Comparison of Milk and Maize Based Diets in Kwashiorkor

The dual sugar test of intestinal permeability is a reliable non-invasive way of assessing the response of the small intestinal mucosa to nutritional rehabilitation. Our aim was to compare a local mix of maize soya egg to the standard milk diet in the treatment of kwashiorkor. The diets were alternated three monthly in the sequence milk-maize-milk. There' were a total of 533 kwashiorkor admissions of at least' five days during the study who received either milk or maize. Intestinal permeability was assessed at weekly intervals by the lactulose-rhamnose test in 100 kwashiorkor cases, including 55 on milk and 45 on the maize diet. Permeability ratios (95% confidence interval) on the milk diet improved by a mean of 6.4 (1.7 to 11.1) compared with - 6.8 (-16.8 to 5.0) in the maize group. The improved permeability on milk occurred despite more diarrhoea, which constituted 34.8% of hospital days compared to 24.3% in the maize group. Case fatality rates for all 533 kwashiorkor admissions were 13.6% v 20,9%, respectively, giving a relative risk of death in the maize group of 1.54 (1.04 to 2,28). The maize group also had more  clinical sepsis.(60% v 31%) and less weight gain (2.9 v 4.4 g/kg/day) than the milk group. Milk is superior to a local maize based diet in the treatment of kwashiorkor in terms of mortality, weight gain, clinical sepsis, and improvement in intestinal permeability

Risk factors in hospital deaths in severely malnourished children in Kampala, Uganda

BACKGROUND: Although the risk factors for increased fatality among severely malnourished children have been reported, recent information from Africa, during a period of HIV pandemic and constrained health services, remains sketchy. The aim of this study has been to establish the risk factors for excess deaths among hospitalized severely malnourished children of below five years of age. METHOD: In 2003, two hundred and twenty consecutively admitted, severely malnourished children were followed in the paediatric wards of Mulago, Uganda's national referral and teaching hospital. The children's baseline health conditions were established by physical examination, along with haematological, biochemical, microbiological and immunological indices. RESULTS: Of the 220 children, 52 (24%) died, with over 70% of the deaths occurring in the first week of admission. There was no significant difference by sex or age group. The presence of oedema increased the adjusted odds-ratio, but did not reach significance (OR = 2.0; 95% CI = 0.8 – 4.7), similarly for a positive HIV status (OR = 2.6, 95% CI = 0.8 – 8.6). Twenty four out of 52 children who received blood transfusion died (OR = 5.0, 95% CI = 2 – 12); while, 26 out of 62 children who received intravenous infusion died (OR = 4.8, 95% CI = 2 – 12). The outcome of children who received blood or intravenous fluids was less favourable than of children who did not receive them. Adjustment for severity of disease did not change this. CONCLUSION: The main risk factors for excess hospital deaths among severely malnourished children in Mulago hospital include blood transfusion and intravenous infusion. An intervention to reduce deaths needs to focus on guideline compliance with respect to blood transfusions/infusions

Mid-Upper Arm Circumference based Nutrition Programming: evidence for a new approach in regions with high burden of Acute Malnutrition

In therapeutic feeding programs (TFP), mid-upper arm circumference (MUAC) shows advantages over weight-for-height Z score (WHZ) and is recommended by the World Health Organization (WHO) as an independent criterion for screening children 6-59 months old. Here we report outcomes and treatment response from a TFP using MUAC ≤118 mm or oedema as sole admission criteria for severe acute malnutrition (SAM)

An assessment of food supplementation to chronically sick patients receiving home based care in Bangwe, Malawi : a descriptive study

BACKGROUND: The effect of food supplementation provided by the World Food Programme to patients and their families enrolled in a predominantly HIV/AIDS home based care programme in Bangwe Malawi is assessed. METHODS: The survival and nutritional status of patients and the nutritional status of their families recruited up to six months before a food supplementation programme started are compared to subsequent patients and their families over a further 12 months. RESULTS: 360 patients, of whom 199 died, were studied. Food supplementation did not improve survival but had an effect (not statistically significant) on nutritional status. Additional oil was given to some families; it may have improved survival but not nutritional status. CONCLUSION: Food supplementation to HIV/AIDS home based care patients and their families does not work well. This may be because the intervention is too late to affect the course of disease or insufficiently targeted perhaps due to problems of distribution in an urban setting. The World Food Programme's emphasis on supplementary feeding for these families needs to be reviewed

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions--a prospective multicenter cohort study.

BACKGROUND: Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above. METHODS: This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate. RESULTS: In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p < 0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p < 0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %). CONCLUSION: The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activityAntimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.The authors thank T.T. Diagana (Novartis Institute for Tropical Diseases, Singapore) for provision of the compounds, the Red Cross (Australia and the USA) for the provision of human blood for cell cultures, and G. Stevenson for assistance with the triaging of compounds following screening. The authors acknowledge the Bill and Melinda Gates Foundation (grant OPP1040399 to D.A.F. and V.M.A. and grant OPP1054480 to E.A.W. and D.A.F.), the National Institutes of Health (grant R01 AI103058 to E.A.W. and D.A.F., grant R01 AI50234 to D.A.F, and R01 AI110329 to T.J.E.), the Australian Research Council (LP120200557 to V.M.A.) and the Medicines for Malaria Venture for their continued support. P.E.F. and M.I.V. are supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER).info:eu-repo/semantics/publishedVersio

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program