Quantitative bacterial counts in the bone marrow of Vietnamese patients with typhoid fever

Background Bone marrow culture (BMC) is the reference standard for typhoid fever diagnosis. We studied the additional yield of BMC over blood culture (BC) and the relationship between quantitative BMC counts and severe disease. Methods Hospitalised Vietnamese patients with suspected typhoid fever were prospectively investigated with a BC, BMC, faecal culture and quantitative BMC counts. Results Salmonella typhi was isolated in 195 of 231 patients: from BC and BMC in 144 (73.8%), from BMC alone in 33 (16.9%), from BC alone in 12 (6.2%) and from faeces alone in 6 (3.1%). In 167 patients the median extracellular count of S. typhi was 2.5 cfu/mL (interquartile range [IQR] 0–10) and the intracellular count was 10.5 cfu/mL (IQR 2–42) with a ratio of 1.3 bacteria/cell (IQR 0.6–2.5). The median count of intracellular bacteria in 24 patients with severe disease was 46 bacteria/cell (IQR 9–105) compared with 6.5 bacteria/cell (IQR 2–34) in 143 with non-severe disease (p=0.005). The intracellular BMC count was negatively correlated with the peripheral white cell count and positively correlated with hepatomegaly, splenomegaly, aspartate transaminase, a positive BC and the fever clearance time following treatment with azithromycin, ofloxacin or a combination of the two. Conclusions BMC gave a moderate additional yield over BC. Intracellular BMC counts may reflect the bacterial load in typhoid fever

ẢNH HƯỞNG CỦA MỘT SỐ YẾU TỐ ĐẾN QUÁ TRÌNH CHẾ TẠO NANO BẠC SỬ DỤNG DỊCH CHIẾT LÁ VỐI LÀM TÁC NHÂN KHỬ

In this study, we use the aqueous extract of Robusta plant leaves as a reducing agent and alginate as a surfactant to synthesize silver nanoparticles from silver nitrate (AgNO3). The influence of extraction time and the solid-liquid ratio, the concentration of AgNO3, the volume ratio between silver nitrate solution and the extract of Robusta leaves, and the reaction time on the synthesis were investigated. The optimal conditions are as follows: 15 g of leaves/200 mL, silver nitrate concentration 4 mM, Vextract/VAgNO3 4:100, 1% sodium alginate solution, and reaction time 45 minutes. The obtained solution of silver nanoparticles has a yellow-brown color. The TEM, XRD, and FT-IR measurements of the samples show that the silver nanoparticles have been successfully synthesized. The particles are spherical with an even size and 19.0-26.6 nm in diameter.Trong nghiên cứu này, chúng tôi trình bày phương pháp điều chế dung dịch nano bạc (Ag) từ bạc nitrate (AgNO3) sử dụng dịch chiết lá vối làm tác nhân khử và alginate là chất hoạt động bề mặt. Chúng tôi khảo sát ảnh hưởng của nồng độ AgNO3, tỷ lệ thể tích giữa AgNO3 và dịch chiết lá vối và thời gian phản ứng đến quá trình tạo nano Ag. Điều kiện tối ưu để tổng hợp nano Ag sử dụng dịch chiết lá vối gồm nồng độ AgNO3 4 mM, tỷ lệ thể tích Vdịch chiết /VAgNO3 = 4:100, nồng độ alginate 1%, thời gian phản ứng 45 phút tại nhiệt độ phòng. Dung dịch nano Ag thu được có màu vàng nâu đồng nhất. Kết quả đo TEM, SEM, XRD và FT-IR của các mẫu cho thấy nano Ag đã được tổng hợp thành công; hạt nano có dạng hình cầu, cấu trúc đồng đều với kích thước hạt khoảng 19,0–26,6 nm

Prevalence of carbapenem resistance and its potential association with antimicrobial use in humans and animals in rural communities in Vietnam

Background Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant Enterobacteriaceae (CRE), particularly Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) and also Acinetobacter baumannii (CRAB) are emerging threats worldwide. Methods We investigated healthy humans (n = 652), chickens (n = 237), ducks (n = 150) and pigs (n = 143) in 400 small-scale farms in the Mekong Delta of Vietnam. Samples (rectal swabs, faecal swabs) were investigated for carriage of CRE/CRAB and were further characterized phenotypically and genotypically. Results In the Mekong Delta of Vietnam, the prevalence of CRE isolates in human rectal swabs was 0.6%, including 4 CREC and 1 CRKP. One pig was infected with CREC (prevalence 0.7%). CRAB was isolated from chickens (n = 4) (prevalence 2.1%) and one duck (prevalence 0.7%). CRKP was isolated from a human who was also colonized with CREC. The CRKP strain (ST16), from an 80 year-old person with pneumonia under antimicrobial treatment, genetically clustered with clinical strains isolated in a hospital outbreak in southern Vietnam. The prevalence of CRE was higher among humans that had used antimicrobials within 90 days of the sampling date than those had not (4.2% versus 0.2%) (P = 0.005). All CRE/CRAB strains were MDR, although they were susceptible to colistin and neomycin. The carbapenemase genes identified in study strains were blaNDM and blaOXA. Conclusions The finding of a CRKP strain clustering with previous hospital outbreak raises concerns about potential transmission of carbapenem-resistant organisms from hospital to community settings or vice-versa

Natural and recombinant equine chorionic gonadotropins past and future in animal reproductive technology

Equine Chorionic Gonadotropin (eCG) previously named Pregnant Mare Serum Gonadotropin (PMSG) has been widely used since the 40s in animal reproduction control. It is extracted from the blood of pregnant mares between days 40 and 120 of gestation. Animal welfare organizations have voiced concerns against mares bleeding conditions. There is currently no effective substitute for the natural PMSG. In this review, we summarize the basic knowledge of the structure and biology of eCG, and the research on recombinant eCG production in the past five years

A study of consumer behavior and willingness to pay towards cosmetic products of generation Z in Hochiminh city

The global cosmetics industry is experiencing robust growth and Generation Z (Gen Z) is a potential customer source of this market. This research examines customers’ intentions to purchase cosmetic goods of Gen Z in Hochiminh city using perceived value factors as the antecedents of attitude in the model. A cross-sectional study, applying a convenient sampling method, was conducted to collect data from Gen Z people in January 2023. There were no specific cosmetics products included in the study. Descriptive analysis and Partial Least Square (PLS) method of Structural Equation Modeling (SEM) with SmartPLS 4.0.8.7 software were used to analyze the research data. The PLS-SEM analysis of 723 responses showed that attitudes toward purchasing cosmetic products are significantly positively impacted by perceived environmental value. A more positive attitude would result from increased brand credibility and product understanding of cosmetics. There was no evidence to support the impact of other perceived values (specifically, health, safety, social, spiritual, and ethical) on attitudes toward consumer behavior. Attitude was important in predicting willingness to pay (both direct and indirect). This study helps industry professionals to advance the qualities of cosmetic products by increasing and improving environmental value, product knowledge, and brand credibility. The eco-friendly pattern of production and marketing strategies focusing on product ingredients, manufacturing processes, and quality standards are necessary to enhance brand credibility and product understanding, align with consumer preferences and achieve greater success in the market

A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial

Background: Late treatment failures after artemisinin-based combination therapies (ACTs) for falciparum malaria have increased in the Greater Mekong subregion in southeast Asia. Addition of amodiaquine to artemether-lumefantrine could provide an efficacious treatment for multidrug-resistant infections. Methods: We conducted an open-label, randomised trial at five hospitals or health centres in three locations (western Cambodia, eastern Cambodia, and Vietnam). Eligible participants were male and female patients aged 2-65 years with uncomplicated Plasmodium falciparum malaria. Patients were randomly allocated (1:1 in blocks of eight to 12) to either artemether-lumefantrine alone (dosed according to WHO guidelines) or artemether-lumefantrine plus amodiaquine (10 mg base per kg/day), both given orally as six doses over 3 days. All received a single dose of primaquine (0·25 mg/kg) 24 h after the start of study treatment to limit transmission of the parasite. Parasites were genotyped, identifying artemisinin resistance. The primary outcome was Kaplan-Meier 42-day PCR-corrected efficacy against recrudescence of the original parasite, assessed by intent-to-treat. Safety was a secondary outcome. This completed trial is registered at ClinicalTrials.gov (NCT03355664). Findings: Between March 18, 2018, and Jan 30, 2020, 310 patients received randomly allocated treatment; 154 received artemether-lumefantrine alone and 156 received artemether-lumefantrine plus amodiaquine. Parasites from 305 of these patients were genotyped. 42-day PCR-corrected treatment efficacy was noted in 151 (97%, 95% CI 92-99) of 156 patients with artemether-lumefantrine plus amodiaquine versus 146 (95%, 89-97) of 154 patients with artemether-lumefantrine alone; hazard ratio (HR) for recrudescence 0·6 (95% CI 0·2-1·9, p=0·38). Of the 13 recrudescences, 12 were in 174 (57%) of 305 infections with pfkelch13 mutations indicating artemisinin resistance, for which 42-day efficacy was noted in 89 (96%) of 93 infections with artemether-lumefantrine plus amodiaquine versus 73 (90%) of 81 infections with artemether-lumefantrine alone; HR for recrudescence 0·44 (95% CI 0·14-1·40, p=0·17). Artemether-lumefantrine plus amodiaquine was generally well tolerated, but the number of mild (grade 1-2) adverse events, mainly gastrointestinal, was greater in this group compared with artemether-lumefantrine alone (vomiting, 12 [8%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·03; and nausea, 11 [7%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·05). Early vomiting within 1 h of treatment, requiring retreatment, occurred in no patients of 154 with artemether-lumefantrine alone versus five (3%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·06. Bradycardia (≤54 beats/min) of any grade was noted in 59 (38%) of 154 patients with artemether-lumefantrine alone and 95 (61%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·0001. Interpretation: Artemether-lumefantrine plus amodiaquine provides an alternative to artemether-lumefantrine alone as first-line treatment for multidrug-resistant P falciparum malaria in the Greater Mekong subregion, and could prolong the therapeutic lifetime of artemether-lumefantrine in malaria-endemic populations

Risk factors for the development of severe typhoid fever in Vietnam

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. Methods We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993–1995 and 1997–1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. Results The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035). Conclusions In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation