Can boxing relieve symptoms of Parkinson's disease and improve quality of life? A qualitative study of the experiences of participants attending the Danish Parkinson boxing concept.

PURPOSE: To explore how people with Parkinson's (PwP) experience the impact of attending Parkinson Boxing (PB) on their symptoms and quality of life. METHODS: The authors NMAY and PeB conducted participant observations of four PB sessions and eight semi-structured interviews with PwP who participated in PB in Denmark. The empirical material was systematically analyzed using thematic analysis. RESULTS: Four main themes arose. The participants experience a sense of community from being part of a group where they share the same diagnosis. They described various bodily experiences related to their physical and cognitive functioning and well-being, as well as emotional experiences including feelings of joy, gratitude, and mental well-being. They are motivated to participate in the training sessions, and participation further motivates them to retain their exercise practice. CONCLUSIONS: The experienced impact of participating in PB relates to physical relief of symptoms and improved functioning in everyday life, as well as a mental lift, energy, and joy during and after training sessions. Participants described being motivated to attend PB and to continue their training practice. Thus, PB entails experiences of relief of symptoms and presumably improved quality of life for the participants.

Physical activity is an effective complementary treatment to experience improvement in health and well-being for people affected by Parkinson's disease.The Danish concept, Parkinson Boxing, inspired by the concept Rock Steady Boxing from USA, shows promise to relieve symptoms, improve mental and physical well-being and create social relationships.The motivation to engage in physical activity increases when exercising in a diagnosis-specific group as Parkinson Boxing where participants have a shared understanding of each other's challenges and simultaneously achieve social relationships.We recommend that rehabilitation professionals use diagnosis-specific group-based interventions which in addition to physical benefits creates basis for a sense of community, mental well-being and motivation to maintain physical activity among participants.

Occurrence, antibiotic resistance profiles and associated risk factors of Klebsiella pneumoniae in poultry farms in selected districts of Somalia Reginal State, Ethiopia.

BACKGROUND: Klebsiella pneumoniae is an opportunistic infection that causes production losses and death in the chicken industry. A cross-sectional study was conducted on exotic chicken breeds reared at the Jigjiga poultry farm from November 2022 to May 2023 to estimate the occurrence, associated risk factors, and antimicrobial susceptibility profiles of Klebsiella pneumoniae. The chickens were selected using systematic random sampling techniques. A total of 384 cloacal swabs were collected aseptically and transported to the laboratory for analysis. For statistical analysis, STATA® version 14.0 statistical software was used. RESULTS: From 384 examined faecal samples, 258 (67.2%) prevalences of Klebsiella pneumoniae were found. Furthermore, the association of the study's risk factors with the prevalence of Klebsiella pneumoniae was explored, and no statistically significant association was identified between sex and age. Nonetheless, relative prevalence at the age level was higher in chickens aged 12 months (67.6%) and Sasso breeds (90.0%). Similarly, male chickens and those raised for meat and egg production had a high prevalence rate of 72.5 and 75.8%, respectively. A total of 30 isolated Klebsiella pneumoniae colonies were tested in vitro for antibiotic sensitivity for six drugs, and it was shown that Klebsiella pneumoniae is moderately sensitive to Penicillin G (43.3%) while having higher resistance to Oxytetracycline (80.0%). CONCLUSIONS: The current findings revealed that the research area had the highest prevalence of Klebsiella pneumoniae, and the isolates were resistant to commonly used drugs in the study area. Thus, a long-term intervention plan, thorough research to determine a nationwide status, as well as further multi-drug resistance patterns and molecular characterization, were urged.

Effect of a novel hygiene intervention on older children's handwashing in a humanitarian setting in Kahda district, Somalia: A cluster-randomised controlled equivalence trial.

INTRODUCTION: Improving handwashing with soap (HWWS) among children in humanitarian emergencies has the potential to reduce the transmission of several important infectious diseases. However, there is limited evidence on which approaches are effective in increasing HWWS among children in humanitarian settings. One recent innovation - the "Surprise Soap" intervention - was shown to be successful in a small-scale efficacy trial in a humanitarian setting in Iraq. This intervention includes soap with embedded toys delivered through a short household session comprising a glitter game, instruction of how and when to wash hands, and HWWS practice. Whilst promising, this approach has not been evaluated at programmatic scale in a complex humanitarian setting. METHODS: We conducted a cluster-randomised controlled equivalence trial of the Surprise Soap intervention in IDP camps in Kahda district, Somalia. Proportionate stratified random sampling was employed to recruit 200 households, with at least one child aged 5-12, across the camps. Eligible households were randomly allocated to receive the Surprise Soap intervention (n = 100) or an active comparator handwashing intervention in which plain soap was delivered in a short household session comprising standard health-based messaging and instruction of how and when to wash hands (n = 100). The primary outcome was the proportion of pre-specified occasions when HWWS was practiced by children aged 5-12 years, measured at baseline, 4-weeks, 12 weeks, and 16 weeks post invention delivery. RESULTS: HWWS increased in both groups (by 48 percentage points in the intervention group and 51 percentage points in the control group, at the 4-week follow up), however, there was no evidence of a difference in HWWS between the groups at the 4-week (adjusted RR (aRR) = 1.0, 95% CI 0.9-1.1), 12-week (aRR = 1.1, 95% CI 0.9-1.3), or 16-week (aRR = 1.0, 95% CI 0.9-1.2) follow-up. CONCLUSIONS: In this complex humanitarian setting, where soap availability and past exposure to handwashing promotion was low, it appears that well-designed, household-level targeted handwashing interventions that include soap provision can increase child HWWS and potentially reduce disease risk, but the Surprise Soap intervention offers no marginal benefit over a standard intervention that would justify the additional costs.

Small bowel obstruction caused by massive ascariasis: two case reports.

Ascaris lumbricoides is an infestation that affects approximately one-seventh of the world's population. Ascaris lumbricoides is a common inhabitant of the intestines of people with low-socioeconomic incomes, especially in underdeveloped countries of the world. Ascaris lumbricoides infestation is more prone to infestation with serious complications such as intestinal obstruction, volvulus, intussusception, and intestinal necrosis at higher rates in children than in adults. Case presentation: The authors present here two cases of small bowel obstruction caused by massive Ascaris lumbricoides that were admitted to the pediatric surgery service after completing a clinical and physical examination, and we operated after rehydration. Both underwent surgical resection with an end-to-end anastomosis. The patient was discharged uneventfully with a plan for de-worming treatment in 6 weeks. Clinical discussion: Ascariasis is a round intestinal worm infestation transmitted by fecal or oral contamination. Eating and excreting ascaris eggs lead to ascariasis and excrete human feces, which contaminate foods, soil, and/or water in unsanitary environments. In contrast, in the first case of this study, the diagnosis was made by ultrasound and erect abdominal radiography, and, in the second case, an abdominal ultrasound result was equivocal and required an abdominal computed tomography scan for confirmation. Treatment of small bowel obstruction by roundworms is usually surgical, but in the absence of signs of peritonitis, medical management can give effective results, even in the case of total obstruction. Conclusion: The type of surgery undertaken is determined by the results of the laparotomy. If the bowel was found to be intact and the obstruction was at the ileum level, milking worms to the cecum can be done with caution to avoid trauma to the bowel wall. Primary anastomosis after resection of a necrotic bowel segment and removal of the worm bolus is a suitable method for treatment of the ascariasis obstruction.

Prevalence of Multidrug-Resistant TB Among Smear-Positive Pulmonary TB Patients in Banadir, Somalia: A Multicenter Study.

Background: Tuberculosis (TB) is an infectious disease that is the second most common cause of death from a single infectious agent. TB infection affects anyone, regardless of age, gender, and ethnicity. Drug-resistant TB is a serious public health problem, which needs treatment with a second-line anti-TB drug and it includes poly-drug resistance (PDR), multi-drug resistance (MDR), and extensive drug resistance (XDR). The goal of this research is to find out the prevalence of MDR TB among pulmonary TB patients in Banadir, Somalia. Methods: This was a multicenter retrospective review of data involving 1732 smear-positive pulmonary TB patients visiting Banadir TB centers between July 1, 2019 and June 30, 2020. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment cards. The data were analyzed using Statistical Package for Social Sciences (SPSS) software (IBM SPSS Statistics version 26). Results: All 1732 pulmonary TB cases were previously diagnosed by the Gene Xpert MTB/RIF test. Among them, 70.4% (1219/1732) were males. The mean age was 31.77 years. Overall, the prevalence of drug resistance TB was 10.56% (183/1732). The MDR TB was 1.96%, poly-drug resistance (PDR) was 0.12%, and extensive drug resistance was 0.06%. Conclusion: This study showed a prevalence of MDR-TB among pulmonary TB patients, which is similar to some of the eastern African countries.

Serological evidence of chronic pulmonary Aspergillosis in tuberculosis patients in Kenya.

BACKGROUND: Pulmonary tuberculosis (PTB) is a significant risk factor for fungal infection. The cavitary lesions post PTB serves as a good reservoir for fungal colonization and subsequent infection. Furthermore, the severe immunosuppression associated with HIV and TB co-infection is another predisposition. The inadequate capacity to investigate and manage fungal infection in PTB patients increases their morbidity and mortality. The study aimed to provide serological evidence of chronic pulmonary aspergillosis (CPA) among PTB patients in Kenya. Towards this, we analysed 234 serum samples from patients presenting with persistent clinical features of PTB infections despite TB treatment in four referral hospitals. METHODS: This was a cross sectional laboratory based study and patients were recruited following an informed consent. Serological detection of Aspergillus fumigatus IgG was done using enzyme-linked immunosorbent assay (Bordier Affinity Products SA). Sputum samples were subjected to microscopy and standard fungal culture. The isolated fungi were subjected to macro and micro morphological identifications and confirmed by sequence analysis of calmadulin, betatubilin and ITS genes. RESULTS: Serological evidence of CPA or fungal sensitization was 46(19.7%) and equivocal or borderline was 14(6.0%). Mycological investigations of sputum resulted in 88(38%) positive for fungal culture. Aspergillus spp. accounted for 25(28%) of which A. fumigatus was 13(14.8%), A. niger 8(9.1%), A. terreus, A. flavus, A. candidus and A. clavatus 1 (1.1%) each. This was followed by Penicillium spp. 10 (11.4%), Scedosporium spp. 5 (5.7%) and Rhizopus spp. 3 (3.4%). Among the yeasts; Candida albicans accounted for 18(20.5%) followed by C. glabrata 5(5.7%). Cryptococcus spp. was isolated from 3(3.4%) of the samples while 13(14.8%) were other yeasts. CONCLUSION: Chronic pulmonary aspergillosis is a significant co-morbidity in PTB patients in Kenya that could be misdiagnosed as relapse or treatment failures in the absence of reliable diagnostic and clinical management algorithm. It could be the cause of persistent clinical symptoms despite TB treatment often misdiagnosed as TB smear/GeneXpert MTB/RIF® negative or relapse. We recommend that all patients with persistent clinical symptoms despite TB treatment should be subjected to fungal investigations before retreatment.

Social contacts and other risk factors for respiratory infections among internally displaced people in Somaliland.

BACKGROUND: Populations affected by humanitarian crises experience high burdens of acute respiratory infections (ARI), potentially driven by risk factors for severe disease such as poor nutrition and underlying conditions, and risk factors that may increase transmission such as overcrowding and the possibility of high social mixing. However, little is known about social mixing patterns in these populations. METHODS: We conducted a cross-sectional social contact survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland. We included questions on household demographics, shelter quality, crowding, travel frequency, health status, and recent diagnosis of pneumonia, and assessed anthropometric status in children. We present the prevalence of several risk factors relevant to transmission of respiratory infections, and calculated age-standardised social contact matrices to assess population mixing. RESULTS: We found crowded households with high proportions of recent self-reported pneumonia (46% in children). 20% of children younger than five are stunted, and crude death rates are high in all age groups. ARI risk factors were common. Participants reported around 10 direct contacts per day. Social contact patterns are assortative by age, and physical contact rates are very high (78%). CONCLUSIONS: ARI risk factors are very common in this population, while the large degree of contacts that involve physical touch could further increase transmission. Such IDP settings potentially present a perfect storm of risk factors for ARIs and their transmission, and innovative approaches to address such risks are urgently needed.

Epidemiological Characteristics, Antimicrobial Susceptibility Profile, and Surgical Outcome of Complicated Intra-Abdominal Infection at a Tertiary Hospital in Somalia.

Background: Intra-abdominal infections (IAIs) are common surgical emergencies and one of the leading causes of non-trauma deaths in hospitals worldwide. Because of limited resources, most patients in low-income countries experience delayed diagnosis and treatment. To the best of our knowledge, this is the first study to evaluate the epidemiological characteristics, antimicrobial susceptibility profile, and outcome of patients with complicated IAI at a tertiary hospital in Somalia. Methods: This study included all patients with confirmed IAIs who underwent laparotomy or percutaneous drainage, either emergency or elective, and whose cultures showed growth. Sociodemographic and clinical characteristics, culture results, antimicrobial susceptibility profile, and the type of source control were reviewed. Results: The prevalence of CIAI was 5.3%, 144 (70%) were male, and 61 (30%) were female. The mean age was 38.6±8.5 years. Appendicitis was the most common source of infection, accounting for 32%, followed by bowel perforation in 37 (18%). Out of 15 patients with liver abscesses, ten patients had diabetes (67%). E. coli 82 (40%) was the most common isolated organism, followed by Klebsiella pneumonia (n = 44, 21.5%). The prevalence of extended-spectrum beta-lactamase-producing and multidrug-resistant pathogens was 6.8% and 5.9%, respectively. The pathogens revealed a higher antimicrobial resistance against penicillins in 62%, cephalosporins in 54%, and fluoroquinolones in 44%. E. coli showed 2.5-13% antimicrobial resistance against carbapenems, lower than Klebsiella pneumonia in about 4.5%. Tigecycline, teicoplanin, and linezolid revealed the highest sensitivity against pathogens, about 100%. Source control was achieved by laparotomy in 81%, while the 19% were managed in a percutaneous approach. The mortality rate in our study was 9.3%. Conclusion: The prevalence of CIAI in our study was 5.3%, with an increasing number of MDR microorganisms isolated from cultures. CIAI and intra-abdominal abscess are significant sources of high morbidity and mortality with sepsis and poor clinical outcome; thus, early detection and intervention are crucial.

Clarithromycin induced acute pancreatitis: A rare side effect. Case report.

•Rare side effect of clarithromycin.•Drug induced acute pancreatitis.•Macrolide induced acute pancreatitis.•Acute pancreatitis in pneumonia treatment.

Retrospective evaluation of inpatients admitted to a tertiary hospital in Somalia for Pediatric surgery

Objective: The aim is to reflect on the epidemiology of the patient population at a tertiary hospital for pediatric surgery, diagnostic pattern, and mortality in Somalia retrospectively. Methods: In this study, 163 patient who were hospitalized to Pediatric Surgery Clinic of Mogadishu Somalia Turkey Recep Tayyip Erdogan Training and Research Hospital in 2018 were included. Data regarding age, gender, diagnosis, surgical condition, mortality rate and cause of the death were recorded from the patient charts and the institutional digital database Results: Of 163 patients 47 were female (28.8%) and 116 were male (71.2%). The mean age of the patients was 6.4 ± 4.8 years. The main diagnoses were congenital malformation (34.4%), acute abdomen (25.8%), traumatic injury (23.3%), infection (9.8%) and neoplasm (6.1%). Mortality rate was 9.8% and the leading cause of death was sepsis by 87.5%. Perforated appendicitis, intestinal obstruction and intussusception were creating the 68.7% of the diseases that result in death. Conclusions: Our results show that two-thirds of the surgical deaths could be prevented with timely presentation. We think that the health policymakers in Somalia should focus on how to improve the access to surgical care, patient transfer, timely presentation, and training of pediatric surgeons and to overcome the poor surgical outcomes

Strengthening Health Systems in Humanitarian Settings: Multi-Stakeholder Insights on Contraception and Postabortion Care Programs in the Democratic Republic of Congo and Somalia.

Background: In humanitarian settings, strengthening health systems while responding to the health needs of crisis-affected populations is challenging and marked with evidence gaps. Drawing from a decade of family planning and postabortion care programming in humanitarian settings, this paper aims to identify strategic components that contribute to health system strengthening in such contexts. Materials and Methods: A diverse range of key informants from North Kivu (Democratic Republic of Congo, DRC) and Puntland (Somalia), including female and male community members, adolescents and adults, healthcare providers, government and community leaders, participated in qualitative interviews, which applied the World Health Organization health system building blocks framework. Data were thematically analyzed according to this framework. Results: Findings from the focus group discussions (11 in DRC, 7 in Somalia) and key informant interviews (seven in DRC, four in Somalia) involving in total 54 female and 72 male participants across both countries indicate that health programs in humanitarian settings, such as Save the Children's initiative on family planning and postabortion care, could contribute to strengthening health systems by positively influencing national policies and guidance, strengthening local coordination mechanisms, capacitating the healthcare workforce with competency-based training and supportive supervision (benefiting facilities supported by the project and beyond), developing the capacity of Ministry of Health staff in the effective management of the supply chain, actively and creatively mobilizing the community to raise awareness and create demand, and providing quality and affordable services. Financial sustainability is challenged by the chronically limited healthcare expenditure experienced in both humanitarian contexts. Conclusions: In humanitarian settings, carefully designed healthcare interventions, such as those that address the family planning and postabortion care needs of crisis-affected populations, have the potential not only to increase access to essential services but also contribute to strengthening several components of the health system while increasing the government capacity, ownership, and accountability.

"Crazy person is crazy person. It doesn't differentiate": an exploration into Somali views of mental health and access to healthcare in an established UK Somali community.

BACKGROUND: Mental health conditions have been shown to disproportionately affect those from Black, Asian and Minority Ethnic (BAME) communities. Somali communities globally have relatively high levels of mental illness, but low levels of mental health service use, with numerous barriers to care identified. This study was conducted in an established UK Somali community in the South West of England and aimed to explore community beliefs and views about the causes of mental illness, treatment for mental illness, and access to medical services in general. Participants were asked about how mental health and illness are understood and conceptualised, along with the cultural meaning of mental illness and its manifestations in relation to men, women and young people. DESIGN: Using a community-based participatory research design, in partnership with local Somali community organisations, the research team conducted four focus groups with a total of 23 participants aged over 18. Open-ended questions were used to facilitate discussion. Transcripts were analysed thematically. RESULTS: The participants discussed the role of migration and associated stress from the civil war and how that could contribute to mental illness. Participants tended to view the symptoms of mental illness as physical manifestations such as headaches and to describe a strong community stigma where those with mental health conditions were viewed as "crazy" by others. Barriers to accessing healthcare included language barriers, waiting times and a mistrust of doctors. Various ideas for improvements were discussed, including ideas to reduce stigma and ideas for community initiatives. CONCLUSION: Cultural considerations and reducing stigma are vital in improving understanding of mental illness and improving access to mental health services, along with building relationships and trust between the Somali community and health care workers.

Extensive mediastinal thymolipoma mimicking pulmonary edema.

Thymolipoma is a rare benign slow-growing encapsulated tumor of anterior mediastinum that accounts for 2-9% of all thymic neoplasms. About 30-50% of them are asymptomatic and found incidentally. Less than 200 cases have been published in the world literature so far. Here we report a case of thymolipoma of an adult female presented with progressive dyspnea, chest tightness and non-productive chough for 2-month duration. All blood investigations were normal. Radiological examinations suggested the presence of fat and soft tissue within the tumor without invading the neighboring structures. We concluded that the only curative treatment of thymolipoma is surgical excision. Unfortunately, the patient did not give consent despite telling her the outcomes if we do not do the surgical procedure, and a week later she passed away due to respiratory distress secondary to the mass effect of the tumor.

MRI measurements of the thoracic aorta and pulmonary artery.

INTRODUCTION: The purpose of this study was to obtain a range of normal measurements of the adult thoracic aorta and main pulmonary artery using cardiac MRI, and to assess agreement between measurements made on ECG-gated two-dimensional (2D) breath held steady-state-free precession (SSFP), and three-dimensional (3D) breath held SSFP image acquisitions. METHODS: Forty-nine normal volunteers underwent cardiac MRI using a 1.5T system. Two independent examiners measured the ascending aorta, aortic arch, descending thoracic aorta and main pulmonary artery in pre-defined locations. RESULTS: Overall, inter-observer agreement for all measurements was excellent. Close agreement was observed in aortic diameters obtained from the 2D and 3D SSFP methods in six of the nine aortic measurement sites. There was a tendency for the 3D measurements to be smaller than the 2D measurements but this was only significant at two sites, the aortic annulus, and the ascending aorta. There was a significance difference in aortic measurements between the left carotid artery (LC) and the left subclavian artery (LSC). CONCLUSION: Normal values for transverse diameters of the thoracic aorta and main pulmonary artery were established using 2D and 3D non-contrast MR sequences in healthy adults. Overall both inter-observer agreement, and agreement between 2D and 3D techniques was good. Mean diameter differences demonstrated at the aortic annulus, ascending aorta and aortic arch between LC and LSC although significant were less than one millimetre and unlikely to be important in clinical practice.

Intracellular and Plasma Trough Concentration and Pharmacogenetics of Telaprevir.

PURPOSE: Triple therapy for HCV-1 infection consists in boceprevir or telaprevir, ribavirin and PEG-interferon. Telaprevir is a P-glycoprotein substrate and it is metabolized by CYP3A4/5. No data have been published on intracellular penetration of telaprevir. We determined peripheral blood mononuclear cells (PBMCs) and trough plasma S and R telaprevir isomers concentrations; moreover, we evaluated the influence of some single nucleotide polymorphisms (SNPs) on these pharmacokinetic data after 1 month of triple therapy in humans. METHODS: Plasma and intracellular telaprevir concentrations were determined at the end of dosing interval (Ctrough) using ULPC-MS/MS validated methods; allelic discrimination was performed through real-time PCR. RESULTS: Median telaprevir Ctrough plasma concentrations were 2579 ng/mL and 2233 ng/mL for the pharmacologically more active S, and R, enantiomers, respectively, with median S/R plasma ratio of 1.11. In PBMC, the medians were 6863 ng/mL and 1096 ng/mL for S and R, respectively, with median S/R being 5.73. The PBMC:plasma ratio for S was 2.59 for R. Plasma ribavirin concentrations were directly correlated with plasma S-telaprevir concentrations. In linear regression analysis, only CYP24A1_rs2585428 SNP (p=0.003) and body mass index (p=0.038) were able to predict S-telaprevir PBMC concentrations. CONCLUSIONS: Our preliminary data could increase the understanding of mechanisms underlying telaprevir intracellular and plasma exposure, suggesting the implementation of pharmacogenetics in these drug kinetic studies.

Development and validation of a useful UPLC-MS/MS method for quantification of total and phosphorylated-ribavirin in peripheral blood mononuclear cells of HCV+ patients.

The current standard-of-care therapy in HCV consists in ribavirin (RBV) plus pegylated-interferon-α 2a or 2b and, for HCV-1 infected patients, also directly acting antivirals (DAAs). Despite the increase in the number of patients who reach sustained virological response (SVR) for HCV-1, a great inter-individual variability in the response to therapy remains. Whether new drugs are available in combination with RBV and Peg-IFN for HCV-1, the treatment of the other viral genotypes remains the same: this issue highlights the lasting importance of RBV and Peg-IFN in anti-HCV treatment. Moreover, a strong limiting factor to the usefulness of anti-HCV treatment remains the occurrence of adverse events, first of all hemolytic anemia, which have increased with the addition of DAAs, but is mainly an RBV-dependent effect. For these reasons, the monitoring of RBV exposure in the various compartments should be important. Since the routinely determination of RBV in the target cells as the hepatocytes is impracticable for of its invasiveness, the quantification in easier to obtain cells could be a good choice. In this work, we developed and validated an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay method to quantify RBV concentrations in peripheral blood mononucleated cells (PBMCs). QCs were prepared with RBV and RBV-monophosphate (RMP). Each sample was divided into two aliquots, which undergone the same extraction procedure: one was treated with acid phosphatase to convert RBV phosphorylated metabolites into free RBV, the other one was not-treated. The extracts were analyzed with reverse-phase column with UPLC-MS/MS. Calibration curves fitted a least squares model (weighed 1/X) for ribavirin levels in a range from 0.1 ng to 200 ng (mean r(2)=0.9993). Accuracy, intra-day and inter-day precision of the methods were in accordance with FDA guidelines. Moreover, phosphorylated QCs were used to assess the correct determination of total RBV concentration. We tested this method by monitoring RBV concentrations in PBMCs from 20 HCV+ patients, receiving alpha interferon-plus RBV combination therapy. This method showed to be reliable, precise, accurate and suitable for evaluation of intracellular RBV concentrations.

Population genetics analysis during the elimination process of Plasmodium falciparum in Djibouti.

BACKGROUND: Case management of imported malaria within the context of malaria pre-elimination is increasingly considered to be relevant because of the risk of resurgence. The assessment of malaria importation would provide key data i) to select countries with propitious conditions for pre-elimination phase and ii) to predict its feasibility. Recently, a sero-prevalence study in Djibouti indicated low malaria prevalence, which is propitious for the implementation of pre-elimination, but data on the extent of malaria importation remain unknown. METHODS: Djiboutian plasmodial populations were analysed over an eleven-year period (1998, 1999, 2002 and 2009). The risk of malaria importation was indirectly assessed by using plasmodial population parameters. Based on 5 microsatellite markers, expected heterozygosity (H.e.), multiplicity of infection, pairwise Fst index, multiple correspondence analysis and individual genetic relationship were determined. The prevalence of single nucleotide polymorphisms associated with pyrimethamine resistance was also determined. RESULTS: Data indicated a significant decline in genetic diversity (0.51, 0.59, 0.51 and 0 in 1998, 1999, 2002 and 2009, respectively) over the study period, which is inconsistent with the level of malaria importation described in a previous study. This suggested that Djiboutian malaria situation may have benefited from the decline of malaria prevalence that occurred in neighbouring countries, in particular in Ethiopia. The high Fst indices derived from plasmodial populations from one study period to another (0.12 between 1999 and 2002, and 0.43 between 2002 and 2009) suggested a random sampling of parasites, probably imported from neighbouring countries, leading to oligo-clonal expansion of few different strains during each transmission season. Nevertheless, similar genotypes observed during the study period suggested recurrent migrations and imported malaria. CONCLUSION: In the present study, the extent of genetic diversity was used to assess the risk of malaria importation in the low malaria transmission setting of Djibouti. The molecular approach highlights i) the evolution of Djiboutian plasmodial population profiles that are consistent and compatible with Djiboutian pre-elimination goals and ii) the necessity to implement the monitoring of plasmodial populations and interventions at the regional scale in the Horn of Africa to ensure higher efficiency of malaria control and elimination.

A UPLC-MS/MS method for the simultaneous plasma quantification of all isomeric forms of the new anti-HCV protease inhibitors boceprevir and telaprevir.

HCV infection affects over 170 milions people in the world. Up to now standard-of-care therapy consisted in ribavirin plus interferon-α 2a or 2b. Recently, two new Direct Acting Antivirals (DAA), inhibitors of NS3 HCV protease, have been developed and approved for the routine use on HCV genotype 1 infected patients: boceprevir and telaprevir. Protease inhibitors show complex pharmacokinetics (strong metabolism of both drugs by CYP3A and drug interactions), they require a TID dosage and, furthermore, they are present in plasma patients in two different isomeric forms. In this work, we developed and validated an UPLC-tandem mass spectrometry assay method capable of monitoring the telaprevir and boceprevir concentrations in plasma, discriminating each isomer of both drugs. Blank plasma used for Standards and QCs preparation, was obtained from blood of healthy donors. The calibration curves for each isomer of telaprevir and boceprevir were linear in a range from 46.87 ng/mL to 6000 ng/mL and from 23.43 to 3000 ng/mL, respectively (mean r(2)>0.998 for all analytes). QCs at three different concentration were prepared: High, Medium and Low. Each Standard, QC and patient sample was treated with a protein precipitation protocol with a solution containing acidified acetonitrile and Internal Standard (6,7-Dimethyl-2,3-di(2-pyridyl)quinoxaline). An aliquot of supernatant was diluted and then directly analyzed by reverse-phase UPLC-MS/MS. Accuracy (mean 98.47%), intra-day (mean <5.21%) and inter-day (mean <7.57%) precision for telaprevir and boceprevir quality controls fitted all FDA guidelines. All compounds resulted stable in our method conditions and the extraction procedure showed a recovery near to 100%. Finally, we tested this method by monitoring plasma concentrations in 9 HCV+ patients, for each triple combined therapy, with good results. The observed median ratio between S and R isomers for boceprevir and telaprevir were 1.22 (IQR 1.10-1.33) and 1.52 (IQR 1.21-1.67), respectively. The use of this simple assay method could be an important tool for management of HCV-1 DAAs treated patients.