Streptococcus pneumoniae among the children of Aden, Yemen: a cross-sectional report of post-pneumococcal conjugate vaccine.

INTRODUCTION: Streptococcus pneumoniae cause a significant global health challenge. We aimed to determine nasopharyngeal carriage, serotypes distribution, and antimicrobial profile of pneumococci among the children of Aden. METHODOLOGY: A total of 385 children, aged 2-17 years, were included. Asymptomatic samples were randomly collected from children in selected schools and vaccination centers. Symptomatic samples were obtained from selected pediatric clinics. The nasopharyngeal swabs were tested for pneumococci using culture and real time polymerase chain reaction (RT-PCR). Serotyping was done with a pneumotest-latex kit and antimicrobial susceptibility was tested by disc diffusion and Epsilometer test. RESULTS: The total pneumococcal carriage was 44.4% and 57.1% by culture and RT-PCR, respectively. There was a statistically significant association between carriage rate and living in single room (OR = 7.9; p = 0.00001), sharing a sleeping space (OR = 15.1; p = 0.00001), and low monthly income (OR = 2.02; p = 0.007). The common serotypes were 19, 1, 4, 5, 2, and 23. The proportion of non-pneumococcal conjugate vaccine (non-PCV13) serotypes was 24%. Pneumococci were resistant to penicillin (96.5%), cefepime (15.8%), ceftriaxone (16.4%), and amoxicillin-clavulanate (0%). Erythromycin, azithromycin, and doxycycline had resistance rates of 48%, 31%, and 53.3%, respectively. CONCLUSIONS: A high pneumococcal carriage rate was observed in Yemeni children, particularly in low-income households and shared living conditions. There was significant penicillin resistance at meningitis breakpoint. Furthermore, non-PCV13 serotypes were gradually replacing PCV13 serotypes. The findings underscore the urgent need for enhanced surveillance and stewardship to improve vaccination and antibiotic policies in Yemen.

Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Staphylococcus aureus nasal colonization and susceptibility profile to antimicrobials in hemodialysis patients using a protocol of seven collections.

BACKGROUND: Patients colonized with Staphylococcus aureus in their nasal passages have a higher risk of acquiring infection, especially if they are immunocompromised or have comorbidities such as chronic renal failure undergoing hemodialysis (HD). OBJECTIVE: This study aimed to report the prevalence of nasal carriage of S. aureus among HD patients utilizing a seven-week sampling protocol and to assess the susceptibility of these isolates to various antimicrobial agents. METHODS: Over seven consecutive weeks, nasal swab samples were collected from 47 HD patients, resulting in a total of 329 samples. The microorganisms were identified using biochemical methods and subjected to antimicrobial susceptibility testing via disk diffusion and microdilution techniques. RESULTS: Out of all the patients analyzed, 25 individuals (53.19%) were found to be colonized by S. aureus, with 21 of them displaying intermittent colonization. Additionally, 38% showed positive results for S. aureus in only the 6th or 7th week of sampling. Within the 58 isolates, 17.2% (n=10) exhibited methicillin (oxacillin)-resistance and 25.86% (n=15) displayed elevated vancomycin MIC values (2 µg/ml). Based on the results, daptomycin and gentamicin were found to be effective treatment options. However, 31% of the isolates (n=18) exhibited a MIC of 1 µg/ml for daptomycin. CONCLUSION: Over half of the patients were colonized by S. aureus, but mostly on an intermittent basis. The identification of oxacillin resistance and high vancomycin and daptomycin MICs serve as warnings for possible future complications in managing bacteremia caused by S. aureus in these patients.

Leptospira infection and carrier survey on rats from wet market areas in Kuala Lumpur, Malaysia.

BACKGROUND OBJECTIVES: Leptospirosis is an important zoonotic infection that has caused significant mortality and morbidity worldwide. This disease is endemic in Malaysia and as a developing tropical country, leptospirosis is concerning as it threatens Malaysian public health and the country's economic sectors. However, there is limited information on leptospirosis in Malaysia, especially regarding leptospiral seroepidemiology among carriers in Malaysia. Therefore, more epidemiological information on the source of the disease and reservoir are needed for better disease control and source intervention. The objectives of this study are to gather information on Leptospira infection and the carrier status of rats captured from selected wet markets of Kuala Lumpur metropolitan city in Malaysia. METHODS: Live rat trappings were performed in four major wet markets in Kuala Lumpur, namely, Pudu, Chow Kit, Datuk Keramat, and Petaling Street. Animal samplings were performed for 12 months in 2017, where blood and kidney samples were collected and tested for anti-leptospiral antibodies via Microscopic Agglutination Test (MAT) and pathogenic Leptospira screening via Polymerase Chain Reaction (PCR) amplification offlaB gene. RESULTS: MAT showed that 34.7% (n = 50/144) of the captured rats were positive for anti-leptospiral antibody of which the most prominent serovar was Malaya followed by a local strain, IMR LEP 175. In parallel, 50 rats were also positive for pathogenic Leptospira DNA. INTERPRETATION CONCLUSION: This study showed that there are persistent Leptospira infections among rats in Kuala Lumpur wet markets and these rats are important reservoir hosts for the bacteria.

Carriage of antimicrobial-resistant Enterobacterales among pregnant women and newborns in Amhara, Ethiopia.

OBJECTIVES: Infections are one of the most common causes of neonatal mortality, and maternal colonization has been associated with neonatal infection. In this study, we sought to quantify carriage prevalence of extended-spectrum-beta-lactamase (ESBL) -producing and carbapenem-resistant Enterobacterales (CRE) among pregnant women and their neonates and to characterize risk factors for carriage in rural Amhara, Ethiopia. METHODS: We conducted a prospective cohort study nested in the Birhan field site. We collected rectal and vaginal samples from 211 pregnant women in their third trimester and/or during labor/delivery and perirectal or stool samples from 159 of their neonates in the first week of life. RESULTS: We found that carriage of ESBL-producing organisms was fairly common (women: 22.3%, 95% CI: 16.8-28.5; neonates: 24.5%, 95% CI: 18.1-32.0), while carriage of CRE (women: 0.9%, 95% CI: 0.1-3.4; neonates: 2.5%, 95% CI: 0.7-6.3) was rare. Neonates whose mothers tested positive for ESBL-producing organisms were nearly twice as likely to also test positive for ESBL-producing organisms (38.7% vs 21.1%, P-value = 0.06). Carriage of ESBL-producing organisms was also associated with Woreda (district) of sample collection and recent antibiotic use. CONCLUSION: Understanding carriage patterns of potential pathogens and antibiotic susceptibility among pregnant women and newborns will inform local, data-driven recommendations to prevent and treat neonatal infections.

Distribution of Staphylococcus aureus carriage among healthcare workers in a Japanese convalescent and rehabilitation hospital.

Earlobes, nasal cavities, and fingers of 145 healthcare workers in convalescent and rehabilitation hospital (60 nurses and 85 rehabilitation healthcare workers) were sampled. Of the 3 sites sampled, Staphylococcus aureus was detected in one or more sites in 25 nurses and 27 rehabilitation workers. S. aureus was detected in all 3 sites in 2 (8.0%) nurses and 2 (7.4%) rehabilitation workers, and the S. aureus isolates in each case showed related PFGE pattern. S. aureus was detected in both the fingers and nasal cavities of 5 (18.5%) of the rehabilitation healthcare workers; in all 5 cases, the PFGE patterns of the S. aureus isolates from each site belonged to same cluster based on PFGE. Of the 2 cases in which methicillinresistant S. aureus (MRSA) was recovered from earlobes, fingers, and nasal cavities, in both cases, MRSA isolates from the 3 sites were the same clone according to PFGE analysis and SCCmec type IV. As S. aureus was detected in pierced earlobes of nurses, hand hygiene must be practiced after touching pierced earlobes and before patient contact. The same S. aureus clone in the nasal cavity and earlobes indicates that the route of transmission is through the fingers.

Streptococcus pneumoniae as a colonizing agent of the Nasopharynx - Oropharynx in adults: A systematic review and meta-analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.

Prevalence and factors associated with methicillin-resistant Staphylococcus aureus colonization on admission to geriatric care units: impact on screening practices.

OBJECTIVES: Universal screening for methicillin-resistant Staphylococcus aureus (MRSA) entails additional costs, and there is no consensus for targeted screening for high-risk units. The aims of this study were to determine the prevalence of MRSA in geriatric care units, and to identify the factors associated with MRSA colonization on admission. METHODS: This retrospective case-control study (1:1) in the geriatric care unit of six Belgian hospitals covered the period from 1st January 2021 to 31st December 2022. Cases were patients with a positive MRSA screening result within 48 h of admission to the geriatric care unit, and controls were patients with a negative screening result. RESULTS: In total, 556 patients were included in this study (278 in each group). Prevalence per 100 admissions for the total sample was 2.3 [95% confidence interval (CI) 2.2-2.6]. Significant multi-variate factors associated with MRSA carriage on admission were: history of MRSA, nursing home origin, and chronic skin lesions. Applying these three factors would give an area under the receiver operating characteristic (ROC) curve of 0.73 (95% CI 0.71-0.77), and would allow screening to be carried out in only 55.4% of cases (95% CI 51.2-59.6%). CONCLUSIONS: Using these factors as screening criteria in geriatric care units could significantly reduce the number of patients screened for MRSA, while maintaining satisfactory sensitivity and specificity.

Prevalence, serogroup distribution and risk factors of Neisseria meningitidis carriage in high school and university students in Hungary.

Neisseria meningitidis causes life-threatening invasive meningococcal disease (IMD) with high mortality worldwide. Asymptomatic pharyngeal meningococcus colonisation is an important reservoir for the spread of the bacterium. The aim of this study was to determine N. meningitidis colonisation rates in asymptomatic high school and university students and to identify risk factors for carriage. Oropharyngeal swab samples and data from a self-reported questionnaire were obtained from overall 610 students, among them 303 university students and 307 high school students, aged between 15 and 31 years in Budapest, Hungary, between November 2017 and December 2018. Meningococcal carriage and serogroup of N. meningitidis were determined by RT-PCR from DNA extracted directly from the specimen. N. meningitidis was identified in 212 (34.8 %) of the participants. Significantly higher carriage rate was found among high school students (48.9 %) compared to university students (20.5 %). Peak of colonisation rate was among 17-19-year-old students (48.7 %). Most carriage isolates were non-typable (87.3 %). From the 212 meningococcus carriers, 19 were colonised by serogroup B (9 %), 5 by serogroup C (2.4 %), and 1 had serogroup Y (0.5 %). Significantly higher colonisation rate was found among males (42.4 %) than in females (33.1 %). Antibiotic use in the past 2 months has decreased the rate of meningococcal colonisation. Recent respiratory infection, active or passive smoking and attending parties have not influenced meningococcal colonisation rate significantly. In conclusion, we have found high asymptomatic meningococcus carriage rate among high school students and young adults, however, the majority of the colonizing meningococci were non-typable.

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13.

Introduction: Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Methods: Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. Results: The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. Discussion: We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.

Geographical distribution of invasive meningococcal disease and carriage: A spatial analysis.

Little information exists concerning the spatial relationship between invasive meningococcal disease (IMD) cases and Neisseria meningitidis (N. meningitidis) carriage. The aim of this study was to examine whether there is a relationship between IMD and asymptomatic oropharyngeal carriage of meningococci by spatial analysis to identify the distribution and patterns of cases and carriage in South Australia (SA). Carriage data geocoded to participants' residential addresses and meningococcal case notifications using Postal Area (POA) centroids were used to analyse spatial distribution by disease- and non-disease-associated genogroups, as well as overall from 2017 to 2020. The majority of IMD cases were genogroup B with the overall highest incidence of cases reported in infants, young children, and adolescents. We found no clear spatial association between N. meningitidis carriage and IMD cases. However, analyses using carriage and case genogroups showed differences in the spatial distribution between metropolitan and regional areas. Regional areas had a higher rate of IMD cases and carriage prevalence. While no clear relationship between cases and carriage was evident in the spatial analysis, the higher rates of both carriage and disease in regional areas highlight the need to maintain high vaccine coverage outside of the well-resourced metropolitan area.

Nasopharyngeal carriage of Streptococcus pneumoniae among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction.

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China.

BACKGROUND: The thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China. METHODS: From March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors. RESULTS: Pneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7-3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1-1.8), living with siblings (aOR = 1.3, 95% CI: 1.0-1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1-2.0). In contrast, completion of 3-4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4-0.9). CONCLUSIONS: We established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.

Longitudinal study of meningococcal carriage in adolescents and young adults in South Australia 2017-2020.

BACKGROUND: This analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years. METHODS: Data from the "B Part of It" study, which included a state-wide cluster randomized controlled trial in secondary-school students (n = 34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17-25 years (n = 4028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2). RESULTS: Among school leavers, 50 (1.7%, total n = 2980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤15 years; OR = 1.97 (95%CI 1.0, 3.86); p = 0.048). CONCLUSION: Whilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.

Molecular epidemiology of pneumococcal carriage in children from Seville, following implementation of the PCV13 immunization program in Andalusia, Spain.

INTRODUCTION: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination programme was introduced in December 2016 in Andalusia. METHODS: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period), were used for comparison of serotype/genotype distributions and antibiotic resistance rates. RESULTS: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11% vs 38%, p = 0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (p = 0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. CONCLUSIONS: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.

Bacterial nasopharyngeal colonisation in children in South Africa before and during the COVID-19 pandemic: an observational study.

BACKGROUND: Deployment of non-pharmaceutical interventions such as face masking and physical distancing during the COVID-19 pandemic could have altered the transmission dynamics and carriage of respiratory organisms. We evaluated colonisation with Streptococcus pneumoniae and other upper respiratory tract bacterial colonisers before and during the COVID-19 pandemic. METHODS: We did two cross-sectional surveys in Soweto, South Africa from July 3 to Dec 13, 2018 (pre-COVID-19 period) and from Aug 4, 2021, to March 31, 2022 (COVID-19 period) in healthy children (aged ≤60 months) who had recorded HIV status and had not received antibiotics in the 21 days before enrolment. At enrolment, we collected nasopharyngeal swab samples from child participants. Following nucleic acid extraction, nanofluidic quantitative PCR was used to screen all samples for 92 S pneumoniae serotypes and 14 other bacteria. The primary objective was to compare the prevalence and density of pneumococcal nasopharyngeal colonisation, overall and stratified by 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and non-vaccine serotypes. Secondary study objectives included a comparison of serotype-specific pneumococcal colonisation and density, as well as colonisation by the 14 other bacteria in the COVID-19 versus pre-COVID-19 period. We used an adjusted multiple logistic and linear regression model to compare the colonisation prevalence and density between study periods. FINDINGS: We analysed nasopharyngeal swabs from 1107 children (n=571 in the pre-COVID-19 period; n=536 in the COVID-19 period). We observed no change in overall pneumococcal colonisation between periods (274 [51%] of 536 in the COVID-19 period vs 282 [49%] of 571 in the pre-COVID-19 period; adjusted odds ratio [aOR] 1·03 [95% CI 0·95-1·12]). The prevalence of PCV13 serotypes was lower in the COVID-19 than in the pre-COVID-19 period (72 [13%] vs 106 [19%]; 0·87 [0·78-0·97]), whereas the prevalence of non-typeable S pneumoniae was higher (34 [6%] vs 63 [12%]; 1·30 [1·12-1·50]). The mean log10 density for overall pneumococcal colonisation was lower in the COVID-19 period than in the pre-COVID-19 period (3·96 [95% CI 3·85-4·07] vs 4·72 [4·63-4·80] log10 genome equivalents per mL; p<0·0001). A lower density of non-vaccine serotypes (3·63 [3·51-3·74] vs 4·08 [3·95-4·22] log10 genome equivalents per mL; p<0·0001) and non-typeable S pneumoniae (3·11 [2·94-3·29] vs 4·41 [4·06-4·75] log10 genome equivalents per mL; p<0·00001) was also observed in the COVID-19 period. There was no difference in the density of PCV13 serotypes between the periods. The prevalence of colonisation during the COVID-19 versus pre-COVID-19 period was lower for non-typeable Haemophilus influenzae (280 [49%] vs 165 [31%]; aOR 0·77 [95% CI 0·71-0·84]), Moraxella catarrhalis (328 [57%] vs 242 [45%]; 0·85 [0·79-0·92]), and Neisseria lactamica (51 [9%] vs 13 [2%]; 0·64 [0·52-0·78]), but higher for Acinetobacter baumannii (34 [6%] vs 102 [19%]; 1·55 [1·35-1·77]) and Staphylococcus aureus (29 [5%] vs 52 [10%]; 1·28 [1·10-1·50]). INTERPRETATION: There were variable effects on the colonisation prevalence and density of bacterial organisms during the COVID-19 compared with the pre-COVID-19 period. The lower prevalence of PCV13 serotype together with other respiratory organisms including non-typeable H influenzae and M catarrhalis could have in part contributed to a decrease in all-cause lower respiratory tract infections observed in South Africa during the initial stage of the COVID-19 pandemic. The pathophysiological mechanism for the increase in A baumannii and S aureus colonisation warrants further investigation, as does the clinical relevance of these findings. FUNDING: The Bill & Melinda Gates Foundation.

Detection of Staphylococcus aureus from nares of elderly living in a Brazilian nursing home.

Asymptomatically nasal colonization by Staphylococcus aureus is a well-established risk factor for S. aureus infections. The aimed of the study was to identify the prevalence and factors associated with nasal carriage of S. aureus and Methicillin-resistant S. aureus (MRSA) from individuals residing in one Brazilian nursing home (NH). Three time-separate nasal swab collections were obtained from the elderly enrolled. The S. aureus isolates identified were submitted to Antimicrobial Susceptibility test (AST). The study showed a high prevalence of S. aureus (n = 9; 60%) and MRSA (n = 4; 26.7%) among elderly. Resistance to erythromycin was the most detected. S. aureus or MRSA colonization could not be associated to the data collected on demographics, personal habits, and medical history of the participants. Despite the small number of individuals enrolled, our study can contribute to improve the control of S. aureus and MRSA dissemination within the community, especially among the most vulnerable like the elderly.

Variation in pneumococcal invasiveness metrics is driven by serotype carriage duration and initial risk of disease.

Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease. The most common invasiveness metrics use cross-sectional data (i.e., invasive odds ratios (IOR)), or longitudinal data (i.e., attack rates (AR)). To assess the reliability of these metrics we developed an epidemiological model of carriage and invasive disease. Our mathematical analyses illustrate qualitative failures with the IOR metric (e.g., IOR can decline with increasing invasiveness parameters). Fitting the model to both longitudinal and cross-sectional data, our analysis supports previous work indicating that invasion risk is maximal at or near time of colonization. This pattern of early invasive disease risk leads to substantial (up to 5-fold) biases when estimating underlying differences in invasiveness from IOR metrics, due to the impact of carriage duration on IOR. Together, these results raise serious concerns with the IOR metric as a basis for public health decision-making and lend support for multiple alternate metrics including AR.

Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota.

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors. METHODS: We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing. FINDINGS: Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers. INTERPRETATION: M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members. FUNDING: Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi.

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into "Metabolic genotypes" (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.