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Background: Hypofibrinolysis resulting from the up-regulation of plasminogen activator inhibitor-1 (PAI-1) usually occurs in patients with type 2 diabetes mellitus (T2DM), rendering them hypercoagulable. This study assessed the plasma antigen and activity levels of the PAI-1 enzyme in T2DM patients in a district hospital in Ghana., Methods: This was a hospital-based case-control study conducted from December 2018 to May 2019 at Nkenkaasu District Hospital. Sixty subjects with T2DM (30 T2DM subjects with good glycemic control and 30 with poor glycemic control), and 30 apparently healthy blood donors were recruited into the study. Blood specimens were collected for complete blood count, lipid profile, PAI-1 Ag and PAI-1 activity levels. A pre-tested questionnaire was used to obtain demographic and clinical information. The data was analyzed using SPSS version 22.0., Results: Elevated PAI-1 Ag and activity levels were observed in the T2DM subjects compared to the healthy controls, with the levels and activity significantly higher (PAI-1 Ag; p< 0.001, PAI-1 activity level; p = 0.004) in the T2DM subjects with poor glycemic control in comparison to those with good glycemic control. A significant positive correlation was observed between HbA1c and PAI-1 enzymes. PAI-1 Ag levels significantly increased along with increased total cholesterol (Β = 0.262, p = 0.033), triglyceride (Β = -0.273, p = 0.034) and HbA1c (Β = 0.419, p = 0.001). Similarly, PAI-1 activity level was associated with total cholesterol (Β = 0.325, p = 0.009), triglyceride (Β = -0.262, p = 0.042), HbA1c (Β = 0.389, p = 0.003) and VLDL-c (Β = -0.227, p = 0.029)., Conclusion: PAI-1 antigen/activity is enhanced in poorly controlled Ghanaian T2DM subjects. The hypercoagulable state of the affected individuals put them at higher risk of developing cardiovascular diseases. Good glycemic control to regulate plasma PAI-1 levels is essential during T2DM lifelong management. Markers of fibrinolysis should be assessed in these individuals and appropriate anticoagulants given to prevent thrombosis and adverse cardiovascular diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to remain a global challenge. There is emerging evidence of SARS-CoV-2 virus found in the blood of patients from China and some developed countries. However, there is inadequate data reported in Ghana and other parts of Africa, where blood transfusion service heavily relies on voluntary and replacement blood donors. This study aimed to investigate whether plasma of infected individuals could pose significant transfusion transmitted risk of COVID-19 in Ghanaian populations., Methods: This cross-sectional retrospective study was conducted at the Kumasi Centre for Collaborative Research into Tropical Medicine (KCCR), KNUST, Ghana. Study subjects comprised contacts of COVID-19 individuals, those with classical symptoms of COVID-19 and individuals who had recovered based on the new Ghana discharge criteria. Whole blood, sputum or deep coughed saliva samples were collected and transported to KCCR for SARS-CoV-2 testing. Viral nucleic acid was extracted from sputum/nasopharyngeal samples using Da An Gene column based kit and from plasma using LBP nucleic acid extraction kit. Real-Time PCR was performed specifically targeting the ORF1ab and Nucleocapsid (N) genomic regions of the virus., Results: A total of 97 individuals were recruited into the study, with more than half being males (58; 59.7%). The mean age of all subjects was 33 years (SD = 7.7) with minimum being 22 years and maximum 56 years. Majority (76; 78.4%) of all the subjects were asymptomatic, and among the few symptomatic subjects, cough (10; 10.3%) was the most predominant symptom. Of the 97 sputum samples tested, 79 (81.4%) were positive for SARS-CoV-2. We identified SARS-CoV-2 viral RNA in the plasma of 1 (1.03%) subject who had clinically recovered., Conclusion: This study reports the identification of SARS-CoV-2 viral RNA in a convalescent individual in Ghana. Due to the low prevalence observed and the marginal cycling thresholds associated, the risk of transfusion transmission of SARS-CoV-2 is negligible. Well-powered studies and advanced diagnostics to determine infectious viremia is recommended to further evaluate the potential risk of hematogenous transmission among recovered patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Proper detection of disease-causing organisms is very critical in controlling the course of outbreaks and avoiding large-scale epidemics. Nonetheless, availability of resources to address these gaps have been difficult due to limited funding. This report sought to highlight the importance of in-country partners and non-governmental organizations in improving detection of microbiological organisms in Ghanaian Public Health Laboratories (PHLs)., Methods/context: This study was conducted between June, 2018 to August, 2019. U. S CDC engaged the Centre for Health Systems Strengthening (CfHSS) through the Association of Public Health Laboratories to design and implement strategies for strengthening three PHLs in Ghana. An assessment of the three PHLs was done using the WHO/CDS/CSR/ISR/2001.2 assessment tool. Based on findings from the assessments, partner organizations (CfHSS/APHL/CDC) serviced and procured microbiological equipment, laboratory reagents and logistics. CfHSS provided in-house mentoring and consultants to assist with capacity building in detection of epidemic-prone infectious pathogens by performing microbiological cultures and antimicrobial susceptibility tests., Results: A total of 3902 samples were tested: blood (1107), urine (1742), stool (249) and cerebrospinal fluid (CSF) (804). All-inclusive, 593 pathogenic bacteria were isolated from blood cultures (70; 11.8%); urine cultures (356; 60%); stool cultures (19; 3.2%) and from CSF samples (148; 25%). The most predominant pathogens isolated from blood, urine and stool were Staphylococcus aureus (22/70; 31%), Escherichia coli (153/356; 43%) and Vibrio parahaemolyticus (5/19; 26.3%), respectively. In CSF samples, Streptococcus pneumoniae was the most frequent pathogen detected (80/148; 54.1%). New bacterial species such as Pastuerella pneumotropica, Klebsiella oxytoca, Vibrio parahaemolyticus, and Halfnia alvei were also identified with the aid of Analytical Profile Index (API) kits that were introduced as part of this implementation. Streptococcus pneumoniae and Neisseria meningitidis detections in CSF were highest during the hot dry season. Antimicrobial susceptibility test revealed high rate of S. aureus, K. pneumoniae and E. coli resistance to gentamicin (35-55%). In urine, E. coli was highly resistant to ciprofloxacin (39.2%) and ampicillin (34%)., Conclusion: Detection of epidemic-prone pathogens can be greatly improved if laboratory capacity is strengthened. In-country partner organizations are encouraged to support this move to ensure accurate diagnosis of diseases and correct antimicrobial testing.

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV ® , a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

Background: The use of a mobile phone-based Interactive Voice Response (mIVR) System for real time monitoring of childhood illnesses provides an opportunity to improve childhood survival and health systems. However, little is known about the factors that facilitate its use. This study sought to identify key determinants and moderators of mIVR system use among caregivers in a rural district of Ghana using the Unified Theory of Acceptance and Use of Technology (UTAUT) model., Methods: The mIVR system was designed to provide real-time data on common symptoms of childhood illnesses after answering several questions by caregivers with sick children. A structured questionnaire with closed questions was used to collect data from 354 caregivers of children under-five living in rural communities, four (4) months after introducing the system. Regression analysis was used to identify key determinants and moderating factors that facilitate the use of the system based on the UTAUT model., Results: A total of 101 (28.5%) caregivers had used the system and 328 (92.7%) had intention to use the mIVR system. Caregivers' level of education and household wealth were associated with use of the mIVR systems (p<0.001). Behavioural intention (BI) to use mIVR system was positively influenced by performance expectancy (PE) (β = 0.278, 95% CI: 0.207, 0.349), effort expectancy (EE) (β = 0.242, 95% CI: 0.159, 0.326) and social influence (SI) (β = 0.081, 95% CI: 0.044, 0.120). Facilitating conditions (FC) (β = 0.609, 95% CI: 0.502, 0.715) and behavioural intention (β = 0.426, 95% CI: 0.255, 0.597) had a positive influence on user behaviour (UB). Mobile phone experience and household wealth significantly moderated the effect of PE, EE, SI, and FC on behavioural intention and usage of mIVR systems., Conclusion: The perceived usefulness of the mIVR system, ease of use, social influences, and facilitating conditions are key determinants of users' attitude and use of mIVR system. These relationships are significantly moderated by users' phone experience and wealth status., Competing Interests: The authors have declared that no competing interests exist.

Introduction: acute respiratory tract infections (ARIs) are responsible for significant proportions of illnesses and deaths annually. Most of ARIs are of viral etiology, with human coronaviruses (HCoVs) playing a key role. This study was conducted prior to the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to provide evidence about the sero-epidemiology of HCoVs in rural areas of Ghana., Methods: this was a cross-sectional study conducted as part of a large epidemiological study investigating the occurrence of respiratory viruses in 3 rural areas of Ghana; Buoyem, Kwamang and Forikrom. Serum samples were collected and tested for the presence of IgG-antibodies to three HCoVs; HCoV-229E, HCoV-OC43 and HCoV-NL63 using immunofluorescence assay., Results: of 201 subjects enrolled into the study, 97 (48.3%) were positive for all three viruses. The most prevalent virus was HCoV-229E (23%; 95% CI: 17.2 - 29.3), followed by HCoV-OC43 (17%; 95% CI: 12.4 - 23.4), then HCoV-NL63 (8%, 95% CI: 4.6 - 12.6). Subjects in Kwamang had the highest sero-prevalence for HCoV-NL63 (68.8%). human coronaviruses-229E (41.3%) and HCoV-OC43 (45.7%) were much higher in Forikrom compared to the other study areas. There was however no statistical difference between place of origin and HCoVs positivity. Although blood group O+ and B+ were most common among the recruited subjects, there was no significant association (p = 0.163) between blood group and HCoV infection., Conclusion: this study reports a 48.3% sero-prevalence of HCoVs (OC43, NL63 and 229E) among rural communities in Ghana. The findings provide useful baseline data that could inform further sero-epidemiological studies on SARS-CoV-2 in Africa., Competing Interests: The authors declare no competing interests., (Copyright: Michael Owusu et al.)

This mixed methods study aimed to use local terminology to accurately characterize the prevalence and risk factors associated with substance use and risky health behaviors among school-based youth in Monrovia, Liberia. An 86-question survey was validated using qualitative data obtained from focus groups at two secondary schools in central and greater Monrovia. The revised survey was then administered to 400 students from eight different secondary schools in this region. The observed prevalence estimates for lifetime and current substance use were considerably higher than previously reported among adolescents in the West African region. Among students who were former child soldiers, the rates of current substance use were 5.8-33.8% higher compared to the overall study sample. Male gender, academic seniority, and peer approval of substance use were all found to be strong predictors of current substance use among secondary students. Results suggest the need for targeted, trauma-informed interventions to reduce rates of substance use and risky health behaviors among youth in Liberia and similar post-conflict settings., Competing Interests: Disclosure statement The authors declare that they have no conflict of interest.

Background: Global cases of COVID-19 continue to rise, causing havoc to several economies. So far, Ghana has recorded 48,643 confirmed cases with 320 associated deaths. Although summaries of data are usually provided by the Ministry of Health, detailed epidemiological profile of cases are limited. This study sought to describe the socio-demographic features, pattern of COVID-19 spread and the viral load dynamics among subjects residing in northern, middle and part of the southern belt of Ghana., Methods: This was a cross-sectional retrospective study that reviewed records of samples collected from February to July, 2020. Respiratory specimens such as sputum, deep-cough saliva and nasopharyngeal swabs were collected from suspected COVID-19 subjects in 12 regions of Ghana for laboratory analysis and confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR)., Results: A total of 72,434 samples were collected during the review period, with majority of the sampled individuals being females (37,464; 51.9%). The prevalence of SARS-CoV-2 identified in the study population was 13.2% [95%CI: 12.9, 13.4). Males were mostly infected (4,897; 51.5%) compared to females. Individuals between the ages 21-30 years recorded the highest number of infections (3,144, 33.4%). Symptomatic subjects had higher viral loads (1479.7 copies/μl; IQR = 40.6-178919) than asymptomatic subjects (49.9; IQR = 5.5-3641.6). There was significant association between gender or age and infection with SARS-CoV-2 (p<0.05). Among all the suspected clinical presentations, anosmia was the strongest predictor of SARS-CoV-2 infection (Adj. OR (95%CI): 24.39 (20.18, 29.49). We observed an average reproductive number of 1.36 with a minimum of 1.28 and maximum of 1.43. The virus trajectory shows a gradual reduction of the virus reproductive number., Conclusion: This study has described the epidemiological profile of COVID-19 cases in northern, middle and part of the southern belt of Ghana, with males and younger individuals at greater risk of contracting the disease. Health professionals should be conscious of individuals presenting with anosmia since this was seen as the strongest predictor of virus infection., Competing Interests: The authors have declared that no competing interests exist.

Background: In high-income countries, mortality related to hospitalized patients with the Coronavirus disease 2019 (COVID-19) is approximately 4-5%. However, data on COVID-19 admissions from sub-Saharan Africa are scanty., Objective: To describe the clinical profile and determinants of outcomes of patients with confirmed COVID-19 admitted at a hospital in Ghana., Methods: A prospective study involving 25 patients with real time polymerase chain reaction confirmed COVID-19 admitted to the treatment centre of the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana from 1 st June to 27 th July, 2020. They were managed and followed up for outcomes. Data were analysed descriptively, and predictors of mortality assessed using a multivariate logistic regression modelling., Results: The mean age of the patients was 59.3 ± 20.6 years, and 14 (56%) were males. The main symptoms at presentation were breathlessness (68%) followed by fever (56%). The cases were categorized as mild (6), moderate (6), severe (10) and critical (3). Hypertension was the commonest comorbidity present in 72% of patients. Medications used in patient management included dexamethasone (68%), azithromycin (96%), and hydroxychloroquine (4%). Five of 25 cases died (Case fatality ratio 20%). Increasing age and high systolic blood pressure were associated with mortality., Conclusion: Case fatality in this sample of hospitalized COVID-19 patients was high. Thorough clinical assessment, severity stratification, aggressive management of underlying co-morbidities and standardized protocols incountry might improve outcomes., Funding: None declared., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Across the globe, the outbreak of the COVID-19 pandemic is causing distress with governments doing everything in their power to contain the spread of the novel coronavirus (SARS-CoV-2) to prevent morbidity and mortality. Actions are being implemented to keep health care systems from being overstretched and to curb the outbreak. Any policy responses aimed at slowing down the spread of the virus and mitigating its immediate effects on health care systems require a firm basis of information about the absolute number of currently infected people, growth rates, and locations/hotspots of infections. The only way to obtain this base of information is by conducting numerous tests in a targeted way. Currently, in Ghana, there is a centralized testing approach, that takes 4-5 days for samples to be shipped and tested at central reference laboratories with results communicated to the district, regional and national stakeholders. This delay in diagnosis increases the risk of ongoing transmission in communities and vulnerable institutions. We have validated, evaluated and deployed an innovative diagnostic tool on a mobile laboratory platform to accelerate the COVID-19 testing. A preliminary result of 74 samples from COVID-19 suspected cases has a positivity rate of 12% with a turn-around time of fewer than 3 hours from sample taking to reporting of results, significantly reducing the waiting time from days to hours, enabling expedient response by the health system for contact tracing to reduce transmission and additionally improving case management., Funding: Test kits were provided by AngloGold Ashanti Obuasi Mine (AngloGold Ashanti Health Foundation). The American Leprosy Mission donated the PCR machine, and the mobile laboratory van was funded by the Embassy of the Kingdom of the Netherlands (EKN). AAS, YAA was supported by (PANDORA-ID-NET RIA2016E-1609) and ROP supported by EDCTP Senior Fellowship (TMA2016SF), both funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme which is supported under Horizon 2020, the European Union., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest.

Background: Apart from the huge worldwide economic losses often occasioned by bovine coronavirus (BCoV) to the livestock industry, particularly with respect to cattle rearing, continuous surveillance of the virus in cattle and small ruminants is essential in monitoring variations in the virus that could enhance host switching. In this study, we collected rectal swabs from a total of 1,498 cattle, sheep and goats. BCoV detection was based on reverse transcriptase polymerase chain reaction. Sanger sequencing of the partial RNA-dependent RNA polymerase (RdRp) region for postive samples were done and nucleotide sequences were compared with homologous sequences from the GenBank., Results: The study reports a BCoV prevalence of 0.3%, consisting of 4 positive cases; 3 goats and 1 cattle. Less than 10% of all the animals sampled showed clinical signs such as diarrhea and respiratory distress except for high temperature which occurred in > 1000 of the animals. However, none of the 4 BCoV positive animals manifested any clinical signs of the infection at the time of sample collection. Bayesian majority-rule cladogram comparing partial and full length BCoV RdRp genes obtained in the study to data from the GenBank revealed that the sequences obtained from this study formed one large monophyletic group with those from different species and countries. The goat sequences were similar to each other and clustered within the same clade. No major variations were thus observed between our isolates and those from elsewhere., Conclusions: Given that Ghana predominantly practices the extensive and semi-intensive systems of animal rearing, our study highlights the potential for spillover of BCoV to small ruminants in settings with mixed husbandry and limited separation between species.

Objective: Approximately 70% of all hepatitis C (HCV) infections develop chronic disease. Active or exacerbated chronic hepatitis C infection subsequently progress to liver disease. The role of T-cells secretions in achieving viral clearance is still not well understood. Thus, the current study was set to determine the relationship between the T cell cytokine profiles, biochemical parameters and persistent HCV infection or spontaneous recovery., Results: Twenty-five percent (41/163) of the anti-HCV positive participants had recovered from HCV and had significantly higher concentration of IL-10 compared to those with active HCV infection (P < 0.012). Other circulating cytokines measured; IL-2, IFN gamma, TNF alpha, IL-5 and IL-17 were similar in both groups. Participants with active HCV infection had significantly higher aspartate transaminase (AST) (35 units) and alanine transaminase (46 units) compared to those in the recovered state (P < 0.001). Thus, serum levels of IL10 could be explored in larger prospective cohort study as a predictive marker of recovering from an active HCV infection.

Introduction: active or chronic exacerbated forms of hepatitis C virus (HCV) infection subsequently progress to liver disease and human defensins has been determined to have some level of anti-viral properties invitro whilst the expression of T helper-1 cytokines is known to promote complete recovery from acute HCV infection. The study sought to determine relationship between these immune responses., Methods: a cross sectional descriptive study design was employed. Hundred and thirty-two individuals were assessed were assessed for to anti-HCV, HCV RNA, serum levels of human alpha defensins 1 (HAD-1) and human beta defensins 1 (HBD-1). T helper 1 cytokines (IL-2, IFN gamma, TNF alpha) secreted in serum were also analyzed using commercial ELISA assay. The study was conducted in Kumasi, Obuasi and Daboya in Ghana., Results: the serum mean concentrations of HAD-1, HBD-1, IL-2, IFN gamma and TNF alpha showed no significant difference in concentrations among participants with chronic, spontaneously recovered or negative to HCV infection (p>0.05). Persons with hepatitis B co-infection were more likely to develop chronic HCV infection (p=0.039). HAD-1 and HBD-1 showed significant positive association with IL-2 (p=0.000) whilst only HAD-1 positively correlated with IL-2 (p<0.000)., Conclusion: the immunological markers determined had no association with the status of HCV infection. HAD-1 increased with increasing levels of IL-2. These findings suggest that during HCV infection, inflammatory response through the production of cytokines by IL-2 cells may affect the release of HAD-1 and HBD-1., Competing Interests: The authors declare no competing interests., (Copyright: Dorcas Ohui Owusu et al.)

Introduction: Partner notification (PN) is a process aiming to identify, test and treat the sex partners of people (index patients) with sexually transmitted infections (STIs). Accelerated partner therapy (APT) is a PN method whereby healthcare professionals assess sex partners, by telephone consultation, before giving the index patient antibiotics and STI self-sampling kits to deliver to their sex partner(s). The Limiting Undetected Sexually Transmitted infections to RedUce Morbidity programme aims to determine the effectiveness of APT in heterosexual women and men with chlamydia and determine whether APT could affect Chlamydia trachomatis transmission at population level., Methods and Analysis: This protocol describes a cross-over cluster randomised controlled trial of APT, offered as an additional PN method, compared with standard PN. The trial is accompanied by an economic evaluation, transmission dynamic modelling and a qualitative process evaluation involving patients, partners and healthcare professionals. Clusters are 17 sexual health clinics in areas of England and Scotland with contrasting patient demographics. We will recruit 5440 heterosexual women and men with chlamydia, aged ≥16 years.The primary outcome is the proportion of index patients testing positive for C. trachomatis 12-16 weeks after the PN consultation. Secondary outcomes include: proportion of sex partners treated; cost effectiveness; model-predicted chlamydia prevalence; experiences of APT.The primary outcome analysis will be by intention-to-treat, fitting random effects logistic regression models that account for clustering of index patients within clinics and trial periods. The transmission dynamic model will be used to predict change in chlamydia prevalence following APT. The economic evaluation will use mathematical modelling outputs, taking a health service perspective. Qualitative data will be analysed using interpretative phenomenological analysis and framework analysis., Ethics and Dissemination: This protocol received ethical approval from London-Chelsea Research Ethics Committee (18/LO/0773). Findings will be published with open access licences., Trial Registration Number: ISRCTN15996256., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Cattle, goats and sheep are dominant livestock species in sub-Saharan Africa, with sometimes limited information on the prevalence of major infectious diseases. Restrictions due to notifiable epizootics complicate the exchange of samples in surveillance studies and suggest that laboratory capacities should be established domestically. Bovine Coronavirus (BCoV) causes mainly enteric disease in cattle. Spillover to small ruminants is possible. Here we established BCoV serology based on a recombinant immunofluorescence assay for cattle, goats and sheep, and studied the seroprevalence of BCoV in these species in four different locations in the Greater Accra, Volta, Upper East, and Northern provinces of Ghana. The whole sampling and testing was organized and conducted by a veterinary school in Kumasi, Ashanti Region of Ghana. Among sampled sheep (n = 102), goats (n = 66), and cattle (n = 1495), the seroprevalence rates were 25.8 %, 43.1 % and 55.8 %. For cattle, seroprevalence was significantly higher on larger farms (82.2 % vs 17.8 %, comparing farms with >50 or <50 animals; p = 0.027). Highest prevalence was seen in the Northern province with dry climate, but no significant trend following the north-south gradient of sampling sites was detected. Our study identifies a considerable seroprevalence for BCoV in Ghana and provides further support for the spillover of BCoV to small ruminants in settings with mixed husbandry and limited separation between species., (Copyright © 2019. Published by Elsevier B.V.)

Background: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis., Methods: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites., Results: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae., Conclusions: SETA supports public health policy on typhoid immunization strategy in Africa., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana., Methods: This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR., Results: Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 μg/ml., Conclusion: This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.

Background: Ralstonia mannitolilytica is an emerging opportunistic pathogen that is associated with severe disease, including septic shock, meningitis, and renal transplant infections. Reports on this pathogen are limited, however, especially on the African continent., Case Presentation: A 2-year-old Akan child was presented to a hospital in the northeastern part of Ghana with a 1-week history of fever and chills. We identified Ralstonia mannitolilytica in her blood culture using both conventional and 16S ribosomal deoxyribonucleic acid (rDNA) techniques. The patient's condition improved clinically upon treatment with cefuroxime., Conclusion: Our report highlights the potential of Ralstonia mannitolilytica to cause sepsis and thus emphasizes the need for improved laboratory diagnosis and evidence for use of appropriate antibiotics in rural settings of Africa, where presumptive treatment using antimicrobial agents is rife.

Background: Choosing who should be recruited as a community health worker (CHW) is an important task, for their future performance partly depends on their ability to learn the required knowledge and skills, and their personal attributes. Developing a fair and effective selection process for CHWs is a challenging task, and reports of attempts to do so are rare. This paper describes a five-stage process of development and initial testing of a CHW selection process in two CHW programmes, one in Malawi and one in Ghana, highlighting the lessons learned at each stage and offering recommendations to other CHW programme providers seeking to develop their own selection processes., Case Presentation: The five stages of selection process development were as follows: (1) review an existing selection process, (2) conduct a job analysis, (3) elicit stakeholder opinions, (4) co-design the selection process and (5) test the selection process. Good practice in selection process development from the human resource literature and the principles of co-design were considered throughout. Validity, reliability, fairness, acceptability and feasibility-the determinants of selection process utility-were considered as appropriate during stages 1 to 4 and used to guide the testing in stage 5. The selection methods used by each local team were a written test and a short interview., Conclusions: Working with stakeholders, including CHWs, helped to ensure the acceptability of the selection processes developed. Expectations of intensiveness-in particular the number of interviewers-needed to be managed as resources for selection are limited, and CHWs reported that any form of interview may be stressful. Testing highlighted the importance of piloting with CHWs to ensure clarity of wording of questions, interviewer training to maximise inter-rater reliability and the provision of guidance to applicants in advance of any selection events. Trade-offs between the different components of selection process utility are also likely to be required. Further refinements and evaluation of predictive validity (i.e. a sixth stage of development) would be recommended before roll-out.

Background: The study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated., Method: A total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively., Results: The overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection (p<0.05) respectively. HBeAg positivity was associated with severe immunosuppression and higher HIV viral load. Patients aged 18-33 years [aOR = 9.66(1.17-79.61); p = 0.035], male gender [aOR = 2.74(1.15-6.51); p = 0.023], primary education [aOR = 9.60(1.21-76.08); p = 0.032], secondary education [aOR = 14.67(1.82-118.08); p = 0.012] and being single [aOR = 2.88(1.12-7.39); p = 0.028] were independent risk factors of HIV-HBV co-infections but not HIV-HCV co-infections., Conclusion: The present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load., Competing Interests: The authors have declared that no competing interests exist.

The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade ago with worldwide distribution, was believed to be of zoonotic origin from bats with dromedary camels as intermediate hosts. There is a likelihood of other domestic livestock serving as intermediate hosts for this virus. The presence of coronaviruses, closely related to MERS-CoV in Ghanaian bats, presented the opportunity to test the hypothesis of transmissibility of this virus through domestic livestock species. The possible interactions between livestock and bats in 31 household farms were accessed by observation and interviews with farmers. Rectal swabs and serum from cattle, sheep, goats, donkeys, and swine from commercial and household farms were tested for MERS-CoV and a Nycteris sp. bat coronavirus, previously detected in Ghana. A pan-PCR assay to detect clade 2c viruses and recombinant immunofluorescence assay to detect anti-spike IgG antibodies against the target viruses were used. Likely contact between livestock and bats was determined for 13 farms (41.9%) that reported confining their livestock and also observing bats in their homes. Livestock were left unconfined on eight farms (25.8%) that also observed bats roosting in trees close to their homes. No viral RNA or antibodies against the two coronaviruses were detected in any of the livestock species tested. Cattle, sheep, goats, donkeys, and swine are not likely hosts of clade 2c coronaviruses., Competing Interests: The authors declare no conflict of interest.

We provide a catalog for the effects of the human kinome on cell survival in response to DNA-damaging agents, covering all major DNA repair pathways. By treating 313 kinase-deficient cell lines with ten diverse DNA-damaging agents, including seven commonly used chemotherapeutics, we identified examples of vulnerability and resistance that are kinase specific. To investigate synthetic lethal interactions, we tested the response to carmustine for 25 cell lines by establishing a phenotypic fluorescence-activated cell sorting (FACS) assay designed to validate gene-drug interactions. We show apoptosis, cell cycle changes, and DNA damage and proliferation after alkylation- or crosslink-induced damage. In addition, we reconstitute the cellular sensitivity of DYRK4, EPHB6, MARK3, and PNCK as a proof of principle for our study. Furthermore, using global phosphoproteomics on cells lacking MARK3, we provide evidence for its role in the DNA damage response. Our data suggest that cancers with inactivating mutations in kinases, including MARK3, are particularly vulnerable to alkylating chemotherapeutic agents., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Known human coronaviruses are believed to have originated in animals and made use of intermediate hosts for transmission to humans. The intermediate hosts of most of the human coronaviruses are known, but not for HCoV-NL63. This study aims to assess the possible role of some major domestic livestock species as intermediate hosts of HCoV-NL63. We developed a testing algorithm for high throughput screening of livestock sera with ELISA and confirmation with recombinant immunofluorescence assay testing for antibodies against HCoV-NL63 in livestock. Optimization of the ELISA showed a capability of the assay to significantly distinguish HCoV-NL63 from HCoV-229E (U = 27.50, p < 0.001) and HCoV-OC43 (U = 55.50, p < 0.001) in coronavirus-characterized sera. Evaluation of the assay with collected human samples showed no significant difference in mean optical density values of immunofluorescence-classified HCoV-NL63-positive and HCoV-NL63-negative samples ( F (1, 215) = 0.437, p = 0.509). All the top 5% ( n = 8) most reactive human samples tested by ELISA were HCoV-NL63 positive by immunofluorescence testing. In comparison, only a proportion (84%, n = 42) of the top 25% were positive by immunofluorescence testing, indicating an increased probability of the highly ELISA reactive samples testing positive by the immunofluorescence assay. None of the top 5% most ELISA reactive livestock samples were positive for HCoV-NL63-related viruses by immunofluorescence confirmation. Ghanaian domestic livestock are not likely intermediate hosts of HCoV-NL63-related coronaviruses.

Background: Viral hepatitis continues to play significant role in causing morbidity and mortality in sub-Saharan Africa. Apart from the few population based studies available, not many have investigated the burden of these viruses in jaundiced patients. Among the few studies, hepatitis E is the least studied among jaundiced patients. This study was aimed at describing the frequency, distribution and risk of the different hepatitis viruses among jaundiced patients reporting to the second largest teaching hospital in Ghana., Methods: From November, 2015 to April, 2016, a cross-sectional study was conducted among jaundiced patients attending the Komfo Anokye Teaching Hospital. Between 3-5 ml of blood was collected from each patient and screened for viral hepatitis agents using both serologic and molecular-based assays., Results: In the 155 patients recruited, hepatitis B was the most prevalent [54.2% (95% CI = 46.0%-62.2%)] followed by hepatitis E [32.9% (95% CI = 25.6-40.9%)]. Most cases of hepatitis E occurred as co-infections with hepatitis B (18%), with the predominant clinical feature being hepatocellular carcinoma. Risk factor variable analysis showed middle and older aged individuals were more at risk of hepatitis B exposure whereas younger age groups (<18 years) were more at risk of hepatitis E virus infection., Conclusion: Hepatitis viruses are still important in the viral aetiology of jaundice in Ghana. Hepatitis B and hepatitis E co-infections could play significant roles in causing severe disease. A more aggressive approach needs to be adopted in order to reduce the morbidity and mortality associated with hepatitis causing viruses in Ghana and other developing countries., Competing Interests: The authors have declared that no competing interests exist.

Defects in DNA repair can cause various genetic diseases with severe pathological phenotypes. Fanconi anemia (FA) is a rare disease characterized by bone marrow failure, developmental abnormalities, and increased cancer risk that is caused by defective repair of DNA interstrand crosslinks (ICLs). Here, we identify the deubiquitylating enzyme USP48 as synthetic viable for FA-gene deficiencies by performing genome-wide loss-of-function screens across a panel of human haploid isogenic FA-defective cells (FANCA, FANCC, FANCG, FANCI, FANCD2). Thus, as compared to FA-defective cells alone, FA-deficient cells additionally lacking USP48 are less sensitive to genotoxic stress induced by ICL agents and display enhanced, BRCA1-dependent, clearance of DNA damage. Consequently, USP48 inactivation reduces chromosomal instability of FA-defective cells. Our results highlight a role for USP48 in controlling DNA repair and suggest it as a potential target that could be therapeutically exploited for FA.

Melioidosis is an often fatal infectious disease with a protean clinical spectrum, caused by the environmental bacterial pathogen Burkholderia pseudomallei . Although the disease has been reported from some African countries in the past, the present epidemiology of melioidosis in Africa is almost entirely unknown. Therefore, the common view that melioidosis is rare in Africa is not evidence-based. A recent study concludes that large parts of Africa are environmentally suitable for B. pseudomallei . Twenty-four African countries and three countries in the Middle East were predicted to be endemic, but no cases of melioidosis have been reported yet. In this study, we summarize the present fragmentary knowledge on human and animal melioidosis and environmental B. pseudomallei in Africa and the Middle East. We propose that systematic serological studies in man and animals together with environmental investigations on potential B. pseudomallei habitats are needed to identify risk areas for melioidosis. This information can subsequently be used to target raising clinical awareness and the implementation of simple laboratory algorithms for the isolation of B. pseudomallei from clinical specimens. B. pseudomallei was most likely transferred from Asia to the Americas via Africa, which is shown by phylogenetic analyses. More data on the virulence and genomic characteristics of African B. pseudomallei isolates will contribute to a better understanding of the global evolution of the pathogen and will also help to assess potential differences in disease prevalence and outcome.

The diversity of somatic mutations in human cancers can be decomposed into individual mutational signatures, patterns of mutagenesis that arise because of DNA damage and DNA repair processes that have occurred in cells as they evolved towards malignancy. Correlations between mutational signatures and environmental exposures, enzymatic activities and genetic defects have been described, but human cancers are not ideal experimental systems-the exposures to different mutational processes in a patient's lifetime are uncontrolled and any relationships observed can only be described as an association. Here, we demonstrate the proof-of-principle that it is possible to recreate cancer mutational signatures in vitro using CRISPR-Cas9-based gene-editing experiments in an isogenic human-cell system. We provide experimental and algorithmic methods to discover mutational signatures generated under highly experimentally-controlled conditions. Our in vitro findings strikingly recapitulate in vivo observations of cancer data, fundamentally validating the concept of (particularly) endogenously-arising mutational signatures.

Background: Neisseria gonorrhoeae is a Gram-negative bacterium which affects the urethra, throat, rectum and cervix of patients and often associated with sexually transmitted infections. The global epidemiology of the disease is not well characterised especially in resource constraint countries due to poor diagnostic capacity and inefficient reporting systems. Although important, little is known about the propensity of this bacterium to cause sepsis in immunocompetent individuals., Case Presentation: A 32-year-old female presented with fever and generalised malaise to a rural hospital in Ghana. The patient had previously been diagnosed as having enteric fever from a neighbouring health facility. Blood and urine samples were collected from the patient and cultured using standard microbiological and molecular techniques. Neisseria gonorrhoeae was isolated from the blood which was resistant to penicillin, ciprofloxacin and cotrimoxazole. The patient recovered following ceftriaxone and azithromycin treatment., Conclusion: This case highlights the importance of N. gonorrhoeae in causing sepsis and emphasises the need for blood culture investigation in diagnosis of patients presenting with fever.

Background: The World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages., Methods: Children on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low. Bivariate and multivariate analyses were used to examine the factors associated with low Cmax of each drug., Results: Of the 100 children, 58% were male, 50% HIV-infected and 49% younger than 5 years old. The median (interquartile range) Cmax was 5.9 (4.5-7.7) µg/mL for isoniazid, 6.5 (4.9-8.8) µg/mL for rifampin, 26.0 (21.2-33.4) µg/mL for pyrazinamide and 1.7 (0.9-2.7) µg/mL for ethambutol. There was a strong correlation between Cmax and AUC0-8h for all drugs. Low Cmax occurred in 9/100 (9.0%), 61/100 (61.0%), 17/97 (17.5%) and 60/97 (61.9%) for isoniazid, rifampin, pyrazinamide and ethambutol, respectively. In addition, 75/97 (77.3%) children had pyrazinamide Cmax < 35 µg/mL. Factors associated with low Cmax were NAT2 metabolizer phenotype status for isoniazid; height, dosage and HIV coinfection status for rifampin; height for pyrazinamide; and age, dosage and HIV coinfection status for ethambutol., Conclusions: The high frequency of low rifampin and ethambutol Cmax in our study is consistent with emerging pharmacokinetic data in children treated according to the new WHO recommendations. Higher dosages than currently recommended especially for rifampin may be necessary in children.

DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage. This led to the identification of the clinically approved anti-diabetic drug acetohexamide, which promoted clearance of UV-induced DNA damage without the accumulation of chromosomal aberrations, hence promoting cellular survival. Acetohexamide exerted this protective function by antagonizing expression of the DNA glycosylase, MUTYH. Together, our data reveal the existence of an NER-independent mechanism to remove UV-induced DNA damage and prevent cell death., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Maintenance of genome integrity via repair of DNA damage is a key biological process required to suppress diseases, including Fanconi anemia (FA). We generated loss-of-function human haploid cells for FA complementation group C (FANCC), a gene encoding a component of the FA core complex, and used genome-wide CRISPR libraries as well as insertional mutagenesis to identify synthetic viable (genetic suppressor) interactions for FA. Here we show that loss of the BLM helicase complex suppresses FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the FA core complex, hence demonstrating that systematic genome-wide screening approaches can be used to reveal genetic viable interactions for DNA repair defects.

Background: Diarrhoeal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in sub-Saharan Africa. This case-control study was conducted to investigate the bacterial, viral and parasitic pathogens associated with acute diarrhoea among children attending three health facilities in Kumasi, Ghana., Methods: Stool specimens were collected from 240 children under 5 years of age visiting hospitals in Kumasi, Ghana due to acute diarrhoea and from 107 healthy controls of similar age. Both intestinal and malaria parasites were diagnosed by microscopy whereas rota- and adenoviruses were identified by stool antigen immunochromatograhic testing. Bacterial enteropathogens were detected by conventional culture techniques., Results: Of all subjects, 23 (6.6%) were positive for malaria parasitaemia, 139 (40.1%) had at least one bacterial agent in their stool and 25 (7.2%) had ova or parasites. Subjects infected with malaria had the highest odds of having diarrhoea [12.0 (95% CI 1.56, 92.35)] followed by those with rotaviruses [4.4 (95% CI 2.05, 9.47)] and bacterial infection [4.99 (95% CI 1.45, 17.17)]., Conclusion: In conclusion, this study was unique as it looked at the three groups of pathogens (parasites, viruses and bacteria) that cause acute diarrhoea in children in the Kumasi metropolis of Ghana. This study has shown for the first time since 2004 that malaria parasitaemia, rotavirus and bacterial infections still remain common pathogens associated with acute childhood diarrhoea in the Kumasi metropolis of Ghana.

Background: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD., Methods: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015., Results: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ 2  = 28.52, p = 0.001)., Conclusion: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.

Background: Pseudomonas oryzihabitans is a Pseudomonas bacterial organism rarely implicated in human infections. The bacterium has been isolated in a few reported cases of neurosurgical infections and patients with end-stage cirrhosis, sickle cell disease, and community-acquired urinary tract infections. Limited information exists in developing countries, however, because of the lack of advanced microbiological tools for identification and characterization of this bacterium. This case report describes the isolation of a rare Pseudomonas bacterium in a patient presenting with sepsis and skin infection., Case Presentation: A 1-year-old girl was presented to a hospital in the northeastern part of Ghana with a 1-week history of pustular rashes on her scalp and neck, which occasionally ruptured, along with discharge of yellowish purulent fluid. The child is of Mole-Dagbon ethnicity and hails from the northern part of Ghana. Pseudomonas oryzihabitans was identified in the patient's blood culture using the 16S ribosomal deoxyribonucleic acid sequencing technique. The rash on the patient's scalp and skin resolved after continuous treatment with gentamicin while her condition improved clinically., Conclusions: This finding suggests the potential of this bacterium to cause disease in unsuspected situations and emphasizes the need to have evidence for the use of the appropriate antibiotic in clinical settings, particularly in rural settings in Africa. It also brings to the fore the unreliability of conventional methods for identification of Pseudomonas bacteria in clinical samples and thus supports the use of 16S ribosomal deoxyribonucleic acid in making the diagnosis.

Background: Persons with Disabilities (PWDs) are a unique group that are often overlooked in many developing countries due to systemic weaknesses, lack of political commitment and inadequate support from government and non-governmental agencies. The population of these individuals is however steadily on the increase and currently corresponds to 15 % of the world population. Although much data exist on lifestyle and conditions of prisoners with disabilities in the western world, scanty information is available in Africa. In Ghana, there is insufficient data on the occurrence and social characteristics of prisoners with disabilities. The purpose of this current study was therefore to identify the occurrence, types and causes of disabilities among prisoners serving sentences in Ghanaian prisons., Methods: This study was a descriptive cross-sectional survey conducted in the Male and Female Regional Prisons in Kumasi, Sunyani and the Nsawam Medium Security Prison, from November to December 2011. PWDs were selected by prisons officers and interviewed using structured questionnaires on variables such as socio-demographic characteristics, causes of disabilities and accessibility to recreational facilities. Ethical approval was obtained from the security services and the Committee of Human Research Publications and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology (KNUST)., Results: We screened 6114 records of prisoners of which 1852 (30.3 %) were from the Kumasi Central Prisons, 3483 (57 %) from the Nsawam Medium Security and 779 (12.8 %) from the Sunyani Central Prisons. A total of 99 PWDs were identified with the commonest disability being physical, followed by visual, hearing, speech, mental and albinism. Most of the disabilities were caused by trauma (68.8 %) followed by infection (16.7 %), and drug related mental disabilities (6.3 %). Fifty (50.5 %) out of the 99 PWDs were not provided with assistive devices although they admitted the need for such., Conclusion: The present study has demonstrated the occurrence and conditions of PWDs in Ghanaian prisons. Major stakeholders including government agencies and other organisations could develop policies that would improve the conditions and livelihood of prisoners with disabilities in Ghana.

Aim: This study was conducted to determine the prevalence and burden of gastrointestinal (GIT) parasites of Djallonke sheep in Ayeduase, Kumasi from January 2015 to July 2015., Materials and Methods: The presence of nematodal eggs and coccidial oocysts in fecal samples were analyzed using the saturated sodium chloride floatation technique. Identification of eggs or oocysts was done on the basis of morphology and size of the eggs or oocysts., Results: Out of 110 fecal samples of sheep examined, 108 were infected with GIT parasites, representing a prevalence rate of 98.2%. The total infection rate of GIT nematodes and coccidia oocysts were 94.5% and 51.8%, respectively. Strongyle nematode (94.5%) was the most prevalent GIT nematode detected, followed by strongyloides (27.3%). The average nematodal burden in g/feces was significantly higher (p<0.001) in young rams under 1 year (3482.0) than gimmers (1539.0), lamb (825.0), ewes (420.7), and rams over 1 year (313.3). Nematodal burden in gimmers was significantly higher (p<0.001) than that of lambs, ewes, and rams over 1 year. Nematodal counts of lambs, ewes, and rams did not differ significantly (p>0.05) from each other. The average coccidia oocysts count in g/feces was significantly higher (p<0.001) in lambs (2475.0) than rams under 1 year (286.0), gimmers (263.6), ewes (158.6), and rams over 1 year (150.0). There was no significant difference (p>0.05) in the coccidia oocysts count of rams under 1 year, gimmers, ewes, and rams over 1 year. From the studied animals, 40%, 6.36%, 48.18%, and 5.45% had heavy, moderate, light, and no infestation, respectively, with GIT nematodes., Conclusion: Djallonke sheep in Ayeduase, Kumasi, were infested with varying amounts of GIT parasites. The infestation of Djallonke sheep by GIT parasites also varies among different age groups and sexes.

Unlabelled: We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E., Importance: The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Proper development of the immune system is an intricate process dependent on many factors, including an intact DNA damage response. The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofactor, ATMIN (also known as ASCIZ) in T cells is much less clear, and whether ATMIN and NBS1 function in synergy in T cells is unknown. Here, we investigate the roles of ATMIN and NBS1, either alone or in combination, using murine models. We show loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCRα recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment. Intriguingly, the disease causing T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted in severe intestinal inflammation, colitis and premature death. Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1.

Background: Although anti-retroviral therapy has generally improved the survival of HIV infected patients in many developing countries including Ghana, specific socio-demographic factors could still influence outcome of treatment. This study was designed to identify patient-specific factors that could influence the immune recovery of absolute CD4 count in HIV infected patients., Findings: Hospital records were extracted from two health facilities in Ghana. The impact of socio-demographic factors type of ART and baseline category of CD4 counts were assessed at six monthly interval using robust linear mixed models., Results: A total of 214 follow up records were reviewed at Komfo Anokye Teaching Hospital (KATH) and the Kumasi South Hospital (KSH). One hundred (46.7%) were from KATH and 114 (53.3%) were from KSH. There was a general increase in the level of CD4 counts with time, however this increase significantly slowed down with subsequent reviews (p < 0.001). On the average the rate of CD4 count recovery slowed down by 43.6 cells/µl for every 6 months of follow up (SE = 7.69; p < 0.001). Similarly the recovery of CD4 counts in subjects with an initial high baseline CD4 counts decreased by 192.6 cells/µl (SD error = 42.3, p value ≤0.001). All other variables were not significantly associated with recovery of CD4 counts., Conclusion: Our study has demonstrated the well-known phenomenon of CD4 counts increasing after administration of ARTs. CD4 counts increased more rapidly in those with relatively lower initial counts, catching up with those with high CD4 count by 2 years post treatment.

Because some bats host viruses with zoonotic potential, we investigated human-bat interactions in rural Ghana during 2011-2012. Nearly half (46.6%) of respondents regularly visited bat caves; 37.4% had been bitten, scratched, or exposed to bat urine; and 45.6% ate bat meat. Human-bat interactions in rural Ghana are frequent and diverse.

Background: Migrant populations from countries with generalised HIV epidemics make up a significant proportion of all HIV/AIDS cases in many European Union and European Economic Area (EU/EEA) countries, with heterosexual transmission the predominant mode of HIV acquisition. While most of these infections are diagnosed for the first time in Europe, acquisition is believed to have predominantly occurred in the home country. A proportion of HIV transmission is believed to be occurring post-migration, and many countries may underestimate the degree to which this is occurring. Our objectives were to review the literature estimating the proportion of migrants believed to have acquired their HIV post-migration and examine which EU member states are able to provide estimates of probable country of HIV acquisition through current surveillance systems., Methods: A systematic review was undertaken to gather evidence of sexual transmission of HIV within Europe among populations from countries with a generalised epidemic. In addition, national surveillance focal points from 30 EU/EEA Member States were asked to complete a questionnaire about surveillance methods and monitoring of the likely place of HIV acquisition among migrants., Results & Discussion: Twenty-seven papers from seven countries were included in the review and 24 countries responded to the survey. Estimates of HIV acquisition post-migration ranged from as low as 2% among sub Saharan Africans in Switzerland, to 62% among black Caribbean men who have sex with men (MSM) in the UK. Surveillance methods for monitoring post-migration acquisition varied across the region; a range of methods are used to estimate country or region of HIV acquisition, including behavioural and clinical markers. There is little published evidence addressing this issue, although Member States highlight the importance of migrant populations in their epidemics., Conclusions: There is post-migration HIV acquisition among migrants in European countries but this is difficult to quantify accurately with current data. Migrant MSM appear at particular risk of HIV acquisition post-migration. Countries that identify migrants as an important part of their HIV epidemic should focus on using an objective method for assigning probable country of HIV acquisition. Robust methods to measure HIV incidence should be considered in order to inform national prevention programming and resource allocation.

Objective: The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory-confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS-CoV necessitates further surveillance., Methods: A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS-CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection., Results: Six hundred and fifty-one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS-CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS-CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co-infections and 2 (0.2%) FLU A/HRV co-infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample., Conclusions: The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS-CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims., (© 2015 John Wiley & Sons Ltd.)

Background: Hepatitis B virus infection (HBV) is one of the most widespread, chronic viral infections in sub-Saharan Africa, and parts of South America. Therefore, efforts are being made to implement strategies aimed at reducing the incidence of hepatitis B viral infections. One route of HBV transmission is through unsafe blood transfusion, which could occur from the use of less sensitive laboratory diagnostic kits. Information on the sensitivity and specificity of these kits is however limited in many developing countries. This study was therefore performed to describe the prevalence of HBV infections and also to evaluate the performance of five rapid immunochromatographic kits commonly used in Ghana., Methods: A cross-sectional study was designed to describe the prevalence of HBsAg infection and also evaluate the performance of rapid kits used for screening hepatitis B in the northern part of Ghana., Results: A total of 164 prospective blood donors were enrolled in this study from January 2012 to December 2013. The overall true prevalence of HBsAg was 14.6 (95% CI = 9.6 - 21.0). There was no significant association between transmission related factors and HBV infection. The specificities of all five rapid kits were above 97%, however the sensitivities and Youden's indexes were below 60%. A comparison of the reported kit sensitivities to those generated by this study showed significant difference with the study results being lower than the ones reported in the kit literature., Conclusion: Our study has shown that rapid HBsAg kits on the Ghanaian markets may not be helpful for screening blood donor samples. We therefore recommend the use of commercially available enzyme linked immunosorbent assays.

Unresolved replication intermediates can block the progression of replication forks and become converted into DNA lesions, hence exacerbating genomic instability. The p53-binding protein 1 (53BP1) forms nuclear bodies at sites of unrepaired DNA lesions to shield these regions against erosion, in a manner dependent on the DNA damage kinase ATM. The molecular mechanism by which ATM is activated upon replicative stress to localize the 53BP1 protection complex is unknown. Here we show that the ATM-INteracting protein ATMIN (also known as ASCIZ) is partially required for 53BP1 localization upon replicative stress. Additionally, we demonstrate that ATM activation is impaired in cells lacking ATMIN and we define that ATMIN is required for initiating ATM signaling following replicative stress. Furthermore, loss of ATMIN leads to chromosomal segregation defects. Together these data reveal that chromatin integrity depends on ATMIN upon exposure to replication-induced stress., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. This study sought to determine whether human coronaviruses (HCoVs) are associated with upper respiratory tract infections among older children and adults in Ghana., Methods: We conducted a case control study among older children and adults in three rural areas of Ghana using asymptomatic subjects as controls. Nasal/Nasopharyngeal swabs were tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-22E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction., Results: Out of 1,213 subjects recruited, 150 (12.4%) were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95%CI = 2.24-11.78), HCoV-OC43 (OR = 6.16, 95%CI = 1.77-21.65) and combine HCoVs (OR = 2.36, 95%CI = 1.5 = 3.72) were associated with upper respiratory tract infections. HCoVs were found to be seasonally dependent with significant detections in the harmattan season (mainly HCoV-229E) and wet season (mainly HCoV-NL63). A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank., Conclusion: HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural areas of Ghana.

The investigation was undertaken to establish a relationship between key odorants and perceived flavor attributes of dark chocolate as influenced by cocoa fermentation method, roasting and conching conditions, using multivariate data analysis in an attempt to use one variable to predict the other. Eight of the sixteen flavor attributes used by a trained sensory panel to describe and quantify the intensity of attributes in the samples were significantly different (p < 0.05). Roasting significantly reduced astringency in heap-fermented samples but the reduction in tray-fermented samples was not significant. Unconched samples were rated higher in banana attribute than conched samples. Multivariate data analytical tools, Principal Component Analysis (PCA) and Partial Least Squares (PLS) were used to investigate quantitative descriptive analysis and GC-O data and also to relate the two sets of data. PLS 1 models based on single sensory attributes gave better models than PLS2 models based on all sixteen sensory attributes. Ethyl-3-methylbutanoate (fruity, flowery); 2,5-dimethylpyrazine (popcorn); dihydro-2(3H)-furanone, (sweet); linalool oxide (sweet, flowery); benzaldehyde (earthy, nutty) and 2/3-methylbutanal (cocoa, roasted) modeled fruit attribute. It was also possible to model the attribute astringent from the aroma compounds 5-methyl-2-phenyl-2-hexenal (sweet, roasted cocoa), ethyl-3-methylbutanoate and pentyl acetate (green, cucumber). Since fruit attribute was higher in unconched samples and astringent higher in unroasted samples, it may be possible to use the levels of these important aroma compounds as indicators of the sensory attributes fruit and astringent.

We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.