Tropical Medicine and Infectious Disease

23 pages, 5336 KiB

Open AccessArticle

Enhancing the Interpretability of Malaria and Typhoid Diagnosis with Explainable AI and Large Language Models

by Kingsley Attai, Moses Ekpenyong, Constance Amannah, Daniel Asuquo, Peterben Ajuga, Okure Obot, Ekemini Johnson, Anietie John, Omosivie Maduka, Christie Akwaowo and Faith-Michael Uzoka

Trop. Med. Infect. Dis. 2024, 9(9), 216; https://doi.org/10.3390/tropicalmed9090216 - 16 Sep 2024

Abstract

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 [...] Read more.

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

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7 pages, 3729 KiB

Open AccessBrief Report

Murine Extraparenchymal Neurocysticercosis: Appropriate Model for Evaluating Anthelminthic and Anti-Inflammatory Treatment Schedules

by Vinícius Tadeu Oliveira, Tatiane de Camargo Martins, Renato Tavares Conceição, Diego Generoso, Vânia Maria de Vasconcelos Machado, Sabrina Setembre Batah, Alexandre Todorovic Fabro, Marco Antônio Zanini, Edda Sciutto, Agnès Fleury and Pedro Tadao Hamamoto Filho

Trop. Med. Infect. Dis. 2024, 9(9), 215; https://doi.org/10.3390/tropicalmed9090215 - 16 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Section Neglected and Emerging Tropical Diseases)

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14 pages, 311 KiB

Open AccessReview

Community-Wide Active Case Finding for Tuberculosis: Time to Use the Evidence We Have

by Mikaela Coleman, Chris Lowbridge, Philipp du Cros and Ben J. Marais

Trop. Med. Infect. Dis. 2024, 9(9), 214; https://doi.org/10.3390/tropicalmed9090214 - 14 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Implementing TB Elimination Approaches in Indonesia: Operational Research on Case Finding, Treatment and Prevention of TB in Yogyakarta and Timika)

11 pages, 260 KiB

Open AccessArticle

Replacement Therapy with Blood Products in People Living with HIV

by Mihaela Cristina Olariu, Mihaela Adela Iancu, Mihai Hristu Olariu, Victoria Aramă, Mădălina Simoiu, Miruna Maria Cruceru, Ecaterina Constanta Barbu, Paul Balanescu and Mihai Lazar

Trop. Med. Infect. Dis. 2024, 9(9), 213; https://doi.org/10.3390/tropicalmed9090213 - 13 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions)

12 pages, 753 KiB

Open AccessReview

Outbreaks in the Neonatal Intensive Care Unit: Description and Management

by Chryssoula Tzialla, Alberto Berardi, Vito Mondì and on behalf of the Study Group of Neonatal Infectious Diseases

Trop. Med. Infect. Dis. 2024, 9(9), 212; https://doi.org/10.3390/tropicalmed9090212 - 12 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Microbial Infections and Antimicrobial Use in Neonates and Infants)

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7 pages, 217 KiB

Open AccessArticle

Comparative Efficacy and Safety of Moxifloxacin and Levofloxacin in a Short Standardised Rifampicin Resistant TB Regimen: A STREAM 2 Secondary Analysis

by Stella M. Fabiane, Chen-Yuan Chiang, Sarah K. Meredith, Meera Gurumurthy, Adamu Bayissa, Andrew J. Nunn and Ruth L. Goodall

Trop. Med. Infect. Dis. 2024, 9(9), 211; https://doi.org/10.3390/tropicalmed9090211 - 11 Sep 2024

Abstract

(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 [...] Read more.

(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

(This article belongs to the Special Issue Diagnosis and Treatment of Multidrug-Resistant Tuberculosis: Insights from New Research and Clinical Trials)

12 pages, 242 KiB

Open AccessArticle

Admission Point-of-Care Testing for the Clinical Care of Children with Cerebral Malaria

by David Wichman, Geoffrey Guenther, Nthambose M. Simango, Mengxin Yu, Dylan Small, Olivia D. Findorff, Nathaniel O. Amoah, Rohini Dasan, Karl B. Seydel, Douglas G. Postels and Nicole F. O’Brien

Trop. Med. Infect. Dis. 2024, 9(9), 210; https://doi.org/10.3390/tropicalmed9090210 - 11 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Section Vector-Borne Diseases)

11 pages, 1571 KiB

Open AccessArticle

Paving the Way to Innovative, Child-Friendly Pediatric Diagnostic Methods for Tuberculosis: Introduction of Stool-Based Testing in Ukraine

by Olena Diuzheva, Liudmyla Skoklyuk, Nina Zherebko, Anna Barbova, Myroslava Germanovych, Eveline Klinkenberg, Oleksii Bogdanov and Gunta Dravniece

Trop. Med. Infect. Dis. 2024, 9(9), 209; https://doi.org/10.3390/tropicalmed9090209 - 11 Sep 2024

Abstract

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 [...] Read more.

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

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12 pages, 1756 KiB

Open AccessArticle

Untargeted Liquid Chromatography–High-Resolution Mass Spectrometry Metabolomic Investigation Reveals Altered Lipid Content in Leishmania infantum Lacking Lipid Droplet Protein Kinase

by Juliana Martins Ribeiro, Gisele André Baptista Canuto, Alisson Samuel Portes Caldeira, Ezequias Pessoa de Siqueira, Carlos Leomar Zani, Silvane Maria Fonseca Murta and Tânia Maria de Almeida Alves

Trop. Med. Infect. Dis. 2024, 9(9), 208; https://doi.org/10.3390/tropicalmed9090208 - 10 Sep 2024

Abstract

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, [...] Read more.

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

(This article belongs to the Special Issue Advances in Parasitic Neglected Tropical Diseases)

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11 pages, 2142 KiB

Open AccessArticle

Effects of Five Years of Treatment of Onchocerciasis with Ivermectin under Community Guidelines in Resurgent Areas of Burkina Faso: A before-and-after Analysis

by Micheline O. Ouedraogo, Ivlabèhirè Bertrand Meda, Karifa Kourouma, Fanny Yago Wienne, Dieudonné Nare, Clarisse Bougouma, Justin Compaore and Seni Kouanda

Trop. Med. Infect. Dis. 2024, 9(9), 207; https://doi.org/10.3390/tropicalmed9090207 - 9 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Insights on Neglected Tropical Diseases in West Africa)

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10 pages, 231 KiB

Open AccessArticle

Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial

by Danice Romagne Leano, Romina Danguilan, Mel-Hatra Arakama, Vince Apelin, Paolo Pinkerton Alamillo and Eric Chua

Trop. Med. Infect. Dis. 2024, 9(9), 206; https://doi.org/10.3390/tropicalmed9090206 - 9 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Topic One Health Approach in Global Health and Clinical Medicine)

27 pages, 1625 KiB

Open AccessReview

Suppression of Interferon Response and Antiviral Strategies of Bunyaviruses

by Yingying He, Min Shen, Xiaohe Wang, Anqi Yin, Bingyan Liu, Jie Zhu and Zhenhua Zhang

Trop. Med. Infect. Dis. 2024, 9(9), 205; https://doi.org/10.3390/tropicalmed9090205 - 7 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Beyond Borders—Tackling Neglected Tropical Viral Diseases)

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10 pages, 1272 KiB

Open AccessArticle

Eleven-Year Report of High Number of Diphtheria Cases in Children in East Java Province, Indonesia

by Dominicus Husada, Yustika Hartini, Kalista Wahyu Nuringhati, Sandy Grace Tindage, Rahma Ira Mustikasari, Leny Kartina, Dwiyanti Puspitasari, Parwati S. Basuki, Ismoedijanto Moedjito, Zumaroh Zumaroh, Hugeng Susanto, Wahyu Wulandari, Sulvy Dwi Anggraini and Erwin Astha Triyono

Trop. Med. Infect. Dis. 2024, 9(9), 204; https://doi.org/10.3390/tropicalmed9090204 - 7 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Section Infectious Diseases)

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14 pages, 923 KiB

Open AccessArticle

Detection of Genes Related to Antibiotic Resistance in Leptospira

by Santiago Pineda, Juliana María Martínez Garro, Jorge Emilio Salazar Flórez, Sergio Agudelo-Pérez, Fernando P. Monroy and Ronald Guillermo Peláez Sánchez

Trop. Med. Infect. Dis. 2024, 9(9), 203; https://doi.org/10.3390/tropicalmed9090203 - 6 Sep 2024

Abstract

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 [...] Read more.

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 article belongs to the Special Issue Leptospirosis and One Health Approach: Current Status and Future Prospects, 2nd Edition)

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6 pages, 383 KiB

Open AccessCommunication

Factors Contributing to In-Hospital Mortality in Dengue: Insights from National Surveillance Data in Mexico (2020–2024)

by Eder Fernando Ríos-Bracamontes, Oliver Mendoza-Cano, Agustin Lugo-Radillo, Ana Daniela Ortega-Ramírez and Efrén Murillo-Zamora

Trop. Med. Infect. Dis. 2024, 9(9), 202; https://doi.org/10.3390/tropicalmed9090202 - 3 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Beyond Borders—Tackling Neglected Tropical Viral Diseases)

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14 pages, 2650 KiB

Open AccessArticle

Suitable Mouse Model to Study Dynamics of West Nile Virus Infection in Culex quinquefasciatus Mosquitoes

by Lívia Baldon, Silvana de Mendonça, Ellen Santos, Bruno Marçal, Amanda Cupertino de Freitas, Fernanda Rezende, Rafaela Moreira, Viviane Sousa, Sara Comini, Mariana Lima, Flávia Ferreira, João Paulo de Almeida, Emanuele Silva, Siad Amadou, Marcele Rocha, Thiago Leite, Yaovi Todjro, Camila de Carvalho, Viviane Santos, Marta Giovanetti, Luiz Alcantara, Luciano A. Moreira and Alvaro Ferreira Show full author list Hide full author list

Trop. Med. Infect. Dis. 2024, 9(9), 201; https://doi.org/10.3390/tropicalmed9090201 - 2 Sep 2024

Abstract

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 [...] Read more.

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

(This article belongs to the Section Vector-Borne Diseases)

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5 pages, 185 KiB

Open AccessEditorial

Spotlight on Leishmaniasis Research: Insights from the Special Issue “Emerging Topics in Leishmaniasis Research”

by Sandra Regina Maruyama

Trop. Med. Infect. Dis. 2024, 9(9), 200; https://doi.org/10.3390/tropicalmed9090200 - 2 Sep 2024

Abstract

Leishmaniases, caused by dixenous trypanosomatids from the Leishmaniinae subfamily (over 20 Leishmania species), manifest in three primary clinical forms: visceral (VL), cutaneous (CL), and mucocutaneous (MCL) [...] Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

20 pages, 934 KiB

Open AccessReview

Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives

by Domenico Umberto De Rose, Maria Paola Ronchetti, Ludovica Martini, Jole Rechichi, Marco Iannetta, Andrea Dotta and Cinzia Auriti

Trop. Med. Infect. Dis. 2024, 9(9), 199; https://doi.org/10.3390/tropicalmed9090199 - 28 Aug 2024

Abstract

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, [...] Read more.

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

(This article belongs to the Special Issue Microbial Infections and Antimicrobial Use in Neonates and Infants)

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21 pages, 498 KiB

Open AccessArticle

Mixed Methods Evaluation of a Youth-Friendly Clinic for Young People Living with HIV Transitioning from Pediatric Care

by Hannah Chew, Kemberlee Bonnet, David Schlundt, Nina Hill, Leslie Pierce, Aima Ahonkhai and Neerav Desai

Trop. Med. Infect. Dis. 2024, 9(9), 198; https://doi.org/10.3390/tropicalmed9090198 - 28 Aug 2024

Abstract

(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 [...] Read more.

(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

(This article belongs to the Special Issue Adolescent HIV Care and Transition Strategies: Challenges, Outcomes, and Interventions)

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