Risk mapping and eco‐anthropogenic assessment of anthrax in the upper Zambezi basin

In Zambia, anthrax has emerged as a serious disease decimating humans, livestock and wildlife with devastating effects on eco‐tourism resulting in the destabilization of major pristine wildlife sanctuaries. Consequently, the thrust of this study was to establish the spatial distribution of anthrax and determine ecological drivers of its recurrence, maintenance and epidemiological linkage to anthropogenic activities. Environmental and biological samples were collected within the livestock production and conservation areas (n = 80). Each sample was serially tested for Bacillus anthracis positivity through blood agar culture and Gram stain technique, and then confirmation by multiplex polymerase chain reaction (MPCR). Questionnaires (n = 113) were conducted at independently distinct villages in terms of space and time. Most respondents showed that animals that died from anthrax were not properly disposed off. More likely than not, poverty being the main driver for anthrax carcass dressing and meat distribution contributed to environmental contamination with anthrax spores in areas where the animals subsequently died resulting in further environmental contamination, which is the major source of primary infection for livestock and wildlife. From the samples, 15 pure isolates of anthrax were obtained which were spatially distributed across four districts. Twelve, biologically plausible variables were found to be highly significant on multivariable logistic regression analysis model for questionnaires which included herd size (odds = 10.46; P = 0.005; CI 8.8–16), carcass disposal method (odds = 6.9; P = 0.001; CI = 3.4–9.8), access to veterinary services (odds = 10.87; P = 0.004; CI = 4.8–15.9) and management system (odds = 2.57; P = 0.001; CI = 1.3–7.5). In summary, the majority (78.7%) of anthrax outbreaks were observed in areas with low veterinary services (χ2 = 8.6162, P = 0.013) within the newly created districts of Nalolo, Mwandi and Luampa

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

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

Indices of health;clinical haematology and body weights of free-range Guinea Fowl (Numida Meleagris) from Southern Province Zambia

Journal articl

Evaluating Non-Antibiotic Therapeutic Strategies for Controlling Lactococcosis in Nile Tilapia: Investigating the Efficacy of Aloe Vera Extracts, Vitamin D and Selenium Supplement, and Probiotics in Experimental Infections

This study investigated non-antibiotic therapeutic strategies for controlling lactococcosis in Nile tilapia (Oreochromis niloticus). The efficacy of Aloe vera extract, Vitamin E/Selenium supplementation, and multi-strain probiotics was evaluated against Lactococcus garvieae infection in an experimental setting. Two hundred Nile tilapia were divided into four groups: control, Aloe vera, Vitamin E/Selenium, and probiotic. After a 42-day treatment period, fish were challenged with L. garvieae and monitored for 28 days. Clinical signs, mortality rates, and survival were assessed. The control group exhibited severe disease progression with 100% mortality by day 21 post-infection. Aloe vera treatment reduced mortality to 20%, showing moderate efficacy. Vitamin E/Selenium supplementation provided greater protection with only 5% mortality. The probiotic-treated group demonstrated the most remarkable results, with no clinical signs or mortalities throughout the study. Statistical analysis revealed significant differences between treatment groups and the control, with probiotics showing the largest effect size (Cohen's d = 0.98, p < 0.001), followed by Vitamin E/Selenium (Cohen's d = 0.9, p = 0.001) and Aloe vera (Cohen's d = 0.74, p = 0.003). These findings highlight the potential of non-antibiotic interventions in managing L. garvieae infections, with probiotics emerging as the most effective treatment. The study contributes to the development of sustainable aquaculture practices and reduced reliance on antibiotics, aligning with global efforts to mitigate antimicrobial resistance in aquaculture

Modelling the ecological niche of hookworm in Brazil based on climate

Journal article. The distribution of hookworm in schistosomiasis-endemic areas in Brazil was mapped based on climate suitability. Known biological requirements of hookworm were fitted to data in a monthly long-term normal climate grid (18 x 18 km) using geographical information systems. Hookworm risk models were produced using the growing degree day (GDD) water budget (WB) concept. A moisture-adjusted model (MA-GDD) was developed based on accumulation of monthly temperatures above a base temperature of 15 °C (below which there is no lifecycle progression of Necator americanus) conditional on concurrent monthly values (rain/potential, evapotranspiration) of over 0.4. A second model, designated the gradient index, was calculated based on the monthly accumulation of the product of GDD and monthly WB values (GDD x WB). Both parameters had a significant positive correlation to hookworm prevalence. In the northeastern part of Brazil (the Caatinga), low hookworm prevalence was due to low soil moisture content, while the low prevalence in southern Brazil was related to low mean monthly temperatures. Both environmental temperature and soil moisture content were found to be important parameters for predicting the prevalence of N. americanus

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

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