 days post-exposure, indicating successful transmission capacity. These findings highlight the utility of AG129 mice for studying vector competence and WNV–mosquito interactions. Full article

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria. Full article

(1) Background: Adolescents and young adults face challenges when transitioning to adult care due to emerging adulthood and changing providers and insurance. Young people living with HIV (YPLHIV) have additional obstacles with mental health and stigma. During transition, only 55% of YPLHIV are retained in care, and 65% are virally suppressed. To address these challenges, the Adolescent and Young Adult Health Care Transition Clinic (AYAHCTC) was created at Vanderbilt University Medical Center in 2017. This mixed methods study evaluates the initial cohort and solicits YPLHIVs’ perspectives on transition barriers and facilitators. (2) Methods: Quantitative analyses (n = 21) characterized patients’ demographics, clinical engagement, and retention. Qualitative interviews (n = 5) captured patients’ transition experiences. (3) Results: This study, conducted in the Southeastern USA, included a cohort where 47.6% were born abroad, with all participants being US citizens by birth or naturalization. Patients’ mean age at first visit was 19.6 years. The average AYAHCTC duration was 2.21 years. First-year engagement and retention were 100% and 95.5%, respectively. Viral suppression rates improved from 66.7% at the first visit to 81.0% at the last visit. Eleven patients transitioned out of AYAHCTC. Qualitative analyses indicate that barriers to transition include leaving trusted providers, reduced parental guidance, developing autonomy, and perceived loss of confidentiality in adult clinic environment. Transition was facilitated by youth-friendly services, clear communication, and strong relationships with AYAHCTC providers. (4) Conclusions: YPLHIV positively viewed AYAHCTC experiences. Future directions include optimizing services to build YPLHIVs’ independence, supporting YPLHIV experiencing stigma, assuaging concerns about switching providers, collaborating with adult clinics to maintain confidentiality, and designing interventions focused on adherence during transition. Full article

Tuberculosis (TB) is an important infectious disease in relation to global public health and is caused species of the Mycobacterium tuberculosis complex (MTBC). In this study, we used whole-genome sequencing (WGS) and comparative genomics to investigate the genetic diversity of M. tuberculosis (Mtb) isolates circulating in North Santander (NS), Colombia. WGS was used for the phylogenetic and lineage characterization of 18 isolates of Mtb typed with orphan genotypes from 11 municipalities of NS between 2015 and 2018. The isolates studied were included in six sublineages from L4; the most frequent were 4.1.2.1, 4.3.3, and 4.3.4.2, corresponding to a proportion of 22.2%. The genome analysis conducted allowed the identification of a set of genetic variants mainly associated with determinants of virulence and evasion of the immune system (PPE34 and PE_PGRS2); adaptation and survival (PGL/p-HBAD); stress response (sigJ and sigM); geographic variability (PPE34); and carbohydrate and lipid metabolism (aldA, rocA, and cyp144). This is the first description of the molecular epidemiology of Mtb isolates circulating in NS achieved through WGS. It was possible to perform comparative genomics analyses between Mtb isolates against the universal reference H37Rv and Colombian UT205 genome, which can help us to understand the local genetic diversity and is relevant for epidemiological studies, providing insight into TB transmission dynamics in NS. Full article

Objective. Synthesize the approaches used to study the convergence between cardiometabolic and infectious diseases in adults from a syndemic perspective based on the scientific evidence available to date worldwide. Methods. Scoping review that follows the recommendations of the PRISMA statement. The protocol was registered in INPLASY202150048. The search for studies was carried out in MEDLINE, LILACS, Web of Science and Scopus. Results. Since the COVID-19 pandemic, there has been an increase in studies in the field of convergence between cardiometabolic and infectious diseases from a syndemic perspective, but only three studies were classified as true syndemics. There are weaknesses in the adherence to the elements of the syndemic theory, given a low incorporation of population measurements, and until now it has not been possible to find convincing empirical evidence that supports the bio–bio interface. Quantitative methods predominated through models focused on “sum scores”. Conclusions. Future studies should comprehensively address the elements of syndemics, review discrepancies between additive analyses versus other modeling, and incorporate the influence of large-scale social forces. The lack of these aspects distances studies from the notion of syndemic, bringing them closer to comorbidity or multimorbidity approaches. Full article

The United States of America (US) has the highest annual number of human babesiosis cases caused by Babesia microti (Bm). Babesia, like malaria-causing Plasmodium, are protozoan parasites that live within red blood cells (RBCs). Both infectious diseases can be associated with hemolysis and organ damage, which can be fatal. Since babesiosis was made a nationally notifiable condition by the Centers for Disease Control and Prevention (CDC) in January 2011, human cases have increased, and drug-resistant strains have been identified. Both the Bm ligand(s) and RBC receptor(s) needed for invasion are unknown, partly because of the difficulty of developing a continuous in vitro culture system. Invasion pathways are relevant for therapies (e.g., RBC exchange) and vaccines. We hypothesize that there is at least one RBC surface antigen that is essential for Bm invasion and that all Bm hosts express this. Because most RBC surface antigens that impact Plasmodium invasion are in human blood group (hBG) systems, which are generated by 51 genes, they were the focus of this study. More than 600 animals with at least one hBG system gene ortholog were identified using the National Center for Biotechnology Information (NCBI) command-line tools. Google Scholar searches were performed to determine which of these animals are susceptible to Bm infection. The literature review revealed 28 Bm non-human hosts (NHH). For 5/51 (9.8%) hBG system genes (e.g., RhD), no NHH had orthologs. This means that RhD is unlikely to be an essential receptor for invasion. For 24/51 (47.1%) hBG system genes, NHH had 4–27 orthologs. For the ABO gene, 15/28 NHH had an ortholog, meaning that this gene is also unlikely to generate an RBC antigen, which is essential for Bm invasion. Our prior research showed that persons with blood type A, B, AB, O, RhD+, and RhD- can all be infected with Bm, supporting our current study’s predictions. For 22/51 (43.1%) hBG system genes, orthologs were found in all 28 NHH. Nineteen (37.3%) of these genes encode RBC surface proteins, meaning they are good candidates for generating a receptor needed for Bm invasion. In vitro cultures of Bm, experimental Bm infection of transgenic mice (e.g., a CD44 KO strain), and analyses of Bm patients can reveal further clues as to which RBC antigens may be essential for invasion. Full article