A Novel Ex Vivo Drug Assay for Assessing the Transmission-Blocking Activity of Compounds on Field-Isolated Plasmodium falciparum Gametocytes.

The discovery and development of transmission-blocking therapies challenge malaria elimination and necessitate standard and reproducible bioassays to measure the blocking properties of antimalarial drugs and candidate compounds. Most of the current bioassays evaluating the transmission-blocking activity of compounds rely on laboratory-adapted Plasmodium strains. Transmission-blocking data from clinical gametocyte isolates could help select novel transmission-blocking candidates for further development. Using freshly collected Plasmodium falciparum gametocytes from asymptomatic individuals, we first optimized ex vivo culture conditions to improve gametocyte viability and infectiousness by testing several culture parameters. We next pre-exposed ex vivo field-isolated gametocytes to chloroquine, dihydroartemisinin, primaquine, KDU691, GNF179, and oryzalin for 48 h prior to direct membrane feeding. We measured the activity of the drug on the ability of gametocytes to resume the sexual life cycle in Anopheles after drug exposure. Using 57 blood samples collected from Malian volunteers aged 6 to 15 years, we demonstrate that the infectivity of freshly collected field gametocytes can be preserved and improved ex vivo in a culture medium supplemented with 10% horse serum at 4% hematocrit for 48 h. Moreover, our optimized drug assay displays the weak transmission-blocking activity of chloroquine and dihydroartemisinin, while primaquine and oryzalin exhibited a transmission-blocking activity of ~50% at 1 µM. KDU691 and GNF179 both interrupted Plasmodium transmission at 1 µM and 5 nM, respectively. This new approach, if implemented, has the potential to accelerate the screening of compounds with transmission-blocking activity.

Fertility after Endoscopic Surgery for Ectopic Pregnancy Management in Point "G" Teaching Hospital, Bamako-Mali.

Endoscopic surgery of ectopic pregnancy is actually the gold standard for the management of fallopian tubal diseases. A survey was conducted to evaluate fertility in patients who underwent endoscopic management for ectopic pregnancy. A retrospective study was conducted at the department of general and endoscopic surgery of the Point "G" teaching hospital, in Bamako, Mali, from January 1st 2007 to December 31, 2016. Forty-eight (48) patients who underwent endoscopic management of tubal ectopic pregnancy and who have been followed up for fertility were included in this study. Statistical tests used were X2 or Fisher test and their confident interval, p <1 % has been considered as statistically significant. The therapeutic score of Pouly was less than 4 in 25.0% (n = 12). The return to fertility was observed among 48.0% of patients (n = 23). The chance of conception was less than 80.0% after the fourth postoperative year (p=0.001). The outcome of pregnancies has been seventeen full-term pregnancies, three ectopic pregnancies and three miscarriages. The occurrence of pregnancy after endoscopic management indicated for ectopic pregnancy is possible. However, many factors can influence the future conception.

Field application of MALDI-TOF MS on mosquito larvae identification.

In recent years, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as an efficient tool for arthropod identification. Its application for field monitoring of adult mosquitoes was demonstrated, but identification of larvae has been limited to laboratory-reared specimens. Study aim was to test the success of MALDI-TOF MS in correctly identifying mosquito larvae collected in the field. Collections were performed at 13 breeding sites in urban areas of Marseille, a city in the South of France. A total of 559 larvae were collected. Of these, 73 were accurately morphologically identified, with confirmation either by molecular identification (n = 31) or analysis with MALDI-TOF MS (n = 31) and 11 were tested using both methods. The larvae identified belonged to six species including Culiseta longiareolata, Culex pipiens pipiens, Culex hortensis, Aedes albopictus, Ochlerotatus caspius and Anopheles maculipennis. A high intra-species reproducibility and inter-species specificity of whole larva MS spectra was obtained and was independent of breeding site. More than 92% of the remaining 486 larvae were identified in blind tests against the MS spectra database. Identification rates were lower for early and pupal stages, which is attributed to lower protein abundance and metamorphosis, respectively. The suitability of MALDI-TOF MS for mosquito larvae identification from the field has been confirmed.

Longitudinal monitoring of environmental factors at Culicidae larval habitats in urban areas and their association with various mosquito species using an innovative strategy.

BACKGROUND: To prevent the risk of mosquito-borne disease outbreaks, larval source management remains the most sustainable and effective mosquito control strategy. The present study aimed to determine the influence of environmental characteristics of mosquito larval habitats in an urban area of Marseille, France. Fourteen sites containing water were monitored every 2 weeks from May to October 2015 for mosquito species occurrence and larval density, and environmental parameters were measured at each visit. Rapid and accurate species identification of mosquito larvae was performed using an innovative MALDI-TOF MS method. RESULTS: A total of 6753 larvae (L1-L4) and pupae were collected, of which 35.8% (n = 2418) were speciated using MALDI-TOF MS. Correct identifications were obtained for 2259 specimens (93.4%). A total of five mosquito species were found, including Aedes (Ae.) albopictus, Culex (Cx.) p. pipiens, Cx. hortensis, Cx. impudicus, and Culiseta (Cs.) longiareolata. Larvae of the Culex genus were predominant in both density and distribution. Small, shaded pools of shallow water favored Ae. albopictus colonization, whereas the wide distribution of Cx. p. pipiens demonstrated that this species was weakly influenced by environmental changes. CONCLUSIONS: The present work confirms that MALDI-TOF MS is a useful tool for mosquito speciation and suggests that understanding the environmental factors associated with the occurrence and density of mosquito species at the larval stage in Marseille may aid in the future implementation of mosquito control programs. © 2018 Society of Chemical Industry.

Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria.

BACKGROUND: Most malaria-endemic countries use artemisinin-based combination therapy (ACT) as their first-line treatment. ACTs are known to be highly effective on asexual stages of the malaria parasite. Malaria transmission and the spread of resistant parasites depend on the infectivity of gametocytes. The effect of the current ACT regimens on gametocyte infectivity is unclear. OBJECTIVES: This study aimed to determine the infectivity of gametocytes to Anopheles gambiae following ACT treatment in the field. METHODS: During a randomised controlled trial in Bougoula-Hameau, Mali, conducted from July 2005 to July 2007, volunteers with uncomplicated malaria were randomised to receive artemether-lumefantrine, artesunate-amodiaquine, or artesunate-sulfadoxine/pyrimethamine. Volunteers were followed for 28 days, and gametocyte carriage was assessed. Direct skin feeding assays were performed on gametocyte carriers before and after ACT administration. RESULTS: Following artemether-lumefantrine treatment, gametocyte carriage decreased steadily from Day 0 to Day 21 post-treatment initiation. In contrast, for the artesunate-amodiaquine and artesunate-sulfadoxine/pyrimethamine arms, gametocyte carriage increased on Day 3 and remained constant until Day 7 before decreasing afterward. Mosquito feeding assays showed that artemether-lumefantrine and artesunate-amodiaquine significantly increased gametocyte infectivity to Anopheles gambiae sensu lato (s.l.) (p < 10-4), whereas artesunate-sulfadoxine/pyrimethamine decreased gametocyte infectivity in this setting (p = 0.03). CONCLUSION: Different ACT regimens could lead to gametocyte populations with different capacity to infect the Anopheles vector. Frequent assessment of the effect of antimalarials on gametocytogenesis and gametocyte infectivity may be required for the full assessment of treatment efficacy, the potential for spread of drug resistance and malaria transmission in the field.

[Management for esophageal foreign bodies: about 36 cases]. / Prise en charge des corps étrangers enclaves de l'œsophage: à propos de 36 cas.

Esophageal foreign bodies are a frequent reason for consultation in the Pediatric Emergency Department. However, they can occur at all ages. This study aims to highlight the clinical, paraclinical and therapeutic features of esophageal foreign bodies management at the Hospital in Mali. We conducted a prospective study of all cases of ingestion of foreign bodies between January 2011 and December 2014. A total of 36 patients underwent endoscopic or surgical treatment. The average age was 6 years (with a range from 14 months to 62 years). They mainly affected male patients with a sex ratio of 1.75. Foreign bodies were blocked in the cricopharyngeal shrinkage in 69.45% of cases, 22.22% of whom had subsequent aortic shrinkage. The average time of foreign body removal was 7.30 hours. Rigid fibroscopy allowed the removal of the foreign body in 88.89% of cases. Thoracotomy allowed the removal of the foreign body in 5.55%. Esophageal foreign bodies can occur at all ages but they are more frequent among children. Endoscopic removal is the gold standard treatment but surgical removal of a blocked esophageal foreign body, although rare, is the last resort, due to the nature of the foreign body and to the occurrence of complications. The best way to reduce accidents is prevention.

Pregnancy outcomes after laparoscopic sleeve gastrectomy among obese patients.

OBJECTIVE: To analyze pregnancy outcomes after laparoscopic sleeve gastrectomy (LSG) according to body mass index (BMI) at conception and the interval between LSG and pregnancy. METHODS: In a retrospective study, data were obtained for all women who became pregnant after LSG at a center in France between December 2001 and December 2011. Frequencies of perinatal events according to BMI at conception and the interval between LSG and pregnancy were compared. RESULTS: A total of 63 pregnancies occurring in 54 patients were included, among which 52 (83%) occurred after the first postoperative year and 26 (41%) in women who remained obese. Compared with women who were no longer obese at conception, women who were still obese delivered neonates of significantly lower gestational age at birth (P=0.02) and birth weight (P=0.001). Odds of preterm delivery were also increased (odds ratio 4.37, 95% confidence interval 1.17-16.27; P=0.03). Maternal and neonatal outcomes according to the interval between LSG and pregnancy did not differ significantly. CONCLUSION: Women who remain obese following LSG are at increased risk of adverse outcomes, including low gestational age at birth, low birth weight, and preterm delivery, and should be regarded as a risk group.