The basic reproduction number (R0) of ebola virus disease: A systematic review and meta-analysis.

BACKGROUND: Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R0): the average number of new cases associated with an Ebola case in a completely susceptible population. METHODS: We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (Rt). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R0 was determined by a random-effects meta-analysis. R0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R0) × 100 %. RESULTS: The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R0 was 1.95 (95 % CI 1.74-2.15), with high heterogeneity (I2 = 99.99 %; τ2 = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R0 values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R0 was 9.38 (95 % CI 4.16-14.59) in Nigeria, 3.31 (95 % CI 2.30-4.32) in DR Congo, 2.0 (95 % CI 1.25-2.76) in Uganda, 1.83 (95 % CI 1.61-2.05) in Liberia, 1.73 (95 % CI 1.47-2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29-1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective. CONCLUSIONS: Ebola R0 varies widely across countries. Ebola has a much wider R0 range than is often claimed (1.3-2.0). It is possible for an Ebola index case to infect more than two susceptible individuals.

Burden of Shigella in South Asia: a systematic review and meta-analysis.

BACKGROUND: Shigella remains one of the most common causes of diarrhoea in South Asia. Current estimates of the prevalence of Shigella are critical for guiding control measures. We estimated the prevalence of Shigella species and serogroups in South Asia. METHODS: We performed a systematic review using PubMed, EMBASE, Google Scholar and Web of Science for peer-reviewed studies published between 2000 and 19 June 2022. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that detected the presence of Shigella in stool by culture or polymerase chain reaction (PCR). Studies associated with outbreaks were excluded. Two investigators independently reviewed the studies, extracted the data and performed quality assessment. A random-effects meta-analysis was performed to determine the pooled prevalence of Shigella. RESULTS: Our search yielded 5707 studies, of which 91 studies from five South Asian countries were included in the systematic review, 79 in the meta-analysis of Shigella prevalence and 63 in the meta-analysis of Shigella serogroups prevalence. The pooled prevalence of Shigella was 7% [95% confidence interval (CI): 6-7%], with heterogeneity (I2 = 98.7; P < 0.01). The prevalence of Shigella was higher in children aged <5 years (10%; 95% CI: 8-11%), in rural areas (12%; 95% CI: 10-14%) and in studies using PCR (15%; 95% CI: 11-19%). Shigella flexneri (58%) was the most abundant serogroup, followed by Shigella sonnei (19%), Shigella boydii (10%) and Shigella dysenteriae (9%). Shigella flexneri 2a was the most frequently isolated serotype (36%), followed by serotype 3a (12%), serotype 6 (12%) and serotype 1b (6%). The prevalence of non-typeable Shigella was 10.0%. CONCLUSIONS: Although the prevalence of Shigella in South Asia remains generally high, it varies by age group and geographical area, with data lacking in some countries. Effective Shigella vaccines would be advantageous for both endemic communities and travellers.

Shigellosis in Southeast Asia: A systematic review and meta-analysis.

BACKGROUND: Southeast Asia is attractive for tourism. Unfortunately, travelers to this region are at risk of becoming infected with Shigella. We conducted a meta-analysis to provide updates on Shigella prevalence in Southeast Asia, along with their serogroups and serotypes. METHODS: We conducted a systematic search using PubMed, EMBASE, and Web of Science for peer-reviewed studies from 2000 to November 2022. We selected studies that detected Shigella in stools by culture or polymerase chain reaction (PCR). Two reviewers extracted the data using a standardized form and performed quality assessments using the Joanna Briggs Institute checklist. The random effects model was used to estimate the pooled prevalence of Shigella. RESULTS: During our search, we identified 4376 studies. 29 studies (from six Southeast Asian countries) were included in the systematic review, 21 each in the meta-analysis of the prevalence of Shigella (Sample size: 109545) and the prevalence of Shigella serogroups. The pooled prevalence of Shigella was 4% (95% CI: 4-5%) among diarrhea cases. Shigella sonnei was the most abundant serogroup in Thailand (74%) and Vietnam (57%), whereas Shigella flexneri was dominant in Indonesia (72%) and Cambodia (71%). Shigella dysenteriae and Shigella boydii were uncommon (pooled prevalence of 1% each). The pooled prevalence of Shigella was 5% (95% CI: 4-6%) in children aged <5 years. The pooled prevalence showed a decreasing trend comparing data collected between 2000-2013 (5%; 95% CI: 4-6%) and between 2014-2022 (3%; 95% CI: 2-4%). Shigella prevalence was 6% in studies that included participants with mixed pathogens versus 3% in those without. Shigella flexneri serotype 2a was the most frequently isolated (33%), followed by 3a (21%), 1b (10%), 2b (3%), and 6 (3%). CONCLUSIONS: This study provides compelling evidence for the development of effective Shigella vaccines for residents of endemic regions and travellers to these areas.

Complete genomic sequence of Vibrio fluvialis strain IDH5335 isolated from a patient with diarrhea in Kolkata, India.

We isolated a Vibrio fluvialis strain (IDH5335) from a stool sample collected from a patient with diarrhea. In this announcement, we report the complete genomic sequence of this organism, which was obtained by combining Illumina and Oxford Nanopore sequencing data.

Long-Term Kinetics of Serological Antibodies against Vibrio cholerae Following a Clinical Cholera Case: A Systematic Review and Meta-Analysis.

BACKGROUND: Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking. OBJECTIVE: To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case. METHODS: Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against Vibrio cholerae in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged ≥ 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included. RESULTS: Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged ≥ 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis. CONCLUSIONS: This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.

AUF-1 knockdown in mice undermines gut microbial butyrate-driven hypocholesterolemia through AUF-1-Dicer-1-mir-122 hierarchy.

Introduction and objective: Cholesterol homeostasis is a culmination of cellular synthesis, efflux, and catabolism to important physiological entities where short chain fatty acid, butyrate embodied as a key player. This discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance. Methods: Hepatic mir-122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of mir-122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model. We synthesized unique self-transfecting GMO (guanidinium-morpholino-oligo) linked PMO (Phosphorodiamidate-Morpholino Oligo)-based antisense cell-penetrating reagent to selectively knock down the key player in butyrate mediated cholesterol regulation. Results: We showed that butyrate treatment caused upregulation of RNA-binding protein, AUF1 resulting in RNase-III nuclease, Dicer1 instability, and significant diminution of mir-122. We proved the importance of AUF1 and sequential downstream players in AUF1-knock-down mice. Injection of GMO-PMO of AUF1 in mouse caused near absence of AUF1 coupled with increased Dicer1 and mir-122, and reduced serum cholesterol regardless of butyrate treatment indicating that butyrate acts through AUF1. Conclusion: The roster of intracellular players was as follows: AUF1-Dicer1-mir-122 for triggering butyrate driven hypocholesterolemia. To our knowledge this is the first report linking AUF-1 with cholesterol biogenesis.

Characterization of an arabinogalactan isolated from gum exudate of Odina wodier Roxb.: Rheology, AFM, Raman and CD spectroscopy.

Purified gum odina (PGO) from Odina wodier Roxb. was characterized by rheology, AFM, Raman and CD spectroscopy, in vitro antioxidant activity against hydroxyl radical and superoxide radical, and total antioxidant capacity. The PGO dispersions exhibited pseudoplastic behaviour. The viscosity of dispersion increased with increasing PGO concentration, but decreased with increasing temperature and added salt concentration. The loss modulus was higher than storage modulus indicating prevalently viscous characteristics. AFM analysis showed irregular spherical lumps due to inter- and intramolecular interactions. The Raman spectrum of PGO was similar to that of gum arabic. Circular dichroism revealed partial adoption of polyproline II type conformation, suggesting a less compact structure. The PGO was found to scavenge hydroxyl radical (IC50 517.68 ± 3.60 µg/mL) and superoxide radical (IC50 586.21 ± 3.41 µg/mL), and possess total antioxidant capacity (9.64 ± 0.23 mg gallic acid equivalent/g). Overall, this work would exploit PGO as a new hydrocolloid source in the food and pharmaceutical industries.

Prebiotic potential of gum odina and its impact on gut ecology: in vitro and in vivo assessments.

The use of prebiotics to escalate certain gut flora is a current aspect of research for effective gut ecology. In the present study we appraise the efficacy of gum odina obtained from the bark of Odina wodier (Anacardiaceae), which is not fully degraded (16%) in the upper GI tract and becomes available to the lower region, as a prebiotic. An in vitro prebiotic activity assay established a quantitative score to describe the extent to which gum odina supports the selective growth of probiotics with a maximum of 5.60 ± 0.11 for Lactobacillus plantarum MTCC 6160. The polysaccharide, upon fermentation, also liberates lactic acid (0.46 ± 0.003 mg ml(-1)) and acetic acid (1.03 ± 0.003 mg ml(-1)). In vivo studies revealed that natural gum selectively stimulates Lactobacillus sp., and eliminates enteric pathogens with a C.F.U. of 384.48 ± 0.11 and 40.56 ± 0.17 respectively on the 8(th) day. The changes in the level of ß-galactosidase signify maturation of macrophages in the gut environment. It also boosts the immune system by increasing sIgA upon infection from the 5(th) day in the gut, when incorporated into the feed of mice. Moreover an increase in levels of IFNγ on the 5(th) day also manifest additional protection against various pathogen-induced primary and secondary infections. Thus, gum odina is a potential prebiotic which not only provides nutrition but also improves gut ecology.

Synthesis, structure, spectral characterization, electrochemistry and evaluation of antibacterial potentiality of a novel oxime-based palladium(II) compound.

The title monomeric Pd(II) compound, [Pd(L)(Cl)], was synthesized in moderate yield out of the reaction of equimolar proportion of Na2[PdCl4] and 3-[(5-bromo-2-hydroxy-benzylidene)-hydrazono]-butan-2-one oxime (LH) in tetrahydrofuran milieu. LH is a 1:1 Schiff-base condensate of 2,3-butanedionemonoxime monohydrazone and 5-bromosalicylaldehyde. [Pd(L)(Cl)] has been characterized by C, H and N microanalyses, (1)H and (13)C NMR, FAB-MS, FT-IR, Raman spectra, UV-Vis spectra and molar electrical conductivity measurements. [Pd(L)(Cl)] is diamagnetic. Structural elucidation reveals that the palladium center in [Pd(L)(Cl)] is nested in 'N2OCl' coordination environment. The geometry around Pd in [Pd(L)(Cl)] is distorted square-planar. The redox behavior of [Pd(L)(Cl)] in DMF shows a reduction couple, Pd(II)/Pd(I) at -0.836 V versus Ag/AgCl. The in vitro antimicrobial activity of [Pd(L)(Cl)] was screened against both Gram-positive and Gram-negative human pathogenic bacteria. This bioactivity was substantiated with SEM study. [Pd(L)(Cl)] exhibits satisfactory bactericidal as well as bacteriostatic activity.