On the Environmental Presence of Burkholderia pseudomallei in South-Central Ghana.

Burkholderia pseudomallei is a Gram-negative soil saprophyte with the potential to cause melioidosis, an opportunistic disease with a high mortality potential. Periodic case reports of melioidosis in or imported from Africa occur in the literature dating back decades. Furthermore, statistical models suggest Western sub-Saharan Africa as a high-risk zone for the presence of B. pseudomallei. A recent case report from the United Kingdom of a returning traveler from Ghana highlights the need for environmental studies in Ghana. We examined 100 soil samples from a rice farm in south-central Ghana. Soil was subjected to selective enrichment culture for B. pseudomallei using threonine-basal salt solution with colistin (TBSS-C50) and erythritol medium, as described in the literature. Bacterial cultures were identified with standard biochemical tests, a rapid antigen detection assay, and real-time PCR specific for B. pseudomallei. Of the 100 soil samples, 55% yielded cultures consistent with B. pseudomallei on Ashdown's agar as well as by capsular polysaccharide antigen production. This is the first confirmatory report of culture-confirmed B. pseudomallei in the environment of Ghana. Our study emphasizes the need for further exploration of the burden of human melioidosis in Ghana. We recommend that local clinicians familiarize themselves with the diagnosis and clinical management of melioidosis, while laboratories develop capacity for the safe isolation and identification of B. pseudomallei. IMPORTANCE We present the first confirmation of the presence of B. pseudomallei in the environment of Ghana. This study will bring attention to a disease with the potential to cause significant morbidity and mortality in Ghana, but which has gone completely unrecognized until this point. Furthermore, this work would encourage local clinicians to familiarize themselves with the diagnosis and clinical management of melioidosis and laboratories to develop capacity for the safe isolation and identification of B. pseudomallei.

A nationwide cross-sectional review of in-hospital hepatitis B virus testing and disease burden estimation in Ghana, 2016 - 2021.

BACKGROUND AND AIMS: Data are needed to inform hepatitis B virus (HBV) testing and treatment policies in Ghana to make progress towards achieving the 2030 WHO elimination targets. This study investigated testing patterns for HBV and described the age, sex, and region-specific prevalence of HBV infection in Ghana using hospital data. METHODS: A nationwide multi-centre cross-sectional study was performed where hospital-based registers were reviewed. These included review of 139,966 laboratory, 169,048 blood bank, and 83,920 delivery register entries from 22 healthcare institutions in Ghana. Frequencies and proportions, and crude and pooled estimates reported. Chi squared test was used for tests of independence. Logistic regression was used to identify factors associated with a positive test result. RESULTS: The crude HBsAg seroprevalence was 8.48% (95%CI 8.25-8.57%) with pooled estimate of 11.40% (95%CI 10.44-12.35). HBsAg seroprevalence among children under 5 years was 1.87% (95%CI 1.07-3.27) and highest age-specific seroprevalence was in those 40-49 years. The highest region-specific seroprevalences was in the Savannah (22.7%). Predictors of a positive HBsAg RDT test included female sex (OR 0.81 95% CI 0.74-0.88), and age (OR 1.005 95%CI 1.002-1.007). The proportion of parturient women receiving HBsAg testing increased between 2017 (87.2%) and 2020 (94.3%) (p < 0.001). The crude HBsAg seroprevalence in parturient women was 6.14% (95% CI 5.97-6.31). Among blood donors the crude HBsAg seroprevalence was 5.69% (95%CI 5.58-5.80). Data from 2 teaching hospitals indicated that in 2020, although 1500 HBsAg positive tests were recorded only 746 serological profile and 804 HBV DNA tests were performed. HBV e antigen seroprevalence was 6.28% (95%CI 4.73-7.84). CONCLUSION AND RECOMMENDATIONS: Ghana remains a country with high HBV burden. There is an unequal distribution, with higher HBsAg seroprevalence in the north of the country. Furthermore, PCR testing is not widely available outside of large teaching hospitals, which limits diagnostic work-up. Hepatitis reporting systems and registers should be improved to facilitate data capture of indicators and standardised across the country to allow for comparability. Furthermore, where gains have been made in testing among pregnant women, there is a need for linkage to appropriate care.

Carbapenem Resistance Determinants Acquired through Novel Chromosomal Integrations in Extensively Drug-Resistant Pseudomonas aeruginosa.

Two novel blaDIM-1- or blaIMP-1-containing genomic islands (GIs) were discovered by whole-genome sequence analyses in four extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates from inpatients at a tertiary hospital in Ghana. The strains were of sequence type 234 (ST234) and formed a phylogenetic clade together with ST111, which is recognized as a global high-risk clone. Their carbapenem resistance was encoded by two Tn402-type integrons, In1592 (blaDIM-1) and In1595 (blaIMP-1), both carrying complete tni mobilization modules. In1595 was bound by conserved 25-bp inverted repeats (IRs) flanked by 5-bp direct repeats (DRs) associated with target site duplication. The integrons were embedded in two GIs that contained cognate integrases and were distinguished by a lower GC content than the chromosomal average. PAGI-97A (52.659 bp; In1592), which encoded a P4-type site-specific integrase of the tyrosine recombinase family in its 3' border, was integrated into tRNA-Pro(ggg) and bracketed by a 49-bp perfect DR created by 3'-end target duplication. GIs with the same structural features, but diverse genetic content, were identified in 41/226 completed P. aeruginosa genomes. PAGI-97B (22,636 bp; In1595), which encoded an XerC/D superfamily integrase in its 5' border, was inserted into the small RNA (sRNA) PrrF1/PrrF2 locus. Specific insertions into this highly conserved locus involved in iron-dependent regulation, all leaving PrrF1 intact, were identified in an additional six phylogenetically unrelated P. aeruginosa genomes. Our molecular analyses unveiled a hospital-associated clonal dissemination of carbapenem-resistant ST234 P. aeruginosa in which the XDR phenotype resulted from novel insertions of two GIs into specific chromosomal sites.

Cost-effectiveness and budget impact of whole blood pathogen reduction in Ghana.

BACKGROUND: Despite the promise of pathogen reduction for reducing transfusion-associated adverse events in sub-Saharan Africa, no health-economic assessment is publicly available. STUDY DESIGN AND METHODS: We developed a mathematical risk reduction model to estimate the impact of nationwide whole blood pathogen reduction in Ghana on the incidence of six infectious and one non-infectious transfusion-associated adverse events. We estimated the lifetime direct healthcare costs and disability-adjusted life years lost for each adverse event. For HIV, HCV, and HBV, we simulated disease progression using Markov models, accounting for the likelihood and timing of clinical detection and treatment. We performed probabilistic and univariate sensitivity analysis. RESULTS: Adding whole blood pathogen reduction to Ghana's blood safety portfolio would avert an estimated 19,898 (11,948-27,353) adverse events and 38,491 (16,444-67,118) disability-adjusted life years annually, primarily by averting sepsis (49%) and malaria (31%) infections. One year of pathogen reduction would cost an estimated $8,037,191 ($6,381,946-$9,880,760) and eliminate $8,656,389 ($4,462,614-$13,469,448) in direct healthcare spending on transfusion-associated adverse events. We estimate a 58% probability that the addition of pathogen reduction would reduce overall direct healthcare spending. Findings were most sensitive to uncertainty in the probability that a bacterially contaminated blood donation causes sepsis. CONCLUSION: Whole blood pathogen reduction would substantially reduce the burden of known transfusion-associated adverse events in Ghana and may reduce overall healthcare spending. Additional benefits not captured by this analysis may include averting secondary transmission of infectious diseases, reducing non-medical costs, and averting new or re-emerging transfusion-transmitted infections.

Bacterial contamination of blood products in Africa.

BACKGROUND: Bacterial contamination of blood components (notably platelets) remains a leading infectious risk to the blood supply. There has been extensive research in high-income countries to characterize the risk of bacterial contamination along with adoption of strategies to mitigate that risk. By contrast, related data in Africa are lacking. STUDY DESIGN AND METHODS: An electronic survey was distributed to members of African Society of Blood Transfusion to assess existing or planned measures at African blood centers and hospitals to mitigate bacterial contamination of blood products. A literature review of studies pertaining to related transfusion-associated risk in Africa was conducted to complement the findings. RESULTS: Forty-five responses were received, representing 16 African countries. All respondents were urban, either in blood centers (n = 36) or hospital-based transfusion services (n = 9). Reported measures included skin disinfection (n = 41 [91.1%]); diversion pouches (n = 14 [31.1%]); bacterial culture (n = 9 [20%]); pathogen reduction (PR) (n = 3 [6.7%]); and point-of-release testing (PoRT) (n = 2 [4.4%]). Measures being considered for implementation included: skin disinfection (n = 2 [4.4%]); diversion pouches (n = 2 [4.4%]); bacterial culture n = 14 (31.1%); PR (n = 11 [24.4%]); and PoRT (n = 4 [8.9%]). Of the 38 respondents who reported collection of platelets, 14 (36.8%) and 8 (21.1%) reported using diversion pouches and bacterial culture, respectively. The literature review identified 36 studies on the epidemiology of bacterial contamination and septic transfusion reactions in Africa; rates of contamination ranged from 0% to 17.9%. CONCLUSIONS: The findings suggest that prevention of bacterial contamination of blood components and transfusion-associated sepsis in Africa remains neglected. Regional preventive measures have not been widely adopted.

Nasopharyngeal carriage of Streptococcus pneumoniae among healthy children in Kassena-Nankana districts of Northern Ghana.

BACKGROUND: Pneumococcal vaccine immunizations may be responsible for alterations in serotype epidemiology within a region. This study investigated the pneumococcal carriage prevalence and the impact of the 13-valent pneumococcal conjugate vaccine (PCV-13) on circulating serotypes among healthy children in Northern Ghana. METHODS: This was a cross sectional study conducted in the Kassena-Nankana districts of Northern Ghana from November to December during the dry season of 2018. Nasopharyngeal swabs collected from 193 participants were cultured per standard microbiological protocols and pneumococcal isolates were serotyped using the latex agglutination technique and the capsular Quellung reaction test. We examined for any association between the demographic characteristics of study participants and pneumococcal carriage using chi-square test and logistic regression. RESULTS: Of the 193 participants that were enrolled the mean age was 8.6 years and 54.4% were females. The carriage rate among the participants was 32.6% (63/193), and twenty different serotypes were identified. These included both vaccine serotypes (VT), 35% (7/20) and non-vaccine serotypes (NVT), 65% (13/20). The predominant serotypes (34 and 11A), both of which were NVT, accounted for a prevalence of 12.8%. PCV-13 covered only 35% of serotypes identified whiles 40% of serotypes are covered by PPV 23. CONCLUSION: Post-vaccination carriage of S. pneumoniae is high and is dominated by non-vaccine serotypes. There is therefore a need for the conduct of invasive pneumococcal disease surveillance (IPD) to find out if the high non-vaccine serotype carriage translates to disease. And in addition, a review of the currently used PCV-13 vaccine in the country would be considered relevant.

Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana.

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.

Prevalence of vulvovaginal candidiasis, bacterial vaginosis and trichomoniasis in pregnant women attending antenatal clinic in the middle belt of Ghana.

BACKGROUND: Vaginal infections usually caused by Candida sp, organisms responsible for bacterial vaginosis and Trichomonas vaginalis are associated with considerable discomfort and adverse outcomes during pregnancy and child birth. The study determined the prevalence of vulvovaginal candidiasis (VVC), bacterial vaginosis (BV) and trichomoniasis (TV) in pregnant women attending antenatal clinic at the Kintampo Municipal Hospital. METHODS: A study adopted a cross sectional design and recruited 589 pregnant women after seeking their informed consent from September, 2014 to March, 2015. Semi-structured questionnaire were administered to participants and vaginal swabs were collected. The samples were analysed using wet mount method and Gram stain (Nugent criteria) for vaginal infection. Univariate and multivariate analysis were used to investigate association of risk factors to vaginal infections. RESULTS: The overall prevalence of at least one vaginal infection was 56.4%. The prevalence of vulvovaginal candidiasis, bacterial vaginosis and trichomoniasis were 36.5, 30.9 and 1.4% respectively. Women with more than four previous pregnancies (OR: 0.27, 95% CI: 0.13-0.58) and those in the third trimester of pregnancy (OR: 0.54, CI: 0.30-0.96) were associated with a lower risk of bacterial vaginosis. Douching and antibiotic use were neither associated with VVC or BV. CONCLUSION: The prevalence of vaginal infections was high among pregnant women in the Kintampo area. There is the need for interventions such as adequate investigations and early treatment of vaginal infections to reduce the disease burden to avoid associated complications.

Effect of Plasmodium inactivation in whole blood on the incidence of blood transfusion-transmitted malaria in endemic regions: the African Investigation of the Mirasol System (AIMS) randomised controlled trial.

BACKGROUND: Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites. METHODS: For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥ 18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana. The main exclusion criteria were symptoms of clinical malaria, antimalaria treatment within 7 days before randomisation, fever, and haemorrhage expected to require transfusion with up to two units of whole blood during the 3 days following study entry. Eligible patients were randomly assigned 1:1 by computer-generated permuted block randomisation (block size four) list to receive transfusion with either pathogen-reduced whole blood (treated) or whole blood prepared and transfused by standard local practice (untreated). Patients, health-care providers, and data collectors were masked to treatment allocation. Patients in both groups received up to two whole blood unit transfusions that were retrospectively tested for parasitaemia. Pre-transfusion and post-transfusion blood samples (taken on days 0, 1, 3, 7, and 28) were tested for presence and amount of parasite genome, and assessed for haematological and biochemical parameters. The primary endpoint was the incidence of transfusion-transmitted malaria in non-parasitaemic recipients exposed to parasitaemic whole blood, defined as two consecutive parasitaemic post-transfusion samples with parasite allelic matching, assessed at 1-7 days after transfusion. Secondary endpoints included haematological parameters and a safety analysis of adverse events in patients. This study is registered with ClinicalTrials.gov, number NCT02118428, and with the Pan African Clinical Trials Registry, number PACTR201406000777310. FINDINGS: Between March 12, 2014, and Nov 7, 2014, 227 patients were enrolled into the study, one of whom was subsequently excluded because she did not meet the inclusion criteria. Of the 226 randomised patients, 113 were allocated to receive treated whole blood and 113 to receive standard untreated whole blood. 223 patients (111 treated and 112 untreated) received study-related transfusions, whereas three patients (two treated and one untreated) did not. 214 patients (107 treated and 107 untreated) completed the protocol as planned and comprised the per-protocol population. Overall, 65 non-parasitaemic patients (28 treated and 37 untreated) were exposed to parasitaemic blood. The incidence of transfusion-transmitted malaria was significantly lower for the pathogen-reduced (treated) patients (1 [4%] of 28 patients) than the untreated group (8 [22%] of 37 patients) in this population (p=0.039). Overall, 92 (41%) of 223 patients reported 145 treatment-related emergent adverse events during the conduct of the study, with a similar incidence of adverse events between groups receiving untreated or treated whole blood. No transfusion-related deaths occurred in the trial. INTERPRETATION: Treatment of whole blood with the Mirasol pathogen reduction system for whole blood reduced the incidence of transfusion-transmitted malaria. The primary endpoint of the study was achieved in the population of non-parasitaemic patients receiving parasitaemic whole blood. The safety profile and clinical outcomes were similar across the two treatment groups. FUNDING: Terumo BCT Inc.

Characterization of posttransfusion Plasmodium falciparum infection in semi-immune nonparasitemic patients.

BACKGROUND: Transfusion-transmitted malaria (TTM) has not been studied with molecular means in hyperendemic areas where it is assumed to occur frequently. The African Investigation of the Mirasol System (AIMS) trial provided the opportunity to study TTM from standard whole blood (WB) units. STUDY DESIGN AND METHODS: The Plasmodium genome in transfused WB units and patient samples both before transfusion and 1, 3, 7, and 28 days after transfusion was screened and quantified using real-time polymerase chain reaction. Parasitemic samples were confirmed, three alleles were sequenced, and the percentage homology was determined between paired WB units and patient samples. Anti-Plasmodium titers were quantified by serial dilution. Clinical symptoms and microscopic detection of malaria were monitored. RESULTS: Microscopy was negative below 3 × 10(6) genome copies/mL. Thirty-seven patients who were nonparasitemic before transfusion were exposed to parasitemic WB. The amount of Plasmodium genome load transfused ranged between 0.1 × 10(6) and 2.0 × 10(9) copies. The parasite load received through transfusion by 13 patients with TTM was higher than that received by patients without TTM (p = 0.01). Patients with a single parasitemic posttransfusion sample were not considered to have TTM. Four elements critical to predict outcome emerged: parasite load, patient anti-Plasmodium titer pretransfusion, percentage clearance of parasites at Day 1, and level of anti-Plasmodium humoral immune response. Four patients with TTM became parasite-free at Day 28 (effective control), four patients with TTM maintained relatively stable levels of parasitemia (uncertain control), and five patients reached high levels of parasitemia at Day 28 posttransfusion, indicating ineffective control of malarial infection by semi-immune individuals. CONCLUSIONS: TTM in endemic areas is relatively frequent (13 of 112 donations; 11.6%) and, although largely controlled by semi-immunity in recipient patients, may require antimalarial treatment.

Transfusion-transmitted malaria: donor prevalence of parasitaemia and a survey of healthcare workers knowledge and practices in a district hospital in Ghana.

BACKGROUND: Transfusion-transmitted malaria (TTM) is a risk of transfusion that has not been well described in malaria endemic regions. The risk of the recipient getting malaria is related to the prevalence of malaria in the blood donors. There is however little information on the prevalence of malaria among donors in Akatsi district of Ghana. Further, the knowledge and practices of healthcare workers to TTM is unknown. The study was undertaken to determine the prevalence of malaria parasite infection among blood donors and to evaluate the knowledge and practices of healthcare workers to TTM in the Akatsi district of Ghana. METHODS: The study was conducted at Akatsi South District Hospital between May and August 2014. To screen for Plasmodium falciparum, 5 µl of capillary blood was obtained by finger prick from 200 participants (100 donors and 100 healthy controls). Plasmodium falciparum screening was done using CareStart™ Malaria Antigen kit. To obtain information regarding TTM knowledge and practices, questionnaires were completed by 100 health workers including nurses, doctors and laboratory staff. RESULTS: The prevalence of P. falciparum was the same (10 %) in both donors and controls. All those who were malaria RDT positive were aged 15-25 years. Out of the 100 healthcare workers (31 males and 69 females) surveyed, 45 % of respondents (45/100) had never heard of transfusion-transmitted malaria. Almost all respondents (91 %) had not attended any lecture/seminar/workshop on blood transfusion in the past 12 months. There were 44 respondents (44 %) who wrongly said malaria was being screened for prior to transfusion in their hospital. However, 98.2 % (54/55) of those who had heard about TTM rightly stated that TTM can be prevented. CONCLUSION: The prevalence of P. falciparum parasitaemia is 10 % in healthy blood donors in the Akatsi district and represents a risk for TTM though the extent of this risk is unclear. Knowledge about TTM in healthcare workers in the district is low. Continuous education and in-service training may be a means to improve TTM knowledge and preventive practices by the health workers in the district.

Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses.

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.

Use what you have: leveraging microbiology support to develop a cumulative antibiotic susceptibility report for antimicrobial stewardship at a district hospital in Ghana.

Background: Antibiograms provide effective support for empirical prescribing and antimicrobial stewardship programmes (ASPs). In low-resource settings, microbiology systems to develop antibiograms may be rudimentary or entirely lacking, which may place such facilities at a disadvantage. Notwithstanding this, facilities should use what they have to support ASPs to inform evidence-based antibiotic use. We report how an antibiogram was developed at a district hospital in Ghana to support its ASP. Methods: This was a retrospective analysis of antibiotic susceptibility testing (AST) results from the University Hospital, KNUST from January to December 2021. Data were exported from the hospital's laboratory information system to Microsoft Excel (Version 2013). IBM SPSS Statistics (Version 25) and Epi Info™ Version 7 were used for statistical analyses. Results: Overall, 1949 cultures were performed, 392 (20.1%) growing bacterial pathogens. Per the CLSI M39-A4 standard guidelines for antibiograms, only 360 of the bacterial isolates were used for the analyses. The majority of isolates were from urine (187; 51.9%). Among the Gram-negative bacteria, there was low susceptibility to amoxicillin/clavulanic acid (28%), cephalosporins (11%-35%) and meropenem (21%), but high susceptibility to amikacin (96%) and levofloxacin (81%). Low susceptibility of Gram-positive isolates to amoxicillin/clavulanic acid (34%), meropenem (34%) and penicillins (27%-35%) was also recorded, but high susceptibility to ciprofloxacin (80%), gentamicin (79%) and vancomycin (76%). Conclusion: High levels of bacterial resistance to cephalosporins and meropenem in the antibiogram were reported. This antibiogram highlighted the urgent need for pragmatic steps to curb antibiotic resistance through ASPs using strategies that positively improve clinicians' knowledge and prescribing practices.

Sepsis endotypes identified by host gene expression across global cohorts.

BACKGROUND: Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups. METHODS: Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494). RESULTS: We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis. CONCLUSIONS: Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.

Sepsis is a life-threatening multi-organ failure caused by the body's immune response to infection. Clinical symptoms of sepsis vary from one person to another likely due to differences in host factors, infecting pathogen, and comorbidities. This difference in clinical symptoms may contribute to the lack of effective interventions for sepsis. Therefore, approaches tailored to targeting groups of patients who present similarly are of great interest. This study analysed a large group of sepsis patients with diverse symptoms using laboratory markers and mathematical analysis. We report four patient groups that differ by risk of death and immune response profile. Targeting these defined groups with tailored interventions presents an exciting opportunity to improve the health outcomes of patients with sepsis.

Phylogenetic and phenotypic characterization of Burkholderia pseudomallei isolates from Ghana reveals a novel sequence type and common phenotypes.

Melioidosis is a potentially severe disease caused by the gram-negative soil-dwelling bacterium called Burkholderia pseudomallei. The true breadth of the distribution of this tropical pathogen is starting to emerge with environmental and clinical isolates frequently characterized in new countries and regions. Even so, isolates, clinical cases, and genetic data from the continent of Africa remain scant. We previously confirmed the presence of B. pseudomallei in the environment of Ghana, unmasking a new area of endemicity for this pathogen. Here, we describe the genetic characteristics of isolates obtained from that environmental survey. Twenty-one isolates were subjected to whole genome sequencing and found to represent three discrete sequence types (ST), one of which was novel, and designated ST2058. Phylogenetic analysis places this novel isolate within a B. pseudomallei clade that includes genomes derived from the Americas, although it is closely related to a sub-clade that includes isolates from Africa. Importantly, phenotypic characterization demonstrates common features including API 20NE profiles and B. pseudomallei CPS to support existing diagnostics, and susceptibility to standard of care antibiotics often used in the clinical management of melioidosis. These findings add to our knowledge about the presence and distribution of B. pseudomallei in Africa and represent the first published genomes out of Ghana.

Gene expression signatures in blood from a West African sepsis cohort define host response phenotypes.

Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.

Transfusion-transmitted malaria in Ghana.

BACKGROUND: In sub-Saharan Africa, the prevalence of malaria parasitemia in blood donors varies from 0.6% to 50%. Although the burden of TTM in malaria-endemic countries is unknown, it is recommended that all donated blood is screened for malaria parasites. This study aimed to establish the incidence of TTM and identify a suitable screening test. METHODS: Pregnant women, children, and immunocompromised malaria-negative transfusion recipients in a teaching hospital in Ghana were recruited over the course of 1 year. Parasites detected in recipients within 14 days of the transfusion were genotyped and compared to parasites in the transfused blood. The presence of genotypically identical parasites in the recipient and the transfused blood confirmed transfusion-transmitted malaria. Four malaria screening tests were compared to assess their usefulness in the context of African blood banks. RESULTS: Of the 50 patients who received transfusions that were positive for Plasmodium falciparum by polymerase chain reaction (PCR), 7 recipients developed PCR-detectable parasitemia. In only 1 of the 50 recipients (2%) was the parasite identical to that in the transfused blood. The prevalence of P. falciparum malaria in transfused blood was 4.7% (21/445) by microscopy, 13.7% (60/440) by rapid diagnostic test, 18% (78/436) by PCR, and 22.2% (98/442) by enzyme immunoassay. CONCLUSIONS: Although malaria parasites are commonly detected in blood donors in malaria-endemic areas, transfusion-transmitted malaria occurs infrequently. Policies recommend screening blood donors for malaria, but none of the commonly used methods is sufficiently sensitive to be used by blood banks in malaria-endemic countries.

Prevalence of carbapenem-resistant and extended-spectrum beta-lactamase-producing Enterobacteriaceae in a teaching hospital in Ghana.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and Extended-spectrum beta-lactamase (ESBL) production among Gram-negative Enterobacteriaceae is an increasing global challenge due to the high morbidity and mortality associated with their infections, especially in developing countries where there are little antibiotic treatment options. Despite these challenges, few studies in Ghana have described the burden of CRE. Therefore, this study aimed to determine the prevalence of carbapenem-resistant Enterobacteriaceae isolated from patients at the Cape Coast Teaching Hospital (CCTH) in the Central region of Ghana. METHODOLOGY/PRINCIPAL FINDINGS: Enterobacteriaceae isolates were collected from April to July 2019 at the bacteriology unit of CCTH using a consecutive sampling method. Isolates were identified by standard microbiological techniques and confirmed using API 20E. Kirby Bauer disc diffusion method was used to determine the antibiogram of isolates. Isolates were also subjected to ESBL testing using the single-disc combination method. Carbapenem-resistant isolates were identified by the Kirby Bauer disc diffusion method and then examined genotypically for the presence of blaKPC-1, blaIMP-1, blaVIM-1, blaNDM-1, and blaOXA-48 genes via polymerase chain reaction (PCR). Of the 230 isolates comprising E. coli (40.9%), Citrobacter spp. (32.6%), K. pneumoniae (9.1%), P. mirabilis (6.1%), P. vulgaris (5.2%), Enterobacter spp (3.5%)., K. oxytoca (2.2%), and Serratia marcenses (0.4%). Most isolates were from urine 162(70.4%) and wound samples. The isolates showed high resistance to ampicillin 171 (74.3%) and cefuroxime 134(58.3%). The prevalence of MDR was 35.2% (81), with E. coli 40(42.6%) being the majority that exhibited MDR. Of the 230 isolates, 113(49.1%) were ESBL producers, with E. coli 54(57.5%) accounting for the majority, while Serratia marcenses was the least. Of the 13 (5.7%) CRE isolates that showed resistance towards carbapenem in the disc diffusion method, 11 showed the presence of the blaNDM-1 gene, while all isolates showed the presence of the blaOXA-48 gene. CONCLUSION: The prevalence of carbapenem resistance and ESBL-producing Enterobacteriaceae pathogens among patients at the Cape Coast Teaching Hospital is high and alarming. Therefore, it is imperative to consider effective infection prevention and control measures should be implemented at the hospital to prevent the rapid spread of these dangerous organisms.

Knowledge, attitudes and practices regarding antimicrobial use and resistance among healthcare seekers in two tertiary hospitals in Ghana: a quasi-experimental study.

OBJECTIVE: To evaluate knowledge of antimicrobial resistance (AMR), to study how the judgement of health value (HVJ) and economic value (EVJ) affects antibiotic use, and to understand if access to information on AMR implications may influence perceived AMR mitigation strategies. DESIGN: A quasi-experimental study with interviews performed before and after an intervention where hospital staff collected data and provided one group of participants with information about the health and economic implications of antibiotic use and resistance compared with a control group not receiving the intervention. SETTING: Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana. PARTICIPANTS: Adult patients aged 18 years and older seeking outpatient care. MAIN OUTCOME MEASURES: We measured three outcomes: (1) level of knowledge of the health and economic implications of AMR; (2) HVJ and EVJ behaviours influencing antibiotic use and (3) differences in perceived AMR mitigation strategy between participants exposed and not exposed to the intervention. RESULTS: Most participants had a general knowledge of the health and economic implications of antibiotic use and AMR. Nonetheless, a sizeable proportion disagreed or disagreed to some extent that AMR may lead to reduced productivity/indirect costs (71% (95% CI 66% to 76%)), increased provider costs (87% (95% CI 84% to 91%)) and costs for carers of AMR patients/societal costs (59% (95% CI 53% to 64%)). Both HVJ-driven and EVJ-driven behaviours influenced antibiotic use, but the latter was a better predictor (reliability coefficient >0.87). Compared with the unexposed group, participants exposed to the intervention were more likely to recommend restrictive access to antibiotics (p<0.01) and pay slightly more for a health treatment strategy to reduce their risk of AMR (p<0.01). CONCLUSION: There is a knowledge gap about antibiotic use and the implications of AMR. Access to AMR information at the point of care could be a successful way to mitigate the prevalence and implications of AMR.

Impact of antibiotic intake on the incidence of extended-spectrum ß-lactamase-producing Enterobacterales in sub-Saharan Africa: results from a community-based longitudinal study.

OBJECTIVES: The global prevalence of intestinal extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) is approximately 17% in communities, with significant variations among regions. This longitudinal study aimed to assess the impact of antibiotic intake on the incidence of intestinal ESBL-PE in Ghanaian pharmacy customers outside of hospitals. METHODS: Screening for ESBL-PE was performed in four independent pharmacies in Kumasi, Ghana, using rectal swabs and an ESBL-PE-selective medium. Pharmacy customers purchasing antibiotics were recruited, and those buying non-antibiotic drugs served as controls. Participants who were negative for ESBL-PE provided follow-up swabs for up to 28 days. RESULTS: At baseline, 302 (75%) of 404 participants were colonized with ESBL-PE. Sixty-three participants who were negative for ESBL-PE at baseline received per-protocol follow-up, including 28 individuals who took antibiotics and 35 controls. The cumulative proportions of ESBL-PE in the antibiotics and control groups were 71% (20/28) and 54% (19/35) at the first follow-up (p 0.258), 86% (24/28) and 80% (28/35) at the second follow-up (p 0.741) and 86% (24/28) and 94% (33/35) at the third follow-up (p 0.393), respectively. DISCUSSION: The rate of intestinal ESBL-PE carriage among pharmacy customers outside of hospitals was higher than expected at baseline and further increased during the 28 days of follow-up, irrespective of antibiotic intake. This alarming finding needs to be considered in the antibiotic treatment of outpatients and emphasizes the urgent need for improved prevention strategies, development of new antibiotic drugs and potential future elimination strategies. Further longitudinal studies on ESBL-PE in African communities, also outside of pharmacy settings, are required.