Pneumococcal Conjugate Vaccine impact assessment in Bangladesh [version 1; referees: 1 approved, 2 approved with reservations]

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh’s national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia.  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Evaluation of the quality of dried distiller's grains with solubles for normal and high sugary corn genotypes during dry–grind ethanol production

High sugary corn genotypes (HSGs; Zea mays L.) have shown the potential to produce higher amounts of ethanol consuming lower quantity of enzymes during dry-grind (DG) ethanol production compared with those of parent field corn lines (PFCs). Dried distiller's grains with solubles (DDGS) is an important co-product for a DG plant, where the market value of DDGS is affected by its quality, particularly the physicochemical composition. In the present work, DDGS samples were studied for both HSGs and PFCs in a conventional and a non-cooking DG ethanol method under two enzymatic conditions to evaluate DDGS composition of the corn genotypes. Irrespective of the enzymatic conditions, the average yield of DDGS among the corn genotypes ranged from 25.07% to 32.44% for the conventional and 26.97%–31.69% for the non-cooking method. Compared to the DDGS of HSGs, significantly higher amounts of starch were recorded in the DDGS of PFCs in both methods when enzyme load was the lowest. Protein content in DDGS samples did not differ significantly between the two enzyme loads and the DG methods individually, but the combined effects of genotypes and DG methods had significant effects on the protein content. All the biochemical components of corn kernels significantly correlated with the respective components in DDGS under all conditions. In conclusion, HSGs produced DDGS with higher amounts of protein and ash, but lower amount of starch than those of PFCs

A comparative evaluation of agronomic performance and kernel composition of normal and high sugary corn genotypes (Zea mays L.) grown for dry-grind ethanol production

High sugary corn genotypes (Zea mays L.) have the potential to reduce enzyme consumption and enhance ethanol yield during dry-grind ethanol production. In the present work, four high sugary and four parent field corn genotypes (HSGs and PFCs, respectively) were studied comparatively to evaluate agronomic performance and kernel composition of the genotypes, as well as predict the effects of these traits on carbohydrate accumulation in the kernels. The corn genotypes were grown over two cropping years (2012 and 2013) under rain fed conditions, and some important agronomic traits and kernel biochemical components were determined. Both HSGs and PFCs varied in the agronomic properties, but these variations were not atypical in HSGs if compared with those of PFCs. The average grain yield ranged from 6.19 Mega gram per hectare (Mg/ha) to 9.43 Mg/ha in HSGs and 5.77 Mg/ha to 10.23 Mg/ha in PFCs. Sugar accumulation in the kernels was found to be negatively correlated with flowering time, grain filling period and physiological maturity of the genotypes. Compared with PFCs, a higher amount of total soluble sugars (TSS) and a lower quantity of starch were recorded in HSGs, which resulted a significant negative correlation between kernel starch and TSS. The agronomic performance and kernel composition of HSGs, particularly with high kernel sugars and low starch contents suggest that these corn genotypes could be promising candidates for producing cost-effective ethanol during dry-grind process

A comparative study on normal and high sugary corn genotypes for evaluating enzyme consumption during dry-grind ethanol production

The necessity of amylolytic enzymes to convert starch into glucose during ethanol production is considered one of the cost increasing factors for corn ethanol. Enzyme consumption could be decreased partially by increasing free sugar contents in corn kernels that will be released and fermented simultaneously with the product of starch hydrolysis, producing an additional amount of ethanol without consuming any enzyme. The present work was conducted to evaluate the effects of grain sugar on the fermentable sugar and ethanol yields as well as enzyme requirement using four high sugary corn genotypes (HSGs) and their parent field corn lines (PFCs). The reducing sugar yield in HSGs did not vary significantly above the enzyme load of 1.5. kg/MT of dry corn, while PFCs showed a range between 2.0 and 2.5. kg/MT. The average final ethanol concentrations in HSGs and PFCs ranged from 15.25% to 17.5%. (v/v) and 11.66% to 13.65%, respectively with the enzyme load at 1.5. kg/MT, which reached to 16.49-17.94% in HSGs and 14.32-16.85% in PFCs as the enzyme load increased to 2.0. kg/MT. These results suggest that high sugar content in corn kernels has the potential for decreasing enzyme consumption during dry-grind ethanol production with higher yields

Evaluation of high sugar containing corn genotypes as viable feedstocks for decreasing enzyme consumption during dry-grind ethanol production

Requirement of costly enzymes (α-amylase and glucoamylase) for converting starch into glucose before fermentation is considered one of the cost increasing factors for corn ethanol. Enzyme consumptions can possibly be reduced during dry-grind ethanol production by increasing free sugar contents in corn kernels that will be released and fermented simultaneously with the product of starch hydrolysis, producing an additional amount of ethanol without consuming any enzyme. A comparative study was conducted to evaluate the effect of kernel sugars on enzyme requirement and yields of both hydrolysis and fermentation, using four high sugary corn genotypes (HSGs) and their parent field corns (PFCs). Enzymatic hydrolysis of the genotypes with four enzyme loads (1, 2, 3 and 4 kg MT-1 of dry corn) showed that HSGs produced higher proportions of reducing sugars (RS) in all conditions than PFCs did. Sufficient amounts of RS were produced by HSGs utilizing an enzyme load of 3 kg MT-1, whereas, PFCs consumed 4 kg MT-1 for their best yields. Likewise, HSGs produced higher concentrations of ethanol consuming lower amount of enzymes during fermentation. Therefore, HSGs could be considered as potential feedstocks for enhancing ethanol yield and reducing enzyme consumptions during dry-grind ethanol production

Clinical Characteristics and Predictors of Mortality in Elderly Patients Hospitalized with COVID-19 in Bangladesh: A Multicenter, Retrospective Study

Purpose. Elderly patients are at high risk of fatality from COVID-19. The present work aims to describe the clinical characteristics of elderly inpatients with COVID-19 and identify the predictors of in-hospital mortality at admission. Materials and Methods. In this retrospective, multicenter cohort study, we included elderly COVID-19 inpatients (n = 245) from four hospitals in Sylhet, Bangladesh, who had been discharged between October 2020 and February 2021. Demographic, clinical, and laboratory data were extracted from hospital records and compared between survivors and nonsurvivors. We used univariable and multivariable logistic regression analysis to explore the risk factors associated with in-hospital death. Principal Results. Of the included patients, 202 (82.44%) were discharged and 43 (17.55%) died in hospital. Except hypertension, other comorbidities like diabetes, chronic kidney disease, ischemic heart disease, and chronic obstructive pulmonary disease were more prevalent in nonsurvivors. Nonsurvivors had a higher prevalence of leukocytosis (51.2 versus 30.7; p=0.01), lymphopenia (72.1 versus 55; p=0.05), and thrombocytopenia (20.9 versus 9.9; p=0.07). Multivariable regression analysis showed an increasing odds ratio of in-hospital death associated with older age (odds ratio 1.05, 95% CI 1.01–1.10, per year increase; p=0.009), thrombocytopenia (OR = 3.56; 95% CI 1.22–10.33, p=0.019), and admission SpO2 (OR 0.91, 95% CI 0.88–0.95; p=0.001). Conclusions. Higher age, thrombocytopenia, and lower initial level of SpO2 at admission are predictors of in-hospital mortality in elderly patients with COVID-19

Paraquat induced acute kidney injury and lung fibrosis: a case report from Bangladesh

Abstract Background Since Bangladesh government issued a ban on the use of highly toxic WHO Class I pesticides, annual consumption of herbicides like Paraquat have been sharply increasing in the markets. Paraquat poisoning is an emerging public health threat and its high mortality rate is responsible for a significant number of deaths. Diagnostic limitations and unavailable sample at presentation have resulted in under-reporting and lack of awareness among the treating physicians, making Paraquat poisoning one of the most neglected toxicological emergencies. Herein, we present a case of Paraquat induced multi-organ failure and emphasis on pitfalls in the management. Case presentation An 18-years-old healthy male was admitted in Sylhet M.A.G Osmani Medical College Hospital with history of attempted suicide by Paraquat ingestion. On admission, he had high serum creatinine but otherwise asymptomatic. He was discharged on day 10 when his renal functions returned to normal. But On day 15, he started having respiratory symptoms—unresponsive to any of the local treatments he received, and by day 30, he developed overt lung fibrosis. We present sequential blood picture, radiographs and CT scans demonstrating Paraquat induced kidney and lung injury over the course of 30 days. Conclusion Paraquat poisoning can lead to death and fatal long-term consequences. All cases of Paraquat poisoning, regardless of symptoms, must be hospitalized and observed for early detection of complications. Distribution of Paraquat should be restricted and/or banned as 38 other countries have done so, which we believe will greatly reduce poisoning related mortality