Association of Antibody Responses to the Conserved Plasmodium falciparum Merozoite Surface Protein 5 with Protection against Clinical Malaria

Background

Plasmodium falciparum merozoite surface protein 5 (PfMSP5) is an attractive blood stage vaccine candidate because it is both exposed to the immune system and well conserved. To evaluate its interest, we investigated the association of anti-PfMSP5 IgG levels, in the context of responses to two other conserved Ags PfMSP1p19 and R23, with protection from clinical episodes of malaria in cross-sectional prospective studies in two different transmission settings.

Methods

Ndiop (mesoendemic) and Dielmo (holoendemic) are two Senegalese villages participating in an on-going long-term observational study of natural immunity to malaria. Blood samples were taken before the transmission season (Ndiop) or before peak transmission (Dielmo) and active clinical surveillance was carried out during the ensuing 5.5-month follow-up. IgG responses to recombinant PfMSP5, PfMSP1p19 and R23 were quantified by ELISA in samples from surveys carried out in Dielmo (186 subjects) and Ndiop (221 subjects) in 2002, and Ndiop in 2000 (204 subjects). In addition, 236 sera from the Dielmo and Ndiop-2002 surveys were analyzed for relationships between the magnitude of anti-PfMSP5 response and neutrophil antibody dependent respiratory burst (ADRB) activity.

Results

Anti-PfMSP5 antibodies predominantly IgG1 were detected in 60–74% of villagers, with generally higher levels in older age groups. PfMSP5 IgG responses were relatively stable for Ndiop subjects sampled both in 2000 and 2002. ADRB activity correlated with age and anti-PfMSP5 IgG levels. Importantly, PfMSP5 antibody levels were significantly associated with reduced incidence of clinical malaria in all three cohorts. Inclusion of IgG to PfMSP1p19 in the poisson regression model did not substantially modify results.

Conclusion

These results indicate that MSP5 is recognized by naturally acquired Ab. The large seroprevalence and association with protection against clinical malaria in two settings with differing transmission conditions and stability over time demonstrated in Ndiop argue for further evaluation of baculovirus PfMSP5 as a vaccine candidate.     

Impact of Annual Praziquantel Treatment on Urogenital Schistosomiasis in a Seasonal Transmission Focus in Central Senegal

In Sub-Saharan Africa, urogenital schistosomiasis remains a significant public health problem, causing 150.000 deaths/year with approximately 112 million cases diagnosed. The Niakhar district is a disease hotspot in central Senegal where transmission occurs seasonally with high prevalences. The aim of this study was to determine the effect of annual treatment over 3 years on the seasonal transmission dynamics of S. haematobium in 9 villages in the Niakhar district. Adults and children aged between 5 and 60 years were surveyed from 2011 to 2014. Urine samples were collected door-to-door and examined for S. haematobium eggs at baseline in June 2011, and all participants were treated in August 2011 with PZQ (40 mg/kg). After this initial examination, evaluations were conducted at 3 successive time points from September 2011 to March 2014, to measure the efficacy of the annual treatments and the rates of reinfection. Each year, during the transmission period, from July to November-December, malacological surveys were also carried out in the fresh water bodies of each village to evaluate the infestation of the snail intermediate hosts. At baseline, the overall prevalence of S. haematobium infection was 57.7%, and the proportion of heavy infection was 45.3%, but one month after the first treatment high cure rates (92.9%) were obtained. The overall infection prevalence and proportion of heavy infection intensities were drastically reduced to 4.2% and 2.3%, respectively. The level of the first reinfection in February-March 2012 was 9.5%. At follow-up time points, prevalence levels varied slightly between reinfection and treatment from 9.5% in June 2012 to 0.3% in March 2013, 11.2 in June 2013, and 10.1% April 2014. At the end of the study, overall prevalence was significantly reduced from 57.7% to 10.1%. The overall rate of infested Bulinid snails was reduced after repeated treatment from 0.8% in 2012 to 0.5% in 2013. Repeated annual treatments are suggested to have a considerable impact on the transmission dynamics of S. haematobium in Niakhar, due to the nature of the epidemiological system with seasonal transmission. Thus, to maintain this benefit and continue to reduce the morbidity of urogenital schistosomiasis, other approaches should be integrated into the strategy plans of the National program to achieve the goal of urogenital schistosomiasis elimination in seasonal foci in Senegal.     

Phylogenetic Analysis and Epidemic History of Hepatitis C Virus Genotype 2 in Tunisia,North Africa

HCV genotype 2 (HCV-2) has a worldwide distribution with prevalence rates that vary from country to country. High genetic diversity and long-term endemicity were suggested in West African countries. A global dispersal of HCV-2 would have occurred during the 20^th century, especially in European countries. In Tunisia, genotype 2 was the second prevalent genotype after genotype 1 and most isolates belong to subtypes 2c and 2k. In this study, phylogenetic analyses based on the NS5B genomic sequences of 113 Tunisian HCV isolates from subtypes 2c and 2k were carried out. A Bayesian coalescent-based framework was used to estimate the origin and the spread of these subtypes circulating in Tunisia. Phylogenetic analyses of HCV-2c sequences suggest the absence of country-specific or time-specific variants. In contrast, the phylogenetic grouping of HCV-2k sequences shows the existence of two major genetic clusters that may represent two distinct circulating variants. Coalescent analysis indicated a most recent common ancestor (tMRCA) of Tunisian HCV-2c around 1886 (1869–1902) before the introduction of HCV-2k in 1901 (1867–1931). Our findings suggest that the introduction of HCV-2c in Tunisia is possibly a result of population movements between Tunisia and European population following the French colonization.     

Melatonin ingestion after exhaustive late-evening exercise improves sleep quality and quantity,and short-term performances in teenage athletes

ABSTRACT

The present study aimed to explore the effects of a single 10-mg dose of melatonin (MEL) administration after exhaustive late-evening exercise on sleep quality and quantity, and short-term physical and cognitive performances in healthy teenagers. Ten male adolescent athletes (mean ± SD, age = 15.4 ± 0.3 years, body-mass = 60.68 ± 5.7 kg, height = 167.9 ± 6.9 cm and BMI = 21.21 ± 2.5) performed two test sessions separated by at least one week. During each session, participants completed the Yo-Yo intermittent-recovery-test level-1 (YYIRT-1) at ~20:00 h. Then, sleep polysomnography was recorded from 22:15 min to 07:00 h, after a double blind randomized order administration of a single 10-mg tablet of MEL (MEL-10 mg) or Placebo (PLA). The following morning, Hooper wellness index was administered and the participants performed the Choice Reaction Time (CRT) test, the Zazzo test and some short-term physical exercises (YYIRT-1, vertical and horizontal Jumps (VJ; HJ), Hand grip strength (HG), and five-jump test (5-JT)). Evening total distance covered in the YYIRT-1 did not change during the two conditions (p > 0.05). Total sleep time (Δ = 24.55 mn; p < 0.001), sleep efficiency (Δ = 4.47%; p < 0.001), stage-3 sleep (N3 sleep) (Δ = 1.73%; p < 0.05) and rapid-eye-movement sleep (Δ = 2.15%; p < 0.001) were significantly higher with MEL in comparison with PLA. Moreover, sleep-onset-latency (Δ = –8.45mn; p < 0.001), total time of nocturnal awakenings after sleep-onset (NA) (Δ = –11 mn; p < 0.001), stage-1 sleep (N1 sleep) (Δ = –1.7%; p < 0.001) and stage-2 sleep (N2 sleep) (Δ = ?1.9%; p < 0.05) durations were lower with MEL. The Hooper index showed a better subjective sleep quality, a decrease of the subjective perception of fatigue and a reduced level of muscle soreness with MEL. Moreover, MEL improved speed and performance but not inaccuracy during the Zazzo test. CRT was faster with MEL. Morning YYIRT-1 (Δ = 82 m; p < 0.001) and 5-JT (Δ = 0.08 m; p < 0.05) performances were significantly higher with MEL in comparison with PLA. In contrast, HG, VJ and HJ performances did not change during the two conditions (p > 0.05). The administration of a single dose of MEL-10 mg after strenuous late-evening exercise improved sleep quality and quantity, selective attention, subjective assessment of the general wellness state, and some short-term physical performances the following morning in healthy teenagers.     

A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children

Summary

In the Sahel, most malaria deaths occur among children 1–4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives.

Methods

2102 children aged 6–59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP.

Findings

The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76–1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30–0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group.

Conclusions

Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00132548","term_id":"NCT00132548"}}NCT00132548     

Abundance and distribution of bacterioplankton in the Gambia River,West Africa

Four ecological zones of the Gambia River were sampled during four different hydrologic seasons for determination of microbial, nutrient, and physical parameters. A Greco-Latin Square experimental design was used to define the particular transect, station, depth, and tide/time-of-day of samples taken. Ranges of total bacterioplankton densities (10⁶ cells/ml) were similar to those of tropical and temperate environments. Numbers of free bacteria were similar temporally, whereas attached bacteria numbers were greater during periods of high stream flows when suspended solids concentrations were higher. Free bacteria were usually twice as numerous in the freshwater zones than in the estuarine zones. Attached bacterial densities were approximately four times greater in the estuarine zones than in the freshwater zones. Uptake of³H-glucose on both a sample volume and per-cell basis increased from the early stages of the flood (6.95±SE 1.37 ng/liter/hour and 3.8 pg/hour/10⁶ cells, respectively) and reached observed annual maximums during the dry season (21.01±SE 3.05 ng/ liter/hour and 13.0 pg/hour/10⁶ cells, respectively). Spatially,³H-glucose uptake per sample volume and per cell was highest in the upper river zone and lowest in the lower estuary zone. The lower estuary zone consistently acted out of concert with the other river zones in terms of³H-glucose and¹⁴C-bicarbonate uptake. Analysis of variance (ANOVA) indicated that free and attached bacterioplankton densities were not homogeneous among transects, stations, depths, and tide/time-of-day at the different zones during the four hydrologic seasons. The results suggested that heterotrophy overshadowed autotrophy in the river and that the bacterial abundance, distribution, and glucose uptake activity in this tropical floodplain river were greatly influenced by the annual flood and the presence of extensive mangrove forests in the estuary.     

International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study

BackgroundGestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.Methods and findingsSecondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery.We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m². Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks’ gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19⁺⁵ weeks’ gestation, a change of −0·6 (95% CI −0.8 to −0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks’ gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study’s main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.ConclusionsOur findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.

Lauren Green and colleagues study blood pressure in pregnant women across a range of countries.     

Self-assembly of the octapeptide lanreotide and lanreotide-based derivatives: the role of the aromatic residues.

We investigated the spectroscopic properties of the aromatic residues in a set of octapeptides with various self-assembly properties. These octapeptides are based on lanreotide, a cyclic peptide analogue of somatostatin-14 that spontaneously self-assembles into very long and monodisperse hollow nanotubes. A previous study on these lanreotide-based derivatives has shown that the disulfide bridge, the peptide hairpin conformation and the aromatic residues are involved in the self-assembly process and that modification of these properties either decreases the self-assembly propensity or modifies the molecular packing resulting in different self-assembled architectures. In this study we probed the local environment of the aromatic residues, naphthyl-alanine, tryptophan and tyrosine, by Raman and fluorescence spectroscopy, comparing nonassembled peptides at low concentrations with the self-assembled ones at high concentrations. As expected, the spectroscopic characteristics of the aromatic residues were found to be sensitive to the peptide-peptide interactions. Among the most remarkable features we could record a very unusual Raman spectrum for the tyrosine of lanreotide in relation to its propensity to form H-bonds within the assemblies. In Lanreotide nanotubes, and also in the supramolecular architectures formed by its derivatives, the tryptophan side chain is water-exposed. Finally, the low fluorescence polarization of the peptide aggregates suggests that fluorescence energy transfer occurs within the nanotubes.     

Somatic embryogenesis and plant regeneration from shoot-tip explants inPhoenix dactylifera L.

For maximum avoidance of somaclonal variation risks, the commonly used medium for somatic embryogenesis inPhoenix dactylifera has been lowered in growth regulators and activated charcoal. When initially cultured on MS basal medium containing only 150 mg dm^?3 charcoal, 5 mg dm^?3 2,4-dichlorophenoxyacetic acid (2,4-D) and 5 mg dm^?3 benzylaminopurine (BAP), 10 to 20% of shoot-tip explants developed into embryogenic calli. The embryogenic potential has been maintained for over 24 months with no decline. In addition, this medium has been found to be more efficient than conventionaly one containing 3 g dm^?3 charcoal, 100 mg dm^?3 2,4-D and 3 mg dm^?3 2-isopentyladenosine (2IP). Plantlet regeneration was achieved when somatic embryos were subcultured to medium with 0.1 mg dm^?3 2,4-D and 0.5 mg dm^?3 BAP or without growth regulators.