11 research outputs found
Likelihood of development renal dysfunction after one year of treatment with tenofovir(TDF) in HIV/AIDS patients at the UTH: An analytical cross-section study
Studies have suggested that Sub-Sahara Africans are prone to HIV-related renal dysfunction. A study done in Zambia showed increased deaths among HIV/AIDS patients who had renal dysfunction. Tenofovir Disoproxil Fumarate (TDF) one of the first line antiretroviral drugs in Zambia, has been associated with renal tubulopathy and nephrotoxicity in many studies. In Zambia, TDF has been in use since 2007. This study was set out to determine whether TDF had similar Nephrotoxic effects in patients receiving TDF- based regimen at the largest Antiretroviral Therapy (ART) Centre in Lusaka. It aimed at determining the likelihood of patients with no renal dysfunction (CLcr method) at initiation of therapy developing renal dysfunction after 1 year of treatment with TDF- based regimen compared to those on non- TDF- based regimen (these patients were either on Stavudine (D4T)- based regimen or Zidovudine (AZT)- based regimen).
An analytical cross- sectional study involved analysis of data obtained from 549 randomly selected HIV/AIDS patient files that were started on ART between September, 2007 and January, 2013. Out of the 549 patients, 275 patients were on TDF- based regimen and 274 patients were on non- TDF- based regimen.
Findings showed a significantly larger number of participants on TDF developing renal dysfunction from having no renal dysfunction at baseline compared to those on non- TDF- based regimen; 51 out of 180 verses 8 out of 207, P< 0.001. Upon controlling for age and sex, logistic regression model showed that HIV/AIDS patients on TDF- based regimen were 8.77 times more likely to develop renal dysfunction after one year of therapy from having no renal dysfunction at baseline compared to those on non- TDF- based regimen.
It was concluded that treatment with TDF- based regimen was strongly associated with developing renal dysfunction after 1 year of treatment compared to non TDF- based regimen. There is need for follow up of patients on TDF- based regimen or therapy modification to reduce cases of renal dysfunction in patients on treatment thereby allowing them benefit fully by the treatment
Chronic kidney disease among HIV-positive Zambian adults with tenofovir-associated nephrotoxicity at University Teaching Hospital (UTH) in Lusaka
Predicting Mortality in Hospitalized COVID-19 Patients in Zambia: An Application of Machine Learning
The coronavirus disease 2019 (COVID-19) has wreaked havoc globally, resulting in millions of cases and deaths. The objective of this study was to predict mortality in hospitalized COVID-19 patients in Zambia using machine learning (ML) methods based on factors that have been shown to be predictive of mortality and thereby improve pandemic preparedness. This research employed seven powerful ML models that included decision tree (DT), random forest (RF), support vector machines (SVM), logistic regression (LR), Naïve Bayes (NB), gradient boosting (GB), and XGBoost (XGB). These classifiers were trained on 1,433 hospitalized COVID-19 patients from various health facilities in Zambia. The performances achieved by these models were checked using accuracy, recall, F1-Score, area under the receiver operating characteristic curve (ROC_AUC), area under the precision-recall curve (PRC_AUC), and other metrics. The best-performing model was the XGB which had an accuracy of 92.3%, recall of 94.2%, F1-Score of 92.4%, and ROC_AUC of 97.5%. The pairwise Mann–Whitney U-test analysis showed that the second-best model (GB) and the third-best model (RF) did not perform significantly worse than the best model (XGB) and had the following: GB had an accuracy of 91.7%, recall of 94.2%, F1-Score of 91.9%, and ROC_AUC of 97.1%. RF had an accuracy of 90.8%, recall of 93.6%, F1-Score of 91.0%, and ROC_AUC of 96.8%. Other models showed similar results for the same metrics checked. The study successfully derived and validated the selected ML models and predicted mortality effectively with reasonably high performance in the stated metrics. The feature importance analysis found that knowledge of underlying health conditions about patients’ hospital length of stay (LOS), white blood cell count, age, and other factors can help healthcare providers offer lifesaving services on time, improve pandemic preparedness, and decongest health facilities in Zambia and other countries with similar settings
Escherichia coli Antimicrobial Susceptibility Reduction amongst HIV-Infected Individuals at the University Teaching Hospital, Lusaka, Zambia
Increased antimicrobial resistance among Human Immunodeficiency Virus (HIV)-infected individuals to commonly used antibiotics in the treatment of gastroenteritis is a public health concern, especially in resource-limited settings. We set out to compare the antimicrobial susceptibility pattern of Escherichia coli (E. coli) isolates from HIV-infected and HIV-uninfected individuals at a tertiary hospital in Lusaka, Zambia. An analytical cross-sectional study was conducted at the University Teaching Hospital from May 2019 to August 2019. Stool samples were screened, and 79 HIV-infected individuals matched by age and sex with 84 HIV-uninfected individuals that presented with E. coli associated gastroenteritis were studied. Demographics were collected from the Laboratory Information System (LIS) and stool samples were collected in a sterile leak-proof container. Samples were cultured and only those where E. coli was isolated were included in the study and tested for antimicrobial susceptibility by the Kirby–Bauer disk diffusion technique. HIV-positive individuals were 3 times (adjusted odds ratio (AOR) = 3.17; 95% CI (1.51, 6.66); p < 0.001) more likely to be resistant to quinolones compared with their HIV-negative counterparts. Similarly, HIV-positive individuals were almost 4 times (AOR = 3.97, 95% CI (1.37, 11.46); p = 0.011) more likely to have multidrug-resistant E. coli compared with those who were HIV-negative. HIV infection was associated with reduced E. coli susceptibility to commonly used antibiotics, and most cases showed resistance
Soil: The great connector of our lives now and beyond COVID-19
Humanity depends on the existence of healthy soils, both for the production of food and for ensuring a healthy, biodiverse environment, among other functions. COVID-19 is threatening food availability in many places of the world due to the disruption of food chains, lack of workforce, closed borders and national lockdowns. As a consequence, more emphasis is being placed on local food production, which may lead to more intensive cultivation of vulnerable areas and to soil degradation. In order to increase the resilience of populations facing this pandemic and future global crises, transitioning to a paradigm that relies more heavily on local food production on soils that are carefully tended and protected through sustainable management is necessary. To reach this goal, the Intergovernmental Technical Panel on Soils (ITPS) of the Food and Agriculture Organization of the United Nations (FAO) recommends five active strategies: improved access to land, sound land use planning, sustainable soil management, enhanced research, and investments in education and extension. The soil is the great connector of lives, the source and destination of all. It is the healer and restorer and resurrector, by which disease passes into health, age into youth, death into life. Without proper care for it we can have no community, because without proper care for it we can have no life. © Author(s) 2020
Urine kidney injury molecule-1 predicts subclinical kidney disease among persons living with HIV initiating tenofovir disoproxil fumarate-based ART in Zambia
IntroductionAntiretroviral therapy (ART) increases the life expectancy of persons living with HIV (PLWH), but not without potentially serious adverse effects. Tenofovir disoproxil fumarate (TDF) can cause nephrotoxicity, manifesting as acute kidney injury (AKI) that may persist after treatment discontinuation. Kidney injury biomarkers such as kidney injury molecule-1 (KIM-1), retinol-binding protein-4 (RBP-4), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) can aid early diagnosis and predict TDF-associated nephrotoxicity. This study aimed to determine whether the change from baseline in urine KIM-1 (δKIM-1) and NGAL (δNGAL) following 2 weeks of TDF use could predict subclinical TDF-associated nephrotoxicity before the overt manifestation as acute kidney disease after 3 months.MethodsA prospective cohort study of 205 PLWH was conducted at the Adult Center for Infectious Disease Research (AIDC) in Lusaka, Zambia. ART-naïve PLWH who were starting treatment with TDF with intact kidney function [estimated glomerular filtration rate (eGFR)> 60 mL/min/1.73m2] were followed at initiation, 2 weeks, and approximately 3 months to determine the incidence of TDF-associated nephrotoxicity. We measured urine KIM-1 and NGAL at baseline and after 2 weeks of treatment to determine if it predicted subclinical nephrotoxicity. The presence of TDF-associated nephrotoxicity was defined according to the established acute kidney disease and disorders criteria (AKD) as having either 1) one or more episodes of eGFR< 60ml/min/1.73m2 within 3 months, 2) a reduction in eGFR of greater than 35% (from baseline) within 3 months, and/or 3) an increase in serum creatinine of more than 50% (from baseline) within 3 months.ResultsThe incidence of TDF-associated nephrotoxicity was 22%. Baseline eGFR, creatinine, age, female sex, and BMI predicted the risk of overt TDF-associated nephrotoxicity. The median baseline KIM-1-to-creatinine and NGAL-1-to-creatinine ratios of the participants who developed overt TDF-associated nephrotoxicity and those who did not were not significantly different. However, every 1 pg/mg increase in δKIM-1 was associated with a 41% higher risk of TDF-associated nephrotoxicity. No association was observed with δNGAL.ConclusionsThe incidence of TDF-associated nephrotoxicity was high. Change in KIM-1 level within 2 weeks of the initiation of TDF treatment predicted subclinical TDF-associated nephrotoxicity before overt manifestation as acute kidney disease while δNGAL within the same period did not predict subclinical TDF-associated nephrotoxicity
Prognostic model for nephrotoxicity among HIV-positive Zambian adults receiving tenofovir disoproxil fumarate-based antiretroviral therapy.
Persons living with HIV (PLWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) risk suffering TDF-associated nephrotoxicity (TDFAN). TDFAN can result in short- and long-term morbidity, including permanent loss of kidney function, chronic kidney disease (CKD), and end-stage kidney disease (ESKD) requiring dialysis. Currently, there is no model to predict this risk or discern which patients to initiate TDF-based therapy. Consequently, some patients suffer TDFAN within the first few months of initiating therapy before switching to another suitable antiretroviral or a lower dose of TDF. In a prospective observational cohort study of adult Zambian PLWH, we modelled the risk for TDFAN before initiating therapy to identify individuals at high risk for experiencing AKI after initiating TDF-based therapy. We enrolled 205 HIV-positive, ART-naïve adults initiating TDF-based therapy followed for a median of 3.4 months for TDFAN at the Adult Infectious Disease Research Centre (AIDC) in Lusaka, Zambia. We defined TDFAN as meeting any of these acute kidney disease (AKD) criteria: 1) An episode of estimated glomerular filtration rate (eGFR) 35% within 3 months or 3) increased serum creatinine by> 50% within 3 months. A total of 45 participants (22%) developed acute kidney disease (AKD) after TDF-based therapy. The development of AKD within the first 3 months of commencing TDF-based therapy was associated with an increase in baseline serum creatinine, age, baseline eGFR and female sex. We concluded that baseline characteristics and baseline renal function biomarkers predicted the risk for AKD within the first 3-months of TDF-based therapy
Asymptomatic carriage of intestinal protists is common in children in Lusaka Province, Zambia.
BackgroundPCR-based screenings on the presence of diarrhoea-causing intestinal protist species are limited in Zambia, resulting in inaccurate current prevalence and epidemiological data. Sensitive PCR-based methods are particularly well suited for detecting subclinical infections in apparently healthy carriers.MethodologyIn this prospective cross-sectional study, we investigated the occurrence of the most common intestinal protists in an apparently healthy paediatric population (5-18 years) in Lusaka Province, Zambia. We collected single stool samples (n = 256) and epidemiological questionnaires on demographics, behavioural habits, drinking water and toilet access from participating children. We used PCR for the initial screening of samples for the presence of intestinal protist species and Sanger and next-generation sequencing for genotyping. We conducted statistical analyses to assess the association of the gathered variables with an increased likelihood of the investigated pathogens.Principal findingsBlastocystis sp. was the most prevalent intestinal protist found (37.9%, 97/256; 95% CI: 31.9-44.1), followed by Giardia duodenalis (30.9%, 79/256; 95% CI: 25.3-36.90), Entamoeba dispar (13.3%, 34/256; 95% CI: 9.4-18.1), and Cryptosporidium spp. (4.3%, 11/256, 95% CI: 2.2-7.6). Entamoeba histolytica was not detected. Based on Sanger sequencing results, subtypes ST2 (44.3%, 43/97), ST1 (35.1%, 34/97), and ST3 (20.6%, 20/97) were identified within Blastocystis sp. and assemblages B (71.0%), A+B (16.1%), and A (12.9%) within G. duodenalis. Cryptosporidium parvum (81.8%) and C. hominis (18.2%) were the only two Cryptosporidium species found. Living in the Kafue District was positively associated with higher infection rates by G. duodenalis and Blastocystis sp. Schoolchildren living in Chongwe District were more likely to be infected by Cryptosporidium spp.Conclusions/significanceIntestinal protist infection/colonization is a common finding in apparently healthy children in Lusaka Province, Zambia. Asymptomatic carriers may play an underestimated role as spreaders of gastrointestinal parasitic infections. This study improves our current understanding of the epidemiology of diarrhoea-causing protists in Zambia and sub-Saharan Africa and indicates that the role of asymptomatic carriers of gastrointestinal parasites in transmission should be further explored
Antimicrobial Resistance Patterns and Serological Diversity of Shigella Species from Patient Isolates at University Teaching Hospital in Lusaka, Zambia
Background: Shigella species are the leading cause of human shigellosis. In Zambia, more than 30% of children experiencing diarrhea are infected with Shigella species. The increasing resistance of Shigella species to the recommended therapy is of great concern. Therefore, this study investigated the antibiotic resistance profiles and phenotypic and genotypic characteristics of Shigella isolates at the largest referral hospital in Zambia. Methodology: Of the forty-eight archived presumptive Shigella isolates, thirty-two were serologically confirmed and subjected to antimicrobial susceptibility testing using the Kirby Bauer disk diffusion method. Thereafter, polymerase chain reaction was performed to detect the bla genes. Results: Most isolates were Shigella flexneri (16/32, 50%) and Shigella sonnei (14/32, 44%), while Shigella boydii and Shigella dysenteriae were rare. High resistance rates were noted for sulfamethoxazole/trimethoprim (78%) and tetracycline (75%), while 15.6% of the isolates showed resistance to ciprofloxacin and/or azithromycin. The blaTEM gene encoding beta-lactamase was detected in 7/32 (22%) of isolates. Conclusions: In this study, a significant number of multidrug-resistant isolates were identified. Additionally, Shigella species resistant to the World Health Organization-recommended drugs call for strengthened laboratory diagnosis and close monitoring of these pathogens to guide the clinical management of shigellosis
In silico characterization of chromosomally integrated blaCTX-M genes among clinical Enterobacteriaceae in Africa: insights from whole-genome analysis
Antimicrobial resistance (AMR) mediated by extended-spectrum β-lactamases (ESBLs) is a growing global concern, particularly among Enterobacteriaceae. The CTX-M-type ESBLs, encoded by the blaCTX-M gene, are of significant public health importance due to their high prevalence and broad geographic distribution. Typically located on plasmids and often co-occurring with other AMR genes, blaCTX-M contributes to multidrug resistance (MDR). However, increasing evidence suggests secondary chromosomal integration of blaCTX-M, sometimes alongside other resistance determinants. The extent and implications of this mechanism remain poorly characterized, especially in Africa, where genomic surveillance is limited. In this study, we retrieved 295 chromosomal sequences of Enterobacteriaceae of African origin from the GenBank and performed in silico predictions of blaCTX-M and other AMR genes. blaCTX-M-carrying sequences were further characterized by in silico multilocus sequence typing and genome annotation. Chromosomal insertions were identified through alignment with reference genomes. Overall, 47 of 295 sequences (15.9%) harbored the blaCTX-M gene, with the highest prevalence in Klebsiella pneumoniae (29/157, 18.5%), followed by Escherichia coli (13/72, 18.1%), Enterobacter spp. (4/38, 10.5%), and Shigella spp. (1/12, 8.3%). The most common allele was blaCTX-M-15 (31/47, 66.0%), followed by blaCTX-M-14 (12/47, 25.5%), blaCTX-M-55 (3/47, 6.4%), and blaCTX-M-27 (1/27, 3.7%). Co-occurrence of blaCTX-M with additional AMR genes was frequently observed, with integration events often associated with mobile genetic elements such as ISEcp1 and IS26. Notably, strains from the same hospital setting were phylogenetically related and shared sequence types and AMR gene profiles, suggesting local clonal dissemination. These findings reveal a notable presence of chromosomally integrated blaCTX-M among African Enterobacteriaceae, frequently in association with other resistance genes, thereby facilitating stable MDR propagation independent of plasmid maintenance. This evolutionary adaptation may have significant implications for the persistence and spread of MDR in clinical settings
