Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. MethodsIn this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0•32 [95% CI 0•27-0•37]) and 82% at 8 weeks (0•18 [0•14-0•23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Serotype distribution and antibiotic resistance (AR) among group B streptococci (GBS) affect GBS disease prevention strategies, but vary among patient groups. A multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay was used to compare the distributions of GBS serotypes, serotype III subtypes and AR-associated genes among 666 invasive isolates from 663 patients, divided into five age groups: infants, early-onset (EO; 0-6 days) and late-onset (LO; 7-90 days); children (aged 3 months to 14 years); women of childbearing age (WCBA; aged 15-45 years); and other adults (males aged >15 years; females aged >45 years). Serotypes Ia and V and serosubtype III-1 accounted for 60% of infections. Serosubtype III-2, which corresponds to a virulent clone belonging to sequence type (ST)17, was relatively uncommon overall (7%), but was associated strongly with LO infant infections, in which it was significantly more common than in adult infections (25/104 (24%) vs. 9/392 (2%), p <0.0001) or in EO infections (25/104 (24%) vs. 14/155 (9%), p <0.005). Erythromycin resistance genes were found in 8% of all isolates (ermB 3%, ermA 2.5% and mefA/E 2%), in 11-15% of isolates of serotypes II and V and subtype III-1, but in none of the isolates of serosubtype III-2 (III-2, 0/49 vs. all others, 54/618 (9%), p <0.04). In summary, the virulent serosubtype III-2 was associated strongly with LO infant GBS infection, but was less likely than other serotypes or serosubtype III-1 to carry AR genes.

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/ subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/ emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (.97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/Tantigen as a vaccine target.

We applied an emm cluster typing system to group A Streptococcus strains in New Zealand, including those associated with acute rheumatic fever (ARF). We observed few so-called rheumatogenic emm types but found a high proportion of emm types previously associated with pyoderma, further suggesting a role for skin infection in ARF.T wo of the most significant consequences of group A streptococcal (GAS) infection are acute rheumatic fever (ARF) and its sequelae, rheumatic heart disease (RHD). New Zealand has among the highest incidences of ARF in the developed world, with the greatest burden of disease in indigenous New Zealand (Ma ori) and Pacific populations (1).Contemporary molecular typing of GAS is carried out by sequence analysis of the hypervariable region of the emm gene that encodes the M protein (2). Studies in the United States have suggested an association between distinct GAS emm types (so-called rheumatogenic strains, such as emm3, emm5, emm6, and emm18) and ARF (3). However, more recent epidemiological studies in areas where ARF is common today have found that ARF is not restricted to these rheumatogenic strains (4), raising questions around the concept of rheumatogenicity and emm type. It has further been postulated that certain GAS emm types (most notably emm3) may be rheumatogenic due to the presence of a specific collagen-binding motif, designated peptide associated with rheumatic fever (PARF), which elicits an immune response to type IV collagen (5, 6). To date, however, the presence of the PARF motif has not been systematically assessed in a large collection of GAS strains temporally associated with ARF.Recently, an Australian and New Zealand GAS vaccine development program (the Coalition to Accelerate New Vaccines Against Streptococcus [CANVAS]) was formed with the aim of identifying suitable vaccine GAS candidates for both the Australian and New Zealand settings, and more widely (7). At present, the most clinically advanced GAS vaccine candidates are those that target the N-terminal region of the M protein, such as an experimental 30-valent M-protein vaccine (8). While this vaccine includes the classical rheumatogenic emm types, there have been few analyses to inform the coverage of contemporary ARF strains. Recently, an emm cluster-based typing system that classifies known emm types into 48 related emm clusters has been applied to several collections of GAS isolates and has shed new insights into the epidemiology of GAS and the potential vaccine coverage of M-protein-based vaccines (9, 10). The emm cluster system also predicts an emm pattern type that in turn correlates well with tissue tropism (pattern A-C for pharyngeal, pattern D for skin, and pattern E for either) (9). Accordingly, the aims of this study were to (i) compare the molecular epidemiology and theoretical vaccine coverage of GAS isolates associated with ARF in New Zealand with those of GAS isolates recovered from other GAS-related clinical syndromes, and (ii) identify GAS isolates containing the PARF motif and associate the pre...

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