Sulphadoxine-pyrimethamine plus azithromycin may improve birth outcomes through impacts on inflammation and placental angiogenesis independent of malarial infection

Abstract Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) and SP plus azithromycin (SPAZ) reduces low birthweight (<2,500 g) in women without malarial and reproductive tract infections. This study investigates the impact of SPAZ on associations between plasma biomarkers of inflammation and angiogenesis and adverse pregnancy outcomes in 2,012 Papua New Guinean women. Concentrations of C-reactive protein (CRP), α-1-acid glycoprotein (AGP), soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at enrolment and delivery in a trial comparing SPAZ to SP plus chloroquine (SPCQ). At antenatal enrolment higher CRP (adjusted odds ratio 1.52; 95% confidence interval [CI] 1.03–2.25), sEng (4.35; 1.77, 10.7) and sFlt1 (2.21; 1.09, 4.48) were associated with preterm birth, and higher sEng with low birthweight (1.39; 1.11,3.37), in SPCQ recipients only. Increased enrolment sFlt1:PlGF ratios associated with LBW in all women (1.46; 1.11, 1.90). At delivery, higher AGP levels were strongly associated with low birthweight, preterm birth and small-for-gestational age babies in the SPCQ arm only. Restricting analyses to women without malaria infection did not materially alter these relationships. Women receiving SPAZ had lower delivery AGP and CRP levels (p < 0.001). SPAZ may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection

Development of an Ultrasensitive Impedimetric Immunosensor Platform for Detection of <i>Plasmodium</i> Lactate Dehydrogenase

Elimination of malaria is a global health priority. Detecting an asymptomatic carrier of Plasmodium parasites to receive treatment is an important step in achieving this goal. Current available tools for detection of malaria parasites are either expensive, lacking in sensitivity for asymptomatic carriers, or low in throughput. We investigated the sensitivity of an impedimetric biosensor targeting the malaria biomarker Plasmodium lactate dehydrogenase (pLDH). Following optimization of the detection protocol, sensor performance was tested using phosphate-buffered saline (PBS), and then saliva samples spiked with pLDH at various concentrations. The presence of pLDH was determined by analyzing the sensor electrical properties before and after sample application. Through comparing percentage changes in impedance magnitude, the sensors distinguished pLDH-spiked PBS from non-spiked PBS at concentrations as low as 250 pg/mL (p = 0.0008). Percentage changes in impedance magnitude from saliva spiked with 2.5 ng/mL pLDH trended higher than those from non-spiked saliva. These results suggest that these biosensors have the potential to detect concentrations of pLDH up to two logs lower than currently available best-practice diagnostic tools. Successful optimization of this sensor platform would enable more efficient diagnosis of asymptomatic carriers, who can be targeted for treatment, contributing to the elimination of malaria

Radioiodine therapy for thyroid cancer and dysfunction of the salivary and lachrymal glands in the START study: results at 6 months follow-up

International audienceBackgroundUnderstanding of changes in salivary and lachrymal gland functions after radioiodine therapy (131I-therapy) remains limited; and, to-date no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lachrymal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy related risk factors for salivary/lachrymal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions.MethodsA study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeters measurements. Salivary and lachrymal functions were assessed at baseline (T0, i.e., immediately prior to 131I-therapy), and 6 months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions.ResultsThere was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared to baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the last 3 months were found to be significantly associated with salivary or lachrymal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: e.g. per 1-Gy increase in mean dose to the salivary glands, OR=1.43 (95%CI 1.02-2.04) for dry mouth sensation, ß=-0.08 (95%CI -0.12;-0.02) mL/min for stimulated saliva flow, and ß= 1.07 (95%CI 0.42;1.71) mmol/L for salivary potassium concentration. Conclusions This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lachrymal dysfunctions in DTC patients 6 months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, by identifying risk factors, this study encourages clinicians to adapt the therapy for patients at risk of salivary/lachrymal complications

Salivary Dysfunctions and Conséquences After RadioiodineTreatment for Thyroid Cancer: Protocol for a Self-Controlled Study(START Study)

International audienceBackground: Following radioiodine (131I) therapy of differentiated thyroid cancer, salivary glands may become inflamed, leading to dysfunctions, then leading to decreases in patients’ nutrition and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define patients at risk, allowing the delivered activity to be adapted to the expected risk of salivary dysfunctions.Objective: this study aims to estimate the incidence of salivary dysfunctions after 131I-therapy, to characterize patients at risk of developing post-treatment dysfunctions using clinical, biomolecular and biochemical factors, and to validate a dosimetric method to calculate the dose received at the salivary gland level in order to analyze the dose response relationship between absorbed doses to salivary glands and salivary dysfunctions.Methods: This prospective cohort aims to include patients for whom a 131I-therapy is indicated within the treatment of their differentiated thyroid cancer in a Paris hospital (40 and 80 patients in a 1.1 GBq and a 3.7 GBq groups respectively). The follow-up is based on 3 scheduled visits: at inclusion (T0, immediately before 131I-therapy), 6 months (T6) and 18 months (T18) after treatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (HAD-scale, MOS-SF-36), and nutritional status are administered by a trained clinical research associate. At T0 and at T6, saliva samples and individual measurement of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before radioiodine administration and removed 5 days after treatment. From dosimeters, an estimation of the dose received at the salivary glands will be performed using physical and computational phantoms.Genetic and epigenetic analyses will be performed in order to look for potential biomarkers of predisposition to develop salivary dysfunctions after 131I-therapy.Results: 139 patients (71% women, mean age=47.4 (±14.3) years old) were included between September 2020 and April 2021 (45 and 94 patients in 1.1GBq and 3.7GBq groups respectively). The 6-months follow-up is still ongoing, and the 18-months follow-up will start in February 2022. Statistical analyses will study the links between salivary dysfunctions and absorbed doses to the salivary glands, taking into account associated factors. In addition, impacts on the patients' quality of life will be analyzed.Conclusions: To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions, and thus to propose to clinicians a more adapted follow-up and/or countermeasures to adverse effects

Dysfunction of the salivary and lacrimal glands after radioiodine treatment: Preliminary results of a self-controlled study in france

International audienceFollowing radioiodine (131I) therapy of differentiated thyroid cancer, salivary and lacrimal glands may become inflamed, leading to dysfunctions. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define patients at risk. The aims of this study are 1) to characterize the dysfunction of salivary and lacrimal glands after 131I-therapy, 2) to identify risk factors of salivary and lacrimal dysfunction.START (Salivary dysfuncTion After Radioiodine Treatment) is a prospective study including 139 patients, candidates for a 131I-therapy in the context of their differentiated thyroid cancer (45 and 94 patients in 1.1GBq and 3.7GBq groups respectively). The follow-up was based on 2 scheduled visits: immediately before 131I-therapy (T0) and 6-months after (T6). At each visit, questionnaires on salivary disorders (validated French tool) and dry eye (OSDI© Questionnaire) were administered, and individual salivary flow measurements (without and with salivary gland stimulation) were performed. Descriptive analyses and paired comparisons tests between T0 and T6 were computed.The T6 follow-up started in March 2021, and is still ongoing. Complete information was provided for 122 patients (71% women, mean age=47.4 (±14.3) y). At 6 months after 131I-therapy, stimulated saliva flow rate decreased (from 6.98 (±3.35) to 6.07 (±3.15) mL/min, p<0.01), as well as the difference between stimulated and unstimulated saliva flow rates (from 1.40 (±0.67) to 1.21 (±0.63) mL/min, p<0.01). Also, after 131I-therapy, 19% and 21% of the study population reported dry eye or dry mouth feeling, respectively.This work presents preliminary results of the START study, showing a decrease in salivary and lacrimal gland activity after 131I-therapy. Further analyses will be performed, including saliva biochemical composition, genetic and epigenetic variants, and dose-response relationships (using dosimetric reconstructions)

Dysfunction of the salivary and lacrimal glands after radioiodine treatment: Preliminary results of a self-controlled study in france

International audienceFollowing radioiodine (131I) therapy of differentiated thyroid cancer, salivary and lacrimal glands may become inflamed, leading to dysfunctions. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define patients at risk. The aims of this study are 1) to characterize the dysfunction of salivary and lacrimal glands after 131I-therapy, 2) to identify risk factors of salivary and lacrimal dysfunction.START (Salivary dysfuncTion After Radioiodine Treatment) is a prospective study including 139 patients, candidates for a 131I-therapy in the context of their differentiated thyroid cancer (45 and 94 patients in 1.1GBq and 3.7GBq groups respectively). The follow-up was based on 2 scheduled visits: immediately before 131I-therapy (T0) and 6-months after (T6). At each visit, questionnaires on salivary disorders (validated French tool) and dry eye (OSDI© Questionnaire) were administered, and individual salivary flow measurements (without and with salivary gland stimulation) were performed. Descriptive analyses and paired comparisons tests between T0 and T6 were computed.The T6 follow-up started in March 2021, and is still ongoing. Complete information was provided for 122 patients (71% women, mean age=47.4 (±14.3) y). At 6 months after 131I-therapy, stimulated saliva flow rate decreased (from 6.98 (±3.35) to 6.07 (±3.15) mL/min, p<0.01), as well as the difference between stimulated and unstimulated saliva flow rates (from 1.40 (±0.67) to 1.21 (±0.63) mL/min, p<0.01). Also, after 131I-therapy, 19% and 21% of the study population reported dry eye or dry mouth feeling, respectively.This work presents preliminary results of the START study, showing a decrease in salivary and lacrimal gland activity after 131I-therapy. Further analyses will be performed, including saliva biochemical composition, genetic and epigenetic variants, and dose-response relationships (using dosimetric reconstructions)