Prevalence and predictors for cisplatin-induced toxicities in Zimbabwean women with cervical cancer.

Aim: To describe treatment-induced toxicities (TITs) and associated factors in Zimbabwean cancer patients receiving cisplatin.Methods: In total, 252 Zimbabwean women with cervical cancer, receiving cisplatin were followed up over 12 months for TITs and disease status.Results: Peripheral neuropathy (70%) and ototoxicity (53%) were most prevalent. Advanced disease (OR = 1.3; 95% CI = 1.1-1.5; p = 0.02), pain comedications (OR = 1.3; 95% CI = 1.1-1.5; p = 0.03), alcohol (OR = 2.8; 95% CI = 1.1-7.5; p = 0.04) and comorbidities (OR = 1.2; 95% CI = 1.1-1.4; p = 0.04) increased peripheral neuropathy and ototoxicity risk. Older age increased risk of disease progression (OR = 1.9; 95% CI = 1.4-3.0; p = 0.033).Conclusion: High peripheral neuropathy and ototoxicity prevalence were observed, which are not routinely monitored in Zimbabwe. There is a need for capacity building to incorporate comprehensive TIT testing and optimize cancer care in Zimbabwe.

Cancer treatment has side effects, also known as treatment-induced toxicities (TITs), that can lead to death if not management properly. African populations are more likely to develop TITs, however, not many studies research on TITs in Africans and why they are more prone to TITs. This study followed up 252 Zimbabwean women with cervical cancer, over 12 months for TITs and found that loss of sensation and ear complications most commonly occurred after treatment. Advanced disease, prescribed pain medication, alcohol consumption history and underlying diseases such as diabetes increased likelihood of TITs, while older age increased risk of unresponsive cancer. This study highlights a need to incorporate comprehensive monitoring for TITs for at-risk individuals toward improving cancer care.

Prevalence and risk factors for diabetic foot complications among people living with diabetes in Harare, Zimbabwe: a cross-sectional study.

BACKGROUND: Diabetic foot disease (DF) is a common diabetes-related complication; however, the prevalence and associated risk factors for DF are not well characterised among people living with diabetes (PLWD) in Zimbabwe. This may suggest the unavailability of adequate strategies to diagnose and treat DF in the country. This study aimed to determine the prevalence of DF and associated risk factors for PLWD in Harare, Zimbabwe. METHODS: This was a cross-sectional study, employing a quantitative approach. In total, 352 PLWD were recruited from 16 primary care clinics in Harare. Sociodemographic and clinical data were collected via face-to-face interviews and clinical records reviews. The DF screening included an evaluation for peripheral neuropathy, ankle-brachial index (ABI), ulceration, and amputation. Self-administered questionnaires were used to assess knowledge, attitudes, and practices (KAPs), and KAP was scored using Bloom's cut-off. Chi-Square goodness-of-fit tests were performed, and regression analyses were used for association analysis. The threshold for significance was p < 0.05. RESULTS: This group included 82 men and 279 women, with a combined mean age of 57.9 ± 14 years. Twenty one (~ 26%) men and 41 (15%) women had type 1 diabetes. The diabetes type distribution significantly differed by gender (p < 0.001). Oral hypoglycaemics (71%) were most commonly administered for management. DF was observed in 53% (95% CI = 50-56) of PLWD. Other DF symptoms observed were abnormal ABI (53%), peripheral neuropathy (53%), foot ulceration (17%) and amputation (3%). Peripheral neuropathy increased the risk of ulceration (OR = 1.7; 95% CI = 1.1-2.6; p = 0.019), while insulin use was protective against amputation (OR = 0.1; 95% CI = 0.1-0.9; p = 0.049). Most (87%) of the participants demonstrated good DF knowledge and the importance of adhering to medication to prevent DF. However, 96% did not know that smoking was a risk factor for DF. Nearly two-thirds (63%) demonstrated poor attitudes and practices. Poor attitudes and practices were not predictors of DF ulceration risk (p > 0.05). CONCLUSION: This study showed that there was a high prevalence of DF (53%) in PLWD in Zimbabwe, and insulin use was protective against DF. There is an urgent need for policy revisions to include foot screening in routine primary care and increasing insulin use for PLWD to prevent complications such as DF as an integral part of primary care.

A cervical cancer biorepository for pharmacogenomics research in Zimbabwe.

BACKGROUND: Research infrastructures such as biorepositories are essential to facilitate genomics and its growing applications in health research and translational medicine in Africa. Using a cervical cancer cohort, this study describes the establishment of a biorepository consisting of biospecimens and matched phenotype data for use in genomic association analysis and pharmacogenomics research. METHOD: Women aged > 18 years with a recent histologically confirmed cervical cancer diagnosis were recruited. A workflow pipeline was developed to collect, store, and analyse biospecimens comprising donor recruitment and informed consent, followed by data and biospecimen collection, nucleic acid extraction, storage of genomic DNA, genetic characterization, data integration, data analysis and data interpretation. The biospecimen and data storage infrastructure included shared -20 °C to -80 °C freezers, lockable cupboards, secured access-controlled laptop, password protected online data storage on OneDrive software. The biospecimen or data storage, transfer and sharing were compliant with the local and international biospecimen and data protection laws and policies, to ensure donor privacy, trust, and benefits for the wider community. RESULTS: This initial establishment of the biorepository recruited 410 women with cervical cancer. The mean (± SD) age of the donors was 52 (± 12) years, comprising stage I (15%), stage II (44%), stage III (47%) and stage IV (6%) disease. The biorepository includes whole blood and corresponding genomic DNA from 311 (75.9%) donors, and tumour biospecimens and corresponding tumour DNA from 258 (62.9%) donors. Datasets included information on sociodemographic characteristics, lifestyle, family history, clinical information, and HPV genotype. Treatment response was followed up for 12 months, namely, treatment-induced toxicities, survival vs. mortality, and disease status, that is disease-free survival, progression or relapse, 12 months after therapy commencement. CONCLUSION: The current work highlights a framework for developing a cancer genomics cohort-based biorepository on a limited budget. Such a resource plays a central role in advancing genomics research towards the implementation of personalised management of cancer.

Clinical and demographic characteristics of cervical cancer patients presenting at Parirenyatwa Hospital, Zimbabwe.

Cervical cancer is the leading cause of cancer deaths in women in Africa, predominately due to late diagnosis. This study aims to identify risk factors, potential prognostic indicators, and optimal treatment modalities for Zimbabwean cervical cancer patients. Medical records for 1063 cervical cancer patients were reviewed for sociodemographic, clinical, treatment, and response data. All data were analysed using SPSS version 25. More than half of the cohort was pre-menopausal (63%) with low (2%) history of cervical cancer screening. Schistosoma ova were observed in 2.4% of the tumour specimens. More than 50% were diagnosed at stage 3 and later, with a high frequency of comorbidities (~68%). This study highlights a need for improving screening education and uptake in Zimbabwe. Moreover, the current data provides a dataset for understanding cervical cancer pathogenesis and treatment responses in an African cohort.

Needs assessment of diabetic foot services in Zimbabwe.

INTRODUCTION: Due to the increasing incidence of diabetes in Zimbabwe, complications such as diabetic foot (DF) are anticipated. Establishing local gaps and needs in DF healthcare is paramount for tailoring management strategies. AIMS: To determine the status of DF services in the healthcare system and explore awareness of DF management and practices among registered general nurses (RGNs) in Zimbabwe. METHODS: A mixed-methods approach was applied. Thirty-one RGNs from 16 public health facilities in Harare, Zimbabwe attending a DF workshop were administered with a cross-sectional survey instrument and a semi-structured questionnaire. Data collected included presence/absence of DF services and podiatrists in healthcare facilities, healthcare system approaches in DF care and availability of DF training/education programs for RGNs. Analysis was performed using Stata and Nvivo software. RESULTS: No respondents reported availability of podiatrists. Only 1 (3%) of RGNs reported DF screening in primary care. Sixty percent (18) did not know or had never screened for DF. The RGNs reported inadequate DF educational programs/modules in primary care settings. CONCLUSION: This data highlights a need to improve DF education for RGNs at the frontline of managing PLWD. Understanding the needs for DF services may guide interventions to improve education and awareness programs that are appropriately tailored to local constraints in the health system. The non-communicable diseases director is encouraged to develop DF educational programmes for frontline health care workers.

Pain management strategies among cervical cancer patients in Zimbabwe.

Aim: To describe pain management regulations, prevalence of pain and pain management practices in a Zimbabwean setting. Materials & methods: A multi-methods approach was used, consisting of: policy and guideline review; review of 410 cervical cancer patient records for pain symptoms and pain management data; and semistructured interviews with oncology healthcare practitioners. Results: We found a lack of policies that are specific for cervical cancer pain management. Although prevalence of pain was 68% (n = 278), only 42% of the patient records indicated pain drugs had been prescribed. Barriers to pain management included inadequate use of pain assessment tools, inaccessibility of key drugs and limited capacity. Conclusion: Cancer pain management in Zimbabwe can be improved by tailoring assessment protocols, improving drug accessibility and strengthening healthcare systems.

Lay abstract Although cancer pain has potential life-altering impact, it is not well studied in developing countries. This study aims to report on cancer pain management in Zimbabwe by reviewing policies of pain management, patient records for prevalence and assessing the practices of cancer pain management, using 410 cervical cancer patients as a model. In total, 278 (68%) cancer patients presented with pain, yet only 42% of patient records had documented prescribed pain management. We report that these findings can be consequences of restrictive policies, inadequate patient pain assessment, inaccessible pain drugs, unrecorded prescriptions and limitations of resources in the facility. Our study is important because it identifies gaps that can be addressed to improve care for cancer patients in resource-limited settings.

High-risk HPV genotypes in Zimbabwean women with cervical cancer: Comparative analyses between HIV-negative and HIV-positive women.

BACKGROUND: High-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women. METHODS: This was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA. RESULTS: Forty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1-0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1-1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0-6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8-15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8-15), HPV31/52 (OR = 6.2; 95% CI = 1.8-15), HPV39/56 (OR = 11 95% CI = 8-12), HPV59/68 (OR = 8.2; 95% CI = 5.3-12.4), HPV66/68 (OR = 7; 95% CI = 2.4-13.5), independent of age and HIV status. CONCLUSION: We found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.

Singapore COVID-19 Pandemic Response as a Successful Model Framework for Low-Resource Health Care Settings in Africa?

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to spread and evolve across the planet. The crosscutting impacts of the virus, individual country responses to the virus, and the state of preparedness of local public health systems greatly vary across the world. The ostensibly late arrival of the virus in Africa has allowed learning, innovation, and adaptation of methods that have been successful in the early-hit countries. This article analyzes how Singapore has responded to the COVID-19 pandemic and proposes that adaptations of the Singapore pandemic response model would bode well for Africa's response to the COVID-19 pandemic in ways that also take into account regional differences in health care infrastructures, socioeconomic resilience, poverty, and the vast population diversity in the African continent. As the pandemic evolves, the lessons learned in Asia, in particular, and the emerging new experiences in African countries should inform, ideally in real time, how best to steer the world populations into safety, including those in low-resource health care settings. Finally, we note that the current COVID-19 pandemic is also a test for our collective ability to scale and surge public health in response to future and likely equally challenging zoonosis infections that jump from animals to humans, not to mention climate change-related planetary health calamities in the 21st century. Hence, what we learn effectively from the current COVID-19 pandemic shall have broad, enduring, and intergenerational relevance for the future of planetary heath and society.

The splice 1 variant of HTLV-1 bZIP factor stabilizes c-Jun.

HBZ is expressed by the complex retrovirus, Human T-cell Leukemia Virus type 1, and implicated in pathological effects associated with viral infection. From the nucleus, HBZ alters gene expression by interacting with a variety of transcriptional regulatory proteins, among which is c-Jun. Previously, one of the three HBZ variants, HBZUS, was reported to decrease c-Jun expression by promoting its degradation. Here we show that another variant, HBZS1, produces the opposite effect. In the presence of HBZS1, c-Jun expression increases due to its stabilization. Our data suggest that this effect requires the ability of HBZS1 to interact with c-Jun. We provide evidence that HBZS1 inhibits the proteosomal degradation of c-Jun initiated by the Cop1-containing ubiquitin ligase complex. HBZS1 is the most abundant variant in HTLV-1-infected T-cells, and our data indicate that levels of c-Jun expression in infected cells are consistent with effects of HBZS1.

Understanding Ethical, Legal and Societal Issues (ELSIs) in Human Biobanking and Genomics for Research and Healthcare in Zimbabwe: The Genomics Inheritance Law Ethics and Society (GILES) initiative.

Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe there is limited understanding of ethical, legal, and societal issues (ELSI) for biobanking and genomics. The Genomics Inheritance Law Ethics and Society (GILES) initiative was established in 2015 to explore the current status and gaps in the ethical and legal frameworks, knowledge among various stakeholders, and to establish capacity for addressing ELSI of biobanking and genomics as applied in biomedical and population research, and healthcare. A multi-methods approach was applied including document reviews, focus group discussions and in-depth interviews among health and research professionals, and community members in six provinces comprising urban, peri-urban and rural areas. Emerging findings indicates a need for updating guidelines and policies for addressing ELSI in biobanking and genomics research in Zimbabwe. Emerging terminologies such as biobanking and genomics lack clarity suggesting a need for increased awareness and educational tools for health professionals, research scientists and community members. Common concerns relating to consent processes, sample and data use and sharing, particularly where there is trans-national flow of biospecimens and data, call for nationally tailored ELSI frameworks aligned to regional and international initiatives. This paper describes the strategy undertaken for the development and implementation of the GILES project and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa. Conducting this explorative study among a wide range of stakeholders over a countrywide geographical regions, established one of the most comprehensive studies for ELSI of human biobanking and genomics in Africa.

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Human papillomavirus (HPV) is an essential but not a sufficient cervical cancer etiological factor. Cancer promoters, such as host genetic mutations, significantly modulate therapeutic responses and susceptibility. In cervical cancer, of interest have been viral clearing genes and HPV oncoprotein targets, for which conflicting data have been reported among different populations. This expert analysis evaluates cervical cancer genetic susceptibility biomarkers studied in African populations. Notably, the past decade has seen Africa as a hotbed of biomarker and precision medicine innovations, thus potentially informing worldwide biomarker development strategies. We conducted a critical literature search in PubMed/MEDLINE, Google Scholar, and Scopus databases for case-control studies reporting on cervical cancer genetic polymorphisms among Africans. We found that seven African countries conducted cervical cancer molecular epidemiology studies in one of Casp8, p53, CCR2, FASL, HLA, IL10, TGF-beta, and TNF-alpha genes. This analysis reveals a remarkable gap in cervical cancer molecular epidemiology among Africans, whereas cervical cancer continues to disproportionately have an impact on African populations. Genome-wide association, whole exome- and whole-genome sequencing studies confirmed the contribution of candidate genes in cervical cancer. With such advances and omics technologies, the role of genetic susceptibility biomarkers can be exploited to develop novel interventions to improve current screening, diagnostic and prognostic methods worldwide. Exploring these genetic variations is crucial because African populations are genetically diverse and some variants or their combined effects are yet to be discovered and translated into tangible clinical applications. Thus, translational medicine and flourishing system sciences in Africa warrant further emphasis in the coming decade.

Cervical cancer in Zimbabwe: a situation analysis.

INTRODUCTION: Despite the wide-spread availability of cervical cancer prevention and screening programs in developed countries, the morbidity and mortality rates of cervical cancer in Zimbabwe are still very high. Limited resources as well as the high HIV prevalence are contributors to the high burden of cervical cancer. This paper aims to analyse the policies, frameworks and current practices in the management of cervical cancer in Zimbabwe. METHODS: A review of national documents and published literature on cervical cancer prevention, screening, treatment and knowledge in Zimbabwe was done. Informal interviews were conducted to assess the practices of cervical cancer management. RESULTS: Through strategic collaboration, a pilot for the HPV vaccination program is underway. The VIAC national cervical cancer screening program is being adopted into the current healthcare system. With regards to the treatment of precancerous lesions we found that the "see and treat" program has been implemented in colposcopy clinics. In addition, there are two multidisciplinary cancer treatment clinics installed in two central public hospitals. The general knowledge and understanding of cervical cancer is poor in Zimbabwe. CONCLUSION: Limitations in resources, infrastructure, manpower, delays in treatment and patient knowledge play a role in the high morbidity and mortality of cervical cancer in Zimbabwe. The Ministry of Health needs to increase funding to expedite the availability of HPV vaccine and screening programs. Community engagement initiatives to raise awareness on cervical cancer should be established to provide education on how to prevent the development of cervical cancer, as well as promote screening for early detection.