[Show abstract][Hide abstract] ABSTRACT: In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal.
Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage.
A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence.
The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts.
PACTR201305000551876 ( http://www.pactr.org ).
[Show abstract][Hide abstract] ABSTRACT: Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).
Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in
included studies was evaluated based on study design, methodology and missing data.
Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5–64.9) on day 1 to 6.7 %
(95 % CI: 4.8–8.7) on day 2 and 0.9 % (95 % CI: 0.5–1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08–1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06–2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21–3.44), P = 0.008); areas of low/moderate transmission setting
(AOR = 2.71 (95 % CI: 1.38–5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14–4.51), P = 0.020, compared to dihydroartemisinin-piperaquine).
Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
BMC Medicine 09/2015; 13:212. · 7.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare the shaping ability of two single-file systems and conventional rotary instruments in severely curved root canals of extracted human molars.
Mesiobuccal canals of 120 mandibular molars with angles of curvature ranging between 25(°) and 35(°) and radii of curvature from 5 to 9 mm, were divided into three groups (n=40). In each group the canals were instrumented with either WaveOne (W), Reciproc (R) or ProTaper (P). The time required for canal shaping and the frequency of broken instruments were recorded. The standardized pre and post-instrumentation radiographs were taken to determine changes in working length (WL) and straightening of canal curvature. The presence of blockage or perforation was also evaluated. Data were analyzed using the one-way analysis of variance (ANOVA) and post-hoc Tukey's test. The level of significance was set at 0.05.
Both single-instrument systems reduced the canal preparation time by approximately 50% (P<0.05). No incidence of broken instruments from single-file systems was reported; however, two F2 instruments in the P group were broken (P<0.05). Reduction in WL and straightening of canal curvature was observed in all three systems with the highest scores belonging to P system (P<0.05). No case of blockage or perforation was found during shaping in any group.
Single-file systems shaped curved canals with substantial saving in time and a significant decrease in incidence of instrument separation, change in WL, and straightening of canal curvature.
[Show abstract][Hide abstract] ABSTRACT: Background:
Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination
therapies (ACTs) to t
malaria in Africa. We investigated the impact of
different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.
Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance
Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression
model with shared frailty across study sites.
Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%)
treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with
e of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a
non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%)
with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median
dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated
with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25
(median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg
[IQR: 27-39.0]. After adjusting for rei
nfections, the corrected antimalarial efficacy on day 28 after treatment
was similar for co-blistered NFDC (97.9% [95% confiden
ce interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI:
= 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30
(95.0% [95% CI: 94.1%-95.9%]) (
< 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and
region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted
hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12],
< 0.001) compared to FDC, and treatment with loose NFDC-30 was
associated with a higher risk of recrudescence at only three sites.
There was substantial variation in the total dose of amodiaquine administered in different AS-AQ
combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial
treatment efficacy than the loose individual tablets in all age categories.