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Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity and vaccine escape among others. Genome sequencing is a technique that allows scientists to read the genetic code of an organism and has become a powerful tool for studying emerging infectious diseases. Here, we conducted a cross-sectional study in selected districts of the Eastern Province of Zambia, from November 2021 to February 2022. We analyzed SARS-CoV-2 samples (n = 76) using high-throughput sequencing. A total of 4097 mutations were identified in 69 SARS-CoV-2 genomes with 47% (1925/4097) of the mutations occurring in the spike protein. We identified 83 unique amino acid mutations in the spike protein of the seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 and XT). Of these, 43.4% (36/83) were present in the receptor binding domain, while 14.5% (12/83) were in the receptor binding motif. While we identified a potential recombinant XT strain, the highly transmissible BA.2 sublineage was more predominant (40.8%). We observed the substitution of other variants with the Omicron strain in the Eastern Province. This work shows the importance of pandemic preparedness and the need to monitor disease in the general population.
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COVID-19 , Genoma Viral , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Zâmbia/epidemiologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , COVID-19/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Estudos Transversais , Estudos Retrospectivos , Filogenia , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
OBJECTIVES: To develop two ethical checklists to evaluate (i) management of ethical concerns in research projects and (ii) awareness of ethical conduct of healthcare laboratory professionals. METHODS: Comprehensive discussion among the members of IFCC Task Force on Ethics based on pertinent literature. RESULTS: This Checklist for Clinical Research Projects should be useful to evaluate research proposals from an ethical perspective before submitting it to an IRB or its equivalent, thereby diminishing rejection rates and resulting in more time-effective projects. The checklist designed to evaluate the ethical conduct in laboratory medicine could be useful for self evaluation (internal audits) and for certification/accreditation processes performed by third parties. CONCLUSIONS: These checklists are simple but powerful tools useful to guide professionals to adhere to ethical principles in their practice, especially in developing countries where accredited ethics committees may be difficult to find.
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Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic anemia in HIV are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation of erythropoietin production, and persistent immune activation. Chronic inflammation from HIV infection adversely affects erythropoiesis, erythrocyte lifespan, and erythropoietin response, leading to a heightened risk of co-infections such as tuberculosis, persistent severe anemia, and increased mortality. Additionally, chronic anemia exacerbates the progression of HIV-associated nephrotoxicity and contributes to cardiovascular risk through immune activation and inflammation. This review highlights the cardinal role of chronic inflammation as a link connecting persistent anemia and cardiovascular complications in PLWH, emphasizing the need for a universal understanding of these interconnected pathways for targeted interventions.
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Anemia , Infecções por HIV , Humanos , Anemia/virologia , Doenças Cardiovasculares/virologia , Doença Crônica , Eritropoetina , Infecções por HIV/complicações , Inflamação/virologiaRESUMO
BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.
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Antibacterianos , Gonorreia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Neisseria gonorrhoeae/genética , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/microbiologia , Tipagem de Sequências Multilocus , Zâmbia/epidemiologia , Estudos Transversais , Farmacorresistência Bacteriana/genética , Tetraciclina , Ciprofloxacina , Penicilinas , Testes de Sensibilidade MicrobianaRESUMO
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
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Infecções do Sistema Nervoso Central , Infecções por Vírus Epstein-Barr , Infecções por HIV , Adulto , Humanos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Zâmbia/epidemiologia , DNA Viral , Infecções do Sistema Nervoso Central/complicações , Sistema Nervoso Central , Infecções por HIV/complicações , Infecções por HIV/diagnósticoRESUMO
BACKGROUND: Whilst malaria is a prominent aetiology associated with acute kidney injury (AKI) in many parts of Africa, a shift in the traditional AKI aetiologies has been witnessed in sections of the continent. Additionally, limited access to dialysis worsens patient outcomes in these low-resource settings. This retrospective cross-sectional study aimed to determine the associated aetiologies, predictors of need for dialysis and malaria-associated AKI (MAKI), and outcomes of AKI and dialysis among children evaluated by the renal service in Lusaka, Zambia. METHODS: The study sampled all children aged 16 years or below, diagnosed with AKI between 2017 and 2021, by the renal unit at the University Teaching Hospitals- Children's Hospital (UTH-CH), and retrospectively abstracted their records for exposures and outcomes. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Frequency and percentage distributions were used to describe the occurrence of AKI aetiologies and treatment outcomes. Predictors of the need for dialysis, MAKI, and poor treatment outcome were identified by using multivariable logistic regression models. RESULTS: A total of 126 children diagnosed with AKI were included in this study. Malaria was the most frequent aetiology of AKI(61.1% (77/126, 95% Confidence Interval (CI): 52.0%-69.7%)). Of the 126 children with AKI, 74.6% (94) underwent dialysis. Predictors of the need for dialysis were oliguria (p = 0.0024; Odds ratio (OR) = 7.5, 95% CI: 2.1-27.7) and anuria (p = 0.0211; OR = 6.4, 95% CI = 1.3, 30.7). A fifth (18.3%, 23/126) of the children developed chronic kidney disease (CKD), 5.6% (7/126) died and, a year later, 77% (97/126) were lost to follow-up. CONCLUSION: At UTH-CH, malaria is the most frequent aetiology among children with AKI undergoing dialysis and children from low-medium malaria incidence areas are at risk; a considerable proportion of children with AKI need dialysis and Tenchoff catheter use in AKI is advocated.
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Injúria Renal Aguda , Malária , Criança , Humanos , Estudos Retrospectivos , Zâmbia/epidemiologia , Diálise Renal/efeitos adversos , Estudos Transversais , Fatores de Risco , Malária/complicações , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapiaRESUMO
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother-infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children.
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Background: Hypertension is common in people living with HIV (PLWH) on antiretroviral therapy (ART). In the general population and in experimental animal models, the incidence of hypertension is greater in males than in females, especially during the premenopausal period. However, it is not known whether there are sex differences in hypertension associated with HIV and ART, and the factors contributing to incident hypertension among PLWH have not been well characterized. In this study, we aimed to determine the time course, sex differences and factors associated with incident hypertension in PLWH initiating ART. Methods and results: We conducted a retrospective study in which we used programmatic data from the ART registry to identify sex differences in the determinants of incident hypertension among PLWH initiating the ART regimen from Livingstone University Teaching Hospital in Zambia and followed for 8 years. Males developed hypertension earlier, 2 years after initiating ART, compared to 6 years in females. In multivariable analysis, increasing age, baseline systolic blood pressure and baseline mean arterial pressure (MAP) were associated with increased risk for developing incident hypertension. Also, participants who switched to the integrase strand transfer inhibitor, dolutegravir (DTG) or the protease inhibitor, lopinavir boosted with ritonavir were 2 and 3 times more likely to develop hypertension when compared to those on non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, these relationships were abrogated by sex, as self-reported male sex was the major contributor in predicting incident hypertension. While none of the factors remained significantly associated with incident hypertension upon multivariate analysis among females, body mass index (BMI), and use of protease inhibitors remained strongly associated with hypertension among males. Conclusion: Our results indicate that the use of protease inhibitors and BMI are important predictors of incident hypertension among males. Thus, blood pressure and BMI should be closely monitored, particularly in males living with HIV on protease inhibitors. In addition, identifying specific factors that protect females from developing hypertension early is important but remains to be determined.
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Transmission dynamics and the maintenance of mammarenaviruses in nature are poorly understood. Using metagenomic next-generation sequencing (mNGS) and RT-PCR, we investigated the presence of mammarenaviruses and co-infecting helminths in various tissues of 182 Mastomys natalensis rodents and 68 other small mammals in riverine and non-riverine habitats in Zambia. The Luna virus (LUAV) genome was the only mammarenavirus detected (7.7%; 14/182) from M. natalensis. Only one rodent from the non-riverine habitat was positive, while all six foetuses from one pregnant rodent carried LUAV. LUAV-specific mNGS reads were 24-fold higher in semen than in other tissues from males. Phylogenetically, the viruses were closely related to each other within the LUAV clade. Helminth infections were found in 11.5% (21/182) of M. natalensis. LUAV-helminth co-infections were observed in 50% (7/14) of virus-positive rodents. Juvenility (OR = 9.4; p = 0.018; 95% CI: 1.47-59.84), nematodes (OR = 15.5; p = 0.001; 95% CI: 3.11-76.70), cestodes (OR = 10.8; p = 0.025; 95% CI: 1.35-86.77), and being male (OR = 4.6; p = 0.036; 95% CI: 1.10-18.90) were associated with increased odds of LUAV RNA detection. The role of possible sexual and/or congenital transmission in the epidemiology of LUAV infections in rodents requires further study, along with the implications of possible helminth co-infection.
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Simply detecting Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) is insufficient to diagnose EBV-associated diseases. The current literature around EBV-DNA detection from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-positive non-lymphoma patients was systematically reviewed and a meta-analysis reporting the estimated pooled prevalence in this population when PCR methods are employed, targeting different sequence segments within the EBV genome, was conducted. Using a combination of three key concepts-Epstein-Barr virus detection, central nervous system disease, and human cerebrospinal fluid-and their MeSH terms, the PubMed database was searched. A total of 273 papers reporting the detection of EBV in CNS were screened, of which 13 met the inclusion criteria. The meta-analysis revealed a pooled prevalence of EBV-DNA in CSF of 20% (CI: 12-31%). The highest pooled prevalence was from studies conducted on the African population at 39% (CI: 27-51%). The investigation of the presence of EBV-DNA in the CSF was also very varied, with several gene targets used. While most patients from the articles included in this review and meta-analysis were symptomatic of CNS disorders, the pathogenicity of EBV in non-lymphoma HIV patients when detected in CSF has still not been determined. The presence of EBV-DNA in the CNS remains a concern, and further research is warranted to understand its significance in causing CNS disorders.
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Whether the human brain is a robust reservoir for HIV-1 subtype C has yet to be established. We aimed to determine whether HIV-1 subtype C infection can be detected in the brain tissue of a viremic individual at post-mortem and whether the viral burden was differential between different brain regions. This study reports a 38-year-old Zambian female decedent with severe wasting who was on Atripla for antiretroviral therapy. The cause of death was determined to be HIV/AIDS end-stage disease. The QuantStudio 3 Real-Time PCR System analyzed formalin-fixed paraffin-embedded tissue DNA from a systematic sampling of the entire left-brain hemisphere. Plasma and cerebral spinal fluid HIV-1 RNA loads were 576,123 and 14,962 copies/mL, respectively. The lymph node DNA viral load was 2316 copies per 106 cells. Two hundred and six (96.3%) tissue blocks had amplifiable DNA. HIV-1 viral DNA was detected in 35.9% of the blocks, the highest in the basal ganglia (66.7%) and the frontal lobe (46%). Overall, HIV detection was random, with low viral copies detected by quantitative polymerase chain reaction (qPCR); the lowest was observed in the occipital (median, IQR, range) 0.0 [0.0-0.0], 0.0-31.3, and the highest in the basal ganglia (mean ± SD, range, 125.1149.5, 0.0-350.0). Significant differences in HIV-1 DNA distribution were observed between the occipital versus parietal (p = 0.049), occipital versus frontal (p = 0.019), occipital versus basal ganglia (p = 0.005), cerebellum versus frontal (p = 0.021), cerebellum versus basal ganglia (p = 0.007), and temporal versus frontal (p = 0.034).
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Adulto , Feminino , Humanos , Encéfalo , Infecções por HIV/genética , HIV-1/genética , Reação em Cadeia da Polimerase em Tempo Real , Carga ViralRESUMO
BACKGROUND: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor effect of salt is viewed as a chronic effect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this effect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. METHODS: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2 g of sodium chloride; their BP was monitored for 120 minutes in intervals of 10 minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. RESULTS: Median age was 30 years (interquartile range, 22-46 years) and 52% were female patients. An increase of ≥10 mmHg in mean arterial pressure (MAP), considered a clinically significant IPROS, was present in 62% of participants. Systolic BP 30 minutes after the salt load was a significant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. CONCLUSIONS: We confirm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30 minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30 minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral salt-loads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our findings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP.
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BACKGROUND: Neisseria gonorrhoeae, the causative agent for sexually transmitted infection (STI) gonorrhoea, has emerged with a significant public health impact on acquiring resistance to antimicrobials available for treatment. The resistance of N. gonorrhoeae limit treatment options and contributed to high morbidity associated with gonorrhoea. Data on antimicrobial resistance (AMR) profiles in N. gonorrhoeae is scares in Zambia. This study aimed to determine the antibiotic susceptibilities in N. gonorrhoeae isolates from Lusaka, Zambia. METHODS: A prospective cross-sectional study was conducted on 630 STI patients who presented with urethral or vaginal discharge from 2019 to 2020. Urethral and endocervical secretions were cultured on Modified Thayer Martin agar and incubated at 36 °C ± 1 °C in 5% CO2 for 24 h. Identification of N. gonorrhoeae isolates was achieved by Gram stain, oxidase, nitrocefin disk, BactiCard Neisseria, and Viteck® Compact. The AMR profiles were determined using E-test. Statistical significant was determined by Pearson's Chi-square test, Mann-Whitney U test, or logistic regression with p-values of < 0.05 indicating significance. RESULTS: A total of 630 patients were recruited of which 46% (290/630) with the median of 29 years and interquartile range (IQR) of 19-39 years were male. The median of the females was 26 years and IQR of 15-37 years. Neisseria gonorrhoeae was isolated from 19.4% (122/630) patients of which 72.9% (89/122) were male, with highest prevalence of isolation in the age category of 25-34 years. The prevalence of resistance was high to penicillin (85.2%), tetracycline (68.9%) and ciprofloxacin (59.8%) with MIC90 of 32 µg/mL, 8 µg/mL, and 8 µg/mL respectively. The isolates had reduced susceptibility to cefixime (1.6%), spectinomycin (4.9%) and (4.9%) for azithromycin. All isolates were susceptible to ceftriaxone. Risk factors associated with AMR were douching in females (AOR 6.69, 95% CI; 1.11-40.31, p = 0.039), female gender (AOR 7.64, 95% CI; 1.11-52.33, p = 0.048), HIV-positivity (AOR 26.59, 95% CI; 3.67-192.7, p = 0.005), no condom use or unprotected sex (AOR 5.48, 95% CI; 1.17-22.75 p = 0.026), sex trading (AOR 4.19, 95% CI; 1.55-11.33, p = 0.010), and over-counter treatment of ciprofloxacin (AOR 3.44, 95% CI; 1.17-22.75, p = 0.023). CONCLUSION: The N. gonorrhoeae resistance to penicillin, tetracycline and ciprofloxacin was high necessitating revision of the treatment guidelines. However, no resistance to ceftriaxone was detected. Therefore, monitoring of antibiotic resistance remains critical in Zambia.
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Anti-Infecciosos , Gonorreia , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Estudos Transversais , Farmacorresistência Bacteriana , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Hospitais Urbanos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Penicilinas/farmacologia , Estudos Prospectivos , Tetraciclina/farmacologia , Zâmbia/epidemiologiaRESUMO
BACKGROUND: People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. RESULTS: We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28-42) years and 31(25-36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465-702.5 cells/mm3] vs 345 [157-483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827-23,686 pg/ml] vs. 9,508 [5,514-15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990-24,206 pg/ml] vs 9,505 [5,400-15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087-22,584 pg/ml] vs 10,413 [7,397-14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36-0.72; p < 0.0001) and r = 0.48 (95% CI 0.15-0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0-0.28] vs 0.007 [0-0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. CONCLUSIONS: This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.
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Infecções por HIV/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Coinfecção/complicações , Estudos Transversais , Feminino , Infecções por HIV/complicações , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Masculino , Mycobacterium tuberculosis/patogenicidade , Tuberculose/complicações , Tuberculose Pulmonar/complicações , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Zâmbia/epidemiologiaRESUMO
Introduction: the coronavirus disease 2019 (COVID-19) has negatively impacted the mental health of students across the globe. In Zambia, little is known about the psychological impacts of COVID-19 on healthcare students. This study assessed the psychological impact of COVID-19 on health professions students at the University of Zambia. Methods: this cross-sectional study was conducted from August 2021 to October 2021. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). The multivariable logistic regression model was used to identify the factors associated with anxiety and depression among the participants. Data were analysed using Stata 16.1. Results: of the 452 students, 57.5% were female, with the majority aged between 19 and 24 years. Overall, 65% (95% CI: 60.5-69.4) experienced anxiety, while 86% (95% CI: 82.7-89.3) experienced depression. Participants whose income was affected were more likely to experience anxiety (aOR; 2.09, 95% CI: 1.29-3.37) and depression (aOR; 2.87, 95% CI: 1.53-5.38). Anxiety was associated with difficulty in observing the COVID-19 preventive measures (aOR; 1.84, 95% CI: 1.21-2.81). Being depressed was associated with having a chronic condition (aOR; 3.98, 95% CI: 1.67-9.50) or a relative or friend who died from COVID-19 (aOR: 1.98, 95% CI: 1.06-3.70). Conclusion: many students experienced anxiety and depression during the COVID-19 third wave of infections. This calls for mitigation measures because continued anxiety and depression can affect the academic performance of students. Fortunately, most of the associated factors are modifiable and can easily be targeted when formulating interventions to reduce anxiety and depression among students.
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COVID-19 , Estudantes de Ciências da Saúde , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Estudos Transversais , SARS-CoV-2 , Depressão/epidemiologia , Depressão/etiologia , Inquéritos e Questionários , Ansiedade/etiologia , Ocupações em Saúde , Estresse Psicológico/etiologiaRESUMO
As COVID-19 vaccines are becoming more available, there is also a growing need to understand the population receiving the doses, existing inequalities and the intention to getting the second vaccine dose among the populations that receive the vaccines. We evaluated gender inequalities and intention to uptake of the second dose of COVID-19 AstraZeneca vaccine among adult populations in selected urban facilities of Lusaka, Zambia. A cross-sectional study design was conducted between May and June 2021 among adults who received AstraZeneca vaccine from three selected urban facilities of Lusaka, Zambia. Phone-based interviews were conducted 6 weeks after the first dose of the vaccine. Descriptive analysis and mixed-effect logistic regression were done using STATA version 16.2. Of the 1321 adults who had received AstraZeneca vaccine, 868 respondents completed the questionnaire. About, 47% (408/868) were females and 53% (460/868) were males. Median age in the study was 40 years. Majority of males were educated (54%) and employed (57%). Furthermore, majority of females that got the first dose of AstraZeneca reported experiencing side effects (76.98%) compared to males (64.24%). Among study participants, 93.7% intended to receive the AstraZeneca vaccine, of whom 46.7% (380/814) were females and 52.9% (434/814) were males. Majority of participants that did not intend to get a second dose were not married (55.56%). Only age (AOR, 1.05; 95% CI, 1.02-1.08) predicted intention to getting a second dose of AstraZeneca vaccine. We found important gender-dependent differences in the side effects reported by females that received the first dose of Astra Zeneca. Finding that intention to get the second dose of the vaccine increased with age suggests a need for enhancing COVID-19 vaccination programmes targeting young people and a need for further research to identify specific adverse effects of COVID-19 Astra Zeneca vaccines.
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Aim: This study aimed to assess the awareness and acceptance of COVID-19 vaccines and associated factors among pharmacy students in Zambia. Materials and Methods: We conducted a cross-sectional study among 326 undergraduate pharmacy students in Lusaka, Zambia, from February to April 2021. Data were analysed using Stata version 16.1. Multivariable logistic regression was used to determine key factors influencing vaccine acceptance. Results: Of the 326 participants, 98.8% were aware of the COVID-19 vaccines, but only 24.5% would accept vaccination. Compared to other religions, being of Christian faith was associated with reduced odds of awareness of the COVID-19 vaccine (aOR=0.01, 95% CI: 0.01-0.20). Conversely, factors associated with vaccine acceptance were being male, single and unemployed. Compared to females, male respondents were 86% more likely to accept the vaccine if it was made available (aOR=1.86, 95% CI: 1.10-3.14). In addition, unmarried respondents were 2.65 times as likely to accept vaccination than married respondents (aOR=2.65, 95% CI: 1.06-6.63). Conversely, unemployed respondents were less likely to accept vaccination than their employed counterparts (aOR=0.32, 95% CI: 0.16-0.46). Barriers to the acceptability of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness (10.2%). Conclusion: There was significant vaccine hesitancy toward COVID-19 vaccines among Zambian pharmacy students despite their awareness of the vaccines. Health authorities must work collaboratively with training institutions to mitigate vaccine hesitancy, especially with healthcare students being a key part of the future healthcare workforce overseeing disease prevention strategies.
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COVID-19 , Estudantes de Farmácia , Feminino , Masculino , Humanos , Vacinas contra COVID-19 , Zâmbia , Estudos Transversais , COVID-19/prevenção & controleRESUMO
BACKGROUND: Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. OBJECTIVES: To study the spectrum of lymphoma subtypes prevalent within the Zambian population. METHODS: Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher's exact test was used for significance testing. RESULTS: During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin's lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin's lymphoma (CHL) was seen in 39 (16.3%). Burkitt's lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). CONCLUSION: Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.
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Doença de Hodgkin , Linfoma não Hodgkin , Doença de Hodgkin/epidemiologia , Hospitais Universitários , Humanos , Linfoma não Hodgkin/epidemiologia , Organização Mundial da Saúde , Zâmbia/epidemiologiaRESUMO
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.
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Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias/genética , Fatores de Transcrição/genética , Antineoplásicos/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proto-Oncogene Mas , Fatores de Transcrição/metabolismo , Transcriptoma , Resultado do TratamentoRESUMO
INTRODUCTION: The novel Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in Africa is characterised by a more substantial proportion of asymptomatic (or mildly symptomatic) individuals thought to be playing a role in the spread of the infection. The exact proportion and degree of infectiousness of asymptomatic individuals remains unclear. Studies however indicate that their management is crucial for control of SARS-CoV-2 transmission. METHODOLOGY: We developed a simplified deterministic susceptible-exposed-infectious-removed (SEIR) mathematical model to assess the effect of active isolation of SARS-CoV-2 infected but asymptomatic individuals through blanket testing for control of the outbreak in Lusaka Province of Zambia. Here we modelled two scenarios; (1) assuming asymptomatic individuals comprised 70% of all COVID-19 cases and (2) asymptomatic individuals comprised only 50% of the cases. For contrast, the model was assessed first under the assumption that asymptomatic individuals are equally as infectious as symptomatic individuals and then secondly, and more likely, assuming asymptomatic individuals are only half as infectious as symptomatic individuals. RESULTS: For the model assuming 70% asymptomatic cases, a minimum sustained daily blanket testing rate of ≥ 7911 tests/100000 population was sufficient to control the outbreak if asymptomatic individuals are only half as infectious while if equal infectiousness was assumed then a testing rate of ≥ 10028 tests/ 100000 population would be required. For 50% asymptomatic, minimum blanket testing rates of ≥ 4540 tests/ 100000 population was sufficient to control the outbreak at both assumed levels of infectiousness for asymptomatic individuals relative to symptomatic individuals. DISCUSSION AND CONCLUSION: Our model predicts that active isolation of COVID-19 cases, including asymptomatic individuals, through blanket testing can be used as a possible measure for the control of the SARS-Cov-2 transmission in Lusaka, Zambia, but it would come at a high cost.