Department of Medical Laboratory Sciences
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Item Role of CTX-M-15 gene in spread of extended-spectrum beta-lactamases among immunocompetent patients in Ghana(African Journal of Laboratory Medicine, 2023) Obeng-Nkrumah, N.; Tawiah-Abrokwa, G.D.; Owusu, E.; et al.Background: Patients with faecal carriage of extended-spectrum beta-lactamases (ESBL)- producing Enterobacterales serve as reservoirs and sources of dissemination and infection. Objective: This report examined immunocompetent patients for faecal carriage of ESBL producing Enterobacterales in a district care hospital setting in Ghana. Methods: Between March 2019 and May 2020, cross-sectional sampling was performed to enrol patients and conduct questionnaire-structured interviews for factors that predispose patients to ESBL faecal carriage. Faecal samples from study patients were quantified for ESBL producing Enterobacterales. The ESBL genes were characterised by polymerase chain reaction and sequencing. Results: The overall proportion of ESBL faecal carriage was 35.5% (n = 38/107). The blaCTX-M gene, mostly CTX-M-15, was detected in 89.5% (n = 34/38) of the ESBL-producing isolates. The other ESBL types included blaSHV (n = 3) and blaOXA (n = 1). The CTX-M-15-positive isolates, when present in a faecal sample compared to the non-ESBL-CTX-M-15 isolates, constituted the predominant faecal Enterobacterales, with significantly higher colony counts than all other enterobacteria in that sample. In multivariate regression, independent risk factors for faecal carriage of ESBL-producing Enterobacterales were hospitalisation in the past year, infections since admission, use of antibiotics in the past 6 weeks, and admission from another hospital. Conclusion: The study found that CTX-M-15-producing isolates were the predominant faecal Enterobacterales, and that further investigations are needed to determine the reasons behind this dominance. What this study adds: The CTX-M-15-producing isolates dominance in this study shows the misuse and abuse of antibiotics in an African medical facility and indicates the potential role of immunity in controlling ESBL spread, which is to be investigated further.Item Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients(Experimental Biology and Medicine, 2023) Amakye, D.; Gyan, P.O.; Santa, S.; et al.Preeclampsia increases the risk of pregnancy-related complications. nevertheless, a successful spiral vessel remodeling and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion and activation of MMP-2 largely depends on on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragment sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78±6.39) years and body mass index (BMI) (33.09±7.27) kg/m2 compared with the normotensive counterparts (32.33±5.56) years and (32.33±5.56) kg/m2, respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34±7.07) compared with the normotensives (25.63±4.56) (P<0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95–14.75; P<0.0001). Decreased activity of MMP-2 and rs424243T/G SNPs of the EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.Item Bridging the Access Gap for Comprehensive Sickle Cell Disease Management Across Sub-Saharan Africa: Learnings for Other Global Health Interventions?(Annals of Global Health, 2023) Hegemann, L.; Narasimhan, V.; Ofori-Acquah, S.; et al.Background: Sickle cell disease (SCD) is a major unresolved global health issue, with the highest disease burden in sub-Saharan African countries; yet, SCD care has not proportionally reached patients in these regions, and the disease has received limited attention in the past. Addressing the burden of SCD in sub-Saharan Africa requires a holistic, collaborative approach to ensure solutions are both comprehensive, i.e., cover the entire continuum of care from early diagnosis to treatment—and sustainable—i.e., co-created and co-owned with local partners and integrated into existing local systems to enable long-term independence without the need for continuous external support. Objective: We outline a set of recommendations for enhancing the provision of comprehensive healthcare for prevalent diseases in resource-constraint settings, gathered from the Novartis Africa SCD Program, that could serve as ‘blueprint’ for public-private partnerships to tackle global health priorities. Methods: The Novartis Africa SCD program was initiated with the aim of bridging access gaps to SCD care and provide comprehensive and innovative treatment solutions for SCD, especially in SSA, where the disease burden is highest. The Program was first inaugurated in 2019 in Ghana through a public-private partnership with the Ministry of Health of the Government of Ghana, the Ghana Health Service, and the Sickle Cell Foundation of Ghana. Through engagement with these partners, as well as with support from other organizations with complementary competencies and resources, several targeted solutions were implemented to help strengthen the healthcare ecosystem and allow for comprehensive SCD management. The learnings from these interventions are highlighted as best practice consideration as a catalyst and to activate more public-private actors for this neglected global health issue. Findings and Conclusions: A solid understanding of the access barriers to comprehensive care has to be acquired by listening to and learning from patients, civil society, and local experts. Access barriers need to be addressed at multiple levels, i.e., by not only makingmedicines available and affordable but also by strengthening healthcare systems. building capacity and fostering local research and development. Partnerships across governmental, public, academic, non-profit, and private organizations are needed to secure political will, pool resources, and gather expertise with understanding of the local context, and allow integration into all levels of existing local healthcare structures and the wider society.Item Haematological parameters and their correlation with the degree of malaria parasitaemia among outpatients attending a polyclinic(Malaria Journal, 2023) Antwi‑Bafour, S.; Mensah, B.T.; Johnson, G.; Armah, D.N.O.; Ali‑Mustapha, S.; Annison, L.Background Malaria is a parasitic disease caused by various species of the blood parasite Plasmodium; of all the para‑ sitic diseases, malaria has the highest prevalence and mortality with an estimated 247 million cases and 619,000 deaths recorded worldwide as of 2021. Malaria causes febrile illness with several changes in blood cell parameters. Some of these changes include leucopenia, thrombocytopenia, and anaemia. If these changes could be correlated with the degree of parasitaemia, it can serve as a guide to physicians when treating malaria. This study was therefore aimed at correlating haematological parameters with levels of parasitaemia during malaria infection. Methods The study was a cross-sectional study involving 89 malaria positive patients. About 5 ml of blood was col‑ lected from each participant who gave his or her informed consent to partake in the study. A full blood count was performed on their samples to determine their haematological parameters using a haematology auto-analyzer. A parasite count was also performed via microscopy to determine the degree of parasitaemia. The data obtained from the study was entered into a database and statistically analysed using Statistical Package for Social Sciences (SPSS) version 23 and Microsoft Excel 2016. Results The study comprised of 89 participants out of which 35 were males and 54 were females with the mean age of 26.15 years. Secondary education participants were the highest with quaternary education the lowest. The highest parasite count recorded was 398,174 parasites/µl of blood, lowest count was 101 with the average being 32,942.32584. There was also a signifcant positive Pearson’s correlation between total WBC and parasitaemia and with the WBC diferentials, neutrophils, lymphocytes and monocytes had positive correlations while eosinophils and basophils had negative correlations. Furthermore, platelets, total RBC’s, haemoglobin, MCH, MCHC and Hct all showed negative correlations. Linear regression also showed a linear relationship between parasite density and the various haematological parameters. Conclusion The linear relationship (correlation) between WBC and MCH were the only signifcant ones at 95% and 99% confdence interval, respectively based on a two-tail t-test. Also, based on the regression analysis, the changes caused by WBC and PLT were the only signifcant changes at 95% confdence level in a two-tailed t-test.Item Comparative analysis of glycated haemoglobin, fasting blood glucose and haematological parameters in Type-2 diabetes patients(BMC Research Notes, 2023) Antwi-Baffour, S.; Mensah, B.T.; Armah, D.N.O.; Ali-Mustapha, S.; Annison, L.Objective Diabetes remains a major health problem, and Glycated hemoglobin (HBA1c) and fasting blood glucose (FBG) levels play important roles in its management. Also, chronic hyperglycemia coupled with high HBA1c levels impact inflammation and may alter haematological parameters in diabetes. Hence, the need to assess and correlate HBA1c and FBG levels with selected haematological parameters in patients with type-2 diabetes mellitus as the main objective of this study. The study was cross-sectional involving 384 participants. Five milliliters of blood was collected from each participant and analyzed for HBA1c, FBG levels and full blood count which were correlated statistically. Results From the data obtained and analyzed, there were statistically significant correlations between HBA1c and neutrophil count (p<0.013), plateletcrit (p<0.036), mean platelet volume (p<0.019) and platelet distribution width (p<0.002). There were also significant differences in FBG (p<0.014), neutrophil count (p<0.029), red cell distribution width (p<0.046), mean platelet volume (p<0.032) and platelet distribution width (p<0.013) between diabetes patients with HBA1c less than 7.0% and HBA1c more than or equal to 7.0%. The outcome of the study indicates significant correlation of HBA1c with selected haematological parameters. This could make routine haematological parameters a cost-effective means of predicting poor glucose control in diabetes mellitus patients.Item IGJ and SPATS2L immunohistochemistry sensitively and specifically identify BCR::ABL1+ and BCR::ABL1-like B-acute lymphoblastic leukaemia(British Journal of Haematology, 2023) Gestrich, C.K.; Pateva, I.; Yalley, A.K.; et al.Therapeutic management and prognostication for patients with B-acute lympho blastic leukaemia (B-ALL) require appropriate disease subclassification. BCR::ABL1- like B-ALL is unique in that it is defined by a gene expression profile similar to BCR::ABL1+ B-ALL rather than a unifying recurrent translocation. Current molecu lar/cytogenetic techniques to identify this subtype are expensive, not widely acces sible, have long turnaround times and/or require an adequate liquid biopsy. We have studied a total of 118 B-ALL cases from three institutions in two laboratories to iden tify surrogates for BCR::ABL1+/like B-ALL. We report that immunoglobulin joining chain (IGJ) and spermatogenesis associated serine-rich 2-like (SPATS2L) immuno histochemistry (IHC) sensitively and specifically identify BCR::ABL1+/like B-ALL. IGJ IHC positivity has a sensitivity of 83%, a specificity of 95%, a positive predictive value (PPV) of 89% and a negative predictive value (NPV) of 90%. SPATS2L stain ing has similar sensitivity and NPV but lower specificity (85%) and PPV (70%). The presence of either IGJ or SPATS2L staining augments the sensitivity (93%) and NPV (95%). While these findings would need to be validated in larger studies, they suggest that IGJ and/or SPATS2L IHC may be utilized in identifying BCR::ABL1-like B-ALL or in selecting B-ALL cases for confirmatory molecular/genetic testing, particularly in resource-limited settings.Item Knowledge, attitudes and practices regarding malaria prevention and control in communities in the Eastern Region, Ghana, 2020(PLOS ONE, 2023) Lopez, A.R.; Brown, C.A.Background In sub-Saharan Africa countries including Ghana, the malaria burden remains unacceptably high and still a serious health challenge. Evaluating a community’s level of knowledge, atti tude, and practice (KAP) regarding malaria is essential to enabling appropriate preventive and control measures. This study aimed to evaluate knowledge of malaria, attitudes toward the disease, and adoption of control and prevention practices in some communities across the Eastern Region of Ghana. Methods A cross-sectional based study was carried out in 13 communities across 8 districts from Jan uary -June, 2020. Complete data on socio-demographic characteristics and KAP were obtained from 316 randomly selected household respondents by a structured pre-tested questionnaire. Associations between KAP scores and socio-demographic profiles were tested by Chi-square and binary logistic regression. Data analysis was done with SPSS ver sion 26.0. Results Most respondents (85.4%) had good knowledge score about malaria. Preferred choice of treatment seeking place (50.6%) was the health center/clinic. All respondents indicated they would seek treatment within 24 hours. Mosquito coils were the preferred choice (58.9%) against mosquito bites. Majority of households (58.5%) had no bed nets and bed net usage was poor (10.1%). Nearly half of the respondents (49.4%) had a positive attitude toward malaria and 40.5% showed good practices. Chi-square analysis showed significant associa tions for gender and attitude scores (p = 0.033), and educational status and practice scores (p = 0.023). Binary logistic regression analysis showed that 51–60 year-olds were less likely to have good knowledge (OR = 0.20, p = 0.04) than 15–20 year-olds. Respondents with complete basic schooling were less likely to have good knowledge (OR = 0.33, p = 0.04) than those with no formal schooling. A positive attitude was less likely in men (OR = 0.61, p = 0.04). Good malaria prevention practice was lower (OR = 0.30, p = 0.01) in participants with incomplete basic school education compared to those with no formal schooling. Conclusion Overall scores for respondents’ knowledge, though good, was not reflected in attitudes and levels of practice regarding malaria control and prevention. Behavioral change communica tioItem Infammatory cytokines as potential biomarkers for early diagnosis of severe malaria in children in Ghana(Malaria Journal, 2023) Obeng‑Aboagye, E.; Frimpong, A.; Amponsah, J.A.; Danso, S.E.; Owusu, E.D.A.; Ofori, M.F.Background Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identifed cytokine profles that diferentiate the vari‑ ous clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in diferentiating between the disease states in terms of cut-of values has not yet been determined. Methods The plasma levels of 22 pro-infammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-infammatory cytokines (IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines. Results The level of the pro-infammatory cytokine, IL-17A, was signifcantly higher in the SM group as compared to the UM group. Levels of the anti-infammatory cytokines however did not difer signifcantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis. Conclusion The data show that levels of pro-infammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment.Item Dynamics of viral disease outbreaks: A hundred years (1918/ 19–2019/20) in retrospect ‐ Loses, lessons and emerging issues(Reviews in Medical Virology, 2023) Nii‐Trebi, N.I.; Mughogho, T.S.; Abdulai, A.; Tetteh, F.; et al.nfectious diseases continue to be the leading cause of morbidity and mortality, and a formidable obstacle to the development and well‐being of people worldwide. Viruses account for more than half of infectious disease outbreaks that have plagued the world. The past century (1918/19–2019/20) has witnessed some of the worst viral disease outbreaks the world has recorded, with overwhelming impact especially in low‐ and middle‐income countries (LMIC). The frequency of viral dis ease outbreak appears to be increasing. Generally, although infectious diseases have afflicted the world for centuries and humankind has had opportunities to examine the nature of their emergence and mode of spread, almost every new outbreak poses a formidable challenge to humankind, beating the existing pandemic preparedness systems, if any, and causing significant losses. These underscore in adequacy in our understanding of the dynamics and preparedness against viral disease outbreaks that lead to epidemics and pandemics. Despite these challenges, the past 100 years of increasing frequencies of viral disease outbreaks have engendered significant improvements in response to epidemics and pandemics, and offered lessons to inform preparedness. Hence, the increasing frequency of emer gence of viral outbreaks and the challenges these outbreaks pose to humankind, call for the continued search for effective ways to tackle viral disease outbreaks in real time. Through a PRISMA‐based approach, this systematic review examines the outbreak of viral diseases in retrospect to decipher the outbreak patterns, losses inflicted on humanity and highlights lessons these offer for meaningful preparation against future viral disease outbreaks and pandemics.Item Dynamics of viral disease outbreaks: A hundred years (1918/ 19–2019/20) in retrospect ‐ Loses, lessons and emerging issues(Reviews in Medical Virology, 2023) Nii‐Trebi, N.I.; Mughogho, T.S.; Abdulai, A.; Tetteh, F.; et al.Infectious diseases continue to be the leading cause of morbidity and mortality, and a formidable obstacle to the development and well‐being of people worldwide. Viruses account for more than half of infectious disease outbreaks that have plagued the world. The past century (1918/19–2019/20) has witnessed some of the worst viral disease outbreaks the world has recorded, with overwhelming impact especially in low‐ and middle‐income countries (LMIC). The frequency of viral dis ease outbreak appears to be increasing. Generally, although infectious diseases have afflicted the world for centuries and humankind has had opportunities to examine the nature of their emergence and mode of spread, almost every new outbreak poses a formidable challenge to humankind, beating the existing pandemic preparedness systems, if any, and causing significant losses. These underscore in adequacy in our understanding of the dynamics and preparedness against viral disease outbreaks that lead to epidemics and pandemics. Despite these challenges, the past 100 years of increasing frequencies of viral disease outbreaks have engendered significant improvements in response to epidemics and pandemics, and offered lessons to inform preparedness. Hence, the increasing frequency of emer gence of viral outbreaks and the challenges these outbreaks pose to humankind, call for the continued search for effective ways to tackle viral disease outbreaks in real time. Through a PRISMA‐based approach, this systematic review examines the outbreak of viral diseases in retrospect to decipher the outbreak patterns, losses inflicted on humanity and highlights lessons these offer for meaningful preparation against future viral disease outbreaks and pandemicsItem Did Ghana Do Enough? A Scientometric Analysis of COVID-19 Research Output from Ghana within the African Context(Diseases, 2023) Yalley, A.K.; Ahiatrogah, S.; Yalley, A.B.; Yankson, I.K.; Nii-Trebi, N.I.; Yalley, A.AThe COVID-19 pandemic has generated worldwide research efforts to provide knowledge about the disease. Yet little is known about how Ghana contributed to this critical knowledge production. This scientometric analysis was conducted to ascertain Ghana’s COVID-19 research output within the African context to gain understanding and identify potential future directions. The study retrieved relevant research, spanning 2019 to 2022, from the Scopus database in December 2022. The retrieved data were assessed using various established indices, including collaboration patterns, productive institutions, citation patterns, and major research sponsors, among others. Ghana came seventh in Africa with a total of 1112 publications. For international collaborations, the United States and the United Kingdom were the major partners, while South Africa was the main African collaborator with Ghana. Out of the top 21 most productive authors, 85.7% were males and 14.3% were females, demonstrating a great gender gap in research output in Ghana. Although Ghana has made some contributions to the global COVID-19 research output, there are few intra-continental research collaborations, which limits Africa’s overall research output. Our study demonstrates a critical need for the Ghanaian government to prioritize research and funding and address barriers to women’s research productivity.Item Larval habitat stability and productivity in two sites in Southern Ghana(Malaria Journal, 2023) Forson, A.O.; Hinne, I.A.; Sraku, I.K.; Afrane, Y.A.Background Mosquito larval source management (LSM) is a valuable additional tool for malaria vector control. Understanding the characteristics of mosquito larval habitats and its ecology in different land use types can give valuable insight for an effective larval control strategy. This study determined the stability and productivity of potential anopheline larval habitats in two different ecological sites: Anyakpor and Dodowa in southern Ghana. Methods A total of 59 aquatic habitats positive for anopheline larvae were identified, and sampled every two weeks for a period of 30 weeks using a standard dipping method. Larvae were collected using standard dippers and were raised in the insectary for identification. Sibling species of the Anopheles gambiae sensu lato (s.l.) were further identified by polymerase chain reaction. The presence of larval habitats, their stability and larvae positive habitats were compared between the two sites using Mann–Whitney U and the Kruskal–Wallis test. Factors affecting the presence of An. gambiae larvae and physicochemical properties at the sites were determined using multiple logistic regression analysis and Spearman’s correlation. Results Out of a total of 13,681 mosquito immatures collected, 22.6% (3095) were anophelines and 77.38% (10,586) were culicines. Out of the 3095 anophelines collected, An. gambiae s.l. was predominant (99.48%, n=3079), followed by Anopheles rufpes (0.45%, n=14), and Anopheles pharoensis (0.064%, n=2). Sibling species of the An. gambiae consisted of Anopheles coluzzii (71%), followed by An. gambiae s.s. (23%), and Anopheles melas (6%). Anopheles mean larval density was highest in wells [6.44 (95% CI 5.0–8.31) larvae/dip], lowest in furrows [4.18 (95% CI 2.75–6.36) larvae/ dip] and man-made ponds [1.20 (95% CI 0.671–2.131) larvae/dip].The results also revealed habitat stability was highly dependent on rainfall intensity, and Anopheles larval densities were also dependent on elevated levels of pH, conductivity and TDS. Conclusion The presence of larvae in the habitats was dependent on rainfall intensity and proximity to human settlements. To optimize the vector control measures of malaria interventions in southern Ghana, larval control should be focused on larval habitats that are fed by underground water, as these are more productive habitats.Item Moderate doses of Mucuna pruriens seed powder is safe and improves sperm count and motility(Elsevier B.V., 2023) Dagadu, P.; Adjei, S.; Amoah, B.Y.; et al.A B S T R A C T Background: Conventional remediation techniques involving male fertility include hormonal therapy, in vitro fertilization and surgery. However, the use of natural products continues to be a popular option. Emerging new products that have not been well investigated is the use of Mucuna pruriens seed powder. Aim: This study aimed at determining the efficacy and safety of Mucuna pruriens (MP) seed powder on the male fertility using normal animal models. Methodology: Four groups of seven (7) male Sprague-Dawley rats were used. Groups comprised Control (distilled water), Low dose (500 mg/kg b.wt MP), Medium dose (1000 mg/kg b.wt MP) and high dose (2000 mg/kg b.wt MP). Test groups were administered aqueous crude extract of MP by gavage over 90 days. Upon sacrifice, the following assays were performed: FSH, testosterone, oestrogen, PSA, semen analyses, histology of reproductive organs, and general haematological and biochemical analyses. Results: FSH increased, whilst oestrogen decreased, across groups: however, it was not statistically significant between groups. Although testosterone increases were not statistically significant, increases were dose- dependant. Sperm count increased significantly between the Control and Medium dose groups (p<0.001). Motility significantly increased with the Medium and High dose groups compared to Control group (p = 0.022, p = 0.029, respectively). Additionally, immotility significantly decreased in all treatment groups compared to control group (p = 0.013). No abnormality was observed in biochemical, haematological and histological analyses. Conclusion: This study demonstrates a margin of safety and improved spermogram pattern between the low and medium dose administration of Mucuna pruriens seed powder.Item A Randomized, Open-Label Study of the Tolerability and Efficacy of One or Three Daily Doses of Ivermectin Plus Diethylcarbamazine and Albendazole (IDA) Versus One Dose of Ivermectin Plus Albendazole (IA) For Treatment of Onchocerciasis(PLOS Neglected Tropical Diseases, 2023) Opoku, N.O.; Weil, G.J.; et al.Background Onchocerciasis (“river blindness”) has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. Methods and findings The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/ kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/ 261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced %of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. Conclusions Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings.Item Mucin 4 protein is expressed in B-acute lymphoblastic leukemia and is restricted to BCR::ABL1-positive and BCR::ABL-like subtypes(Human Pathology, 2023) Gestrich, C.K.; Lancy, S.J.D.; Yalley, A.; et al.Mucin 4 (MUC4) is a transmembrane mucin that, like most mucins, is not expressed in normal hematopoietic cells, but little is known about its expression in malignant hematopoiesis. B-acute lymphoblastic leukemia (B-ALL) consists of genetically distinct disease subtypes with similarities and differences in gene expression most frequently studied at the mRNA level, which is less amenable to widespread routine clinical use. Here, we demonstrate using immunohistochemistry (IHC) that MUC4 protein is expressed in less than 10% of B-ALL, with expression restricted to BCR::ABL1þ and BCR::ABL1-like (CRLF2 rearranged) subtypes of B-ALL (4/13, 31%). None (0/36, 0%) of the re maining B-ALL subtypes expressed MUC4. We compare clinical and pathologic features of MUC4þ and MUC4 BCR::ABL1þ/like cases and most significantly report a possible shorter time to relapse for MUC4þ BCR::ABL1 B-ALL that would need to be validated in larger studies. In conclusion, MUC4 is a specific, albeit insensitive, marker for these high-risk subtypes of B-ALL. We propose that MUC4 IHC may be used diagnostically to rapidly identify these B-ALL subtypes, particularly in resource-limited settings or when an aspirate sample is not available for ancillary genetic studies.Item Prevalence of Hepatitis B Virus Infection among Inmates at the Monrovia Central Prison, Liberia(Tropical Medicine Infection Disease, 2023) Vessellee, D.B.; Yalley, A.K.; Adjei, D.N.; Odoom, P.N.; et al.Determination of hepatitis B virus (HBV) infections in key populations including prison inmates is crucial for formulating appropriate intervention approaches. However, in many low income countries, such as Liberia, there is hardly any documentation on HBV prevalence among inmates. This study determined and evaluated the prevalence of HBV infections among incarcerated persons in the Monrovia Central Prison, Liberia. One hundred participants comprising 76 males and 24 females were studied. Participants’ demographic and potential risk factors information were obtained using a semi-structured questionnaire, and blood samples were collected for the analysis. Plasma was tested for five HBV serological markers, namely, HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb. The seroreactivity of actively infected persons was confirmed by nucleic acid detection. Results of the serological assay showed that 34% of the participants had been exposed to the virus and 14% were actively infected. qPCR confirmed HBV DNA in seven actively infected samples. Statistical analysis indicated that a low level of education, a history of blood transfusion, and intravenous drug use, were significant predictors of active HBV infection and HBV exposure, respectively. These findings might make the testing and vaccination of convicts against HBV infection prior to their admission into prison facilities imperative.Item High level of colonization with third-generation cephalosporin-resistant Enterobacterales in African community settings, Ghana(Diagnostic Microbiology and Infectious Disease, 2023) Obeng-Nkrumah, N.; Opinta, J.A.; Newman, M.J.; et al.A cross-sectional survey was conducted in eight Ghanaian communities to investigate the extent of intestinal colonization with 3rd-generation cephalosporin-resistant Enterobacterales. The study collected faecal samples and corresponding lifestyle data from 736 healthy residents to assess the occurrence of cephalosporin resistant Escherichia coli and Klebsiella pneumoniae, with a focus on genotypes of plasmid-mediated ESBLs, AmpCs, and carbapenemases. The results showed that 371 participants (50.4%) carried 3rd-generation cephalosporin-resistant E. coli (n=362) and K. pneumoniae (n=9). Most of these were ESBL-producing E. coli (n=352, 94.9%), carrying CTX-M genes (96.0%, n=338/352), mostly for CTX-M-15 (98.9%, n=334/338). Nine participants (1.2%) carried AmpC-producing E. coli that harboured blaDHA-1 or blaCMY-2 genes, and two participants (0.3%) each carried a carbapenem-resistant E. coli that harboured both blaNDM-1 and blaCMY-2. Quinolone resistant O25b: ST131 E. coli were recovered from six participants (0.8%) and were all CTX-M-15 ESBL-producers. Having a household toilet facility was significantly associated with a reduced risk of intestinal colonization (adjusted odds ratio, 0.71; 95% CI, 0.48-0.99; P-value=0.0095) in multivariate analysis. These findings raise serious public health concerns, and effective control of the spread of antibiotic-resistant bacteria is possible by providing better sanitary conditions for communities.Item Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage(Viruses, 2023) Appah, A.; Amoah, L.E.; Nii-Trebi, N.I.; et al.The greatest HIV-1 genetic diversity is found in West/Central Africa due to the pandemic’s origins in this region, but this diversity remains understudied. We characterized HIV-1 subtype diversity (from both sub-genomic and full-genome viral sequences), drug resistance and coreceptor usage in 103 predominantly (90%) antiretroviral-naive individuals living with HIV-1 in Ghana. Full genome HIV-1 subtyping confirmed the circulating recombinant form CRF02_AG as the dominant (53.9%) subtype in the region, with the complex recombinant 06_cpx (4%) present as well. Unique recombinants, most of which were mosaics containing CRF02_AG and/or 06_cpx, made up 37% of sequences, while “pure” subtypes were rare (<6%). Pretreatment resistance to at least one drug class was observed in 17% of the cohort, with NNRTI resistance being the most common (12%) and INSTI resistance being relatively rare (2%). CXCR4-using HIV-1 sequences were identified in 23% of participants. Overall, our findings advance our understanding of HIV-1 molecular epidemiology in Ghana. Extensive HIV-1 genetic diversity in the region appears to be fueling the ongoing creation of novel recombinants, the majority CRF02_AG-containing, in the region. The relatively high prevalence of pretreatment NNRTI resistance but low prevalence of INSTI resistance supports the use of INSTI based first-line regimens in Ghana.Item Patient-level performance evaluation of a smartphone-based malaria diagnostic application(Malaria Journal, 2023) Yu, H.; Mohammed, F.O.; Hamid, M.A.; Owusu, E.D.A.; Yerlikaya, S.; Dittrich, S.; Jaeger, S.; et al.Background Microscopic examination is commonly used for malaria diagnosis in the feld. However, the lack of well-trained microscopists in malaria-endemic areas impacted the most by the disease is a severe problem. Besides, the examination process is time-consuming and prone to human error. Automated diagnostic systems based on machine learning ofer great potential to overcome these problems. This study aims to evaluate Malaria Screener, a smartphone-based application for malaria diagnosis. Methods A total of 190 patients were recruited at two sites in rural areas near Khartoum, Sudan. The Malaria Screener mobile application was deployed to screen Giemsa-stained blood smears. Both expert microscopy and nested PCR were performed to use as reference standards. First, Malaria Screener was evaluated using the two reference standards. Then, during post-study experiments, the evaluation was repeated for a newly developed algorithm, PlasmodiumVF-Net. Results Malaria Screener reached 74.1% (95% CI 63.5–83.0) accuracy in detecting Plasmodium falciparum malaria using expert microscopy as the reference after a threshold calibration. It reached 71.8% (95% CI 61.0–81.0) accuracy when compared with PCR. The achieved accuracies meet the WHO Level 3 requirement for parasite detection. The processing time for each smear varies from 5 to 15 min, depending on the concentration of white blood cells (WBCs). In the post-study experiment, Malaria Screener reached 91.8% (95% CI 83.8–96.6) accuracy when patient-level results were calculated with a diferent method. This accuracy meets the WHO Level 1 requirement for parasite detection. In addition, PlasmodiumVF-Net, a newly developed algorithm, reached 83.1% (95% CI 77.0–88.1) accuracy when compared with expert microscopy and 81.0% (95% CI 74.6–86.3) accuracy when compared with PCR, reaching the WHO Level 2 requirement for detecting both Plasmodium falciparum and Plasmodium vivax malaria, without using the testing sites data for training or calibration. Results reported for both Malaria Screener and PlasmodiumVF-Net used thick smears for diagnosis. In this paper, both systems were not assessed in species identification and parasite counting, which are still under development.Item Patient-level performance evaluation of a smartphone-based malaria diagnostic application(Malaria Journal, 2023) Yu, H.; Mohammed, F.O.; Hamid, M.A.; Fang, F.; Kassim, Y.M.; Mohamed, A.O.; Maude, R.J.; Ding, X.C.; Owusu, E.D.A.; Yerlikaya, S.; Dittrich, S.; Jaeger, S.Background Microscopic examination is commonly used for malaria diagnosis in the field. However, the lack of well-trained microscopists in malaria-endemic areas impacted the most by the disease is a severe problem. Besides, the examination process is time-consuming and prone to human error. Automated diagnostic systems based on machine learning ofer great potential to overcome these problems. This study aims to evaluate Malaria Screener, a smartphone-based application for malaria diagnosis. Methods A total of 190 patients were recruited at two sites in rural areas near Khartoum, Sudan. The Malaria Screener mobile application was deployed to screen Giemsa-stained blood smears. Both expert microscopy and nested PCR were performed to use as reference standards. First, Malaria Screener was evaluated using the two reference standards. Then, during post-study experiments, the evaluation was repeated for a newly developed algorithm, PlasmodiumVF-Net. Results Malaria Screener reached 74.1% (95% CI 63.5–83.0) accuracy in detecting Plasmodium falciparum malaria using expert microscopy as the reference after a threshold calibration. It reached 71.8% (95% CI 61.0–81.0) accuracy when compared with PCR. The achieved accuracies meet the WHO Level 3 requirement for parasite detection. The processing time for each smear varies from 5 to 15 min, depending on the concentration of white blood cells (WBCs). In the post-study experiment, Malaria Screener reached 91.8% (95% CI 83.8–96.6) accuracy when patient-level results were calculated with a different method. This accuracy meets the WHO Level 1 requirement for parasite detection. In addition, PlasmodiumVF-Net, a newly developed algorithm, reached 83.1% (95% CI 77.0–88.1) accuracy when compared with expert microscopy and 81.0% (95% CI 74.6–86.3) accuracy when compared with PCR, reaching the WHO Level 2 requirement for detecting both Plasmodium falciparum and Plasmodium vivax malaria, without using the testing sites data for training or calibration. Results reported for both Malaria Screener and PlasmodiumVF-Net used thick smears for diagnosis. In this paper, both systems were not assessed in species identifcation and parasite counting, which are still under development.