A tetravalent Shigella Outer Membrane Vesicles based candidate vaccine offered cross-protection against all the serogroups of Shigella in adult mice
Microbes Infect. 2023 Jan 22:105100. doi: 10.1016/j.micinf.2023.105100. Online ahead of print.
In today's world and mostly in low and middle income countries, S. flexneri and S. sonnei remains the major causative agent of clinical bacillary dysentery. Based on contemporary epidemiology, a tetravalent Outer Membrane Vesicle (OMVs) based immunogen was formulated using the most commonly circulating Shigella strains, namely, S. flexneri 2a, S. flexneri 3a, S. flexneri 6 and S. sonnei I, in a 1:1:1:1 ratio. Adult BALB/c mice were orally immunized in a prime-boost-boost manner. Tetravalent Shigella OMVs immunogen induced significant and persistent serum and mucosal antibodies against OMVs, Outer Membrane Proteins (OMPs) and lipopolysaccharides (LPS). Tetravalent OMVs also primed cell mediated immune response effectively. Protective efficacy against six heterologous Shigella strains was checked in an intra-peritoneal mouse model. Immunized mice survived lethal infection better than the non-immunized mice cohort with fewer replicating bacteria isolated from their gut. This study establishes the possibilities of tetravalent OMVs immunogen to become a potent vaccine candidate against human shigellosis, overcoming the limitations of sero-specific cross-protection of Shigella species.
Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia
BMC Public Health. 2023 Jan 23;23(1):152. doi: 10.1186/s12889-023-15051-w.
BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia.
METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA).
RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%).
CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.
Conjugative RP4 Plasmid-Mediated Transfer of Antibiotic Resistance Genes to Commensal and Multidrug-Resistant Enteric Bacteria In Vitro
Microorganisms. 2023 Jan 12;11(1):193. doi: 10.3390/microorganisms11010193.
Many antibiotic-resistant bacteria carry resistance genes on conjugative plasmids that are transferable to commensals and pathogens. We determined the ability of multiple enteric bacteria to acquire and retransfer a broad-host-range plasmid RP4. We used human-derived commensal Escherichia coli LM715-1 carrying a chromosomal red fluorescent protein gene and green fluorescent protein (GFP)-labeled broad-host-range RP4 plasmid with ampR, tetR, and kanR in in vitro matings to rifampicin-resistant recipients, including Escherichia coli MG1655, Dec5α, Vibrio cholerae, Pseudomonas putida, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter rodentium, and Salmonella Typhimurium. Transconjugants were quantified on selective media and confirmed using fluorescence microscopy and PCR for the GFP gene. The plasmid was transferred from E. coli LM715-1 to all tested recipients except P. aeruginosa. Transfer frequencies differed between specific donor-recipient pairings (10-2 to 10-8). Secondary retransfer of plasmid from transconjugants to E. coli LM715-1 occurred at frequencies from 10-2 to 10-7. A serial passage plasmid persistence assay showed plasmid loss over time in the absence of antibiotics, indicating that the plasmid imposed a fitness cost to its host, although some plasmid-bearing cells persisted for at least ten transfers. Thus, the RP4 plasmid can transfer to multiple clinically relevant bacterial species without antibiotic selection pressure.
Math Biosci Eng. 2022 Aug 25;19(12):12427-12447. doi: 10.3934/mbe.2022580.
In this paper, we consider an age-structured cholera model with saturation incidence, vaccination age of vaccinated individuals, infection age of infected individuals, and biological age of pathogens. First, the basic reproduction number is calculated. When the basic reproduction number is less than one, the disease-free equilibrium is locally stable. Further, the existence of backward bifurcation of the model is obtained. Numerically, we also compared the effects of various control measures, including basic control measures and vaccination, on the number of infected individuals.
Mechanisms of cholera transmission via environment in India and Bangladesh: state of the science review
Rev Environ Health. 2023 Jan 16. doi: 10.1515/reveh-2022-0201. Online ahead of print.
OBJECTIVES: Cholera has a long history in India and Bangladesh, the region where six out of the past seven global pandemics have been seeded. The changing climate and growing population have led to global cholera cases remaining high despite a consistent improvement in the access to clean water and sanitation. We aim to provide a holistic overview of variables influencing environmental cholera transmission within the context of India and Bangladesh, with a focus on the mechanisms by which they act.
CONTENT: We identified 56 relevant texts (Bangladesh n = 40, India n = 7, Other n = 5). The results of the review found that cholera transmission is associated with several socio-economic and environmental factors, each associated variable is suggested to have at least one mediating mechanism. Increases in ambient temperature and coastal sea surface temperature support cholera transmission via increases in plankton and a preference of Vibrio cholerae for warmer waters. Increased rainfall can potentially support or reduce transmission via several mechanisms.
SUMMARY AND OUTLOOK: Common issues in the literature are co-variance of seasonal factors, limited access to high quality cholera data, high research bias towards research in Dhaka and Matlab (Bangladesh). A specific and detailed understanding of the relationship between SST and cholera incidence remains unclear.
MMWR Morb Mortal Wkly Rep. 2023 Jan 13;72(2):21-25. doi: 10.15585/mmwr.mm7202a1.
On September 30, 2022, after >3 years with no confirmed cholera cases (1), the Directorate of Epidemiology, Laboratories and Research (DELR) of the Haitian Ministry of Public Health and Population (Ministère de la Santé Publique et de la Population [MSPP]) was notified of two patients with acute, watery diarrhea in the metropolitan area of Port-au-Prince. Within 2 days, Haiti's National Public Health Laboratory confirmed the bacterium Vibrio cholerae O1 in specimens from the two patients with suspected cholera infection, and an outbreak investigation began immediately. As of January 3, 2023, >20,000 suspected cholera cases had been reported throughout the country, and 79% of patients have been hospitalized. The moving 14-day case fatality ratio (CFR) was 3.0%. Cholera, which is transmitted through ingestion of water or food contaminated with fecal matter, can cause acute, severe, watery diarrhea that can rapidly lead to dehydration, shock, and death if not treated promptly (2). Haiti is currently facing ongoing worsening of gang violence, population displacement, social unrest, and insecurity, particularly in the metropolitan area of Port-au-Prince, including Belair, Bas-Delmas, Centre-Ville, Martissant, Cité Soleil, Croix-des Bouquets, and Tabarre, creating an environment that has facilitated the current resurgence of cholera (3). This report describes the initial investigation, ongoing outbreak, and public health response to cholera in Haiti. Cholera outbreak responses require a multipronged, multisectoral approach including surveillance; case management; access to safe water, sanitation, and hygiene (WASH) services; targeted oral cholera vaccine (OCV) campaigns; risk communication; and community engagement. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.
Zhonghua Yi Shi Za Zhi. 2022 Nov 28;52(6):354-361. doi: 10.3760/cma.j.cn112155-20220621-00091.
The cholera epidemic in 1919 started from coastal cities in the south of China and the cities near Russia in the north. It centered on those cities with relatively developed economies with well-developed transportation, and spread along railway lines and coastal lines in both directions to the North and the South, based on the reports in Ta Kung Pao. It covered 14 provinces, the municipalities under the Central Government and the special administrative regions. To prevent and control the 1919 cholera epidemic, the Republic of China government took some effective measures, such as reminding people of prevention, providing medical assistance, controlling the flow of people and cutting off transmission routes. It was found that some serious issues were exposed in the process of preventing and controlling the 1919 cholera epidemic, such as corrupt government, the ignorance of part of the population and poor medical services and technology. Analysing the historical materials of the 1919 cholera epidemic and summarising its experience and lessons in Ta Kung Pao can provide references for future epidemic prevention and control.
Int J Mol Sci. 2022 Dec 28;24(1):531. doi: 10.3390/ijms24010531.
Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT that is responsible for protection remains to be clarified. A library of one-hundred, twenty-two 15-mer peptides covering the entire sequence of the three chains of the CT protein (CTP) was prepared by SPOT synthesis. The immunoreactivity of membrane-bound peptides with sera from mice vaccinated with an oral inactivated vaccine (Schankol™) allowed the mapping of continuous B-cell epitopes, topological studies, multi-antigen peptide (MAP) synthesis, and Enzyme-Linked Immunosorbent Assay (ELISA) development. Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three V. cholera specific epitopes, Vc/TxA-3, Vc/TxB-11, and Vc/TxP-16, were synthesized as MAP4 and used to coat ELISA plates in order to screen immunized mouse sera. Sensitivities and specificities of 100% were obtained with the MAP4s of Vc/TxA-3 and Vc/TxB-11. The results revealed a set of peptides whose immunoreactivity reflects the immune response to vaccination. The array of peptide data can be applied to develop improved serological tests in order to detect cholera toxin exposure, as well as next generation vaccines to induce more specific antibodies against the cholera toxin.
Emerg Infect Dis. 2023 Jan;29(1):149-153. doi: 10.3201/eid2901.220641.
Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.
J Water Health. 2022 Dec;20(12):1755-1760. doi: 10.2166/wh.2022.262.
Cholera is an ancient disease that persists as an issue of public health in many conflict-affected countries worldwide. Cholera is a diarrheal infection caused by ingested water or food contaminated with the bacterium Vibrio cholerae. On 10 September 2022, the Ministry of Health in Syria declared a cholera outbreak. Poor water and sanitation systems, disease surveillance breakdown, the collapse of the health system, and deteriorated socioeconomic conditions are potential risk factors for the outbreak's spread. Identifying the context-related factors associated with the spread of disease is a core to developing practical response mechanisms. In this study, we suggested a multisectoral approach that addresses context-specific elements contributing to the cholera outbreak spread in Syria; public health determinants, geopolitics, risk factors, and pandemic fatigue.
Vertical transmission rate of HIV exposed twin pregnancies and associated factors in West Bengal, India; A retrospective cohort study
Jpn J Infect Dis. 2022 Dec 28. doi: 10.7883/yoken.JJID.2022.562. Online ahead of print.
Twin pregnancy is often associated with adverse obstetric outcomes. Mother to child transmission of HIV in twin pregnancy is less explored. The present study aimed to determine the risk of vertical transmission of HIV in HIV exposed twin pregnancy in comparison to singleton and to explore associated factors. We conducted a retrospective cohort study involving 348 HIV exposed babies (58 twin and 290 singleton) through systematic sampling from program database of West Bengal, India from April 2016 to March 2021. HIV vertical transmission rate was compared between single and twin live births. The effects of factors like maternal age, timing of maternal HIV diagnosis, duration of Antiretroviral Treatment, mode of delivery, birth weight and gender of baby etc. were determined. The HIV transmission rate for twin pregnancy (15.52% ) was significantly higher than single live-birth (5.5%) [Adjusted Odds Ratio = 3.08 (1.15-8.23)]. Among twin deliveries, maternal HIV diagnosis during intrapartum and postpartum period was associated with HIV transmission [Crude Odds Ratio= 11.0 (2.2-54.9)]. In conclusion perinatal HIV transmission is more common in twin pregnancies and linked with time of detection of maternal HIV. Early HIV detection and additional Antiretroviral regimen may be thought of for twin pregnancies.
Pre-emptive oral cholera vaccine (OCV) mass vaccination campaign in Cuamba District, Niassa Province, Mozambique: feasibility, vaccination coverage and delivery costs using CholTool
BMJ Open. 2022 Sep 7;12(9):e053585. doi: 10.1136/bmjopen-2021-053585.
INTRODUCTION: Mozambique suffers from regular floods along its principal river basins and periodic cyclones that resulted in several cholera epidemics during the last decades. Cholera outbreaks in the recent 5 years affected particularly the northern provinces of the country including Nampula and Niassa provinces. A pre-emptive oral cholera vaccine (OCV) mass vaccination campaign was conducted in Cuamba District, Niassa Province, and the feasibility, costs, and vaccination coverage assessed.
METHODS: WHO prequalified OCV (Euvichol-Plus), a killed whole-cell bivalent vaccine containing Vibrio cholerae O1 (classical and El Tor) and O139, was administered in two doses with a 15-day interval during 7-31 August 2018, targeting around 180 000 people aged above 1 year in Cuamba District. Microplanning, community sensitisation, and training of local public health professionals and field enumerators were conducted. Feasibility and costs of vaccination were assessed using CholTool. Vaccination coverage and barriers were assessed through community surveys.
RESULTS: The administrative coverage of the first and second rounds of the campaign were 98.9% (194 581) and 98.8% (194 325), respectively, based on the available population data that estimated total 196 652 inhabitants in the target area. The vaccination coverage survey exhibited 75.9% (±2.2%) and 68.5% (±3.3%) coverage for the first and second rounds, respectively. Overall, 60.4% (±3.4%) of the target population received full two doses of OCV. Barriers to vaccination included incompatibility between working hours and campaign time. No severe adverse events were notified. The total financial cost per dose delivered was US$0.60 without vaccine cost and US$1.98 including vaccine costs.
CONCLUSION: The pre-emptive OCV mass vaccination campaign in remote setting in Mozambique was feasible with reasonable full-dose vaccination coverage to confer sufficient herd immunity for at least the next 3 to 5 years. The delivery cost estimate indicates that the OCV campaign is affordable as it is comparable with Gavi's operational support for vaccination campaigns.