Hospital For Tropical Diseases Research Articles

Improving the diagnostic performance of the neural network for COVID-19VN via weight assignment to pathological symptoms

In this article, we present how to create a database of Covid-19 diseases at National Hospital of Tropical Diseases (called the CovidVN database) and then develop a learning neural network based on this database to diagnose this disease. The CovidVN Database is built based on the processing of real diagnostic test results of Covid-19 patients with a large number of samples and in accordance with the structure of the Israeli Health System Covid-19 disease database (called COVIDIsr Database). Then two MLP Artificial Neural Networks corresponding to these two databases will be developed using the Deep Learning Toolbox of MATLAB software; the results of training these networks and their accuracy are compared with each other to assess the relative quality of the CovidVN database. Other, the paper presents the method of assigning weight corresponding to pathological symptoms for network input parameters. The results showed that the weighting of input attributes corresponding to the pathological symptoms is significant.

OBESITY AND IN-HOSPITAL OUTCOMES AMONG PATIENTS WITH SEVERE COVID-19 IN VIET NAM

Introduction: COVID-19 (Coronavirus disease 2019) is a global pandemic. Overweight and obesity are risk factors related to mortality as well as disease severity. Overweight and obesity are also increasing in Vietnam. Data related to the characteristics of COVID-19 in this vulnerable population was limited in Vietnam. The study was conducted (1) to describe the outcomes of overweight and obese COVID-19 patients, and (2) to investigate factors associated with the outcomes of overweight and obese COVID-19 patients. Methods: A cross-sectional description was conducted at the Hospital for Tropical Diseases from July 2021 to December 2021. Patients who were (1) ≥ 18 years old (2) diagnosed with COVID-19 with a positive RT-PCR SARS-CoV-2 result and (3) had BMI ≥ 23 kg/m2. Female pregnant women or ascites were excluded from this study. To determine factors associated with mortality and ICU admission, chi-square and Fisher's Exact were used. Variables with p < 0.05 were included in the logistic regression model to investigate independent risk factors. Cases directly admitted to the ICU were excluded when analyzing risk factors for ICU admission. Results: 173 patients were recruited (70 patients (40.46%) were overweight, 74 patients (42.77%) were obesity class I and 29 patients (16.76%) were obesity class II). The overall mortality rate was 28.9%. The ICU admission rate was 46.2% with a median ICU stay of 9 (6 – 15.25) days. The rate of respiratory support was 83.8%, of which 31.8% of patients required invasive mechanical ventilation and the median duration of respiratory support was 12 (6.5 – 16.5) days. Independently factors associated with ICU admission were diabetes (OR = 2.92 (1.27 – 6.67)) and a severe or critical condition at admission (OR = 8.82 (2.51 – 31.08). Independently factors associated with death were vaccination (OR = 0.23 (0.08 – 0.63)), a severe or critical at admission (OR = 15.74 (3.46 – 71.55)) and remdesivir usage (OR = 0.78 (0.16 – 0.87)). Recommendation: Vaccination against COVID-19 has been shown to be effective in the obese and overweight population.

Advising the immunocompromised traveller: a review of immunocompromise at The London Hospital for Tropical Diseases Travel Clinic between 1st April 2019 and 30th April 2020.

Immunocompromised travellers (ICTs) face greater infectious and non-infectious travel-associated risks than their immunocompetent counterparts. Increasing travel and emergence of novel immunosuppressants poses great challenges for travel medicine practitioners to confidently provide up-to-date evidence-based risk management advice and pre-travel care for ICTs. We reviewed the records of ICTs attending the London Hospital for Tropical Diseases (HTD) Travel Clinic between 1st April 2019 and 30th April 2020 with the aim to describe demographic and travel characteristics, type, and severity of immunocompromise, the degree of risk associated with intended travel and evaluate travel advice. Of the 193 ICTs identified, immunocompromise was due to physiological reasons (42%), chronic infection (17.1%) and immunosuppressive therapy (16.6%). Median age was 38 (range 9 months to 84 years) and male to female ratio 0.75 (83:110). Travel was intended to 80 countries for a median of 16 days (range 2 to 3167), predominantly for leisure (53%), non-medical work (17%) and visiting friends and relatives (12%). Live vaccine safety dominated discussion in the pre-travel consultation. Existing guidelines arguably fell short in dealing with travel risks associated with hyper-specific conditions, targeted immunosuppressants and non-vaccine preventable infections. Our cohort represents a wide spectrum of immunocompromise, for whom we arguably need more measurable ways to approach travel-associated risks. We propose prospective qualitative participatory research to inform our unit of the priorities of ICTs in the pre-travel consultation. We further recommend the formation of a repository of specialists and formulary of complex cases to direct subsequent informative systematic review and prospective risk studies.

Association of Various Factors and HIV Infection in Pregnancy: A Clinico- Epidemiological Review

HIV infection among pregnant women has been on the rise, demanding efforts to prevent vertical transmission. This study analyzed the epidemiological and clinical characteristics of HIV-positive pregnant women treated at the Hospital of Tropical Diseases of the Federal University of Tocantins between 2015 and 2019. Out of the 85 pregnant women analyzed, the majority were between 26 and 34 years old, with 37.64% completing high school. Most resided in Tocantins and had stable partners, with 44.11% unaware of their serological status. Women aged ≥25 years showed lower viral load detection. The majority already had HIV before prenatal care, but only 45.88% started follow-up in the first trimester. Treatment adherence was high, but 14.10% dropped out. The analysis highlighted the need for specific strategies for young pregnant women, emphasizing the importance of prenatal exams for early diagnosis and immediate treatment initiation, reducing vertical transmission. Adherence to antiretroviral therapy (ART) was crucial, although cases of dropout underscored the need for emotional support. The results reinforce the importance of health policies tailored to the needs of HIV-positive pregnant women, aiming to ensure a holistic and effective approach to this vulnerable population.

Predictors to Intensive Care Unit admission among patient with coronavirus disease in Sukraraj Tropical and Infectious Disease Hospital, Nepal: A case-control study.

The clinical features of COVID-19 are vary widely, ranging from asymptomatic states or mild upper respiratory tract infections to severe pneumonia. Previous studies have shown that 20.0% of COVID-19 patients are hospitalized, out of which 10.0-20.0% are admitted to the Intensive Care Unit. The present study aims to assess predictors associated with COVID-19 leading to Intensive Care Unit admission among reverse transcriptase- polymerase chain reaction (RT-PCR) positive patients in Sukraraj Tropical and infectious disease hospital, Nepal. A case-control study was conducted from June 2022 to July 2022 among patients admitted to Sukraraj Tropical and Infectious Disease Hospital. A hospital-based age (± 2 years) and sex-matched case-control study design were adopted in which ICU admitted (case group, n = 33) and general ward admitted (control group, n = 66) were included. Data were collected using a structured questionnaire comprising of socio-demographic, clinical, and preventive predictors. Data were analyzed using the Statistical Package for Social Science version 11.5. The Chi-square test and conditional logistic regression to determine the predictors associated with ICU admission. High blood pressure, high C-reactive protein and poor application of preventive practices were found to be the predictors of ICU admission. Conditional logistics regression analyses revealed that independent risk factors associated with ICU admission were elevated blood pressure (AOR = 2.22; 95% CI 1.05-4.71, p = 0.015) and abnormal C-Reactive Protein (AOR = 2.92; 95% CI 1.24-6.84, p = 0.012) at the time of hospital admission were more likely to get admitted to ICU. Likewise, patients with poor preventive practice (AOR = 3.34; 95% CI 1.19-9.31, p = 0.02) more likely to get admitted to ICU than patient with good preventive practices.These research findings hold potential significance for facilitating early triage and risk assessment in COVID-19 patients.

Primaquine in glucose-6-phosphate dehydrogenase deficiency: an adaptive pharmacometric assessment of ascending dose regimens in healthy volunteers

Background:Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of Plasmodium vivax malaria. The 8-aminoquinolines cause dose-dependent haemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd). G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused.Methods:We conducted an adaptive pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15–20 days. In Part 2 conducted at least 6 months later, a single primaquine 45 mg dose was given.Results:24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1–5.9; relative decline of 26% [range: 15–40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9–4.1; relative fall of 12% [range: 7–30% decrease]). The ascending dose primaquine regimens gave seven times more drug but resulted in only double the haemoglobin decline.Conclusions:In patients with Southeast Asian G6PDd variants, full radical cure treatment can be given in under 3 weeks compared with the current 8-week regimen.Funding:Medical Research Council of the United Kingdom (MR/R015252/1) and Wellcome (093956/Z/10/C, 223253/Z/21/Z).Clinical trial number:Thai Clinical Trial Registry: TCTR20170830002 and TCTR20220317004.

Acceptance and User Experiences of a Wearable Device for the Management of Hospitalized Patients in COVID-19-Designated Wards in Ho Chi Minh City, Vietnam: Action Learning Project.

Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors. A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system. We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail. In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology. Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period.

CLINICAL AND SUB-CLINICAL CHARACTERISTICS OF MENINGITIS CAUSED BY VARICELLA ZOSTER VIRUS

Encephalitis - meningitis today is still a serious public health problem with a high mortality rate.Objectives: To describe the clinical and subclinical characteristics of encephalitis-meningitis caused by Varicella zoster virus (VZV) in people from 15 years old.Material and methods: A retrospective descriptive research on 40 patients with encephalitis-meningitis diagnosed based on positive VZV PCR results in cerebrospinal fluid treated at the National Hospital of Tropical Diseases and Bach Mai Hospital from January 2020 to June 2023.Results: Common clinical manifestations of VZV meningitis are headache (90.6%), fever (59.4%), and nausea (43.8%). Common manifestations of encephalitis are behavioral and language disorders (75%), and fever (50%). In the cerebrospinal fluid, the median number of white blood cells in the two meningitis and encephalitis groups were 235.5 (100 - 440) cells/mL and 157 (46 - 497) cells/mL, respectively, of which white blood cells were lymphocytes predominate, protein of the two meningitis and encephalitis groups are 1.0 (0.5 - 1.6) G/L and 2.1 (0.9 - 5.7) G/L, respectively. We can find out brain damage on CT or MRI in the temporal lobe, frontal lobe, and insula lobe. In addition, demyelinating lesions occur in 25%.

CLINICAL SYMPTOMS CHANGES IN POST-COVID-19 MILD AND MODERATE PATIENTS AT NATIONAL HOSPITAL FOR TROPICAL DISEASE

Patients recovering from SARS-CoV-2 infection may still have persistent symptoms. There is a need forstudies on many different groups to have an overview of the clinical manifestations after recovery.Objectives: Describe the clinical symptoms persist in patients and compare the difference in those symptomsat 3 and 6 months after recovery in patients with mild and morderate COVID-19 infection at Department ofInternal Medicine, National Hospital for Tropical Diseases from October 2021 to October 2022.Methods: Descriptive prospective study on 166 patients with SARS-CoV-2 RT-PCR positive, with mildand moderate severity, and met the criteria to be cured for discharge according to the Vietnam Ministry ofHealth's COVID-19 Diagnosis and Treatment Guidelines.Results: Common clinical manifestations at 3 month post infection were: cough (50%), fatigue (31.9%),sore throat (29.7%); 6 months post infection were: hair loss (9%), cough (6.6%), muscle and joint pain(1.8%). The number and severity of clinical manifestations in the 6-month post-discharge period werefewer and milder than in the 3-month post-discharge.Conclusion: The number and severity of clinical manifestations increase in 3-month post-discharge butsignificantly decrease in 6-month post-discharge.

PREVALENCE OF HEPATITIS B AND THE CONCENTRATION OF HEPATITIS B SURFACE ANTIBODY IN THE PATIENT VISITED NATIONAL HOSPITAL FOR TROPICAL DISEASES

Background: Hepatitis B virus infection is currently a major health burden, especially in developing countries. The World Health Organization estimates that 296 million people are living with chronic hepatitis B, with 1.5 million new infections each year, of which 90% are undiagnosed and only about 2% of peopleare infected. Hepatitis B is treated with antiviral drugs. Achieving the goal of eliminating viral hepatitis by 2030 requires significantly increasing screening tests to find infected people and determining HBs antibody levels for vaccination is essential.Objectives: Determine the prevalence of hepatitis B virus infection and the concentration of hepatitis B surface antibody (Anti-HBs/HBsAb) in patients visiting National Hospital for Tropical Diseases.Methods and participants: Cross-sectional study on 576 patients examined at the National Hospital of Tropical Diseases from August 1, 2023 to August 31, 2023.Results: Male accounted for 52.9%, average age: 38.24 ± 18.0 (years old). There were 62 patients infected with HBsAg (+) virus, accounting for 10.8%. The prevalence of HBV infection by age group of patients in the study was highest in the age group 60-86 years old at 16.1%, followed by the 16 - 39 yearold group at 11.8%, the lowest was in the younger group. 16 years old 6.0%. The proportion of HBsAg (+) in men is 12.5% and in women was 9.3%. The proportion of people with anti-HBs (+) or anti-HBs concentration > 10mUI/l is 47%; 53.1% of patients had anti-HBs (-) or anti-HBs concentration < 10mUI/ml. The positive percentage of Anti-HBs in men is 47.1% and in women is 46.8%, the overall rate was 47%. The difference is not statistically significant. The highest proportion of Anti-HBs in the group of aged 60 - 86 is 52.6%, followed by the group under 40-59 years old accounting for 47.5%, the lowest in the group under 16 years old was 44.3%. The difference is statistically significant with p < 0.05.Conclusion: The prevalence of Hepatitis B infection in patients visiting the National Hospital for Tropical Diseases was 10.8%. Hepatitis B vaccination is an effective method to prevent Hepatitis B virus infection.

CLINICAL AND PARACLINICAL CHARACTERISTICS OF FASCIOLIASIS PATIENTS IN THE PERIOD OF 2019 - 2023

Objectives: To describe the clinical andparaclinical characteristics of Fasciola infected patients .Subjets and methods: Cross-sectional descriptive study on 128 patients diagnosed with fascioliasis from January 2019 to June 2023 treated at National Hospital for Tropical Diseases and National Institute of Malariology, Parasitology and Entomology.Results: Clinical symptoms: Right upper quadrant pain accounted for 74.2%, followed by epigastric pain (44.5%), fatigue and loss of appetite (43.8%), weight loss (42.2%), fever (39.8%) and hepatomegaly (7%). Paraclinical findings: Hypereosinophilia accounted for 75%, elevation of AST and ALT accounted for12.5% and 24.2%, respectively. 91% of patients were positive with anti-fasciola antibodies by ELISA testing, 24% of them had fasciola’s eggs in stool. 100% of patients had liver lesions on ultrasound, of which 62.5% were found in the right liver. The lesions sized from 3 - 5,9 cm in 35.9% and from 6 - 8,9 cm in 38.3% of patients.Conclusions: Clinical and paraclinical characteristics of patients infected with fascioliasis are very diverse. Diagnosis should be based on the combination of clinical features, hypereosinophilia, fasciola antibodies and ultrasound images.

DIAGNOSTIC MODEL OF TALAROMYCOSIS IN HIV/AIDS PATIENTS

Introduction: Talaromycosis (formerly penicilliosis), one of the most important opportunistic infections in Southeast Asia, is a common cause of HIV-AIDS-associated death. The current diagnosis of Talaromyces marneffei relies on culture. As microbiological results are often late, taking up to 14 days for pathogens isolation, the mortality rate is high. Serum Mp1p ELISA test was used to determine an earlier diagnosis of Talaromycosis. The research objectives were: (1) to determine the cut-off value, sensitivity, and specificity of the Mp1p ELISA test in AIDS patients; (2) to develop diagnostic models (with and without Mp1p ELISA test) of talaromycosis in AIDS patients. Methods: A descriptive cross-sectional study. HIV-infected patients aged ≥18 years with TCD4 <100 cells/mm3 admitted to Ward E, Hospital for Tropical Diseases from June 2017 to July 2019 were recruited. Data analysis using SPSS 25.0 software. A receiver operating characteristic (ROC) curve and Youden index on the ROC curve was used to determine the cut-off value. The area under the ROC curve (AUC) and the 95% confidence intervals (CIs) were used to determine the discrimination power between cases and controls. Chi-square test, odds ratio (OR), and 95% confidence interval were used to find associations among variables. After multivariate analysis, the model of talaromycosis diagnosis was built by Monogram in R.3.6.3 software. Results: 533 patients meeting the inclusion criteria were enrolled. 78.4% were male; the median age was 34 years (IQR: 29-40), and 77.5% were <40 years-old groups. 70 patients diagnosed with Talaromycosis were compared with other opportunistic infected participants (OIs).. The maximum Youden index=0,856 in correlation with the 0,22 OD cut-off value of serum Mp1p presents the highest sensitivity and specificity, with SEN = 88.6% and SPE = 97.0%, respectively. Two models (with and without serum Mp1p) were built based on the adjusted OR of risk factors. Two models based on living areas, skin lesions, low platelet, and Mp1p result. The two models have high accuracy in diagnostic talaromycosis. The SEN and SPEC of the model without Mp1p were 68.6% and 98.1%, and the SEN and SPEC of the model with Mp1p were 85.7% and 98.7%. Recommendation: Serum Mp1p ELISA as well as Diagnostic models of talaromycosis are considered as novel tools for early diagnosis of Talaromycosis in AIDS patients.

Public healthcare system utilization for chronic hepatitis C infection in Vietnam

BackgroundHealthcare utilization is typically adversely affected when the treatment is expensive and requires multiple visits. We examined the determinants of healthcare-seeking for Hepatitis C virus (HCV) infection which is asymptomatic, chronic, and requires costly treatment in an urban tertiary care referral hospital in Vietnam.MethodsWe conducted a secondary analysis of hospital data for patients attending the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam between 2017 and 2020 specifically for HCV infection treatment. Poisson regression was used to determine the effect of personal factors (age, sex, comorbidities) and structural factors (health insurance, proximity to the facility, seasonality, year of visit) on the number of hospital visits.ResultsFrom 2017 to 2020 a total of 22,052 eligible patients sought treatment in the hospital. Among the patients, 50.4% were males and 58.7% were > 50 years of age. The mean number of visits per person was 2.17. In the multivariate analysis compared to 2017, the number of hospital visits increased by 4% in 2018 and then significantly decreased in 2019 and 2020. Visit numbers were significantly lower (6%) among South East region residents compared to those from Central Highlands and for those who lived further away from the hospital. The visit numbers were significantly higher among older age groups (5–11%), those with health insurance (6%), and those with comorbidities (5%) compared to others. Although the number of hospital visits by females was higher (7%) than males in 2017, it significantly decreased in subsequent years.ConclusionsOur study indicated that there are both structural and individual factors affecting the number of visits for HCV treatment. To meet the global strategy for elimination of HCV, Vietnam Government needs to address the structural and personal barriers to healthcare seeking, with a special focus on women.

Gametocyte prevalence and risk factors of P. falciparum malaria patients admitted at the Hospital for Tropical Diseases, Thailand: a 20-year retrospective study

BackgroundThe incidence of malaria in Thailand has dramatically declined over the past two decades, and the goal is to eliminate malaria by 2025. Despite significant progress, one of the key challenges to malaria elimination are undetected gametocyte carriers. Human migration adds complexity to the malaria situation, as it not only sustains local transmission but also poses the risk of spreading drug-resistant parasites. Currently, no study has assessed the prevalence of gametocytes across multiple years in Plasmodium falciparum malaria patients in Thailand, and the risk factors for gametocyte carriage have not been fully explored.MethodsMedical records of all P. falciparum malaria patients admitted from January 1, 2001 to December 31, 2020 at the Hospital for Tropical Diseases, Thailand, were retrospectively examined and a total of 1962 records were included for analysis. Both P. falciparum parasites and gametocytes were diagnosed by microscopy. A regression model was used to evaluate predictors of gametocyte carriage.ResultsThe study demonstrated gametocyte prevalence in low malaria transmission areas. Nine risk factors for gametocyte carriage were identified: age between 15 and 24 years [adjusted odds ratio (aOR) = 1.96, 95% confidence interval (CI) 1.18−3.26], Karen ethnicity (aOR = 2.59, 95% CI 1.56−4.29), preadmission duration of fever > 7 days (aOR = 5.40, 95% CI 3.92−7.41), fever on admission (> 37.5 °C) (aOR = 0.61, 95% CI 0.48−0.77), haemoglobin ≤ 8 g/dL (aOR = 3.32, 95% CI 2.06−5.33), asexual parasite density > 5000−25,000/µL (aOR = 0.71, 95% CI 0.52−0.98), asexual parasite density > 25,000−100,000/µL (aOR = 0.74, 95% CI 0.53−1.03), asexual parasite density > 100,000/µL (aOR = 0.51, 95% CI 0.36−0.72), platelet count ≤ 100,000/µL (aOR = 0.65, 95% CI 0.50−0.85, clinical features of severe malaria (aOR = 2.33, 95% CI 1.76−3.10) and dry season (aOR = 1.41, 95% CI 1.10−1.80). An increasing incidence of imported transnational malaria cases was observed over the past two decades.ConclusionsThis is the first study to determine the prevalence of gametocytes among patients with symptomatic P. falciparum malaria, identify the risk factors for gametocyte carriage, and potential gametocyte carriers in Thailand. Blocking transmission is one of the key strategies for eliminating malaria in these areas. The results might provide important information for targeting gametocyte carriers and improving the allocation of resources for malaria control in Thailand. This study supports the already nationally recommended use of a single dose of primaquine in symptomatic P. falciparum malaria patients to clear gametocytes.Graphical

Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial

Molnupiravir and ritonavir-boosted nirmatrelvir are the two leading oral COVID-19 antiviral treatments, but their antiviral activities in patients have not been compared directly. The aim of this ongoing platform trial is to compare different antiviral treatments using the rate of viral clearance as the measure of antiviral effect. PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. The component of the trial reported here was conducted in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. We recruited low-risk adult patients aged 18-50 years with early symptomatic COVID-19 (<4 days of symptoms). Eligible patients were randomly assigned using block randomisation via a centralised web app to one of seven treatment groups: molnupiravir, ritonavir-boosted nirmatrelvir, casirivimab-imdevimab, tixagevimab-cilgavimab, favipiravir, fluoxetine, or no study drug. The no study drug group comprised a minimum proportion of 20% of patients at all times, with uniform randomisation ratios applied across the active treatment groups. Results for the concurrently randomised molnupiravir, ritonavir-boosted nirmatrelvir, and no study drug groups are reported here. The primary endpoint was the rate of oropharyngeal viral clearance assessed in a modified intention-to-treat population, defined as patients with more than 2 days of follow-up. Safety was assessed in all participants who took at least one dose of the medication. The viral clearance rate was derived under a Bayesian hierarchical linear model fitted to the log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 1 week (18 measurements). Treatment groups with a probability of more than 0·9 that viral clearance was accelerated by more than 20% compared with no drug entered a non-inferiority comparison (with a 10% non-inferiority margin) compared with the platform's current most effective drug. This ongoing trial is registered at ClinicalTrials.gov, NCT05041907. Between June 6, 2022, and Feb 23, 2023, 209 patients in Thailand were enrolled and concurrently randomly assigned to molnupiravir (n=65), ritonavir-boosted nirmatrelvir (n=59), or no study drug (n=85). 129 (62%) of the patients were female and 80 (38%) were male. Relative to the no study drug group, the rates of viral clearance were 37% (95% credible interval 16-65) faster with molnupiravir and 84% (54-119) faster with ritonavir-boosted nirmatrelvir. In the non-inferiority comparison, viral clearance was 25% (10-38) slower with molnupiravir than ritonavir-boosted nirmatrelvir. Molnupiravir was removed from the study platform when it reached the prespecified inferiority margin of 10% compared with ritonavir-boosted nirmatrelvir. Median estimated viral clearance half-lives were 8·5 h (IQR 6·7-10·1) with ritonavir-boosted nirmatrelvir, 11·6 h (8·6-15·4) with molnupiravir, and 15·5 h (11·9-21·2) with no study drug. Viral rebound occurred more frequently following nirmatrelvir (six [10%] of 58) compared with the no study drug (one [1%] of 84; p=0·018) or the molnupiravir (one [2%] of 65; p=0·051) groups. Persistent infections following molnupiravir had more viral mutations (three of nine patients had an increased number of single nucleotide polymorphisms in samples collected at 7 or more days compared with those at baseline) than after nirmatrelvir (zero of three) or no study drug (zero of 19). There were no adverse events of grade 3 or worse, or serious adverse events in any of the reported treatment groups. Both molnupiravir and ritonavir-boosted nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance in patients with COVID-19, but the antiviral effect of ritonavir-boosted nirmatrelvir was substantially greater. Measurement of oropharyngeal viral clearance rates provides a rapid and well tolerated approach to the assessment and comparison of antiviral drugs in patients with COVID-19. It should be evaluated in other acute viral respiratory infections. Wellcome Trust through the COVID-19 Therapeutics Accelerator.

Magnitude, Patterns, and Associated Predictors of Cardiovascular Events in Tetanus: A 2-Year, Single-Center, Ambidirectional Cohort Study Involving 572 Patients.

Cardiovascular events (CEs) remain the leading cause of death in patients with tetanus. We examined the incidence, patterns, and associated predictors of CEs among patients with tetanus in Vietnam. An ambidirectional cohort study was conducted on hospitalized adult patients with tetanus at the Hospital for Tropical Diseases between 2019 and 2020. Information on demographics, tetanus disease, CEs and outcomes were collected. Among all 572 included patients, CEs accounted for 10.8% (95%CI 8.6-13.7%) and included Takotsubo cardiomyopathy (40.3%, 95%CI 29.0-52.8%), arrhythmia (19.4%, 95%CI 11.4-30.9%), sudden cardiac arrest (16.1%, 95%CI 9.0-27.2%), myocardial infarction (11.3%, 95%CI 5.6-21.5%), heart failure (6.5%, 95%CI 2.5-15.4%) and pulmonary embolism (6.5%, 95%CI 2.5-15.4%). CEs occurred from day 5 to 20 of illness. Among 62 CE patients, 21% (95%CI 12.7-32.6%) died and 61.3% (95%CI 48.9-72.4%) developed autonomic nervous system dysfunction (ANSD). Three-fourths (24/32) of patients with Takotsubo cardiomyopathy or myocardial infarction had ANSD. CEs were significantly associated with modified Ablett scores (AOR = 2.42, 95%CI 1.1-5.6, P = .04), underlying diseases (AOR = 2.7, 95%CI 1.1-6.8, P = .04) and overweight (AOR = 0.18, 95%CI .04-.8, P = .02). CEs are not rare and associated with high mortality. The most common CE is Takotsubo cardiomyopathy. CEs can occur at any stage of illness, with or without ANSD. To prevent mortality, it is pivotal to screen CEs in patients with tetanus, especially those with underlying diseases, high modified Ablett scores, and a normal or low BMI. More studies are needed to fully elucidate the impact of ANSD on the cardiovascular function and the CE associated mortality in tetanus.

Prevalence of hypertension among travelers and stability of blood pressure control during travel: a cross-sectional descriptive study and prospective cohort study

BackgroundHypertension is a common and important risk factor for cardiovascular disease which is the leading cause of death among the general population and travelers. Data on hypertension among travelers are very limited due to the scarcity of research reports in this specific population. Therefore, this study aimed to determine the prevalence of hypertension among adult travelers and the stability of blood pressure control during international trips using a mobile automated blood pressure device.MethodsThis was a cross-sectional descriptive study conducted at the Thai travel clinic, Hospital for Tropical Diseases in Bangkok, Thailand. All adult travelers completed a questionnaire which included demographic data, medical history, medication use, trip characteristics and hypertension awareness and knowledge. Standard two time blood pressure measurements were performed at the clinic to detect possible undiagnosed hypertension. Travelers with pre-existing hypertension were also invited to monitor their blood pressure level before and during their trip for a total of 14 days by using an automated blood pressure device and reporting the readings back to the study team.ResultDuring July and October 2022, a total of 1,359 adult travelers visited the Thai Travel Clinic before their international trip. The overall prevalence of hypertension was 28.8%, including those with pre-existing hypertension (6.7%) and those with newly diagnosed hypertension (22.2%). Travelers with newly diagnosed hypertension were significantly younger than travelers with pre-existing hypertension (38.5 years vs. 55.6 years, p < 0.001). Eleven travelers agreed to monitor their blood pressure, Most (90.9%, 10/11) had stable blood pressure control during their trip. One participant had > 10 mmHg higher blood pressure during the trip, however this was not clinically significant. All participants remained well, and acute symptoms secondary to hypertension were not reported.ConclusionUp to 28.8% of adult travelers seen in pre-travel consultations had hypertension. Most of them were unaware of their blood pressure condition. Vital signs including blood pressure should be evaluated in all pre-travel visits in order to prevent undiagnosed severe hypertension that might lead to hypertensive crisis.

Automated pupillometry and optic nerve sheath diameter ultrasound to define tuberculous meningitis disease severity and prognosis

BackgroundTuberculous meningitis (TBM) causes high mortality and morbidity, in part due to raised intracranial pressure (ICP). Automated pupillometry (NPi) and optic nerve sheath diameter (ONSD) are both low-cost, easy-to-use and non-invasive techniques that correlate with ICP and neurological status. However, it is uncertain how to apply these techniques in the management of TBM. MethodsWe conducted a pilot study enrolling 20 adults with TBM in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Our objective was to investigate the relationships between baseline and serial measurements of NPi and ONSD and disease severity and outcome. Serial NPi and ONSD were performed for 30 days, at discharge, and at 3-months, with measurements correlated with clinical progression and outcomes. ResultsONSD and NPi measurements had an inverse relationship. Higher ONSD and lower NPi values were associated with lower Glasgow coma score. Baseline NPi was a strong predictor 3-month outcome (median NPi 4.55, interquartile range 4.35–4.65 for good outcomes versus 2.60, IQR 0.65–3.95 for poor outcomes, p = 0.002). Pupil inequality (NPi ≥0.7) was also strongly associated with poor 3-month outcomes (p = 0.006). Individual participants' serial NPi and ONSD were variable during initial treatment and correlated with clinical condition and outcome. ConclusionPupillometry and ONSD may be used to predict clinical deterioration and outcome from TBM. Future, larger studies are need explore the optimal timing of measurements and to define how they might be used to optimise treatments and improve outcomes from TBM.

Role of TaqMan array card in determining causative organisms of acute febrile illness in hospitalized patients.

Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.

BI02 Disseminated toxoplasmosis presenting as panniculitis in an immunocompromised patient

Abstract Inflammatory dermatoses and inflammatory reaction patterns to underlying systemic disease are relatively uncommon in immunosuppressed organ transplant recipients (OTRs) and infection should always be suspected as a possible cause. We present an OTR with biopsy-proven panniculitis resulting from disseminated toxoplasmosis, only identified after extensive histological analysis. A 45-year-old Nigerian woman who was profoundly immunocompromised through a combination of a kidney transplant 12 months earlier, hyposplenism due to sickle cell anaemia and a CD4+ count 74 × 106 cells L–1 (&amp;gt; 455 × 106 L–1) presented with a 3-month history of &amp;gt; 20 painful, red–purple and hyperpigmented subcutaneous nodules and plaques up to 2 cm in diameter limited to her legs, associated with fatigue and weight loss. She only had childhood contact with cats. There was no lymphoedema or lymphadenopathy, and she was HIV negative. Urgent skin biopsy excluded Kaposi sarcoma and demonstrated a lobular, necrotizing panniculitis, a mixed inflammatory cell infiltrate and evidence of vasculitis. The cause was unclear; cultures for mycobacterial, fungal and bacterial infections were negative. However, on rereview of histology, within areas of inflammation and necrosis in the subcutaneous fat, there were a few scattered structures (10–30 μm in diameter) consisting of small basophilic periodic acid–Schiff-positive ‘dots’ within bright eosinophilic cytoplasm, raising the possibility of toxoplasmosis. Toxoplasma immuno­staining was positive. Further tertiary review of histology and immunostaining by the Hospital for Tropical Diseases agreed that there was no other causative organism and the panniculitis and vasculitis were consistent with active toxoplasmosis. The diagnosis of toxoplasma reactivation was supported by positive toxoplasma IgG on pretransplant bloods. Magnetic resonance imaging of the head was consistent with cerebral toxoplasmosis. She received treatment with clindamycin, pyrimethamine and folinic acid and, thereafter, long-term cotrimoxazole prophylaxis. Cutaneous toxoplasmosis is rare, with only three reported cases over the last 10 years. Historically, a wide spectrum of clinical morphologies has been described, including maculopapular rashes, nodules, ulcers, dermatomyositis and even mimicry of varicella and graft-versus-host disease. Most cases affect immunocompromised patients. In our patient, this was the result of reactivation of latent infection, which is more common in West Africa, coinciding with profound immunosuppression. In our case, a diagnosis was only made after extensive histological review. Given the varied morphologies of clinical presentations, it is possible that this condition may be easily missed, with potentially serious consequences. In summary, we highlight the importance of maintaining a high index of suspicion for infection and the need for careful clinicopathological correlation in OTRs presenting with apparently atypical inflammatory skin lesions.