124 research outputs found
Risk factors for Plasmodium falciparum hyperparasitaemia in malarious children
Background: Hyperparasitaemia is a feature of childhood severe malaria but there is little information on the risk
factors for hyperparasitaemia in malarious children
Methods: The risk factors associated with Plasmodium falciparum hyperparasitaemia, defined as asexual
parasitaemia > 250,000/μl, at presentation were evaluated in 3338 malarious children enrolled prospectively
between 2008 and 2010 in an endemic area of southwestern Nigeria.
Results: At enrolment, 97 (3%) of 3338 malarious children had hyperparasitaemia. In a multiple regression model, 3
factors were found to be independent risk factors for the presence of hyperparasitaemia at enrolment: an age ≤ 11
years (Adjusted odds ratio [AOR] = 2.85, 95% confidence interval [CI] 1.23-6.61, P = 0.014), fever (AOR = 2.02, 95%
CI 1.23-3.29, P = 0.005), and enrolment after year 2008 (AOR = 0.42, 95% CI 0.24-0.73, P = 0.002). Duration of illness
≤ 3 d was associated with increased risk of hyperparasitaemia. There was no association between season and
hyperparasitaemia. Compared to non-hyperparasitaemia, hyperparasitaemia was associated with an increased risk of
progression to cerebral malaria (P < 0.0001). The risk of progression in hyperparasitaemic children was higher in <
5-year olds (P = 0.02).
Conclusion: Young age and presence of fever are independent risk factors for hyperparasitaemia which is
associated with an increased risk of progression to cerebral malaria. The findings have implications for case and
community management of childhood hyperparasitaemia and for malaria control efforts in sub-Saharan Africa
where severe malaria is relatively common
Early Changes in Plasmodium falciparum Asexual and Sexual Populations in Children with Acute Infections Following Treatment with Artemisinin-Based Combination Drugs
Artemisinin-based combination therapies (ACTs)
may influence malaria transmission but the early changes
in parasite populations have not been frequently evaluated.
The changes in Plasmodium falciparum asexual and sexual
populations in the first 16 h following treatment with
artemether-lumefantrine (AL) or artesunate-amodiaquine
(AA) were evaluated in 443 children with acute infections.
The effects of gametocyte density on gametocyte sex ratio
(GSR) were characterized in another cohort of 52 children
treated with AL and AA. Stages of asexual and sexual
parasites in peripheral blood were determined morphologically.
In 167 children there were significant increases in
peripheral asexual parasitemia at 1 h, and in 15 of these,
an insignificant increase in gametocytemia at 1 h, followed
thereafter by a precipitous and significant fall in all patients.
Time-course of GSR showed a female-male-female-biased
cycle at 0 h, 4 h, and 8 h. Pre-treatment GSR and time-course
of GSR post-treatment were independent of density in the
additional cohort of 52 gametocyte carriers treated with AL
or AA. Population changes were similar in AL- and AAtreated
children. Treatment with AL or AA is associated
with early increases in asexual and sexual parasites and is
closely followed by rapid elimination of these parasites
Microbial metagenomic approach uncovers the first rabbit haemorrhagic disease virus genome in Sub-Saharan Africa.
Rabbit Haemorrhagic Disease (RHD) causes high morbidity and mortality in rabbits and hares. Here, we report the first genomic characterization of lagovirus GI.2 virus in domestic rabbits from sub-Saharan Africa. We used an unbiased microbial metagenomic Next Generation Sequencing (mNGS) approach to diagnose the pathogen causing the suspected outbreak of RHD in Ibadan, Nigeria. The liver, spleen, and lung samples of five rabbits from an outbreak in 2 farms were analyzed. The mNGS revealed one full and two partial RHDV2 genomes on both farms. Phylogenetic analysis showed close clustering with RHDV2 lineages from Europe (98.6% similarity with RHDV2 in the Netherlands, and 99.1 to 100% identity with RHDV2 in Germany), suggesting potential importation. Subsequently, all the samples were confirmed by RHDV virus-specific RT-PCR targeting the VP60 gene with the expected band size of 398 bp for the five rabbits sampled. Our findings highlight the need for increased genomic surveillance of RHDV2 to track its origin, understand its diversity and to inform public health policy in Nigeria, and Sub-Saharan Africa
A Simple Dose Regimen of Artesunate and Amodiaquine Based on Age or Body Weight Range for Uncomplicated Falciparum Malaria in Children: Comparison of Therapeutic Efficacy With Standard Dose Regimen of Artesunate and Amodiaquine and Artemether–Lumefantrine
A new dose regimen of artesunate and amodiaquine (NDRAA) based on age or body weight range was compared with standard dose regimen of artesunate and amodiaquine (SDRAA) calculated according to body weight and with fixed-dose artesunate–amodiaquine (FDAA) and artemether–lumefantrine (AL) in 304 children afflicted by malaria aged 15 years or younger. In initial comparison (n = 208), children on NDRAA received 1–3 times amodiaquine per kilogram of body weight and 1–1.5 times of artesunate per kilogram of body weight compared with those receiving SDRAA. Parasite but not fever clearance was significantly faster in children who received NDRAA (19.4 ± 8.4 hours vs. 24.6 ± 15.5 hours, P = 0.003). Polymerase chain reaction–uncorrected cure rates on days 28–42 were also significantly higher in children who received NDRAA (P < 0.02 in all cases). Therapeutic responses in children younger than 5 years (n = 96) treated with NDRAA, FDAA, and AL were similar. Changes in hematocrit values and reported adverse events after commencing therapy were similar in those who received NDRAA and SDRAA. All drug regimens were well tolerated. NDRAA based on age or body weight range is simple, is therapeutically superior to SDRAA calculated according to body weight, and is as efficacious as AL in children younger than 5 years
Fall in Hematocrit per 1000 Parasites Cleared From Peripheral Blood: A Simple Method for Estimating Drug-Related Fall in Hematocrit After Treatment of Malaria Infections
A simple method to estimate antimalarial drug-related fall in hematocrit (FIH) after treatment of Plasmodium falciparum infections in the field is described. The method involves numeric estimation of the relative difference in hematocrit at baseline (pretreatment) and the first 1 or 2 days after treatment begun as numerator and the corresponding relative difference in parasitemia as the denominator, and expressing it per 1000 parasites
cleared from peripheral blood. Using the method
showed that FIH/1000 parasites cleared from
peripheral blood (cpb) at 24 or 48 hours were similar
in artemether–lumefantrine and artesunate–
amodiaquine-treated children (0.09; 95% confidence
interval, 0.052–0.138 vs 0.10; 95% confidence
interval, 0.069–0.139%; P = 0.75) FIH/1000
parasites cpb in patients with higher parasitemias
were significantly (P < 0.0001) and five- to 10-fold
lower than in patients with lower parasitemias
suggesting conservation of hematocrit or red cells in
patients with higher parasitemias treated with
artesunate–amodiaquine or artemether–lumefantrine.
FIH/1000 parasites cpb were similar in anemic and
nonanemic children. Estimation of FIH/1000
parasites cpb is simple, allows estimation of
relatively conserved hematocrit during treatment,
and can be used in both observational studies and
clinical trials involving antimalarial drugs
Recrudescent Plasmodium falciparum infections in children in an endemic area following artemisinin–based combination treatments: Implications for disease control
To evaluate the features and risk factors associated with recrudescent infections that arose following artemisinin-based combination drug treatment of the primary infections.
Methods
The clinical features and risk factors associated with subsequent recrudescence of primary Plasmodium falciparum infections were evaluated in 37 of 877 children following artesunate or artemisinin-based combination treatments (ACTs). Recrudescence was determined by polymerase chain reaction
Plasmodium falciparum hyperparasitaemia in Nigerian children: epidemiology, clinical characteristics, and therapeutic responses to oral artemisinin-based combination treatments
To evaluate the epidemiology, clinical
characteristics and response to oral artemisininbased
combination treatments (ACTs) of children
with Plasmodium falciparum hyperparasitaemia
(PfHP).
Methods
All children with febrile or history of febrile illness
who were suspected to be malaria were evaluated for
the presence of PfHP and their parasitological and
clinical characteristics at presentation and follow-up
for four weeks were recorded during a 3-year period.
Patients were treated with oral artemisinin-baesd
combination drugs
Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria
The treatment efficacy and effects of artesunate-mefloquine (AMQ) and mefloquine (MQ) on malariaassociated
anemia (MAA) were evaluated in 342 children ≤ 10 years of age with uncomplicated Plasmodium falciparum
malaria randomized to receive either drug/drug combination. All children recovered clinically. Fever clearance times were
similar. Parasite clearance was significantly faster with AMQ (mean ± SD = 1.4 ± 0.6 days, 95% confidence interval [CI] =
1.3–1.5, P < 0.0001), but polymerase chain reaction–corrected cure rates were similar (97% versus 94%). Gametocyte carriage
rates and the drug-attributable fall in hematocrit were significantly lower with AMQ (mean ± SD = 4.8 ± 3.8%, 95%
CI = 3.6–6.0, P = 0.03), but the rates of resolution of MAA were similar. Both regimens were well tolerated. AMQ clears
parasitemia and reduces gametocyte carriage more rapidly and causes lesser fall in hematocrit than MQ, but both regimens
are effective treatment of uncomplicated P. falciparum malaria in Nigerian children
Use of area under the curve to evaluate the effects of antimalarial drugs on malaria associated anemia after treatment
To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria associated anemia
(MAA), we use the area under curve (AUC) of anemia levels after treatment as an approach to
combine their duration and magnitude. The method involves numerical estimation, by trapezoidal
rule, of AUC from a plot of deficit in hematocrit levels from 30% (the lower threshold of normal)
versus time in anemic children. Using the method, we evaluated, in randomized trials, the effects
of artesunate-mefloquine (AMQ) versus mefloquine alone (MQ), and artemether-lumefantrine
(AL) versus amodiaquine-artesunate (AA) on the time-course of recovery from MAA in 109
children. Anemia resolution times were similar (10.9 ± 6.2 [SD] vs 13.3 ± 8.9 d, P = 0.2) but mean
AUC was significantly lower in AMQ- compared to MQ- treated children (35.5 ± 7.1 [SEM] vs
49.8 ± 11.3 %.h, P = 0.02) indicating larger exposure to anemia in MQ-treated children. In ALand
AA- treated children, both anemia resolution times (8.6 ± 5.3 [SD] vs 8.6 ± 4.8 d, P = 0.98)
and mean AUC (57.1 ± 12.9 [SEM] vs 46.3 ± 8.7 %.h, P = 0.74) were similar. Estimation of AUC
appears more robust than estimation of anemia resolution time in evaluating antimalarial drug
effects and can be used in both observational studies and clinical trials assessing the effects of
therapies on MAA
Early variations in plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance
<p>Abstract</p> <p>Background</p> <p>Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent <it>Plasmodium falciparum </it>drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens.</p> <p>Methods</p> <p>In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of <it>Plasmodium falciparum</it>.</p> <p>Results</p> <p>A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects.</p> <p>Conclusion</p> <p>The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.</p
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