Background Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. Methods and findings In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. Conclusion In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.
With the Climate change effects becoming more and more undoubted in the world populations, the reality of food production trends taking a negative curve is clear. This bring up the questions of whether the farmers will be able to produce food for the sustenance of the world population or not? The rate of developing food shortage coping mechanisms in this regard is slower that the ravaging negative climate change effects of drought and floods on farm performance. This commentary has the aim of requesting a fresh discussion around the fundamentals of what is food, what is a food security and what is nutritional security? It is possible that the humanity has a perception that needs refocusing. This is a perception that some people may choose out of non-food safety issues not to eat certain foods while other however healthily eat such food. It therefore becomes hard to technically accept that food is in short supply for those the opt not to eat that which is edible.
Introduction In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps. Methods We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres. Results Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points. Conclusion We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.
IntroductionAntimicrobial resistance (AMR) is a growing public health problem in low-to-middle income countries which have a high burden of infectious diseases. Poor antimicrobial stewardship in these regions has resulted in a rise in reported cases of AMR creating a need for country specific data to inform policy on the strategies of combating AMR. Here we show antimicrobial susceptibility patterns of Shigella, and E. coli isolated from stools of children under 5 years of age and adults. MethodsThe study was nested under an enterotoxigenic Escherichia coli (ETEC) vaccine clinical trial and diarrhoea surveillance. Stool samples were collected at baseline, during scheduled visits and whenever the participants presented with diarrhoea as per study design. Following microbiological techniques for culture and microorganism identification, pure colonies were run on the BD Phoenix™ 100 for identification and antimicrobial susceptibility. For ETEC identification, colony PCR was done on all E. coli positive samples using heat-labile toxin and stable toxin specific primers, respectively.ResultsAmong the 211 samples analysed, 52.5% were from individuals with diarrhoea. Un-typed E. coli were the most common organism isolated (63.6%), followed by ETEC (12.7%) and 4.8% were Shigella sp. Majority of the organisms isolated were either susceptible or intermedial (80-100%) to all tested antibiotics except for Trimethoprim/Sulfamethoxazole which showed a high resistance of 82 – 93%. We also observed some multi-drug resistance (3.5%) among all organisms tested to the different antibiotics.ConclusionsThe observed high prevalence of co-trimoxazole resistance and intermedial susceptibility to fluoroquinolones among ETEC, Shigella and other un-typed E. coli isolates, is critical for informing policy on the urgent need for antimicrobial stewardship and strengthening of AMR surveillance systems in Zambia.
Background We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrient deficiency as indicated by serum retinol levels on the immune responses to Oral Cholera Vaccine (Shanchol™) in a cohort of participants in Lukanga Swamps, Zambia. Cholera remains endemic in Zambia with vaccines being the only effective preventive measures. However, the effect of these vaccines on populations living with HIV has not been widely documented. Methods HIV testing and confirmation was done using the Alere Determine™ HIV-1/2 and Uni-Gold™ kits while vibriocidal antibody assay was applied for vaccine immunogenicity. Serum retinol analysis was assessed by Shimadzu Prominence HCT-2010 High Performance Liquid Chromatography (HPLC). The primary outcome was log transformed geometric mean titre. Results From 47 participants screened for HIV, 51% (24) tested positive. There was a statistically significant reduction in Ogawa geometric mean ratio (GMR) by 67% (GMR = 0.33; 95% CI: -0.15, 0.76; p-value = 0.009) attributable to HIV positivity with a non-significant reduction in Inaba GMR by about 50% due to HIV positivity. When doubling of retinol levels modelled, GMR reduction against Ogawa were non-significant but that against Inaba resulted in a significant reduction in geometric mean titer (GMT) (GMT-0.33, C.I 0.16–0.66, p-value 0.002). At 1000copies/ml viral load cut off and 350 cells/μl CD4 counts, Ogawa GMT was two times higher 11.16 (95%CI: 8.20–15.19) versus 6.06 (95%CI: 4.04–9.10) in low viremia participants, and three times higher in above threshold CD4 count participants; 24.81 (95%CI: 18.94–32.50) versus 7.07 (95%CI: 5.22–9.58). Conclusion Our results show that while Shanchol™ is immunogenic in both HIV+/- individuals, HIV + participants responded poorly. Viral load and CD4 count affected vaccine immunogenicity. More research is required for detailed understanding of this in order to appropriately inform policy and practice.
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.
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