Alex Owusu-Ofori

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

BACKGROUNDnTransfusion-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.nnnMETHODSnFor 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.nnnFINDINGSnBetween 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.nnnINTERPRETATIONnTreatment 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.nnnFUNDINGnTerumo BCT Inc.

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

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.

Improving the screening of blood donors with syphilis rapid diagnostic test (RDT) and rapid plasma reagin (RPR) in low- and middle-income countries (LMIC)

Syphilis testing conventionally relies on a combination of non‐treponemal and treponemal tests. The primary objective of this study was to describe the positive predictive value (PPV) of a screening algorithm in a combination of a treponemal rapid diagnostic test (RDT) and rapid plasma reagin (RPR) test at Komfo Anokye Teaching Hospital (KATH), Ghana.

Prevention of transfusion-transmitted malaria

Transfusion‐transmitted malaria (TTM) occurs when the Plasmodium found in the transfusion recipient and corresponding blood donor are genotypically identical. All five species of Plasmodium are known to cause TTM. Transfusion transmission of Plasmodium has been estimated between 14 and 28 per cent in regions, where about a quarter to half of the population carries the parasite. The presentation and clinical severity of transfusion‐transmitted malaria may differ between malaria‐endemic and non‐endemic countries. Elements critical to outcomes in recipients include parasite load transfused, patient anti‐Plasmodium titre pretransfusion, per cent clearance of parasites and level of anti‐Plasmodium humoural immune response. Several strategies to prevent TTM include donor deferral, screening, prophylaxis and presumptive treatment and now pathogen reduction. Malaria testing is recommended for endemic countries, but there are no practical, affordable and suitably sensitive screening tests. Microscopy has limited sensitivity, whilst PCR though efficient is cost‐inhibiting. Donor screening in countries facing perennial blood shortages would drastically reduce blood availability. Practice across sub‐Saharan Africa shows no uniformity with screening. WHO advocates for presumptive antimalarial treatment of transfusion recipients in endemic countries, whilst guidelines for malaria programs require parasitological confirmation before medication. Improving safety of blood units without compromising supply in high disease burden areas may be achieved with pathogen reduction technologies applicable to whole blood and red cell concentrates. Countries with high risk for TTM inadvertently have high transfusion rates amongst young children and women and may benefit from applying such technologies to minimize the residual risk of transfusion‐transmissible agents, including malaria.

Multidrug-resistant gram-negative bacterial infections in a teaching hospital in Ghana

BackgroundMultidrug-resistant Gram-negative bacteria have emerged as major clinical and therapeutic dilemma in hospitals in Ghana.To describe the prevalence and profile of infections attributable to multidrug-resistant Gram-negative bacteria among patients at the Komfo Anokye Teaching Hospital in the Ashanti region of Ghana.MethodsBacterial cultures were randomly selected from the microbiology laboratory from February to August, 2015. Bacterial identification and minimum inhibitory concentrations were conducted using standard microbiological techniques and the Vitek-2 automated system. Patient information was retrieved from the hospital data.ResultsOf the 200 isolates, consisting of K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., E. coli, Yersinia spp., Proteus mirabilis, Pasteurella spp., Chromobacterium violaceum, Salmomella enterica, Vibrio spp., Citrobacter koseri, Pantoea spp., Serratia spp., Providencia rettgeri Burkholderia cepacia, Aeromonas spp., Cadecea lapagei and Sphingomonas paucimobilis, 101 (50.5%) and 99 (49.5%) recovered from male and female patients respectively The largest proportion of patients were from age-group ≥60xa0years (24.5%) followed by <u200910xa0years (24.0%) and least 10–19xa0years (9.5%) with a mean patient age of 35.95u2009±u200927.11 (0.2–91) years. The decreasing order of specimen source was urine 97 (48.5%), wound swabs 47 (23.5%), sputum 22 (11.0%) bronchial lavage, nasal and pleural swabs 1 (0.50%). Urinary tract infection was diagnosed in 34.5% of patients, sepsis in 14.5%, wound infections (surgical and chronic wounds) in 11.0%, pulmonary tuberculosis in 9.0% and appendicitis, bacteremia and cystitis in 0.50%. The isolates showed high resistance to ampicillin (94.4%), trimethoprim/sulfamethoxazole (84.5%), cefuroxime (79.0%) and cefotaxime (71.3%) but low resistance to ertapenem (1.5%), meropenem (3%) and amikacin (11%). The average multi-drug resistance was 89.5%, and ranged from 53.8% in Enterobacter spp. to 100.0% in Acinetobacter spp. and P. aeruginosa.ConclusionBacterial infections caused by multi-drug resistant (isolates resistant to at least one agent in three or more antibiotic classes) Gram-negative pathogens among patients at Komfo Anokye Teaching Hospital in Kumasi, Ghana are rife and interventions are necessary for their containment.

Global challenges of malaria risk – perspectives from transfusion‐transmitted malaria

Malaria is a protozoan disease that is transmitted by the Anopheles mosquito. It can however be transmitted by blood transfusion if the blood donor is parasitaemic. Of the five species of Plasmodium that causes malaria, P. falciparum causes the most severe form of malaria. Nearly half of the worlds population is at risk of malaria. Mortality due to malaria has reduced by 48% from 839 000 deaths in 2000 to 438 000 deaths in 2015. This is largely due to a combination of two approaches, vector control and effective antimalarial drugs. There are challenges to be encountered in managing malaria risk. Some have evolved from the interventions while others may be inherent with parasite. The complex life cycle of the plasmodium parasite and the different stages it undergoes both in the mosquito and human requires a multifaceted approach to reduce or eliminate the burden of malaria. The challenges faced in transfusion‐transmitted malaria mirror the global malaria risk. The presence of parasitaemia in blood donors represents a risk for the transmission of malaria by transfusion as well as serving as a reservoir for environmental transmission. Yet, there is no ideal method for parasite detection. There is the need for institutions such as National Blood Services and Malaria Control programmes to collaborate and lead joint interventions that reduce the malaria risk. Such collaborations should also involve stakeholders such as academia, policy makers, funders, governments and international organizations.

Methicillin-resistant Staphylococcus aureus among patients in a teaching hospital in Ghana

Aim: This study determined the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and assessed the resistance profiles of strains. Materials and Methods: Inpatients and outpatients of all age groups presenting with sepsis as well as skin and soft tissue infections were screened from October 2006 to March 2007. Resistance to methicillin (oxacillin) and other relevant antibiotics was determined by the Kirby-Bauer disk diffusion and minimum inhibitory concentration (MICs) by the E-test (AB, Biodisk, Solna, Sweden). Results: Methicillin resistance was 34.8% (87/250), majority (67/87) of which were hospital acquired MRSA. Resistance was 100% to the β-lactams, 78.2% to cotrimoxazole, 75.8% to tetracycline, 59.8% to gentamicin, 56.3% to flucloxacillin, 34.4% to erythromycin, and 32.2% to cefuroxime. MIC ranged from 4-256, 0.125-256, 0.064-32, and 1.5-32, respectively, to oxacillin, gentamicin, cotrimoxazole, and ceftriaxone. Conclusion: Prevalence of MRSA is high in Komfo Anokye Teaching Hospital, and routine surveillance should be put in place to monitor the epidemiology of this pathogen.

Transfusion-transmitted Malaria in Sub-Saharan Africa

The World Health Organisation (WHO) recently reported that global efforts to control and eliminate malaria have saved an estimated 3·3 million lives since 2000, reducing malaria mortality rates in Africa alone by 49%. Despite these encouraging statistics, the burden of malaria in Africa remains high. One area of malaria control which has been neglected is malaria transmission through blood transfusion. In sub‐Saharan African (SSA), little is known about the burden of transfusion transmitted malaria (TTM) and how it contributes to the overall burden of malaria. Most studies from SSA report on the prevalence rates of parasitaemia in blood donors, with some rates as high as 50%. Parasitaemia in donors may not necessarily translate to parasitaemia or clinical disease in semi‐immune recipients living in endemic regions of malaria. Using molecular genotyping, two studies in Ghana recently determined the incidence of TTM to be 2% and 28% in adult populations. These incidence rates may not be representative of what occurs across the continent in view of the varied malaria endemicity and transmission intensity in different regions. This review will discuss the peculiarities of TTM in sub‐Saharan Africa with the view to understand the risks and pathophysiology of the disease. The options of preventive strategies for TTM will also be considered.

1039Urinary Tract Infections in an African Teaching Hospital, a Comparison of Antimicrobial Susceptibility of Inpatient and Outpatient and Catheter Associated Risks.

Background. Nosocomial infections associated with resistant micro-organisms leads to increased morbidity. Urinary tract infections (UTI) especially catheter associated UTI (CAUTI) is one of the common nosocomial infections. We compared isolation rates and antibiotic susceptibility patterns between isolates from In-patients and Outpatients and from CAUTI and non-CAUTI patients. Methods. A four month prospective study involved 2232 urine samples from patients at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Of these, 759 patients were randomly selected and interviewed to determine whether they had been catheterized or not. Bacteria were identified by standard microbiological and biochemical methods. Antimicrobial susceptibility testing was performed on all bacterial isolates. Results. The median age of patients was 28 years and in-patients made up 46.3% of participants. The rate of positive cultures was 26% and the most frequent isolates were E. coli42.5%, Klebsiella spp-25.9%, Coliforms-7.4% and Candida spp3.4%. Inpatients had more positive cultures (31.3% vs 22.8%, p value <0.0001) but the micro-organisms isolated were similar. The odds of a catheterized patients having UTI was 1.99 (95%CI 1.40-2.85). Positive cultures was significantly higher in catheterized than non-catheterized patients (43.4% vs 27.7%, p value < .0001) and Isolates were similar except for Pseudomonas aeruginosabeing the 4th leading isolate from the CAUTI group. The most effective antimicrobials against gram negative bacteria were meropenem and amikacin with sensitivities of 97.4 and 96.7% respectively. Resistance of E. coli to antimicrobials was significantly lower in Outpatient than Inpatient, including gentamicin 48.7% vs 66.1%, ciprofloxacin 57.7% vs 65.6%, ceftriaxone 65.7% vs 87.5% and ceftaxidime 36.8% vs 48.9%. Klebsiella spp had a similar trend as E. coli. There was no significant difference of antimicrobial resistance between isolates from catheterized and non-catheterized patients. Conclusion. E.coli was the commonest pathogen. Resistance rates of urine pathogens amongst In-patients were higher than in Out-patients. These findings suggest that different empirical prescriptions may be necessary for Inpatients and Outpatients. Disclosures. All authors: No reported disclosures.