Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Chewaka District, Ethiopia.

BACKGROUND: The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia. METHODS: The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum. A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection. RESULTS: Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1-98.5) and 96% (95% CI 88.8-99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8-99.2). Based on Kaplan-Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3-11.4). Only three participants 3.8% (95% CI 0.8-10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL. CONCLUSIONS: The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.

Genetic diversity and genotype multiplicity of Plasmodium falciparum infection in patients with uncomplicated malaria in Chewaka district, Ethiopia.

BACKGROUND: Genetic diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity of P. falciparum strains can be used to assess intensity of parasite transmission and identify potential deficiencies in malaria control programmes, which provides vital information to evaluating malaria elimination efforts. This study investigated the P. falciparum genetic diversity and genotype multiplicity of infection in parasite isolates from cases with uncomplicated P. falciparum malaria in Southwest Ethiopia. METHODS: A total of 80 P. falciparum microscopy and qPCR positive blood samples were collected from study participants aged 6 months to 60 years, who visited the health facilities during study evaluating the efficacy of artemether-lumefantrine from September-December, 2017. Polymorphic regions of the msp-1 and msp-2 were genotyped by nested polymerase chain reactions (nPCR) followed by gel electrophoresis for fragment analysis. RESULTS: Of 80 qPCR-positive samples analysed for polymorphisms on msp-1 and msp-2 genes, the efficiency of msp-1 and msp-2 gene amplification reactions with family-specific primers were 95% and 98.8%, respectively. Allelic variation of 90% (72/80) for msp-1 and 86.2% (69/80) for msp-2 were observed. K1 was the predominant msp-1 allelic family detected in 20.8% (15/72) of the samples followed by MAD20 and RO33. Within msp-2, allelic family FC27 showed a higher frequency (26.1%) compared to IC/3D7 (15.9%). Ten different alleles were observed in msp-1 with 6 alleles for K1, 3 alleles for MAD20 and 1 allele for RO33. In msp-2, 19 individual alleles were detected with 10 alleles for FC27 and 9 alleles for 3D7. Eighty percent (80%) of isolates had multiple genotypes and the overall mean multiplicity of infection was 3.2 (95% CI 2.87-3.46). The heterozygosity indices were 0.43 and 0.85 for msp-1 and msp-2, respectively. There was no significant association between multiplicity of infection and age or parasite density. CONCLUSIONS: The study revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations in Chewaka district, Ethiopia, suggesting that both endemicity level and malaria transmission remain high and that strengthened control efforts are needed in Ethiopia.

Hemostatic Abnormality and Associated Factors in Diabetic Patients at Jimma University Specialized Hospital, Jimma, Southwest Ethiopia: A Comparative Cross-sectional Study.

BACKGROUND: Diabetes mellitus is a group of heterogeneous disorders of multiple etiologies characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or insulin action. Diabetes mellitus has been reported to disturb normal hemostasis by various mechanisms. However, data on hemostasis of diabetic patients in the study area are lacking. This study was aimed at determining hemostatic profile and associated factors of hemostatic abnormality in diabetic patients. METHODS: A comparative cross-sectional study was conducted involving a total of 238 (119 diabetic and 119 apparently healthy) individuals who came to the chronic care clinic, Jimma University Specialized Hospital. Socio-demographic and clinical data were collected through a structured questionnaire. A blood sample of 10ml was collected in EDTA (4ml), citrate (3ml) and chemistry (3ml) tubes to do platelet count, coagulation tests, and glucose and lipid profile analysis, respectively. Descriptive statistics as well as the median (25th, 75th) percentile and Mann Whitney U test were used during data analysis. RESULTS: The overall hemostatic abnormality in diabetes individuals was 58.8%. The median (25th, 75th percentile) prothrombin time for diabetic and non-diabetic subjects was (12.8, 15.6) vs. (12.8, 14.2), respectively, and the difference was not statistically significant (p>0.05). The median (25th, 75th percentile) activated partial thromboplastin time was significantly different between the two groups (p<0.0001); (24, 36.8) vs. (36, 39.6). The median (25th, 75th percentile) fibrinogen level was significantly different between the two groups (p<0.0001); (277, 462) vs. (243, 328). The median (25th, 75th percentile) platelet count was also significantly different between the two groups (p<0.0001); (146,248) vs. (190,319). All variables were not significantly associated with hemostatic abnormality in multivariate regression analysis. CONCLUSION: An overall hemostatic abnormality in diabetic patients was found to be high. The APTT and platelet count were lower in diabetic patients whilst the fibrinogen level was higher. Routine coagulation tests should be part of tests among diabetic patients. Advanced coagulation tests should also be considered to identify specific markers so as to pinpoint the particular problem.

Hemostatic abnormality and associated factors in diabetic patients at Jimma University Specialized Hospital, Jimma, Southwest Ethiopia: a comparative cross-sectional study

BACKGROUND: Diabetes mellitus is a group of heterogeneous disorders of multiple etiologies characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or insulin action. Diabetes mellitus has been reported to disturb normal hemostasis by various mechanisms. However, data on hemostasis of diabetic patients in the study area are lacking. This study was aimed at determining hemostatic profile and associated factors of hemostatic abnormality in diabetic patients. METHODS: A comparative cross-sectional study was conducted involving a total of 238 (119 diabetic and 119 apparently healthy) individuals who came to the chronic care clinic, Jimma University Specialized Hospital. Socio-demographic and clinical data were collected through a structured questionnaire. A blood sample of 10ml was collected in EDTA (4ml), citrate (3ml) and chemistry (3ml) tubes to do platelet count, coagulation tests, and glucose and lipid profile analysis, respectively. Descriptive statistics as well as the median (25th,75th) percentile and Mann Whitney U test were used during data analysis. RESULTS: The overall hemostatic abnormality in diabetes individuals was 58.8%. The median (25th, 75th percentile) prothrombin time for diabetic and non-diabetic subjects was (12.8, 15.6) vs. (12.8, 14.2), respectively, and the difference was not statistically significant (p>0.05). The median (25th, 75th percentile) activated partial thromboplastin time was significantly different between the two groups (p<0.0001); (24, 36.8) vs. (36, 39.6). The median (25th, 75th percentile) fibrinogen level was significantly different between the two groups (p<0.0001); (277, 462) vs. (243, 328). The median (25th, 75th percentile) platelet count was also significantly different between the two groups (p<0.0001); (146,248) vs. (190,319). All variables were not significantly associated with hemostatic abnormality in multivariate regression analysis. CONCLUSION: An overall hemostatic abnormality in diabetic patients was found to be high. The APTT and platelet count were lower in diabetic patients whilst the fibrinogen level was higher. Routine coagulation tests should be part of tests among diabetic patients. Advanced coagulation tests should also be considered to identify specific markers so as to pinpoint the particular problem