Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial.

BACKGROUND: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown. METHODS: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy. RESULTS: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel. CONCLUSIONS: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated. TRIAL REGISTRATION: ISRCTN: ISRCTN32849447

Novel use of stir bar sorptive extraction (SBSE) as a tool for isolation of oviposition site attractants for gravid Culex quinquefasciatus

Mosquitoes such as Culex quinquefasciatus Say (Diptera: Culicidae) are important vectors of organisms that cause disease in humans. Research into the development of effective standardized odour baits for blood-fed females (oviposition attractants), to enable entomological monitoring of vector populations, is hampered by complex protocols for extraction of physiologically active volatile chemicals from natural breeding site water samples, which have produced inconsistent results. Air entrainment and solvent extraction are technically demanding methods and are impractical for use in resource poor environments where mosquito-borne disease is most prevalent. This study reports the first use of a simple, robust extraction technique, stir bar sorptive extraction (SBSE), to extract behaviourally active small lipophilic molecules (SLMs) present in water samples collected from Cx. quinquefasciatus breeding sites in Tanzania. Extracts from a pit latrine and from a cess pool breeding site attracted more gravid Cx. quinquefasciatus in pair choice bioassays than control extracts, and coupled gas chromatography-electroantennography (GC-EAG) allowed tentative identification of 15 electrophysiologically active chemicals, including the known oviposition attractant, skatole (3-methylindole). Here, we have demonstrated, using simple pair choice bioassays in controlled laboratory conditions, that SBSE is effective for the extraction of behaviourally and electrophysiologically active semiochemicals from mosquito breeding site waters. Further research is required to confirm that SBSE is an appropriate technique for use in field surveys in the search for oviposition cues for Cx. quinquefasciatus

Laboratory evaluation of broflanilide (TENEBENAL™) against Anopheles gambiae in Moshi, Tanzania – delayed mortality, cross-resistance, and residual efficacy

Introduction: Broflanilide is a novel meta-diamide insecticide, which has a distinct mode of action compared to other active ingredients used for Indoor Residual Spraying (IRS). This study details a laboratory evaluation of broflanilide, of putative discriminating concentrations, potential cross-resistance, and residual efficacy on two substrates. Methods: Mosquitoes were exposed to broflanilide in bottle bioassays to determine lethal concentrations (LC50 and LC95). These were used to calculate resistance ratios between the susceptible Kisumu and the pyrethroid-resistant Muleba-Kis strains of Anopheles gambiae s.s. Prototype wettable powder formulations of broflanilide were applied to mud and concrete to determine the optimal observation period for determining delayed mortality, and a Cox proportional hazards model was fitted to determine a potential dose response effect. Subsequently, residual efficacy of application rates ranging between 25 mg/m2 and 300 mg/m2 were monitored monthly. Results: LC values of tested strains were not significantly different; therefore, the polyfactorial resistance mechanisms possessed by the resistant strain did not confer resistance to broflanilide. A significant effect of concentration and time since spraying was found on mosquito survival, indicating that higher broflanilide concentrations are more effective and that this effect was strongest immediately after spraying. Knockdown at 60min post exposure was negligible, with on average only 1% of all mosquitoes knocked down. On the mud surface, but not on concrete, there was a delayed killing effect, with mortality increasing until 72 hours after exposure. The residual efficacy test indicated that on concrete the 100 mg/m2 and 200 mg/m2 concentrations of both broflanilide 50WP formulations remained efficacious for 9 months post spraying. On mud, there were large variations in mosquito mortality from month to month. Generally, higher concentrations resulted in higher mortality, despite variation over time. Discussion: Cross-resistance to broflanilide was not detected in mosquitoes with multiple resistance mechanisms. This opens up the possibility for wide-scale use of broflanilide, especially in areas with established pyrethroid resistance. Like some other insecticide classes, delayed mortality up to 72 hours post exposure was found for broflanilide. Promising residual efficacy was found with broflanilide 50WP formulations on concrete. On mud, efficacy varied and further testing with a refined formulation is recommended

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Estimation of population parameters for a data deficient Salmostoma bacaila (Hamilton 1822) stock from the Mahananda river (tributary of the Ganges) in NW Bangladesh

403-409Salmostoma bacaila known as Razorbelly minnow (Hamilton in 1822) is an indigenous fish species in Bangladesh. This study emphasizes on population structure, growth pattern (length-weight and length-length relations), growth considerations (asymptotic length, L∞; weight, W∞; growth coefficient, K; age at zero length, t0), size and age at sexual maturity (Lm), growth performance index (φ), life-span (tmax), conditions factor (Allometric, KA; Fulton’s, KF and Relative, KR), prey-predator status through relative weight (WR), form factor (a3.0), total (Z), natural (M) and fishing mortality (F), exploitation rate (E) and maximum sustainable yield (MSY) of S. bacaila in the Mahananda river, northwestern Bangladesh. Total 305 specimens of S. bacaila were hardly sampled (ranging between 5.5 to 11.9 cm total length (TL), and 1.05 – 9.20 g total body weight (BW)) through regular fishing gears during August 2016 – July 2017. The regression coefficient ‘b’ of length-weight relations specified negative allometric growth. Growth parameters (GP) were figured as L∞ = 12.66 cm, K = 0.60 year-1, W∞ = 11.36 g, t0 = 0.048, tmax = 5.00 year-1 and φ’ = 1.98. The Lm was 7.34 cm in TL. Relative weight did not create any significant dissimilarity of 100 that would suggest a healthy habitat for S. bacaila. The a3.0 was 0.0052 specifying that this fish could be described as elongated. In addition, the Z was calculated to be 1.57 year-1. The M and F values obtained were 0.92 and 0.65 year-1, respectively. The E was 0.41 and MSY (Emax) was estimated as 0.35 year-1 by yield per recruitment model. Present research knowledge will be very useful in planning the sustainable and appropriate management of this species in Bangladesh and bordering countries

In vivo anxiolytic and in vitro anti-inflammatory activities of water-soluble extract (WSE) of Nigella sativa (L.) seeds

The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/day) for 72 hours has exhibited slightly better anxiolytic effect (p < 0.05) through the time span (92.33 & 93.33 s) spent in the opened arms of EPM vs. diazepam (1 mg/kg b.w i.p/day; 69.33 s). In HBT, only WSE (200 mg/kg b.w/day) has shown a promising number of mean head pokes (13.27 times/min) vs. diazepam (12.87 times/min). The WSE (62.5-500 mg/mL) exposure has exhibited 40.14-72.18% protection against lysis of RBCs vs. aspirin (57.04-71.48%) whilst 62.67-67.66% inhibition of protein denaturation vs. diclofenac sodium (43.11-80.64%). The current findings suggested WSE has promising anxiolytic and anti-inflammatory activities

Maternal Latent Mycobacterium tuberculosis Does Not Affect the Infant Immune Response Following BCG at Birth: An Observational Longitudinal Study in Uganda

Background: BCG has low efficacy in tropical countries. We hypothesized that maternal latent Mycobacterium tuberculosis (M.tb) infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization. Methods: We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. Cord blood and samples at weeks 1, 4, 6, 10, 14, 24, and 52 were analyzed for cytokine/chemokine responses to M.tb antigens by Luminex 17-plex assay in 6-day whole blood cultures and antibody responses by ELISA. Of the 17 Luminex analytes, seven (IL-2, IL-5, IL-10, IL-13, IL-17A, TNF, and IFN-γ) were included in the main analysis as they were considered most likely to represent T cell responses. Immune sensitization was defined as a detectable cord blood cytokine response to PPD for any of the seven cytokines. Patterns of cytokine and antibody responses were compared between infants of mothers with and without LTBI using linear mixed models adjusting for confounders. Results: Most infants (73%) were sensitized in utero to M.tb antigens, with no overall difference seen between infants born to mothers with or without LTBI. Patterns of post-BCG cytokine and antibody responses to mycobacterial antigens were similar between the two infant groups. Conclusions: Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.UK Medical Research Council; DELTAS Africa Initiative SSACAB; DELTAS Initiative MUIIplus; Commonwealth Scholarships Commission; MRC/UVRI and LSHTM Uganda Research Unit; EU Horizon 2020 programme; MRC London Intercollegiate Doctoral Training Partnership; MRC; UK Medical Research Council (MRC); UK Department for International Development (DFID)

Morphometric and meristic characteristics of Spotted snakehead Channa punctata (Bloch, 1793) in a wetland ecosystem (NW Bangladesh) using multi-linear dimensions

1442-1446This research work affirms the morphometric characters and meristic counts of Channa punctata (Bloch, 1793) in a wetland ecosystem (Gajner Beel) from the northwestern Bangladesh. A sum of 307 specimens of C. punctata were sampled intermittently from the Gajner Beel during July 2017 to December 2018, using different established fishing gears (cast net, gill net and square lift net with mesh size ranges: 1.50-2.50 cm, 1.50-2.00 cm, &amp; ~2.00 cm, respectively). Fin rays were counted by a magnifying glass. Seven diverse morphometric lengths were assessed and BW (body weight) was weighted for each specimen. The fin formula was: dorsal, D. 30-32; pectoral, P1. 15-17; pelvic, P2.5; anal, A. 19-21; and caudal, C. (ii -iv/12-14). Minimum and maximum sizes were 5.80 and 23.00 cm in total length (TL), whereas BWs were1.96 and 126.90 g, respectively. All length-weight relationships (LWRs) were greatly significant (p &lt; 0.001) with r2 &ge; 0.986. Based on r2 value, BW = 0.0112*(TL)2.98 was the most appropriate model among seven equations. Besides, based on r2 values, length-length relationships (LLRs) by TL vs. SL was the finest model among six equations. These findings will help for species identification and further stock/ biomass estimation of C. punctata in the Gajner Beel or connected ecosystems

Temporal variation of condition and prey-predator status for a schilbid catfish Eutropiichthys vacha (Hamilton, 1822) in the Ganges River, northwestern Bangladesh through multi-model inferences

1229-1237The current study provide the baseline information on the temporal (monthly) variations of condition through multiple functions (allometric, KA; Fulton’s, KF; relative, KR) and prey-predator status through relative weight (WR) for Eutropiichthys vacha (Hamilton, 1822) from the Ganges River, northwestern Bangladesh over one year. The smallest individuals were 6.5 and 6.2 cm in TL, whereas the largest were 19.9 and 20.6 cm in TL for males and females, respectively. No significant differences were observed in the length frequency distribution, LFDs (p = 0.8152) for both sexes. KF was significantly correlated with TL for both sexes (p KF was treated as the best condition factor therefore, well-being of E. vachaa. There was no significant correlation among TL vs KA, TL vs KR and TL vs WR for males and females, respectively. But BW showed highly significant correlations with all condition factors, i.e., BW vs KA; BW vs KF; BW vs KR, and BW vs WR (p WR revealed no significant dissimilarities from 100 for males (p = 0.432) unlike females (p = 0.023), based on Wilcoxon signed-rank tests, suggesting that habitat was more suitable for males than females for food availability relative to predator presence. Moreover, this study assessed for the first time the effect of temperature and rainfall on monthly KF for E. vacha in the Ganges River. The Pearson correlation test found no significant relation between temperature and KF (r = 0.2226, p = 0.4868 for males; r = 0.2172, p = 0.4977 for females), but significant correlations were found between rainfall and KF (r = 0.6357, p = 0.0263 for males and r = 0.6983, p = 0.0115 for females)