Effect of Iron Chelation Therapy on Recovery From Deep Coma in Children With Cerebral Malaria

Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine—pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria. (N Engl J Med 1992; 327:1473–7.), CEREBRAL malaria, one of the most severe complications of infection with Plasmodium falciparum, is especially common among young children. Despite therapy with parenteral antimalarial agents and attentive management of complications, the mortality rate is 15 to 50 percent and gross neurologic sequelae persist in about 10 percent of the children who survive.1 2 3 It is estimated that in sub-Saharan Africa alone, over 1 million children die from severe forms of malaria annually.4 , 5 Cerebral malaria is diagnosed when asexual forms of P. falciparum are found in the blood of a patient with signs of an acute, diffuse symmetric encephalopathy not attributable to

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Findings from a Rapid Assessment of Avoidable Blindness (RAAB) in Southern Malawi

BACKGROUND: Data on prevalence and causes of avoidable blindness in Malawi are not readily available. The purpose of this study was to determine the prevalence and causes of blindness in persons aged 50 and above in southern Malawi to plan eye care services for the community. METHODOLOGY: A population-based survey was conducted in 7 districts in southern Malawi. Villages were selected by probability proportionate to size within each district. Clusters were further subdivided into segments. A predetermined number of segments were selected randomly in each cluster. The survey team moved from house to house in each segment until they had examined 50 people over the age of 50. Examination consisted of visual acuity measurement with tumbling "E" chart and ocular examination by an ophthalmologist. Participants were categorized by visual acuity. Those who were visually impaired (VA<6/18 in the better eye with available correction) were assigned a main cause of visual loss. Further information was sought from anyone who had received cataract surgery. RESULTS: A total number of 3,583 persons aged 50 and above were sampled; among these 3,430 (95.7%) were examined. The prevalence of blindness (presenting visual acuity <3/60 in the better eye) among persons aged 50 and above was 3.3% (95% CI 2.5-4.1). Cataract was the most common cause of blindness contributing to 48.2% of all cases, followed by glaucoma (15.8%) and cornea scarring (12.3%). The cataract surgical coverage in blind persons was 44.6%. CONCLUSION: The prevalence of blindness and visual impairment in persons aged 50 and above was lower than the WHO estimate for Malawi. The majority of the causes were avoidable, with cataract accounting for approximately half of all cases of blindness. The data suggests that expansion of eye care programs to address avoidable causes of blindness is necessary in this area of southern Malawi

Findings from a Rapid Assessment of Avoidable Blindness (RAAB) in Southern Malawi

BACKGROUND: Data on prevalence and causes of avoidable blindness in Malawi are not readily available. The purpose of this study was to determine the prevalence and causes of blindness in persons aged 50 and above in southern Malawi to plan eye care services for the community. METHODOLOGY: A population-based survey was conducted in 7 districts in southern Malawi. Villages were selected by probability proportionate to size within each district. Clusters were further subdivided into segments. A predetermined number of segments were selected randomly in each cluster. The survey team moved from house to house in each segment until they had examined 50 people over the age of 50. Examination consisted of visual acuity measurement with tumbling "E" chart and ocular examination by an ophthalmologist. Participants were categorized by visual acuity. Those who were visually impaired (VA<6/18 in the better eye with available correction) were assigned a main cause of visual loss. Further information was sought from anyone who had received cataract surgery. RESULTS: A total number of 3,583 persons aged 50 and above were sampled; among these 3,430 (95.7%) were examined. The prevalence of blindness (presenting visual acuity <3/60 in the better eye) among persons aged 50 and above was 3.3% (95% CI 2.5-4.1). Cataract was the most common cause of blindness contributing to 48.2% of all cases, followed by glaucoma (15.8%) and cornea scarring (12.3%). The cataract surgical coverage in blind persons was 44.6%. CONCLUSION: The prevalence of blindness and visual impairment in persons aged 50 and above was lower than the WHO estimate for Malawi. The majority of the causes were avoidable, with cataract accounting for approximately half of all cases of blindness. The data suggests that expansion of eye care programs to address avoidable causes of blindness is necessary in this area of southern Malawi

Induced ovulation, spawning, egg incubation, and hatching of the cyprinid fish Labeo victorianus in captivity

Ningu Lubeo victorianus is the only labeine fish within Lake Victoria and its catchment (Greenwood 1966; Reid 1985). This species, once widely distributed in the Lake Victoria basin and supporting a commercial fishery until the late 195Os, has declined due to overfishing (Cadwalladr 1965; Ogutu-Ohwayo 1990; Seehausen 1996). The L. victorianus fishery has not only collapsed but the species has also disappeared from some of its former habitats. Recent surveys in Uganda have only found two distant populations-one in the Sio River on the Uganda-Kenya border (0” I3’53”N, 34”00’30’E), and the second in the Kagera River on the Uganda-Tanzania border (0°56’28.1”S, 3 1’46’ 18”E) (Rutaisire 2003) (Fig. 1). Currently, there is growing interest to breed the fish for wild stock enhancement and culture as a food fish

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)