Occurrence and factors associated with Cryptosporidium infection in livestock in three districts of Zambia.

Cryptosporidium is one of the most important enteric diarrhoeal parasites that infect humans and animals worldwide. The current study investigated the occurrence and risk factors associated with Cryptosporidium infection in ruminants aged ≤6 months in Monze, Mumbwa, and Lusaka districts of Zambia. Faecal samples were collected from 328 calves, 190 lambs, and 245 goat kids and analysed for Cryptosporidium oocysts using modified Ziehl Neelsen staining. A closed structured questionnaire was used to obtain epidemiological characteristics and potential risk factors for Cryptosporidium infection. The overall occurrence of Cryptosporidium was 7.9% (60/763), while that in calves, lambs and goat kids was 14.5% (47/328), 5.3% (10/190), and 1.2% (3/245) respectively. Watery/pasty stool and sampling during the rainy season were independently associated with increased risk of infection. In calves, the odds of infection increased during the rainy season, while daily kraal cleaning reduced the infection risk. Lambs showed increased odds of infection with pasty/watery stool and male sex, whereas the wearing of protective clothing by handlers significantly reduced the risk. There were district variations in infection occurrence with Mumbwa district having higher prevalence. The findings of this study show that livestock in Zambia continue to be frequently infected with Cryptosporidium. Protective measures and appropriate farm cleanliness should be implemented in control of this infection. Regional and host-species-specific variations emphasize the need for targeted interventions. These findings, therefore, contribute to effective strategies for Cryptosporidium control, promoting good livestock health and management.

First and Second-Line Anti-Tuberculosis Drug-Resistance Patterns in Pulmonary Tuberculosis Patients in Zambia.

BACKGROUND: Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study. METHODS: A total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants' social-demographic characteristics were obtained using a pre-test checklist. RESULTS: Overall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5-31.6%). A total of 9.8% (13/132, 95% CI: 5.3-16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3-16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1-146.5%) to have drug-resistant TB than those who had no history of being treated for TB. CONCLUSION: This study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring.

Risk factors associated with zoonotic tuberculosis at the animal-human interface in a tuberculosis-endemic sub-Saharan country.

We aimed to assess the proportion of tuberculosis in humans and tuberculosis (TB)-associated abattoir condemnations from the animal sector, as well as determine risk factors of zoonotic tuberculosis at the animal-human interface in Zambia. The study involved 255 presumptive TB patients and 156 cattle carcasses and was conducted from April 2020 to December 2021. Univariable and multivariable logistic regressions were performed for risk factor analysis for zoonotic TB. The overall proportion of bovine tuberculosis in traditional cattle and the proportion of tuberculosis among presumptive TB patients were 39.7% and 10.2%, respectively. Consumption of raw milk (adjusted odds ratio (AOR)=2.72, 95% confidence interval (CI): 1.73-4.28) and history of previous contact with a TB patient (AOR=1.86, 95% CI: 1.17-2.95) were risk factors for zoonotic TB at the animal-human interface of Zambia. Therefore, community campaigns and sensitization on zoonotic TB transmission are recommended.

Experiences of Early and Enhanced Clinical Exposure for Postgraduate Neonatal Nursing Students at the University of Zambia, School of Nursing Sciences: Lessons and Implications for the Future.

Background and Objectives: Early and Enhanced Clinical Exposure immediately places postgraduate students in a clinical setting and incorporates continual hands-on instruction throughout their studies. It aims to motivate students by strengthening their academics, improving clinical and communication skills, and increasing their confidence. The underlying principles are to provide a clinical context and to ensure that the patient remains the centre of learning. The School of Nursing Sciences implemented this model in 2021 to produce hands-on Masters-level neonatal practitioners who can work in multidisciplinary clinical contexts. Therefore, this study explored the experiences of postgraduate nursing students on the Early and Enhanced Clinical Exposure model and draw implications for the future. Methods: A phenomenological study design was utilized at the University of Zambia, School of Nursing Sciences and comprised of eight Master of Science Neonatal Nursing students in their second year. Convenience sampling was used to select the study site and participants. Data was collected between 15th January 2023 and 31st January 2023 using an in-depth interview guide. Audio recording and notes were transcribed immediately after data collection. Data analysis was conducted using thematic analysis and codes and themes were constructed from the coded data. Ethical clearance and permission were sought before conducting the study. Results: Four major themes emerged from the study: identity and role confusion, challenging and hectic experiences, positive educational experiences, and personal and professional growth. These themes contributed to the promotion of evidence-based practice by helping students to assess, diagnose, and treat various conditions, as well as gain interest, experience, knowledge, and exposure. Conclusion: The model has a significant impact on motivation to learn, as evidenced by reported increased skill level with potential for use in clinical practice. It is recommended that it be implemented in all postgraduate programs for full-time students.

Determinants of Knowledge, Attitude, and Practices of Veterinary Drug Dispensers toward Antimicrobial Use and Resistance in Main Cities of Malawi: A Concern on Antibiotic Stewardship.

Antimicrobial resistance (AMR) is an emerging challenge to global public health. The use of antibiotics in the veterinary field is one of the contributing factors to AMR mostly due to poor knowledge, attitudes, and practices (KAP) of dispensers. Veterinary drug dispensers are expected to guide clients on indications, contraindications, and withdrawal periods of veterinary drugs. This study assessed veterinary drug dispensers' KAP toward AMR and associated potential contributing factors. A cross-sectional study, using a structured questionnaire, was conducted in three main cities of Malawi, namely Mzuzu, Lilongwe, and Blantyre. A total of 68 agrovet shops were selected using a simple random sampling technique. The KAP level was presented descriptively. Bivariate and multivariable analyses were run to investigate the relationships between the independent and outcome variable. Overall, the KAP score for knowledge, attitude, and practices was 46.7%, 49.2%, and 41.6%, respectively. The significant determinants of the knowledge were the practice of asking for a written prescription (OR: 16.291, 95% CI: 11.6-24.2) (p = 0.024), female (OR: 0.609, 95% CI: 0.3-0.9) (p = 0.001), and old age (≥35) (OR: 0.227, 95% CI: 0.1-0.5) (p = 0.04). Poor knowledge, negative attitude, and poor practices were observed among most of the participants. Sensitization and training on AMR and antimicrobial stewardship are recommended to address the KAP score gaps and the observed determinants among veterinary drug dispensers.

Antimicrobial Susceptibility of Salmonella Isolated from Chickens and Humans in Wau, South Sudan.

Background: Salmonella infections are a public health problem across the globe. In South Sudan, there is little information regarding the prevalence and antibiotic resistance patterns of Salmonella. Therefore, this study assessed the prevalence and antimicrobial susceptibility of Salmonella isolates from chickens and humans in South Sudan. Fecal samples were collected and cultured on Xylose Lysine Deoxycholate Agar for the isolation of Salmonella and confirmed using biochemical tests and PCR through the amplification of the invA gene. A total of 417 fecal samples were examined, of which 270 (64.7%) were chicken cloacal swabs while 147 (35.3%) were humans' stool specimens. Results: Eleven (11) Salmonella isolates were isolated from humans while nine were from chickens. All 11 isolates from humans were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, streptomycin, cefotaxime, nalidixic acid, and gentamicin. However, 4 (36.7%) isolates showed resistance to ciprofloxacin, 2 (18.9%) to ampicillin, and 1 (9.1%) to tetracycline. All chicken isolates were susceptible to chloramphenicol, streptomycin, sulfamethoxazole-trimethoprim, ciprofloxacin, cefotaxime, nalidixic acid, and gentamicin but showed resistance to tetracycline 2 (22.2%) and ampicillin 1 (11.1%). Conclusion: Antimicrobial resistant isolates were isolated in both chickens and humans. Further, MDR isolates were found in both chicken and human samples, and this is a public health concern. This, therefore, calls for concerted efforts to educate producers and consumers on public health, food safety, food hygiene in food production, and enhancement of surveillance programmes on zoonotic bacteria and antimicrobial susceptibility.

Prevalence and Molecular Identification of Schistosoma haematobium among Children in Lusaka and Siavonga Districts, Zambia.

Schistosomiasis remains a public health concern in Zambia. Urinary schistosomiasis caused by Schistosoma haematobium is the most widely distributed infection. The aim of the current study was to determine the prevalence and risk factors of urinary schistosomiasis and identify the strain of S. haematobium among children in the Siavonga and Lusaka districts in Zambia. Urine samples were collected from 421 primary school children and S. haematobium eggs were examined under light microscopy. A semi-structured questionnaire was used to obtain information on the socio-demographic characteristics and the potential risk factors for urinary schistosomiasis. DNA of the parasite eggs was extracted from urine samples and the internal transcribed spacer gene was amplified, sequenced and phylogenetically analysed. The overall prevalence of S. haematobium was 9.7% (41/421) (95% CI: 7.16-13.08), male participants made up 6.2% (26/232) (95% CI: 4.15-9.03), having a higher burden of disease than female participants who made up 3.5% (15/421) (95% CI: 2.01-5.94). The age group of 11-15 years had the highest overall prevalence of 8.3% (35/421) (5.94-11.48). Participants that did not go fishing were 0.008 times less likely to be positive for schistosomiasis while participants whose urine was blood-tinged or cloudy on physical examination and those that lived close to water bodies were 9.98 and 11.66 times more likely to test positive for schistosomiasis, respectively. A phylogenetic tree analysis indicated that S. haematobium isolates were closely related to pure S. haematobium from Zimbabwe and hybrids of S. haematobium × S. bovis from Benin, Senegal and Malawi. The current study shows that urinary schistosomiasis is endemic in the study areas and is associated with water contact, and S. haematobium isolated is closely related to hybrids of S. bovis × S. haematobium strain, indicating the zoonotic potential of this parasite.

Proteogenomic analysis of pancreatic cancer subtypes.

Pancreatic cancer remains a significant public health problem with an ever-rising incidence of disease. Cancers of the pancreas are characterised by various molecular aberrations, including changes in the proteomics and genomics landscape of the tumour cells. Therefore, there is a need to identify the proteomic landscape of pancreatic cancer and the specific genomic and molecular alterations associated with disease subtypes. Here, we carry out an integrative bioinformatics analysis of The Cancer Genome Atlas dataset, including proteomics and whole-exome sequencing data collected from pancreatic cancer patients. We apply unsupervised clustering on the proteomics dataset to reveal the two distinct subtypes of pancreatic cancer. Using functional and pathway analysis based on the proteomics data, we demonstrate the different molecular processes and signalling aberrations of the pancreatic cancer subtypes. In addition, we explore the clinical characteristics of these subtypes to show differences in disease outcome. Using datasets of mutations and copy number alterations, we show that various signalling pathways previously associated with pancreatic cancer are altered among both subtypes of pancreatic tumours, including the Wnt pathway, Notch pathway and PI3K-mTOR pathways. Altogether, we reveal the proteogenomic landscape of pancreatic cancer subtypes and the altered molecular processes that can be leveraged to devise more effective treatments.

High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs.

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we find that tumours that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment, and prognostic strategies.

Leucocytosis and Asymptomatic Urinary Tract Infections in Sickle Cell Patients at a Tertiary Hospital in Zambia.

Sickle cell anaemia (SCA) is an inherited disease resulting from mutations in the ß-globin chain of adult haemoglobin that results in the formation of homozygous sickle haemoglobin. It is associated with several complications including an altered blood picture and damage in multiple organs, including the kidneys. Kidney disease is seen in most patients with SCA and may affect glomerular and/or tubular function, thereby putting these patients at risk of urinary tract infections. However, there is a paucity of data on the prevalence of urinary tract infections (UTIs) among SCA patients in Zambia. This study aimed to determine the prevalence of UTIs and haematological and kidney function profiles among SCA patients at the University Teaching Hospitals, Lusaka, Zambia. This was a cross-sectional study conducted between April and July 2019 involving 78 SCA patients who presented at the UTH. Blood and midstream urine samples were collected from each participant using the standard specimen collection procedures. Full blood counts and kidney function tests were determined using Sysmex XT-4000i haematology analyser and the Pentra C200 by Horiba, respectively. Bacterial profiles of the urine samples were determined using conventional microbiological methods. We found that all the measured patients' haemoglobin (Hb) levels fell below the WHO-recommended reference range with a minimum of 5 g/dl, a maximum of 10.5 g/dl, and a mean of 8 ± 1 g/dl. Fifty percent of the participants had moderate anaemia, while the other 50% had severe anaemia. The minimum WBC count of the participants was 0.02 × 109/L with a maximum of 23.36 × 109/L and a mean of 13.48 ± 3.87 × 109/L. Using the one-way analysis of variance test, we found no significant difference in mean WBC count and Hb concentration across various age-group categories that we defined. Bacteriuria was found in 25% of participants. The most common bacterial isolates were Staphylococcus aureus (32%) and coagulase-negative Staphylococci (32%). Klebsiella pneumoniae was 16%. We found no significant association between bacterial isolates and white blood cell count, age groups, sex, and anaemia severity p = 0.41. None of the participants were diagnosed with kidney disease. There was a high prevalence of asymptomatic UTIs among SCA patients at UTH, which, when coupled with the marked leukocytosis and anaemia, may negatively impact the clinical outcome of the patients. Therefore, we recommend close monitoring of sickle cell patients in Zambia for such conditions to improve patients' outcomes.

The Use of Dried Blood Spots: A Potential Tool for the Introduction of a Neonatal Screening Program for Sickle Cell Anemia in Zambia.

CONTEXT: Sickle cell disease is a group of hemoglobin (Hb) disorders resulting from the inheritance of the sickle ß-globin gene. It is the most common pathological Hb mutation worldwide with 75% being born in Sub-Saharan Africa. AIMS: This study aims to determine if dried blood spots (DBSs) can be used for diagnosis of sickle cell in newborns. In Zambia, there is no neonatal screening program for sickle cell anemia (SCA), yet it has been proved that early diagnosis by newborn screening (NBS) using DBSs and access to comprehensive care results in survival to adulthood of over 96% of sickle cell patients. SETTINGS AND DESIGN: A cross-sectional study was carried out at the University Teaching Hospital to determine whether DBSs can be used to diagnose sickle cell using Hb electrophoresis. SUBJECTS AND METHODS: Results from DBSs stored for 2 weeks were then compared to those obtained using freshly collected whole blood. STATISTICAL ANALYSIS USED: To evaluate performance characteristics, the following values were used: true positive, false positive, true negative, and false negative. RESULTS: Ninety-seven participants were included in this study. DBSs had a sensitivity of 100%, a specificity of 94.7%, positive predictive value of 96.7%, negative predictive value of 100%, overall efficiency of 97.9%, and a Kappa r2, P < 0.0001 in comparison to fresh whole blood which we used as the gold standard. CONCLUSIONS: The use of DBSs can be recommended for NBS of SCA in Zambia due to its high sensitivity, specificity, and stability of hemoglobin.

Performance Characteristics of Kidney Injury Molecule-1 In Relation to Creatinine, Urea, and Microalbuminuria in the Diagnosis of Kidney Disease.

CONTEXT: The diagnosis and evaluation of impaired renal function remains a challenge owing to lack of reliable biomarker for assessment of kidney function. The existing panel of biomarkers currently displays several limitations, and recently kidney injury molecule-1 (KIM-1) has been suggested as a sensitive biomarker of renal function and proposed to enter clinical practice. AIMS: This study was conducted to determine the diagnostic value of serum creatinine, urea, and microalbuminuria (MAU) in relation to the novel biomarker, KIM-1. MATERIALS AND METHODS: Serum creatinine, urea, MAU, and KIM-1 were measured in forty individuals with and forty without kidney disease. Data were analyzed using multivariate methods of assessing diagnostic efficiency, test agreement, condition effects, and variability. RESULTS: The area under the receiver-operator characteristic curve revealed a diagnostic advantage of creatinine (0.924 ± 0.0066) and urea (0.925 ± 0.0068) over MAU (0.880 ± 0.078) and KIM-1 (0.35 ± 0.124). Overall diagnostic efficiency was higher for creatinine and urea (89.5% and 90.9%, respectively), followed by MAU (85.7%) and then KIM-1 (56.3%). Logistic regression analysis showed that creatinine and urea (R2 = 0.75 and R2 = 0.72, respectively, P < 0.001 for both) were better predictors of kidney disease than MAU (R2 = 0.64, P < 0.001) and KIM-1 (R2 = 0.046, P = 0.116). Further analysis of agreement showed that urea had an excellent agreement with creatinine (kappa r = 0.835, P < 0.001), with KIM-1 (kappa r = -0.198, P = 0.087) showing a poor agreement with creatinine. CONCLUSION: Our results indicate that elevated serum creatinine and urea above specific cutoff points reliably identifies patients with acute kidney injury or chronic kidney disease. However, more researches are warranted to further validate the diagnostic efficiency and application of MAU and for KIM-1 before its implementation in clinical practice.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury.

INTRODUCTION: Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. METHODS: We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. RESULTS: We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). CONCLUSION: The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury.