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BACKGROUND: Helminth and protozoan infections affect more than 1 billion children globally. Improving water quality, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration, while providing other quality of life benefits. METHODS AND FINDINGS: We enrolled geographic clusters of pregnant women in rural western Kenya into a cluster-randomized controlled trial (ClinicalTrials.gov NCT01704105) that tested 6 interventions: water treatment, improved sanitation, handwashing with soap, combined water treatment, sanitation, and handwashing (WSH), improved nutrition, and combined WSH and nutrition (WSHN). We assessed intervention effects on parasite infections by measuring Ascaris lumbricoides, Trichuris trichiura, hookworm, and Giardia duodenalis among children born to the enrolled pregnant women (index children) and their older siblings. After 2 years of intervention exposure, we collected stool specimens from 9,077 total children aged 2 to 15 years in 622 clusters, including 2,346 children in an active control group (received household visits but no interventions), 1,117 in the water treatment arm, 1,160 in the sanitation arm, 1,141 in the handwashing arm, 1,064 in the WSH arm, 1,072 in the nutrition arm, and 1,177 in the WSHN arm. In the control group, 23% of children were infected with A. lumbricoides, 1% with T. trichiura, 2% with hookworm, and 39% with G. duodenalis. The analysis included 4,928 index children (median age in years: 2) and 4,149 older siblings (median age in years: 5); study households had an average of 5 people, <10% had electricity access, and >90% had dirt floors. Compared to the control group, Ascaris infection prevalence was lower in the water treatment arm (prevalence ratio [PR]: 0.82 [95% CI 0.67, 1.00], p = 0.056), the WSH arm (PR: 0.78 [95% CI 0.63, 0.96], p = 0.021), and the WSHN arm (PR: 0.78 [95% CI 0.64, 0.96], p = 0.017). We did not observe differences in Ascaris infection prevalence between the control group and the arms with the individual interventions sanitation (PR: 0.89 [95% CI 0.73, 1.08], p = 0.228), handwashing (PR: 0.89 [95% CI 0.73, 1.09], p = 0.277), or nutrition (PR: 86 [95% CI 0.71, 1.05], p = 0.148). Integrating nutrition with WSH did not provide additional benefit. Trichuris and hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reduced Giardia. Reanalysis of stool samples by quantitative polymerase chain reaction confirmed the reductions in Ascaris infections measured by microscopy in the WSH and WSHN groups. Trial limitations included imperfect uptake of targeted intervention behaviors, limited power to detect effects on rare parasite infections, and that it was not feasible to blind participants and sample collectors to treatment status. However, lab technicians and data analysts were blinded to treatment status. The trial was funded by the Bill & Melinda Gates Foundation and the United States Agency for International Development. CONCLUSIONS: Integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies for Ascaris infections, particularly in similar settings with recent or ongoing deworming programs. Combining nutrition with WSH did not provide further benefits, and water treatment alone was similarly effective to integrated WSH. Our findings provide new evidence that drinking water should be given increased attention as a transmission pathway for Ascaris. TRIAL REGISTRATION: ClinicalTrials.gov NCT01704105.
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Giardiasis/prevención & control , Desinfección de las Manos/tendencias , Evaluación Nutricional , Población Rural/tendencias , Saneamiento/tendencias , Purificación del Agua , Adolescente , Animales , Niño , Preescolar , Femenino , Giardia , Giardiasis/epidemiología , Giardiasis/transmisión , Desinfección de las Manos/métodos , Helmintos , Humanos , Masculino , Saneamiento/métodos , Suelo/parasitología , Resultado del Tratamiento , Purificación del Agua/métodosRESUMEN
Valosin-containing protein (VCP) disease is an autosomal dominant multisystem proteinopathy associated with hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Myopathy frequently results in respiratory muscle weakness, leading to early mortality due to respiratory failure. We investigated the effects of a remotely administered inspiratory muscle training program in individuals with VCP disease. Nine adults with VCP mutation-positive familial myopathy without evidence of dementia were recruited for a 40-week remotely administered study. Baseline performance was established during the first 8 weeks, followed by 32 weeks of inspiratory muscle training. The primary outcome was maximum inspiratory pressure (MIP). The secondary and exploratory endpoints included spirometry, grip strength, Inclusion Body Myopathy Functional Rating Scale (IBMFRS), Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS), timed up and go, and six-minute walk test (6MWT). During the treatment phase, MIP increased significantly by a weekly mean of 0.392cm. H2O (p=0.023). In contrast, grip strength and ALSFRS significantly decreased by 0.088 lbs. (p=0.031) and 0.043 points (p=0.004) per week, respectively, as expected from the natural progression of this disease. A remotely administered inspiratory muscle training program is therefore feasible, safe, and well-tolerated in individuals with VCP disease and results in improved inspiratory muscle strength.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Enfermedades Musculares , Entrenamiento de Fuerza , Adulto , Humanos , Proteína que Contiene Valosina/genética , Respiración , Mutación , Proteínas de Ciclo Celular/genéticaRESUMEN
Background and Objectives: Missense variants of the valosin-containing protein (VCP) gene cause a progressive, autosomal dominant disease termed VCP multisystem proteinopathy (MSP1). The disease is a constellation of clinical features including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), typically reported at a frequency of 90%, 42%, 30%, and 9%, respectively. The Hispanic population is currently underrepresented in previous reports of VCP myopathy. We expand our genotype-phenotype studies in 5 Hispanic families with the c.476G>A, p.R159H VCP variant. Methods: We report detailed clinical findings of 11 patients in 5 Hispanic families with the c.476G > A, p.R159H VCP variant. In addition, we report frequencies of the main manifestations in 28 additional affected members of the extended family members. We also compared our findings with an existing larger cohort of patients with VCP MSP1. Results: FTD was the most prevalent feature reported, particularly frequent in females. PDB was only seen in 1 patient in contrast to the earlier reported cohorts. The overall frequency of the different manifestations: myopathy, PDB, FTD, and ALS in these 5 families was 39%, 3%, 72%, and 8%, respectively. The atypical phenotype and later onset of manifestations in these families resulted in a noticeable delay in the diagnosis of VCP disease. Discussion: Studying each VCP variant in the context of ethnic backgrounds is pivotal in increasing awareness of the variability of VCP-related diseases across different ethnicities, enabling early diagnosis, and understanding the mechanism for these genotype-phenotype variations.
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Fabry disease is an X linked disease caused by pathogenic variants in the GLA gene. The cardiovascular and renal systems are most affected in Fabry patients and may require heart or kidney transplants in the late stages of the disease depending on severity of manifestations. Enzyme replacement therapy (ERT) has proven to delay progression of Fabry disease considerably, especially when started early in life. Current research has shown that individuals who have received cardiac or renal transplants or are currently on dialysis have the greatest probability of developing severe manifestations of COVID-19. It has also been shown that people who contract COVID-19 experience a rapid increase in cytokine levels which can lead to a prothrombotic state and have a greater risk in the presence of comorbidities. A history of cardiac or renal transplants as well as the naturally elevated cytokine levels in Fabry disease make it likely that COVID-19 could have a greater impact on the health of these patients. We report the case of a 67-year-old male with diabetes mellitus, history of kidney transplant, and Fabry disease treated late in progression of the disease first with agalsidase beta ERT, then oral migalastat who developed severe manifestations of COVID-19. The autopsy findings showed acute and organizing hyaline membrane disease consistent with COVID-19 pneumonia and secondary invasive bronchopulmonary aspergillosis with cavitary lesion formation. The sections of the heart showed scattered subendocardial fibrosis, and the transplanted kidneys showed thyroidization and interstitial nephritis potentially secondary to COVID-19, in addition to his long-standing renal disease. This case report serves to chronicle complications in a complex patient with late stage Fabry disease and multiple COVID-19 related complications who succumbed from respiratory failure despite the advanced management for the COVID-19 infection.
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Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment. We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil. We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure. Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households. The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households. The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78-1.13). The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households. Unadjusted and adjusted models gave similar results. We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil. Soil moisture content was also associated with an increased prevalence of STH eggs in soil. Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.
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Composición Familiar , Helmintiasis/prevención & control , Saneamiento/métodos , Suelo/parasitología , Animales , Helmintiasis/epidemiología , Helmintiasis/transmisión , Helmintos/aislamiento & purificación , Humanos , Kenia/epidemiología , Óvulo , Prevalencia , Factores de RiesgoRESUMEN
This study examined sorption of the human and veterinary antibiotic sulfamethoxazole (SMX) at environmentally relevant concentrations from laboratory clean water, surface water, stormwater, and wastewater effluent to wood and wastewater-sludge derived biochars produced under a wide range of conditions. SMX sorption by commercial powdered activated carbon (PAC) was also quantified as a benchmark. Wood-based biochar produced around 850 °C performed similarly to PAC. Biochar sorption capacity increased with surface area up to â¼400 m(2)/g. However, a further increase in surface area did not correspond to an increase in sorption capacity. Sorbent H:C ratios correlated with SMX uptake by PAC and wood-based biochars, but not for the sludge-based biochars. This is possibly due to an indirect influence of the high ash content in sludge-based biochars, as the isolated ash fraction exhibited negligible SMX sorption capacity. The presence of dissolved organic matter (DOM) in the natural and anthropogenic waters fouled most of the sorbents (i.e., decreased SMX uptake). The sludge-based biochars experienced less DOM fouling relative to wood-based biochar, particularly in the wastewater effluent. Biochar and PAC sorption kinetics were similar when examined over a contact time of four-hours, suggesting their performance ranking would be consistent at contact times typically utilized in water treatment systems. In the presence of DOM, SMX relative removal (C/C0) was independent of SMX initial concentration when the initial concentration was below 10 µg/L, thus permitting the relative removal results to be applied for different SMX initial concentrations typical of environmental and anthropogenically impacted waters.