Lower and upper respiratory infections are the fourth highest cause of global mortality (Lozano et al., 2012). Epidemic and pandemic outbreaks of respiratory infection are a major medical concern, often causing considerable disease and a high death toll, typically over a relatively short period of time. Influenza is a major cause of epidemic and pandemic infection. Bacterial co/secondary infection further increases morbidity and mortality of influenza infection, with Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus reported as the most common causes. With increased antibiotic resistance and vaccine evasion it is important to monitor the epidemiology of pathogens in circulation to inform clinical treatment and development, particularly in the setting of an influenza epidemic/pandemic.

Much microbiome research has focused on populations that are predominantly of European descent, and from narrow demographics that do not capture the socio-economic and lifestyle differences which impact human health. Here we examined the airway microbiomes of the Orang Asli, the indigenous peoples of Malaysia. A total of 130 participants were recruited from two sites in the north-eastern state of Terengganu in Peninsular Malaysia. Using 16S rRNA sequencing, the nasal microbiome was significantly more diverse in those aged 5–17 years compared to 50+ years (p = 0.023) and clustered by age (PERMANOVA analysis of the Bray–Curtis distance, p = 0.001). Hierarchical clustering of Bray–Curtis dissimilarity scores revealed six microbiome clusters. The largest cluster (n = 28; 35.4%) had a marked abundance of Corynebacterium. In the oral microbiomes Streptococcus, Neisseria and Haemophilus were dominant. Using conventional microbiology, high levels of Staphylococcus aureus carriage were observed, particularly in the 18–65 age group (n = 17/36; 47.2% 95% CI: 30.9–63.5). The highest carriage of pneumococci was in the <5 and 5 to 17 year olds, with 57.1% (4/7) and 49.2% (30/61), respectively. Sixteen pneumococcal serotypes were identified, the most common being the nonvaccine-type 23A (14.6%) and the vaccine-type 6B (9.8%). The prevalence of pneumococcal serotypes covered by pneumococcal conjugate vaccines support introduction into a Malaysian national immunisation schedule. In addition, the dominance of Corynebacterium in the airway microbiomes is intriguing given their role as a potentially protective commensal with respect to acute infection and respiratory health.

Antimicrobial resistance is one of the most significant challenges facing the global medical community and can be attributed to the use and misuse of antibiotics. This includes use as growth promoters or for prophylaxis and treatment of bacterial infection in intensively farmed livestock from where antibiotics can enter the environment as residues in manure. We characterised the impact of the long-term application of a mixture of veterinary antibiotics alone (tylosin, sulfamethazine and chlortetracycline) on class 1 integron prevalence and soil microbiota composition. Class 1 integron prevalence increased significantly ( p < 0.005) from 0.006% in control samples to 0.064% in the treated plots. Soil microbiota were analysed using 16S rRNA gene sequencing and revealed significant alterations in composition. Of the 19 significantly different ( p < 0.05) OTUs identified, 16 were of the Class Proteobacteria and these decreased in abundance relative to the control plots. Only one OTU, of the Class Cyanobacteria, was shown to increase in abundance significantly; a curiosity given the established sensitivity of this Class to antibiotics. We hypothesise that the overrepresentation of Proteobacteria as OTUs that decreased significantly in relative abundance, coupled with the observations of an increase in integron prevalence, may represent a strong selective pressure on these taxa.

Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs. We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of “graduation” of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact. The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.

Carbapenem-resistant Acinetobacter spp. are considered priority drug-resistant human-pathogenic bacteria. The genomes of two carbapenem-resistant Acinetobacter spp. clinical isolates obtained from the same tertiary hospital in Terengganu, Malaysia, namely, A. baumannii AC1633 and A. nosocomialis AC1530, were sequenced. Both isolates were found to harbor the carbapenemase genes bla_NDM-1 and bla_OXA-58 in a large (ca. 170 kb) plasmid designated pAC1633-1 and pAC1530, respectively, that also encodes genes that confer resistance to aminoglycosides, sulfonamides, and macrolides. The two plasmids were almost identical except for the insertion of ISAba11 and an IS4 family element in pAC1633-1, and ISAba11 along with relBE toxin-antitoxin genes flanked by inversely orientated pdif (XerC/XerD) recombination sites in pAC1530. The bla_NDM-1 gene was encoded in a Tn125 composite transposon structure flanked by ISAba125, whereas bla_OXA-58 was flanked by ISAba11 and ISAba3 downstream and a partial ISAba3 element upstream within a pdif module. The presence of conjugative genes in plasmids pAC1633-1/pAC1530 and their discovery in two distinct species of Acinetobacter from the same hospital are suggestive of conjugative transfer, but mating experiments failed to demonstrate transmissibility under standard laboratory conditions. Comparative sequence analysis strongly inferred that pAC1633-1/pAC1530 was derived from two separate plasmids in an IS1006-mediated recombination or transposition event. A. baumannii AC1633 also harbored three other plasmids designated pAC1633-2, pAC1633-3, and pAC1633-4. Both pAC1633-3 and pAC1633-4 are cryptic plasmids, whereas pAC1633-2 is a 12,651-bp plasmid of the GR8/GR23 Rep3-superfamily group that encodes the tetA(39) tetracycline resistance determinant in a pdif module. IMPORTANCE Bacteria of the genus Acinetobacter are important hospital-acquired pathogens, with carbapenem-resistant A. baumannii listed by the World Health Organization as the one of the top priority pathogens. Whole-genome sequencing of carbapenem-resistant A. baumannii AC1633 and A. nosocomialis AC1530, which were isolated from the main tertiary hospital in Terengganu, Malaysia, led to the discovery of a large, ca. 170-kb plasmid that harbored genes encoding the New Delhi metallo-β-lactamase-1 (NDM-1) and OXA-58 carbapenemases alongside genes that conferred resistance to aminoglycosides, macrolides, and sulfonamides. The plasmid was a patchwork of multiple mobile genetic elements and comparative sequence analysis indicated that it may have been derived from two separate plasmids through an IS1006-mediated recombination or transposition event. The presence of such a potentially transmissible plasmid encoding resistance to multiple antimicrobials warrants vigilance, as its spread to susceptible strains would lead to increasing incidences of antimicrobial resistance.