Randomized controlled trial of artesunate or artemether in Vietnamese adults with severe falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Both artemether and artesunate have been shown to be superior to quinine for the treatment of severe falciparum malaria in Southeast Asian adults, although the magnitude of the superiority has been greater for artesunate than artemether. These two artemisinin derivatives had not been compared in a randomized trial.</p> <p>Methods</p> <p>A randomized double blind trial in 370 adults with severe falciparum malaria; 186 received intramuscular artesunate (2.4 mg/kg immediately followed by 1.2 mg/kg at 12 hours then 24 hours then daily) and 184 received intramuscular artemether (3.6 mg per kilogram immediately followed by 1.8 mg per kilogram daily) was conducted in Viet Nam. Both drugs were given for a minimum of 72 hours.</p> <p>Results</p> <p>There were 13 deaths in the artesunate group (7 percent) and 24 in the artemether group (13 percent); P = 0.052; relative risk of death in the patients given artesunate, 0.54; (95 percent confidence interval 0.28-1.02). Parasitaemia declined more rapidly in the artesunate group. Both drugs were very well tolerated.</p> <p>Conclusions</p> <p>Intramuscular artesunate may be superior to intramuscular artemether for the treatment of severe malaria in adults.</p

Effect of rotational inertia on building response to earthquakes via a closed-form solution

In this article, a widely used building model, comprised of uniform coupled flexural and shear beams, herein improved by allowing for the effects of rotational inertia. Closed-form solutions in terms of trigonometric and hyperbolic functions are obtained, allowing for the explicit formulation of period ratios, modal participation factors (MPFs), mode shapes, and mode shape derivatives based solely on displacement response, without coupling with chord rotations, which is the case for the Timoshenko beam model. This makes the model proposed in this study more convenient for assessing building behavior to ground motion, by explicitly highlighting the effect of rotational inertia in their response to earthquakes, making the case for studying its beneficial effects in mitigating response of buildings to ground motion. It is observed that rotational inertia induces mild fundamental period lengthening, while notably reducing period ratios between higher modes and the fundamental one. This can lead to an enhanced response to ground motion showcasing narrow-band characteristics. However, the most severe effect is found to be on the MPF, which is significantly diminished. This leads to important reductions on the overall response, as a consequence of attenuation of the first-mode response, along with severe undercutting of the effects of higher modes. The results demonstrate that without considering the rotational inertia in the assessment of in-plane structural response to horizontal ground motion can lead to conservative results. Moreover, the results showcase the advantages of providing supplemental rotational inertia as a way to improve the seismic behavior of buildings

Combination Antifungal Therapy for Cryptococcal Meningitis

Background Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. Methods We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. Results A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. Conclusions Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found

MARCO variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and Beijing lineage

Macrophage receptor with collagenous structure (MARCO) has an important role in the phagocytosis of Mycobacterium tuberculosis (M. tuberculosis). We hypothesized that MARCO polymorphisms are associated with phagocytosis, tuberculosis (TB) disease susceptibility and presentation, and infecting lineage. We used a human cellular model to examine how MARCO genotype mediates the immune response; a case-control study to investigate tuberculosis host genetic susceptibility; and a host-pathogen genetic analysis to study host-pathogen interactions. Two MARCO heterozygous (AG) genotypes (single-nucleotide polymorphisms rs2278589 and rs6751745) were associated with impaired phagocytosis of M. tuberculosis trehalose 6,6'-dimycolate-cord factor and β-glucan-coated beads in macrophages. The heterozygous genotypes of rs2278589 and rs6751745 were also associated with increased risk of pulmonary TB (PTB; rs2278589, P=0.001, odds ratio (OR)=1.6; rs6751745, P=0.009, OR=1.4), and with severe chest X-ray abnormalities (P=0.007, OR=1.6). These two genotypes were also associated with the Beijing lineage (rs2278589, P=0.001, OR=1.7; rs6751745, P=0.01, OR=1.5). Together, these results suggest that MARCO polymorphisms may regulate phagocytosis of M. tuberculosis and susceptibility and severity of PTB. They also suggest MARCO genotype and Beijing strains may interact to increase the risk of PT

New technologies to improve healthcare in low- and middle-income countries: Global Grand Challenges satellite event, Oxford University Clinical Research Unit, Ho Chi Minh City, 17th-18th September 2019

We report the outputs of a satellite event in Ho Chi Minh City, Vietnam, organized as part of the "2 nd Global Grand Challenges of Engineering Summit". The event considered challenges and potential solutions for improving low- and middle-income country (LMIC) healthcare systems, with particular reference to critical care. Participants from key regional and local stakeholders in healthcare and engineering discussed how new advances in technology, especially in the field of Artificial Intelligence, could be of potential benefit. This article summarizes the perspectives and conclusions of a group of key stakeholders from LMICs across South and South East Asia

Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1–55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1–5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene–bearing strains, and 3 had nontoxigenic tox gene–bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions

A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease

<p>Abstract</p> <p>Background</p> <p>Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome.</p> <p>Methods</p> <p>A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome.</p> <p>Results</p> <p>57 patients were studied. <it>Cryptococcus neoformans var grubii </it>molecular type VN1 caused 70% of infections; <it>C. gattii </it>accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age ≥ 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for <it>C. neoformans var grubii </it>compared with <it>C. gattii </it>(p < 0.001 and p = 0.01 respectively).</p> <p>Conclusion</p> <p>In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to <it>C. neoformans var grubii</it>. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.</p