Edwin P. Armitage

Background: Africa experiences a high burden of Streptococcus pyogenes disease but has limited epidemiological data. We characterized emm types and emm clusters associated with carriage and disease in The Gambia, a setting with a high rheumatic heart disease burden. Methods: A 1-year household cohort study (2021–2022) recruited 442 participants from 44 households to assess S. pyogenes carriage and noninvasive infection. Pharyngeal and skin swab samples were collected to detect carriage, and pharyngitis and pyoderma swab samples were taken to assess infection. Cultured isolates underwent emm typing and were compared with previous collection from the same region. Results: A total of 221 cultured isolates showed 52 different emm types and 16 emm clusters. Strain diversity was high (Simpson reciprocal index, 29.3 [95% confidence interval, 24.8–36.0]), with the highest diversity seen in pyoderma and the lowest in pharyngitis. Based on available cross-opsonization data, the 30-valent M-protein vaccine candidate would cover 50.8% of the isolates, but cross-opsonization data are unknown for 38.5% of them. The emm clusters showed lower diversity and were stable over time, with 4 clusters defining 65.2% of the isolates; 68% of isolates were collected from skin sites (carriage and pyoderma), with evidence of skin-to-throat transmission in the same host. Conclusions: This study provides a unique molecular analysis of skin and throat isolates prospectively collected from persons with carriage and noninvasive infection in Africa. Despite high strain diversity, 4 clusters included two-thirds of the isolates, representing antigen priorities for broad vaccine coverage. In this rheumatic fever–endemic setting, pyoderma and skin carriage represent an important S. pyogenes reservoir and should be included in further surveillance studies and public health interventions. Clinical Trials Registration: NCT05117528.

Streptococcus pyogenes–related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resource settings, where they are often associated with scabies. The true prevalence of S pyogenes–related pyoderma may be underestimated by bacterial culture. A multiplex quantitative polymerase chain reaction (qPCR) assay for S pyogenes, Staphylococcus aureus, and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children aged emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. Pyoderma lesions with S pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S pyogenes (95% confidence interval {CI}, 77.2%–99.9%) in samples with S pyogenes alone (22/250 [9%]), but 59.9% (95% CI, 52.3%–67.2%) for samples with S aureus coinfection (177/250 [71%]). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including 6 not identified by WGS (total 52 emm-types). Bacterial culture significantly underestimates the burden of S pyogenes in pyoderma, particularly with S aureus coinfection. Molecular methods should be used to enhance the detection of S pyogenes in surveillance studies and clinical trials of preventive measures in RHD-endemic settings.

Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD). In The Gambia, the RHD burden is thought to be very high. However, epidemiological data is minimal, and Strep A control programmes do not exist. This study aimed to explore common beliefs and practices related to sore throats among primary caregivers of children, and healthcare providers in a community with a high Strep A disease burden. Four informal conversations with providers and fifteen semi-structured interviews with caregivers were conducted in the peri-urban area of Sukuta, The Gambia. Sampling was purposive and gradual, beginning from households identified to have recently experienced sore throat through a parallel cohort study. Themes explored in qualitative analysis included: sore throat causal attributions and diagnoses, care practises, health-seeking behaviour, and perceived barriers to using the biomedical sector. We found that sore throats were typically perceived to affect one child in a family, disproportionately or exclusively. Sore throats were rarely perceived as life-threatening, and awareness of links between sore throat and ARF or RHD was not reported among caregivers or providers in this study population. Most cases of sore throat were initially managed at home using traditional medicine which delayed resort to antibiotics, though in two instances of severe pain with the presence of exudate, fear that the child’s life was at risk prompted care-seeking through the formal health system. Our findings can inform the development of tailored strategies to increase community knowledge of the potential long-term consequences of sore throats and appropriate care-seeking, alongside improvements in the health system, to prevent Strep A sequelae effectively.

Background Streptococcus pyogenes (StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. Streptococcus dysgalactiae subsp. equisimilis (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia. Methods A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured. Outcome This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.

Group A Streptococcus (StrepA) bacteria causes a broad spectrum of diseases. The most common manifestations of StrepA infection are sore throat and pus-producing skin infections such as impetigo. Complications of StrepA infection lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD). In The Gambia, the RHD burden is thought to be very high. However, epidemiological data is minimal, and StrepA control programmes do not exist. This study aims to explore common beliefs and practices related to sore throats among primary caregivers of children, and healthcare providers in a community with a high StrepA disease burden. This will inform the design of preventative strategies for StrepA-related sequelae. Four informal conversations with providers and fifteen semi-structured interviews with caregivers were conducted in the peri-urban area of Sukuta, The Gambia. Sampling was purposive and gradual, beginning from households identified to have recently experienced sore throat through a parallel cohort study. Themes explored in qualitative analysis included: sore throat causal attributions and diagnoses, care practises, health-seeking behaviour, and perceived barriers to using the biomedical sector. Sore throats were typically perceived to affect one child in a family, disproportionately or exclusively. Sore throats are rarely perceived as life-threatening, and awareness of links between sore throat and ARF or RHD was not reported among caregivers or providers in this study population. Most cases of sore throat are initially managed at home using traditional medicine which delays resort to antibiotics, though in two instances of severe pain with the presence of exudate, fear that the child’s life was at risk prompted care-seeking through the formal health system. Our findings can inform the development of tailored strategies to increase community knowledge of the potential long-term consequences of sore throats and appropriate care-seeking, alongside improvements in the health system, to prevent StrepA sequelae effectively.

Background Streptococcus pyogenes (StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. Streptococcus dysgalactiae subsp. equisimilis (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia. Methods A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured. Outcome This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.