Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

Background: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature ≥ 38°C and parasitaemia > 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). Conclusion: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa

A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

<p>Abstract</p> <p>Background</p> <p>Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva.</p> <p>Methods</p> <p>A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column.</p> <p>Results</p> <p>Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, <it>p </it>< 0.001). Saliva:plasma concentrations ratio was 0.42.</p> <p>Conclusion</p> <p>Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.</p

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

Background: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature ≥ 38°C and parasitaemia > 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). Conclusion: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa

Patterns of drugs prescribed for dental outpatients in Nigeria: findings and implications.

There are concerns with inappropriate prescribing of medicines among dentists especially antimicrobials. It is more concerning if this increases resistance rates. This study aimed to address this by assessing patterns of drugs prescribed for outpatients attending a hospital dental clinic in Nigeria. The findings will be used to plan future interventions, particularly around antimicrobial prescribing, where there are concerns.Medical records of patients attending the dental clinic of a leading teaching hospital in Nigeria were evaluated. Patients referred for admission, without a prescription, or prescribed medicines without a documented diagnosis were excluded.Overall, 607 prescriptions were analysed, 314 (51.7%) were for females. Periodontal and gum diseases (414; 68.1%) were the most frequent diagnoses, followed by pulpitis (49; 8.2%), and dentoalveolar abscess (43; 7.1%). A total of 1798 medicines were prescribed for all patients with a mean of 3.0 ± 0.48 medicines per prescription. Antimicrobials (1178; 65.5%) and analgesics (620; 34.5%) were the two drug classes prescribed. Ascorbic acid and vitamin B complex were prescribed for 361 (59.5%) patients. Among antimicrobials, amoxicillin (564; 95.1%) either alone or combined with clavulanic acid was the most frequently prescribed, followed by metronidazole (561; 94.6%). Brand name prescribing was also appreciably higher than WHO recommendations.Polypharmacy, brand name prescriptions, and the frequent prescription of antimicrobials were common practices at the dental clinic of this teaching hospital in Nigeria. We suggest a review of the current standard treatment guidelines in Nigeria to guide dentists on current knowledge- and evidence-based treatment of common oral diseases