Plasmodium falciparum gametocyte dynamics after pyronaridine-artesunate or artemether-lumefantrine treatment.

BACKGROUND: Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine-artesunate (PA) or artemether-lumefantrine (AL). METHODS: Kenyan children with uncomplicated Plasmodium falciparum malaria were included and randomly assigned to PA or AL treatment. Filter paper blood samples were collected as a source of RNA for quantitative reverse-transcription PCR (qRT-PCR) and nucleic acid sequence based amplification (QT-NASBA) to detect female gametocytes (targeting Pfs25 mRNA). Male gametocytes were detected by qRT-PCR (targeting PfMGET mRNA). Duration of gametocyte carriage, the female and male gametocyte response and the agreement between qRT-PCR and QT-NASBA were determined. RESULTS: The mean duration of female gametocyte carriage was significantly longer for PA (4.9 days) than for AL (3.8 days) as estimated by QT-NASBA (P = 0.036), but this difference was less clear when determined by Pfs25 qRT-PCR (4.5 days for PA and 3.7 for AL, P = 0.166). qRT-PCR based female gametocyte prevalence decreased from 100% (75/75) at baseline to 6.06% (4/66) at day 14 in the AL group and from 97.7% (83/85) to 13.9% (11/79) in the PA group. Male gametocyte prevalence decreased from 41.3% (31/75) at baseline to 19.7% (13/66) at day 14 in the AL group and from 35.3% (30/85) to 22.8% (18/79) in the PA group. There was good agreement between Pfs25 qRT-PCR and QT-NASBA female gametocyte prevalence (0.85, 95% CI 0.82-0.87). CONCLUSIONS: This study indicates that female gametocyte clearance may be slightly faster after AL compared to PA. Male gametocytes showed similar post-treatment clearance between study arms. Future studies should further address potential differences between the post-treatment transmission potential after PA compared to AL. Trial registration This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1

Organizational Conflict Management Strategies on Employee Job Satisfaction: A Case Study of Nzoia Sugar Company

Conflict is inevitable given the wide range of goals for the different stakeholder in the organization and its absence signifies management emphasizes conformity and stifles innovation. The purpose of this study was to investigate conflict management strategies  and there effect on employees’ job satisfaction in Nzoia Sugar Company, Kenya. The specific objectives of this study were: to examine the main types of work place conflicts, to determine the major sources of work place conflicts, to identify the conflict management strategies most commonly used by management in resolving work place conflict, to establish factors that determine the choice of conflict handling style by Management staff and to find out the effect of conflict management strategies on employee job satisfaction in Nzoia Sugar Company.The target population was 3726 permanent employees in Nzoia Sugar Company. A total sample of 400 employees comprising of 14 top level managers, 18 middle level managers, 18 Low Level Managers (Supervisory staff), and 350 operational staff was selected using purposive sampling and stratified sampling techniques. This was 10% of the target population. Data was collected use of a questionnaires and interview schedule. Data was analyzed through use of both descriptive and inferential stastics and presented by use of of tables and graphs which included pie charts and bar charts. Microsoft Excell (2007) and statistical package for social science (SPSS) version 17.0 helped in data analysis. The study found out that the main causes of conflict in Nzoia Sugar Company were expectation from top management, inadequate salary and remuneration, inadequate income, work overload and stress,  interdependence of departments, inability to involve employees in decision making, low job satisfaction, power struggle, seeking of favours and disciplining employees. The study also found out that the  collaboration  and  compromise  techniques  were  the  most frequently used conflict management strategies in resolving conflict. The study further found out that the main factors which may determine one’s choice of a particular conflict handling style(s) are the emergence of conflict, the nature of the conflict to be handled, the significance of the issues involved, the organizational policy, the intensity  of  conflict, perceptions and the trade union influence, the  importance  and  urgency  of  the  problem  and  people perceptions. This study shades the much needed information on conflict management to various stakeholders in the management of the sugar sector. This research contributes to the body of the existing literature, specifically it will inspire managers in the sugar industry to develop appropriate strategies on how to manage conflicts in their organisations effectively. The study will provide an opportunity to the management, to resolve the issue at the initial stages

Pyronaridine–artesunate and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non-inferiority trial

Abstract Background Pyronaridine–artesunate is a novel artemisinin-based combination therapy. The efficacy and safety of pyronaridine–artesunate were compared with artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children. Methods This phase III open-label randomized controlled non-inferiority trial was conducted in Western Kenya. Children aged 6 months to ≤ 12 years with a bodyweight > 5 kg and microscopically confirmed P. falciparum malaria were randomly assigned in a 1:1 ratio to orally receive pyronaridine–artesunate or artemether–lumefantrine, dosed according to bodyweight, for 3 days. Results Of 197 participants, 101 received pyronaridine–artesunate and 96 received artemether–lumefantrine. The day-28 adequate clinical and parasitological response in the per-protocol population, PCR-corrected for reinfections, was 98.9% (93/94, 95% CI 94.2–99.8) for pyronaridine–artesunate and 96.4% (81/84, 95% CI 90.0–98.8) for artemether–lumefantrine. Pyronaridine–artesunate was found to be non-inferior to artemether–lumefantrine: the treatment difference was 2.5% (95% CI − 2.8 to 9.0). Adverse events occurred in 41.6% (42/101) and 34.4% (33/96) of patients in the pyronaridine–artesunate group and the artemether–lumefantrine group, respectively. No participants were found to have alanine or aspartate aminotransferase levels > 3 times the upper limit of normal. Conclusions Pyronaridine–artesunate was well tolerated, efficacious and non-inferior to artemether–lumefantrine for the treatment of uncomplicated P. falciparum malaria in Kenyan children. Results are in line with previous reports and inclusion of pyronaridine–artesunate in paediatric malaria treatment programmes should be considered. This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine–artesunate&cond=Malaria&cntry=KE&rank=

Plasmodium Detection and Differentiation by Direct-on-Blood PCR Nucleic Acid Lateral Flow Immunoassay Development, Validation, and Evaluation

Decreasing malaria transmission warrants the search for highly sensitive point-of-care diagnostics, especially in resource-limited settings. The direct-on-blood PCR nucleic add lateral flow immunoassay (db-PCR-NALFIA) is a simplified PCR-based technique with a lateral flow readout that does not require sample preparation. Two duplex db-PCR-NALFIAs were developed: a pan-Plasmodium/Plasmodium falciparum (pan/P. falciparum) and a pan-Plasmodium/Plasmodium vivax (pan/P. vivax) assay. Confirmed positive samples (n = 61) and negative controls (n = 40) were used for laboratory validations. A prospective field evaluation of the pan/P. falciparum assay was performed in Kenya (n = 300). In the laboratory validation, sensitivity and specificity of the pan/P. falciparum assay were 100% (95% CI, 94.1%-100%) and 100% (95% CI, 91.2%-100%), respectively. Sensitivity and specificity of the pan/P. vivax assay were 100% (95% CI, 94.1%-100%) and 97.5% (95% CI, 86.8%-99.9%), respectively. In Kenya, sensitivity of the pan/P. falciparum db-PCR-NALFIA was 97.2% (95% CI, 93.0%-99.2%) and specificity was 74.2% (95% CI 67.0%-81.0%) compared with reference standard microscopy. When using real-time quantitative PCR as a reference standard, sensitivity was 84.5% (95% CI 78.7%-89.3%) and specificity was 85.4% (95% CI, 77.1%-91.6%). Db-PCR-NALFIA is a sensitive, specific, and easy method for the detection and species differentiation of Plasmodium. This test is especially of interest for malaria control or elimination programs in low-transmission settings that require accurate detection of low parasite densitie

Molecular detection of residual parasitemia after pyronaridine-artesunate or artemether-lumefantrine treatment of uncomplicated plasmodium falciparum malaria in Kenyan children

Artemisinin resistance is rapidly rising in Southeast Asia andmayspread to African countries, where efficacy estimates are currently still excellent. Extensive monitoring of parasite clearance dynamics after treatment is needed to determine whether responsiveness to artemisinin-based combination therapies (ACT) is changing in Africa. In this study, Kenyan children with uncomplicated falciparum malaria were randomly assigned to pyronaridine-artesunate (PA) or artemether-lumefantrine (AL) treatment. Parasite clearance was evaluated over 7 days following the start of treatment by quantitative polymerase chain reaction (qPCR) and direct-on-bloodPCRnucleic acid lateral flowimmunoassay (db-PCRNALFIA), a simplified molecular malaria diagnostic. Residual parasitemia at day 7 was detected by qPCR in 37.1% (26/70) of AL-treated children and in 46.1% (35/76) of PA-treated participants (P = 0.275). Direct-on-blood PCR nucleic acid lateral flow immunoassay detected residual parasites at day 7 in 33.3% (23/69) and 30.3% (23/76) of AL and PA-treated participants, respectively (P = 0.692). qPCR-determined parasitemia at day 7 was associated with increased prevalence and density of gametocytes at baseline (P = 0.014 and P = 0.003, for prevalence and density, respectively) and during follow-up (P = 0.007 and P = 0.011, respectively, at day 7). A positive db-PCR-NALFIA outcome at day 7 was associated with treatment failure (odds ratio [OR]: 3.410, 95% confidence interval [CI]: 1.513-7.689, P = 0.003), but this association was not found for qPCR (OR: 0.701, 95% CI: 0.312-1.578, P = 0.391). Both qPCR and db-PCR-NALFIA detected substantial residual submicroscopic parasitemia after microscopically successful PA and AL treatment and can be useful tools to monitor parasite clearance. To predict treatment outcome, db-PCR-NALFIA may be more suitable than qPCR

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Additional file 2. Parasite and fever clearance at day 1, 2 and 3

MOESM1 of Pyronaridine–artesunate and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non-inferiority trial

Additional file 1. Weight-based dosing of pyronaridine–artesunate and artemether–lumefantrine

MOESM1 of Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment

Additional file 1. Weight-based dosing of pyronaridine–artesunate and artemether–lumefantrine

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Additional file 3. Haemoglobin (Hb), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values