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.

IntroductionEpstein-Barr virus (EBV) is a ubiquitous virus that infects more than 90% of the world's population, and is implicated in lymphoma pathogenesis. However, in Zambia during the diagnosis of these lymphomas, the association of the virus with the lymphomas is not established. Since most patients with lymphomas have poor prognosis, the identification of the virus within the lymphoma lesion will allow for more targeted therapy. The aim of this study was to provide evidence of the presence of the EBV in lymphomas diagnosed at the University Teaching Hospital (UTH) in Lusaka, Zambia.MethodsOne hundred and fifty archival formalin-fixed paraffin embedded suspected lymphoma tissues stored over a 4-year period in the Histopathology Laboratory at the UTH in Lusaka, Zambia, were analysed. Histological methods were used to identify the lymphomas, and the virus was detected using Polymerase Chain Reaction (PCR). Subtyping of the virus was achieved through DNA sequencing of the EBNA-2 region of the viral genome. Chi square or fisher's exact test was used to evaluate the association between EBV status, type of lymphoma and gender.ResultsThe majority of the lymphomas identified were non-Hodgkin's lymphoma (NHL) (80%) followed by Hodgkin's lymphoma (HL) (20%). EBV was detected in 51.8% of the cases, 54.5% of which were associated with NHL cases, while 40.9% associated with HL cases. The predominant subtype of the virus in both types of lymphomas was subtype 1. One of the lymphoma cases harboured both subtype 1 and 2 of the virus.ConclusionThis study showed that EBV is closely associated with lymphomas. Therefore, providing evidence of the presence of the virus in lymphoma tissues will aid in targeted therapy. To our knowledge this is the first time such data has been generated in Zambia.

Irrational and inappropriate prescribing of antibiotics is a major problem that can lead to the development of antimicrobial resistance (AMR). In Zambia, there is insufficient information on the prescribing patterns of antibiotics according to the World Health Organization (WHO) AWaRe classification. Therefore, this study assessed the prescribing patterns of antibiotics using the AWaRe classification during the COVID-19 pandemic at the University Teaching Hospital in Lusaka, Zambia. A cross-sectional study was conducted using 384 patient medical files at the University Teaching Hospital in Lusaka, Zambia, from August 2022 to September 2022. All antibiotics were classified according to the WHO “AWaRe” tool and assessed for appropriateness using the 2020 Zambian Standard Treatment Guidelines. Of the 384 patient medical files reviewed, antibiotics were prescribed 443 times. The most prescribed antibiotics were ceftriaxone (26.6%), metronidazole (22.6%), amoxicillin (10.4%), amoxicillin/clavulanic acid (5.6%), and azithromycin (5%). The prescribing of 42.1% of “Watch” group antibiotics was greater than the recommended threshold by the WHO. Most antibiotics were prescribed for respiratory infections (26.3%) and gastrointestinal tract infections (16.4%). The most prescribed antibiotic was ceftriaxone, a Watch antibiotic. This is a worrisome observation and calls for strengthened antimicrobial stewardship and implementation of the AWaRe framework in prescribing antibiotics.

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.

Since the earliest reports of the Coronavirus disease - 2019 (COVID-19) in Wuhan, China in December 2019, the disease has rapidly spread worldwide, attaining pandemic levels in early March 2020. However, the spread of COVID-19 has differed in the African setting compared to countries on other continents. To predict the spread of COVID-19 in Africa and within each country on the continent, we applied a Susceptible-Infectious-Recovered mathematical model. Here, our results show that, overall, Africa is currently (May 29, 2020) at the peak of the COVID-19 pandemic, after which we predict the number of cases would begin to fall in June 2020. Furthermore, we predict that the ending phase of the pandemic would be in Mid-August 2020 and that decreasing cases of COVID-19 infections would be detected until around December 2020 and January 2021. Our results also reveal that of the 51 countries with reported COVID-19 cases, only nine, including South Africa, Egypt and Ethiopia, are likely to report higher monthly COVID-19 cases in June 2020 than those reported in the previous months. Overall, at the end of this pandemic, we predict that approximately 279,000 (about 154,000 future cases) individuals in Africa would have been infected with the COVID-19 virus. Here, our predictions are data-driven and based on the previously observed trends in the spread of the COVID-19 pandemic. Shifts in the population dynamics and/or changes in the infectiousness of the COVID-19 virus may require new forecasts of the disease spread.

Cervical cancer has remained the most prevalent and lethal malignancy among women worldwide and accounted for over 250,000 deaths in 2019. Nearly ninety-five per cent of cervical cancer cases are associated with persistent infection with high-risk Human Papillomavirus (HPV), and seventy per cent of these are associated with viral integration in the host genome. HPV-infection imparts specific changes in the regulatory network of infected cancer cells that are of diagnostic, prognostic and therapeutic importance. Here, we conducted a systems-level analysis of the regulatory network changes, and the associated regulatory proteins thereof, in HPV-positive cervical cancer. We applied functional pathway analysis to show that HPV-positive cancers are characterised by perturbations of numerous cellular processes, predominantly in those linked to the cell cycle, mitosis, cytokine and immune cell signalling. Using computational predictions, we revealed that HPV-positive cervical cancers are regulated by transcription factors including, SOX2, E2F, NANOG, OCT4, and MYC, which control various processes such as the renewal of cancer stem cells, and the proliferation and differentiation of tumour cells. Through the analysis of upstream regulatory kinases, we identified the mitogen-activated protein kinases; among others, MAPK1, MAPK3 and MAPK8, and the cyclin-dependent kinases; among others, CDK1, CDK2 and CD4, as the key kinases that control the biological processes in HPV-positive cervical cancers. Taken together, we uncover a landscape of the key regulatory pathways and proteins in HPV-positive cervical cancers, all of which may provide attractive drug targets for future therapeutics.

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.

No abstract