A Positive Correlation between Atypical Memory B Cells and Plasmodium falciparum Transmission Intensity in Cross-Sectional Studies in Peru and Mali

transmission intensity correlates with atypical memory B cell expansion.. In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61–7.28]; U.S. mean: 1.4% [95% CI: 0.92–1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68–15.57]; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09–9.11]; no prior episodes mean: 3.1% [95% CI: 1.52–4.73]; p = 0.028). infection could contribute to our understanding of naturally-acquired malaria immunity

Artemisinin-based combinations versus amodiaquine plus sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali

<p>Abstract</p> <p>Background</p> <p>Because of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL) or artesunate-amodiaquine (AS+AQ) are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs.</p> <p>Methods</p> <p>From July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP), and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP), was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish new from recrudescent <it>Plasmodium falciparum </it>infections.</p> <p>Results</p> <p>397 children 6 to 59 months of age with uncomplicated <it>Plasmodium falciparum </it>malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR) were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p < 0.001); after PCR correction ACPR rates were similar among treatment groups: 95.4%, 96.9%, and 99.2% respectively (p = 0.17). Mean haemoglobin concentration increased across all treatment groups from Day 0 (9.82 ± 1.68 g/dL) to Day 28 (10.78 ± 1.49 g/dL) (p < 0.001), with the greatest improvement occurring in children treated with AQ+SP. On Day 2, the prevalence of parasitaemia was significantly greater among children treated with AQ+SP (50.8%) than in children treated with AS+AQ (10.5%) or AS+SP (10.8%) (p < 0.001). No significant difference in gametocyte carriage was found between groups during the follow-up period.</p> <p>Conclusion</p> <p>The combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated <it>P. falciparum </it>infection in Mali and appears to have the added value of longer protective effect against new infection.</p

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery

Prevention of Malaria in Pregnancy with Intermittent Preventive Treatment and Insecticide Treated Nets in Mali: A Quantitative Health Systems Effectiveness Analysis

Introduction The objectives of the study were to evaluate the health system effectiveness of ANC for the delivery of a dose of IPTp and an ITN to women attending ANC during eligible gestation, and to identify the predictors of systems effectiveness. Methods A cross sectional study was undertaken in 10 health facilities including structured non-participant observations of the ANC process for 780 pregnant women followed by exit interviews. The proportion of pregnant women receiving a dose of IPTp-SP and an ITN was assessed. Predictors of each ineffective intermediate process were identified using multivariable logistic regression. Results Overall, 0% and 24.5% of pregnant women of eligible gestation on the first visit to ANC received a dose of IPTp-SP by DOT at the district and community levels respectively. Ineffective intermediate processes were ‘given IPTp-SP at the ANC’ 63.9% and 74.0% (95% CI 62.0, 83.3), and ‘given IPTp-SP by DOT’ 0% and 34.3% (95% CI 10.5, 69.8), at district and community levels, respectively. Delivery of ITNs was effective where they were in stock; however stock-outs were a problem. Predictors of receiving IPTp-SP at the district level were 4 to 6 months gestation, not reporting symptoms of malaria at ANC visit and the amount of money spent during the visit. At the community level, the predictors were 4 to 6 months gestation, maternal education below primary level, routine ANC visit (not for an illness), palpation of the abdomen, and expenditure of money in ANC. Conclusion In Segou District, the delivery of IPTp-SP was ineffective; whilst ITN delivery was effective if ITNs were in stock. Predictors of receiving IPTp-SP at the district and community levels included gestational age, the amount of expenditure during the ANC visit and no illness

Atypical MBCs in individuals from the U.S., Peru and Mali.

<p>Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of <i>Pf</i>-naive U.S. adults (n = 10), <i>Pf</i>-infected Peruvian adults (n = 18) and <i>Pf</i>-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.</p

Atypical MBCs in Peruvian adults by self-reported history of prior malaria episodes.

<p>Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of <i>Pf</i>-infected Peruvian adults who did (n = 12) or did not (n = 6) self-report a prior history of malaria. Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.</p

Atypical MBCs and immunoglobulin class switching.

<p>Class-switching of atypical MBCs was assessed by measuring cell surface expression of IgG by flow cytometry in the peripheral blood of <i>Pf</i>-naive U.S. adults (n = 10), <i>Pf</i>-infected Peruvian adults (n = 18) and <i>Pf</i>-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.</p

Phenotypic analysis of B cell subsets in individuals from the U.S., Peru and Mali.

<p>The following B cell subsets were quantified by flow cytometry, as detailed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015983#s4" target="_blank"><i>Materials and Methods</i></a>: plasma cells/blasts (CD19⁺ CD21⁻ CD20⁻), activated MBCs (CD19⁺ CD21⁻ CD27⁺CD20⁺), classical MBCs (CD19⁺ CD27⁺ CD21⁺), atypical MBCs (CD19⁺ CD20⁺ CD21⁻ CD27⁻ CD10⁻) naive B cells and immature B cells (CD19⁺ CD10⁺). B cell subsets are expressed as a percentage of total CD19⁺ B cells in the peripheral blood of <i>Pf</i>-naive U.S. adults (n = 10), <i>Pf</i>-infected Peruvian adults (n = 18) and <i>Pf</i>-infected Malian adults (n = 12). The relative proportions of B cell subsets are shown in stacked plots.</p