Assessing the mechanisms of multi-drug resistant non-typhoidal Salmonella (NTS) serovars isolated from layer chicken farms in Nigeria.

BACKGROUND: In Nigeria, there have been reports of widespread multiple antimicrobial resistance (AMR) amongst Salmonella isolated from poultry. To mitigate the impact of mortality associated with Salmonella on their farms, farmers resort to the use of antimicrobials without sound diagnostic advice. We conducted this study to describe the AMR patterns, mechanisms and genetic similarities within some Salmonella serovars isolated from different layer farms. METHOD: We determine the AMR profiles of two hundred Salmonella isolates, selected based on frequency, serovar, and geographical and sample type distribution. We also assessed the mechanisms of multi-drug resistance for specific genetic determinants by using PCR protocols and gene sequence analysis. Pulsed-field gel electrophoresis (PFGE) was conducted on seven selected serovars to determine their genetic relatedness. RESULTS: Of 200 isolates, 97 (48.5%) revealed various AMR profiles, with the multiple antibiotic resistance (MAR) index ranging from 0.07-0.5. Resistance to ciprofloxacin was common in all the multi-drug resistant isolates, while all the isolates were susceptible to cefotaxime, ceftazidime, and meropenem. Genotypic characterization showed the presence of resistance genes as well as mutations in the nucleotide genes with subsequent amino acid substitutions. Fifteen isolates (43%) of S. Kentucky were indistinguishable, but were isolated from four different states in Nigeria (Ogun, n = 9; Kaduna, n = 6; Plateau, n = 3, and: Bauchi, n = 2). PFGE revealed 40 pulsotype patterns (Kentucky, n = 12; Larochelle, n = 9; Virchow, n = 5; Saintpaul, n = 4; Poona, n = 3; Isangi, n = 2, and; Nigeria, n = 2). CONCLUSION: This study recorded strictly related but diversely distributed Salmonella serovars with high AMR rates in poultry. We recommend strict regulation on antimicrobial use and regular monitoring of AMR trends among bacteria isolated from animals and humans to inform public policy.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium's analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps.

Cholera outbreak in some communities in North-East Nigeria, 2019: an unmatched case-control study.

BACKGROUND: Cholera, a diarrheal disease caused by the bacterium Vibrio cholerae, transmitted through fecal contamination of water or food remains an ever-present risk in many countries, especially where water supply, sanitation, food safety, and hygiene are inadequate. A cholera outbreak was reported in Bauchi State, North-eastern Nigeria. We investigated the outbreak to determine the extent and assess risk factors associated with the outbreak. METHODS: We conducted a descriptive analysis of suspected cholera cases to determine the fatality rate (CFR), attack rate (AR), and trends/patterns of the outbreak. We also conducted a 1:2 unmatched case-control study to assess risk factors amongst 110 confirmed cases and 220 uninfected individuals (controls). We defined a suspected case as any person > 5 years with acute watery diarrhea with/without vomiting; a confirmed case as any suspected case in which there was laboratory isolation of Vibrio cholerae O1 or O139 from the stool while control was any uninfected individual with close contact (same household) with a confirmed case. Children under 5 were not included in the case definition however, samples from this age group were collected where such symptoms had occurred and line-listed separately. Data were collected with an interviewer-administered questionnaire and analyzed using Epi-info and Microsoft excel for frequencies, proportions, bivariate and multivariate analysis at a 95% confidence interval. RESULTS: A total of 9725 cases were line-listed with a CFR of 0.3% in the state. Dass LGA had the highest CFR (14.3%) while Bauchi LGA recorded the highest AR of 1,830 cases per 100,000 persons. Factors significantly associated with cholera infection were attending social gatherings (aOR = 2.04, 95% CI = 1.16-3.59) and drinking unsafe water (aOR = 1.74, 95% CI = 1.07-2.83). CONCLUSION: Attending social gatherings and drinking unsafe water were risk factors for cholera infection. Public health actions included chlorination of wells and distribution of water guard (1% chlorine solution) bottles to households and public education on cholera prevention. We recommend the provision of safe drinking water by the government as well as improved sanitary and hygienic conditions for citizens of the state.

A Retrospective Study of the Seroprevalence of Dengue Virus and Chikungunya Virus Exposures in Nigeria, 2010-2018.

Arboviruses are important public health threats in many regions of the world. Nigeria has experienced outbreaks of arboviruses over the past decades, leading to concerns of widespread endemicity, which are frequently misdiagnosed. This study aimed to determine the seroprevalence of dengue virus (DENV) (a flavivirus) and chikungunya virus (CHIKV) (an alphavirus) infections in three major population centers of Nigeria. A convenience sample of 701 sera was collected from both healthy and febrile participants between August 2010 and March 2018. Sera were tested for prior exposure to CHIKV virus and DENV using indirect IgG ELISA. Results showed that 54.1% (379/701) of participants were seropositive for anti-DENV antibodies, 41.3% (290/701) were seropositive for anti-CHIKV antibodies, and 20.1% (141/701) had previous exposure to both. The seropositivity for prior CHIKV exposure and prior exposure to DENV and CHIKV was significantly associated with age (CHIKV: OR = 2.7 (95% CI: 1.7-4.3); DENV and CHIKV: OR = 2.2 (95% CI: 1.2-4.0) for adults compared to participants under 18 years old). Overall, the high seropositivity across all age groups suggests that arboviral infections are prevalent in Nigeria and indicates that surveillance and further epidemiological studies are required to determine the true burden of these infections and the spectrum of diseases associated with these exposures.