Epidemiology and molecular characterization of human and canine hookworm

Among the soil-transmitted helminths (STH), hookworms are a worldwide problem in both humans and animals. They cause non-specific gastrointestinal symptoms, and in young children and animals, they can cause stunting, malnutrition and anemia. Canine hookworms have significant zoonotic potential as a cause of cutaneous larvae migrans and eosinophilic enteritis in humans. To determine the ecological niche of human hookworm in Brazil, two risk models were developed based on the Growing Degree Day-Water Budget (GDD-WB) concept, one based on accumulation of monthly temperatures above a base temperature of 15oC and threshold WB value \u3e0.4. The second was based on a ‘gradient index’ of the product of monthly accumulated GDD and WB values. It was determined that both environmental temperature and moisture are important in the distribution of hookworm. This study supports the validity of the GDD-WB concept for mapping risk of hookworm at a national scale. A cross-sectional survey was conducted in human outpatients in Mutuípe municipality, Brazil, to determine prevalence of soil-transmitted helminths, including hookworm. Mutuípe falls within the permissive zone for the transmission of hookworm. A sucrose double centrifugation flotation technique was used for the concentration of helminth eggs in fecal samples. Hookworm infection was the most prevalent of the STH and the prevalence was highest in adults and males. PCR was then used to determine the species of hookworm present. Necator americanus was confirmed by PCR as the predominant hookworm species. A single case of Ancylostoma ceylanicum was identified. A study on the prevalence of hookworms and other gastrointestinal parasites in shelter dogs in south Louisiana and the anthelminthic protocols used in the shelters was conducted. Fecal samples examined by direct smear, flotation and sedimentation methods revealed that hookworm had the highest prevalence (53.6%) followed by Trichuris vulpis (28.7), Cystoisospora ohioensis (17.2%), Giardia duodenalis (12.0%), C. canis (7.7), Toxocara canis (6.2%), Dipylidium caninum, Alaria spp and Capillaria sp A PCR-RFLP developed to differentiate A. caninum and A. braziliense revealed A. caninum as the only species found. Evaluation of the anthelminthic protocols used in nine shelters showed current methods were inadequate for control of hookworms in shelter dogs

Surveillance of molecular markers for antimalarial resistance in Zambia: Polymorphism of Pfkelch 13, Pfmdr1 and Pfdhfr/Pfdhps genes

Antimalarial resistance is an inevitable feature of control efforts and a key threat to achieving malaria elimination. Plasmodium falciparum, the deadliest of several species causing human malaria, has developed resistance to essentially all antimalarials. This study sought to investigate the prevalence of molecular markers associated with resistance to sulfadoxine-pyrimethamine (SP) and artemether-lumefantrine (AL) in Southern and Western provinces in Zambia. SP is used primarily for intermittent preventive treatment during pregnancy, while AL is the first-line antimalarial for uncomplicated malaria in Zambia. Blood samples were collected from household members of all ages in a cross-sectional survey conducted during peak malaria transmission, April to May of 2017, and amplified by polymerase chain reaction (PCR). Amplicons were then analysed by high-resolution melt following PCR to identify mutations associated with SP resistance in the P. falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps) genes and lumefantrine resistance in the P. falciparum multi-drug resistance 1 (Pfmdr1) gene. Finally, artemether resistance was assessed in the P. falciparum Kelch 13 (PfK13) gene using nested PCR followed by amplicon sequencing. The results showed a high frequency of genotypic-resistant Pfdhps A437G (93.2%) and Pfdhfr C59R (86.7%), N51I (80.9%), and S108N (80.8%) of which a high proportion (82.4%) were quadruple mutants (Pfdhfr N51I, C59R, S108N +Pfdhps A437G). Pfmrd1 N86Y, Y186F, and D1246Y - NFD mutant haplotypes were observed in 41.9% of isolates. The high prevalence of quadruple dhps/dhfr mutants indicates strong antifolate drug pressure from SP or other drugs (e.g., co-trimoxazole). Three samples contained PfK13 mutations, two synonymous (T478 and V666) and one non-synonymous (A578S), none of which have been associated with delayed clearance. This suggests that artemisinin remains efficacious in Zambia, however, the moderately high prevalence of approximately 40% Pfmdr1 NFD mutations calls for close monitoring of AL.publishedVersio

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Nano-biomimetic drug delivery vehicles: potential approaches for COVID-19 treatment

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed

Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study

To perform an epidemiological evaluation of the predictive value of p53 autoantibodies in breast cancer, we measured antibodies against p53 in serum samples from 165 breast cancer patients in comparison with serum samples from 330 healthy controls, selected from the same population as the cases and matched for age, sex and specimen storage time. Median age of patients was 51 years (range 25–64 years). Presence of serum p53 autoantibodies was analysed by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. The lower ELISA reactivities were similar for cases and controls, but presence of high-level reactivity was more common among cases than among controls [odds ratio (OR) 9.03, 95% confidence interval (CI) 2.40–50.43]. Presence of Western blot-detected p53 autoantibodies had a very similar association (OR 10.8, CI 3.0–59.4). Among the cases, we also studied whether there was any correlation between level of anti-p53 antibodies and stage of the disease or survival. There was no significant correlation between presence of antibodies and stage of the disease. There was a significant negative correlation between presence of p53 antibodies and survival (P= 0.003). A stepwise multivariate Cox regression analysis showed that T-stage, age and presence of anti-p53 antibodies were significant independent prognostic variables, with a dose-dependent negative effect on survival for all three variables. We conclude that presence of anti-p53 antibodies are of significance both for the risk of having breast cancer and the risk of dying from breast cancer. 1999 Cancer Research Campaig

Sustainability of agriculture extension services in the face of COVID-19: a study on gender-specific market systems

In the fourth industrial revolution, achieving sustainable agricultural development while feeding a growing world population and maintaining a balanced interrelationship between the economy, society, and the environment has been a significant challenge. However, COVID-19 disrupted agricultural extension and advisory systems, affecting all market participants. The complexity of the pandemic has impacted the private sector, public sector, extension staff, donor funding, education, and research systems, subsequently affecting human nutrition. This paper aims to expertly review COVID-19’s effects on the sustainability of gender-specific agricultural extension service systems. Demand and supply market stakeholders in the extension system are thematically discussed. The findings reveal various consequences of COVID-19 for market actors on both the demand and supply sides of the extension system. Private-sector players often support expansion directly or indirectly, with multi-sectorial support and funding strategies existing for sustainability. In many developing nations, the comprehensive extension system was disrupted by COVID-19, impacting household incomes and nutrition. The pandemic accelerated the adoption of digital technologies in many developing nations, transitioning from a centralized to a decentralized and pluralistic extension model. Multi-sector coordination and execution, especially from health and other sectors, are crucial in managing complex crises that disrupt the market system

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice