Insilico analysis of binding interactions and evaluation of mode of action of hydroxy tyrosol on candida albicans I, ii and parapsilosis

This work was aimed at purifying the most potent antibiofilm principle from Acalypha wilkesiana leaves against Candida species, analyzing its binding interactions with the molecular targets and evaluating its mode of action. Bioassay guided fractionation was carried and purification of the most potent fraction was achieved by Preparative -TLC. Proton NMR -spectroscopy was used to elucidate the structure of the most potent fraction which was hydroxy tyrosol (HT). There was significant (p < 0.05) increase in the IC50 of HT and caspafungin in the presence of sorbitol. In the presence of ergosterol, there was no significant (p > 0.05) increase in the IC50 of HT but there was significant (p < 0.05) increase in the IC50 of voriconazole. Insilico molecular studies revealed a good docking score (-7.7 and 4 hydogen bonds) with glucan synthase and (7.0 and 1 hydrogen bond) with lanosterole-14α- demethylase. The mode of action of HT is most likely by inhibiting the activities of β-1,3-D glucan synthase. The Significant increase in IC50 of HT in the presence of sorbitol showed that its inhibition leads to depletion of cell wall glucan and subsequent lysis of fungal cells

Cryptococcal meningitis associated HIV infection in the Donka national hospital in Conakry (Guinea)

Background Cryptococcal meningitis (CM) is an infection of the brain parenchyma and subarachnoid space by the encapsulated saprophyte yeast organisms such as Cryptococcus neoformans. Over the last twenty years, HIV has created a large and severely immune compromisized population in whom C. neoformans is a dangerous opportunistic infection. In Guinea, the prevalence of CM is unknown. We hypothesized that the occurrence of CM correlates with AIDS/ HIV prevalence.Method This retrospective observational study was carried out at the national Hospital of Conakry (Guinea) between 2001 and 2002. We describe here the epidemiological and clinical and biological characteristics of CM disease in our national hospital.Results Our data show that, 28.6 % of HIV patients with neurological symptoms had Cryptococcus neoformans in their CSF by using Indian ink staining. The median age was 36±3 years and sex ratio (M/F) was 1.8. The major complaints were fever and cephalgia, giddiness while the major complications were altered consciousness and hemiplegia. CSF was clear with low level of glucose and higher level of albumin. The means of lymphocytes in CSF was 8±2/mm3.Conclusion This data therefore becomes relevant in not only focusing of neurological symptoms associated with HIV to be toxoplasmosis but the possibility of C neoformans in these patients; particularly when they present symptoms such as headaches, giddiness and sniff neck etc. This can easily be carried out with Indian ink staining technique

Molecular detection of Leishmania parasites from whole bodies of sandflies collected in Nepal.

Visceral leishmaniasis is endemic in the southern part of the Terai region of Nepal. Natural infections of Phlebotomus species with Leishmania parasites in these endemic areas were analyzed by a polymerase chain reaction (PCR) amplification-based assay. A total of 401 Phlebotomus argentipes and 202 P. papatasi female sandflies were captured in the Dhanusa district from 2004 to 2006 and analyzed. It was found that 6.7% of P. argentipes, but no P. papatasi, were positive for Leishmania parasites, suggesting that P. argentipes is a major vector in these areas. The infectivity of P. argentipes with Leishmania was consistent with the infection rates reported from other areas of the world. This is the first report of naturally infected Leishmania parasites in sandflies collected from Nepal

マラリア感染と治療を繰り返すことにより制御性のCD19陽性B細胞が生じ実験的脳マラリアの発症が抑制される

In African endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. Here, we developed an experimental cerebral malaria (ECM) model for semi-immune mice. C57BL/6 (B6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 104 Plasmodium berghei ANKA without treatment. Our results showed that 100% of naive (0-cure), 67% of 1-cure, 37% of 2-cure and none of 3-cure mice succumbed to ECM within 10 days post challenge infection. In the protected 3-cure mice, significantly higher levels of plasma IL-10 and lower levels of IFN-γ than the others on day 7 post challenge infection were observed. Major increased lymphocyte subset of IL-10 positive cells in 3-cure mice was CD5(?)CD19(+) B cells. Passive transfer of splenic CD19(+) cells from 3-cure mice protected naive mice from ECM. Additionally, aged 3-cure mice were also protected from ECM 12 and 20 months after the last challenge infection. In conclusion, mice became completely resistant to ECM after three exposures to malaria. CD19(+) B cells are determinants in protective mechanism of semi-immune mice against ECM possibly via modulatory IL-10 for pathogenic IFN-γ production.長崎大学学位論文 学位記番号:博(医歯薬)甲第611号 学位授与年月日:平成25年8月7日Author： Lam Quoc Bao , Nguyen Tien Huy , Mihoko Kikuchi, Tetsuo Yanagi, Masachika Senba, Mohammed Nasir Shuaibu, Kiri Honma, Katsuyuki Yui, Kenji HirayamaCitation: PLoS ONE, 8(5), e64836; 2013Nagasaki University (長崎大学)課程博

Improving maternal and newborn health services in Northeast Nigeria through a government-led partnership of stakeholders: a quasi-experimental study.

OBJECTIVES: This study aimed to quantify change in the coverage, quality and equity of essential maternal and newborn healthcare interventions in Gombe state, Northeast Nigeria, following a four year, government-led, maternal and newborn health intervention. DESIGN: Quasi-experimental plausibility study. Repeat cross-sectional household and linked health facility surveys were implemented in intervention and comparison areas. SETTING: Gombe state, Northeast Nigeria. PARTICIPANTS: Each household survey included a sample of 1000 women aged 13-49 years with a live birth in the previous 12 months. Health facility surveys comprised a readiness assessment and birth attendant interview. INTERVENTIONS: Between 2016-2019 a complex package of evidence-based interventions was implemented to increase access, use and quality of maternal and newborn healthcare, spanning the six WHO health system building blocks. OUTCOME MEASURES: Eighteen indicators of maternal and newborn healthcare. RESULTS: Between 2016 and 2019, the coverage of all indicators improved in intervention areas, with the exception of postnatal and postpartum contacts, which remained below 15%. Greater improvements were observed in intervention than comparison areas for eight indicators, including coverage of at least one antenatal visit (71% (95% CI 62 to 68) to 88% (95% CI 82 to 93)), at least four antenatal visits (46% (95% CI 39 to 53) to 69% (95% CI 60 to 75)), facility birth (48% (95% CI 37 to 59) to 64% (95% CI 54 to 73)), administration of uterotonics (44% (95% CI 34 to 54) to 59% (95% CI 50 to 67)), delayed newborn bathing (44% (95% CI 36 to 52) to 62% (95% CI 52 to 71)) and clean cord care (42% (95% CI 34 to 49) to 73% (95% CI 66 to 79)). Wide-spread inequities persisted however; only at least one antenatal visit saw pro-poor improvement. CONCLUSIONS: This intervention achieved improvements in life-saving behaviours for mothers and newborns, demonstrating that multipartner action, coordinated through government leadership, can shift the needle in the right direction, even in resource-constrained settings

Characterization of a Gene Family Encoding SEA (Sea-urchin Sperm Protein, Enterokinase and Agrin)-Domain Proteins with Lectin-Like and Heme-Binding Properties from Schistosoma japonicum

BackgroundWe previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information.Methodology/Principal FindingsHere, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin)-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (KD = 1.605×10?6 M) and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition.ConclusionsThe results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation), and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted

Molecular detection of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts in wild population of tsetse flies collected in Cameroon, Chad and Nigeria

Abstract Background Tsetse flies are cyclical vectors of African trypanosomiasis (AT). The flies have established symbiotic associations with different bacteria that influence certain aspects of their physiology. Vector competence of tsetse flies for different trypanosome species is highly variable and is suggested to be affected by bacterial endosymbionts amongst other factors. Symbiotic interactions may provide an avenue for AT control. The current study provided prevalence of three tsetse symbionts in Glossina species from Cameroon, Chad and Nigeria. Results Tsetse flies were collected and dissected from five different locations. DNA was extracted and polymerase chain reaction used to detect presence of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts, using species specific primers. A total of 848 tsetse samples were analysed: Glossina morsitans submorsitans (47.52%), Glossina palpalis palpalis (37.26%), Glossina fuscipes fuscipes (9.08%) and Glossina tachinoides (6.13%). Only 95 (11.20%) were infected with at least one of the three symbionts. Among infected flies, six (6.31%) had Wolbachia and Spiroplasma mixed infection. The overall symbiont prevalence was 0.88, 3.66 and 11.00% respectively, for Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts. Prevalence varied between countries and tsetse fly species. Neither Spiroplasma species nor S. glossinidius were detected in samples from Cameroon and Nigeria respectively. Conclusion The present study revealed, for the first time, presence of Spiroplasma species infections in tsetse fly populations in Chad and Nigeria. These findings provide useful information on repertoire of bacterial flora of tsetse flies and incite more investigations to understand their implication in the vector competence of tsetse flies

Understanding rural women's preferences for telephone call engagement with primary health care providers in Nigeria: a discrete choice experiment

Background The COVID-19 pandemic has accelerated the use of mobile phones to provide primary health care services and maintain continuity of care. This study aims to understand rural women’s preferences for telephone call engagement with primary health care providers in Nigeria.Methods A discrete choice experiment was conducted alongside an action research project that empowered primary health care workers to develop and implement a telephone call intervention to assess and enhance experiences with facility childbirth care. Between January and March 2022, 30 providers from 10 primary health care facilities implemented the choice experiment among rural women who had institutional childbirth to elicit service user preferences for telephone call engagement. The women were asked to express their preferred scenario for telephone call engagement with their primary health care providers. Generalised linear mixed models were used to estimate women’s preferences.Results Data for 460 women were available for the discrete choice experiment. The study showed that rural women have preferences for telephone call engagement with primary health care providers. Specifically, women preferred engaging with female to male callers (β=1.665 (95% CI 1.41, 1.93), SE=0.13, p<0.001), preferred call duration under 15 min (β=1.287 (95% CI 0.61, 1.96), SE=0.34, p<0.001) and preferred being notified before the telephone engagement (warm calling) (β=1.828 (95% CI 1.10, 2.56), SE=0.37, p<0.001). Phone credit incentive was also a statistically significant predictor of women’s preferences for engagement. However, neither the availability of scheduling options, the period of the day or the day of the week predicts women’s preferences.Conclusions The study highlights the importance of understanding rural women’s preferences for telephone call engagement with healthcare providers in low-income and middle-income countries. These findings can inform the development of mobile phone-based interventions and improve acceptability and broader adoption

Protein expression and antigenicity of the candidate proteins.

<p>(<b>A</b>) SDS-PAGE of recombinant <i>E. coli</i> lysates (lane L) and purified protein without inclusion bodies (lane P). Arrows indicate expected molecular weights of oligomers. Other bands are expected SEA-domain cleavage products. (<b>B</b>) Western blots of recombinant protein expression as in (B), probed with anti-HisG antibody. (<b>C</b>) Anti-HisG probed western blots showing oligomerization of proteins with multiple bands of additive ∼30 kDa subunits, and tetramer as the most stable state. (<b>D</b>) Size exclusion gel filtration chromatography of SjCP3842 showed multiple elution peaks, another evidence of oligomerization. (<b>E</b>) Immunoblots showing reactivity of parasite crude antigen preparations (SEA and SWA) with immune sera. (<b>F</b>) The candidate proteins specifically reacted with infected miniature pig sera in IgG ELISA, indicating potential antigenicity during schistosomiasis. Bars represent standard deviation (SD). * = p<0.05, ** = p<0.01. n = 4 for each group.</p