The Immunogenicity of a Foot-and-Mouth Disease Virus Serotype O Vaccine in Commercial and Subsistence Cattle Herds in Zambia.

The recent introduction of foot-and-mouth disease (FMD) virus serotype O (O/EA-2 topotype) in Southern Africa has changed the epidemiology of the disease and vaccine requirements of the region. Commercial and subsistence cattle herds in Zambia were vaccinated with an FMD virus serotype O Manisa vaccine according to a double- or single-dose vaccination schedule. Heterologous antibody responses induced by this vaccine against a representative O/EA-2 virus from Zambia were determined. Virus neutralisation tests (VNTs) showed double-dosed cattle had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds 56 days after the first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3) 56 dpv. A comparison of these results and those generated by solid-phase competitive ELISA (SPCE) tests showed a statistically significant positive correlation by Cohen's kappa coefficient. Therefore, SPCE might be used in assessing the immunogenicity of vaccines in place of VNT. Furthermore, for this vaccine and field strain, a vaccination regime employing a two-dose primary course and revaccination after 4-6 months is likely to be appropriate.

The first detection of a serotype O foot-and-mouth disease virus in Namibia.

This report describes the molecular characterization of a serotype O foot-and-mouth disease virus (FMDV) recovered from a field outbreak in the Zambezi region, Namibia during July 2021. Sequence analysis demonstrates that this FMDV belongs to the O/EA-2 topotype sharing closest nucleotide identity (99.5%) to FMD viruses collected since 2018 in Zambia. This is the first detection of serotype O in Namibia, and together with the cases that have been recently detected in southern Zambia, represent the first time that this serotype has been detected in the Southern African FMD endemic pool since 2000, when a virus of Asian origin (O/ME-SA/PanAsia) caused an outbreak in South Africa. This incursion poses a new threat for the region and the potential onward spread of O/EA-2 will now need to be closely monitored since serotype O vaccines are not widely used in Namibia, nor in neighbouring countries.

Characterization of Foot-and-Mouth Disease Viruses in Zambia-Implications for the Epidemiology of the Disease in Southern Africa.

The livestock industry supports livelihood and nutritional security of at least 42% of people in the Southern African Development Community region. However, presence of animal diseases such as foot-and-mouth disease poses a major threat to the development of this industry. Samples collected from FMD outbreaks in Zambia during 2015-2020, comprising epithelial tissues samples (n = 47) and sera (n = 120), were analysed. FMD virus was serotyped in 26 samples, while 92 sera samples tested positive on NSP-ELISA. Phylogenetic analysis revealed notable changes in the epidemiology of FMD in Zambia, which included: (i) introduction of a novel FMDV SAT-3 (topotype II) causing FMD cases in cattle in Western Province; (ii) emergence of FMDV serotype O (topotype O/EA-2) in Central, Southern, Copperbelt, Western, Lusaka Provinces; and (iii) new outbreaks due to SAT -2 (topotypes I) in Eastern Zambia. Together, these data describe eight different epizootics that occurred in Zambia, four of which were outside the known FMD high-risk areas. This study highlights the complex epidemiology of FMD in Zambia, where the country represents an interface between East Africa (Pool 4) and Southern Africa (Pool 6). These changing viral dynamics have direct impacts on FMD vaccine selection in the SADC region.

Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure.

Sporadic literature reports describe isolates of pathogenic bacteria that harbor an antibiotic resistance determinant but remain susceptible to the corresponding antibiotic as a consequence of a genetic defect. Such strains represent a source from which antibiotic resistance may reemerge to cause treatment failure in patients. Here, we report a systematic investigation into the prevalence and nature of this phenomenon, which we term silencing of antibiotic resistance by mutation (SARM). Instances of SARM were detected among 1,470 Staphylococcus aureus isolates through side-by-side comparison of antibiotic resistance genotype (as determined by whole-genome sequencing) versus phenotype (as assessed through susceptibility testing). Of the isolates analyzed, 152 (10.3%) harbored a silenced resistance gene, including 46 (3.1%) that exhibited SARM to currently deployed antistaphylococcal drugs. SARM resulted from diverse mutational events but most commonly through frameshift mutation of resistance determinants as a result of point deletion in poly(A) tracts. The majority (∼90%) of SARM strains reverted to antibiotic resistance at frequencies of ≥10-9; thus, while appearing antibiotic sensitive in the clinical microbiology laboratory, most S. aureus isolates exhibiting SARM will revert to antibiotic resistance at frequencies achievable in patients. In view of its prevalence in a major pathogen, SARM represents a significant potential threat to the therapeutic efficacy of antibiotics.IMPORTANCE Antibiotic resistance hinders the treatment of bacterial infection. To guide effective therapy, clinical microbiology laboratories routinely perform susceptibility testing to determine the antibiotic sensitivity of an infecting pathogen. This approach relies on the assumption that it can reliably distinguish bacteria capable of expressing antibiotic resistance in patients, an idea challenged by the present study. We report that the important human pathogen Staphylococcus aureus frequently carries antibiotic resistance genes that have become inactivated ("silenced") by mutation, leading strains to appear antibiotic sensitive. However, resistance can rapidly reemerge in most such cases, at frequencies readily achievable in infected patients. Silent antibiotic resistance is therefore prevalent, transient, and evades routine detection, rendering it a significant potential threat to antibacterial chemotherapy.

Genetic characterisation of African swine fever virus from 2017 outbreaks in Zambia: Identification of p72 genotype II variants in domestic pigs.

African swine fever (ASF) is a contagious haemorrhagic disease associated with causing heavy economic losses to the swine industry in many African countries. In 2017, Zambia experienced ASF outbreaks in Mbala District (Northern province) and for the first time in Isoka and Chinsali districts (Muchinga province). Meanwhile, another outbreak was observed in Chipata District (Eastern province). Genetic analysis of part of the B646L gene, E183L gene, CP204L gene and the central variable region of the B602L gene of ASF virus (ASFV) associated with the outbreaks in Mbala and Chipata districts was conducted. The results revealed that the ASFV detected in Mbala District was highly similar to that of the Georgia 2007/1 isolate across all the genome regions analysed. In contrast, while showing close relationship with the Georgia 2007/1 virus in the B646L gene, the ASFV detected in Chipata District showed remarkable genetic variation in the rest of the genes analysed. These results suggest that the Georgia 2007/1-like virus could be more diverse than what was previously thought, underscoring the need of continued surveillance and monitoring of ASFVs within the south-eastern African region to better understand their epidemiology and the relationships between outbreaks and their possible origin.

Investigation of foot-and-mouth disease outbreaks in the Mbala and Kazungula districts of Zambia.

Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. It is known to be endemic in Zambia, with periodic outbreaks occurring in different geographical areas of the country. This study was conducted to investigate the presence of FMD virus (FMDV) in reported FMD-suspected cases in cattle from the Kazungula and Mbala districts of Zambia. Sixty epithelial tissues or oesophageal-pharyngeal (OP) scrapings (probang samples) were collected from Mbala (n = 51) and Kazungula (n = 9) and examined for FMDV. The FMDV viral RNA and serotypes were examined by realtime reverse transcription polymerase chain reaction (qRT-PCR) and antigen Enzyme- linked immunosorbent assay (ELISA), respectively. Twenty-two samples (36.7%) were positive for the FMDV genome by qRT-PCR with Cycle threshold (Ct) values ranging from 13 to 31. The FMDV-positive samples from epithelial tissues showed relatively higher Ct values compared to those obtained from OP scrapings, irrespective of geographical location. Forty percent (40%; n = 4) of epithelial tissues from Mbala were serotyped into SAT 2 serotype by antigen ELISA. Kazungula samples were serotyped into SAT 1. These findings indicated that Mbala and Kazungula districts had FMD outbreaks in 2012 that were ascribed to at least FMDV serotype SAT 2 and SAT 1 field strains. Furthermore, regular interaction between buffalos from the Mosi-o Tunya Park and domestic animals from surrounding areas could contribute to the occurrence of regular FMD outbreaks in Kazungula, whilst the uncontrolled animal movements across borders between Mbala and Nsumbawanga could be responsible for disease outbreaks in Mbala. In-depth molecular biological studies, including sequencing and phylogeny of the viruses, should be conducted to elucidate the complex epidemiology of FMD in Zambia, thereby providing valuable information needed for the rational control strategy of FMD in Zambia and neighbouring countries.