The risk of sexual transmission of HIV in individuals with low-level HIV viraemia: a systematic review.

BACKGROUND: The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications, especially in resource-limited settings that use alternatives to plasma-based viral load testing. This Article summarises the evidence related to sexual transmission of HIV at varying HIV viral load levels to inform messaging for people living with HIV, their partners, their health-care providers, and the wider public. METHODS: We conducted a systematic review and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, for work published from Jan 1, 2010 to Nov 17, 2022. Studies were included if they pertained to sexual transmission between serodiscordant couples at various levels of viraemia, the science behind undetectable=untransmittable, or the public health impact of low-level viraemia. Studies were excluded if they did not specify viral load thresholds or a definition for low-level viraemia or did not provide quantitative viral load information for transmission outcomes. Reviews, non-research letters, commentaries, and editorials were excluded. Risk of bias was evaluated using the ROBINS-I framework. Data were extracted and summarised with a focus on HIV sexual transmission at varying HIV viral loads. FINDINGS: 244 studies were identified and eight were included in the analysis, comprising 7762 serodiscordant couples across 25 countries. The certainty of evidence was moderate; the risk of bias was low. Three studies showed no HIV transmission when the partner living with HIV had a viral load less than 200 copies per mL. Across the remaining four prospective studies, there were 323 transmission events; none were in patients considered stably suppressed on ART. Among all studies there were two cases of transmission when the index patient's (ie, patient with previously diagnosed HIV infection) most recent viral load was less than 1000 copies per mL. However, interpretation of both cases was complicated by long intervals (ie, 50 days and 53 days) between the transmission date and the most recent index viral load result. INTERPRETATION: There is almost zero risk of sexual transmission of HIV with viral loads of less than 1000 copies per mL. These data provide a powerful opportunity to destigmatise HIV and promote adherence to ART through dissemination of this positive public health message. These findings can also promote access to viral load testing in resource-limited settings for all people living with HIV by facilitating uptake of alternative sample types and technologies. FUNDING: Bill & Melinda Gates Foundation.

Eliminating mother-to-child transmission of human immunodeficiency virus, syphilis and hepatitis B in sub-Saharan Africa.

Triple elimination is an initiative supporting the elimination of mother-to-child transmission of three diseases - human immunodeficiency virus (HIV) infection, syphilis and hepatitis B. Significant progress towards triple elimination has been made in some regions, but progress has been slow in sub-Saharan Africa, the region with the highest burden of these diseases. The shared features of the three diseases, including their epidemiology, disease interactions and core interventions for tackling them, enable an integrated health-systems approach for elimination of mother-to-child transmission. Current barriers to triple elimination in sub-Saharan Africa include a lack of policies, strategies and resources to support the uptake of well established preventive and treatment interventions. While much can be achieved with existing tools, the development of new products and models of care, as well as a prioritized research agenda, are needed to accelerate progress on triple elimination in sub-Saharan Africa. In this paper we aim to show that health systems working together with communities in sub-Saharan Africa could deliver rapid and sustainable results towards the elimination of mother-to-child transmission of all three diseases. However, stronger political support, expansion of evidence-based interventions and better use of funding streams are needed to improve efficiency and build on the successes in prevention of mother-to-child transmission of HIV. Triple elimination is a strategic opportunity to reduce the morbidity and mortality from HIV infection, syphilis and hepatitis B for mothers and their infants within the context of universal health coverage.

La triple élimination est une initiative visant à soutenir l'éradication de la transmission mère-enfant de trois maladies ­ l'infection au virus de l'immunodéficience humaine (VIH), la syphilis et l'hépatite B. Bien que des avancées considérables aient été observées en ce sens dans certaines régions, les progrès demeurent lents en Afrique subsaharienne, pourtant durement touchée par ces maladies. Les caractéristiques communes aux trois affections, notamment leur épidémiologie, les interactions entre elles et les principales interventions nécessaires à leur prise en charge permettent aux systèmes de santé d'adopter une approche intégrée pour éviter la transmission mère-enfant. Plusieurs obstacles entravent actuellement la triple élimination en Afrique subsaharienne, parmi lesquels l'absence de politiques, de stratégies et de ressources pour garantir la disponibilité de traitements préventifs et curatifs bien établis. Les outils existants offrent déjà de nombreuses solutions; mais pour accélérer la progression de cette triple élimination en Afrique subsaharienne, il est indispensable de développer de nouveaux produits et modèles de soins, ainsi qu'un programme de recherche prioritaire. Dans le présent document, nous voulons montrer que si les systèmes de santé collaborent avec les communautés en Afrique subsaharienne, ils pourront obtenir des résultats rapides et durables en vue d'éradiquer la transmission mère-enfant des trois maladies susmentionnées. Néanmoins, une telle démarche implique un soutien politique massif, l'expansion des interventions fondées sur des données scientifiques, et une meilleure utilisation des sources de financement afin d'améliorer l'efficacité et de s'appuyer sur les réussites en matière de prévention de la transmission du VIH de la mère à l'enfant. La triple élimination représente une occasion stratégique de réduire la morbidité et la mortalité liées à l'infection au VIH, à la syphilis et à l'hépatite B, tant chez les mères que chez les nourrissons, dans un contexte de couverture maladie universelle.

La triple eliminación es una iniciativa que apoya la eliminación de la transmisión maternoinfantil de tres enfermedades: la infección por el virus de la inmunodeficiencia humana (VIH), la sífilis y la hepatitis B. En algunas regiones se han logrado avances significativos hacia la triple eliminación, pero los progresos se han desarrollado con mayor lentitud en el África subsahariana, la región con la mayor carga de estas enfermedades. Las características comunes de las tres enfermedades, como su epidemiología, las interacciones entre ellas y las intervenciones básicas para combatirlas, permiten un enfoque integrado de los sistemas de salud para la eliminación de la transmisión maternoinfantil. Los obstáculos actuales para la triple eliminación en el África subsahariana incluyen la falta de políticas, estrategias y recursos para apoyar la adopción de intervenciones preventivas y de tratamiento bien establecidas. Aunque se puede lograr mucho con las herramientas existentes, se necesita el desarrollo de nuevos productos y modelos de atención, así como una agenda de investigación prioritaria, para acelerar el progreso de la triple eliminación en el África subsahariana. En este documento pretendemos demostrar que los sistemas de salud que trabajan conjuntamente con las comunidades del África subsahariana podrían obtener resultados rápidos y sostenibles hacia la eliminación de la transmisión maternoinfantil de las tres enfermedades. Sin embargo, se necesita un mayor apoyo político, la ampliación de las intervenciones basadas en la evidencia y un mejor uso de los flujos de financiación para mejorar la eficiencia y aprovechar los éxitos en la prevención de la transmisión maternoinfantil del VIH. La triple eliminación es una oportunidad estratégica para reducir la morbilidad y la mortalidad de la infección por el VIH, la sífilis y la hepatitis B para las madres y sus hijos en el contexto de la cobertura sanitaria universal.

Use of an Indeterminate Range in HIV Early Infant Diagnosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Expanded access to HIV antiretrovirals has dramatically reduced mother-to-child transmission of HIV. However, there is increasing concern around false-positive HIV test results in perinatally HIV-exposed infants but few insights into the use of indeterminate range to improve infant HIV diagnosis. METHODS: A systematic review and meta-analysis was conducted to evaluate the use of an indeterminate range for HIV early infant diagnosis. Published and unpublished studies from 2000 to 2018 were included. Study quality was evaluated using GRADE and QUADAS-2 criteria. A random-effects model compared various indeterminate ranges for identifying true and false positives. RESULTS: The review identified 32 studies with data from over 1.3 million infants across 14 countries published from 2000 to 2018. Indeterminate results accounted for 16.5% of initial non-negative test results, and 76% of indeterminate results were negative on repeat testing. Most results were from Roche tests. In the random-effects model, an indeterminate range using a polymerase chain reaction cycle threshold value of ≥33 captured over 93% of false positives while classifying fewer than 9% of true positives as indeterminate. CONCLUSIONS: Without the use of an indeterminate range, over 10% of infants could be incorrectly diagnosed as HIV positive if their initial test results are not confirmed. Use of an indeterminate range appears to lead to substantial improvements in the accuracy of early infant diagnosis testing and supports current recommendations to confirm all initial positive tests.

Beyond Early Infant Diagnosis: Changing the Approach to HIV-Exposed Infants.

Despite dramatic global progress with implementing prevention of mother-to-child HIV transmission (PMTCT) programs, there were 160,000 new pediatric HIV infections in 2016. More than 50% of infant HIV infections now occur in the postpartum period, reflecting the relatively high coverage of interventions in the antenatal period and the need for greater attention to the breastfeeding mother and her HIV-exposed infant (HEI). Early diagnosis and treatment are critical to prevent morbidity and mortality in HIV-infected children; however, early infant HIV testing rates remain low in most high HIV-burden countries. Furthermore, systematic retention and follow-up of HEI in the postpartum period and ascertainment of final HIV status remain major program gaps. Despite multiple calls to action to improve infant HIV testing rates, progress has been marginal due to a lack of focus on the critical health care needs of HEI coupled with health system barriers that result in fragmented services for HIV-infected mothers and their families. In this paper, we describe the available evidence on the health outcomes of HEI, define a comprehensive care package for HEI that extends beyond early HIV testing, and describe successful examples of integrated services for HEI.

Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding women and their infants: the promise of innovative service delivery models.

INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. DISCUSSION: Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. CONCLUSIONS: Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake of services for families. However, with decreasing funding, stable HIV incidence, and aspirations for sustainability, it is critical to consider efficient, customized and cost-effective models of care for these populations as we aspire to eliminate mother-to-child transmission of HIV.

Expansion of Viral Load Testing and the Potential Impact on Human Immunodeficiency Virus Drug Resistance.

Increasing the volume, strengthening the quality, and proactively using data of human immunodeficiency virus (HIV) load testing are pivotal to limiting the threat of HIV drug resistance (HIVDR) accumulation,and allow for optimal case-based HIVDR surveillance. Triangulation of viral load (VL) and HIVDR testing data could be pursued to answer key questions and translate data and results for program and public policy. Identification of virologic failure and early management mitigates the greater risk of HIVDR. Routine VL monitoring and evaluation systems are necessary, and countries should consider reviewing system requirements, structural needs, and procedural and technical factors for the entire VL cascade, with special emphasis on post-test result use.

Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

Pregnant adolescents living with HIV: what we know, what we need to know, where we need to go.

INTRODUCTION: HIV-infected pregnant and breastfeeding adolescents are a particularly vulnerable group that require special attention and enhanced support to achieve optimal maternal and infant outcomes. The objective of this paper is to review published evidence about antenatal care (ANC) service delivery and outcomes for HIV-infected pregnant adolescents in low-income country settings, identify gaps in knowledge and programme services and highlight the way forward to improve clinical outcomes of this vulnerable group. DISCUSSION: Emerging data from programmes in sub-Saharan Africa highlight that HIV-infected pregnant adolescents have poorer prevention of mother-to-child HIV transmission (PMTCT) service outcomes, including lower PMTCT service uptake, compared to HIV-infected pregnant adults. In addition, the limited evidence available suggests that there may be higher rates of mother-to-child HIV transmission among infants of HIV-infected pregnant adolescents. CONCLUSIONS: While the reasons for the inferior outcomes among adolescents in ANC need to be further explored and addressed, there is sufficient evidence that immediate operational changes are needed to address the unique needs of this population. Such changes could include integration of adolescent-friendly services into PMTCT settings or targeting HIV-infected pregnant adolescents with enhanced retention and follow-up activities.

Moving toward test and start: learning from the experience of universal antiretroviral therapy programs for HIV-infected pregnant/ breastfeeding women.

: In 2015, the WHO recommended universal antiretroviral therapy (ART) for all people living with HIV after two randomized controlled trials revealed lower rates of mortality and serious illnesses among people living with HIV receiving immediate ART compared with those receiving deferred ART. Many countries in sub-Saharan Africa rapidly adopted this guidance and are implementing 'test and start' programs.As this work begins, lessons learned from prevention of mother-to-child transmission Option B+ programs can inform decisions for new universal HIV treatment programs. The Option B+ approach involved initiation of lifelong treatment for all HIV-infected pregnant and breastfeeding women. Since its inception in Malawi in 2011 and WHO endorsement in 2012, widespread scale-up of Option B+ prevention of mother-to-child transmission programs in most resource-limited countries has resulted in a dramatic increase in ART coverage for HIV-infected pregnant and breastfeeding women.Despite the overall success of the Option B+ universal lifelong treatment approach, program and operational research data highlight the need for additional focus on strategies to retain women in care. In this commentary, we highlight program considerations and lessons learned from Option B+ implementation experience in resource-limited countries, which may help guide decisions and enhance the quality of general 'test and start' programing.

Overcoming Health System Challenges for Women and Children Living With HIV Through the Global Plan.

To meet the ambitious targets set by the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), the initial 22 priority countries quickly developed innovative approaches for overcoming long-standing health systems challenges and providing HIV testing and treatment to pregnant and breastfeeding women and their infants. The Global Plan spurred programs for prevention of mother-to-child HIV transmission to integrate HIV-related care and treatment into broader maternal, newborn, and child health services; expand the effectiveness of the health workforce through task sharing; extend health services into communities; strengthen supply chain and commodity management systems; reduce diagnostic and laboratory hurdles; and strengthen strategic supervision and mentorship. The article reviews the ongoing challenges for prevention of mother-to-child HIV transmission programs as they continue to strive for elimination of vertical transmission of HIV infection in the post-Global Plan era. Although progress has been rapid, health systems still face important challenges, particularly follow-up and diagnosis of HIV-exposed infants, continuity of care, and the promotion of services that are respectful and client centered.

Field Evaluation of Dried Blood Spots for HIV-1 Viral Load Monitoring in Adults and Children Receiving Antiretroviral Treatment in Kenya: Implications for Scale-up in Resource-Limited Settings.

BACKGROUND: The World Health Organization recommends viral load (VL) as the preferred method for diagnosing antiretroviral therapy failure; however, operational challenges have hampered the implementation of VL monitoring in most resource-limited settings. This study evaluated the accuracy of dried blood spot (DBS) VL testing under field conditions as a practical alternative to plasma in determining virologic failure (VF). METHODS: From May to December 2013, paired plasma and DBS specimens were collected from 416 adults and 377 children on antiretroviral therapy for ≥6 months at 12 clinics in Kenya. DBSs were prepared from venous blood (V-DBS) using disposable transfer pipettes and from finger-prick capillary blood using microcapillary tubes (M-DBS) and directly spotting (D-DBS). All samples were tested on the Abbott m2000 platform; V-DBS was also tested on the Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) version 2.0 platform. VF results were compared at 3 DBS thresholds (≥1000, ≥3000, and ≥5000 copies/mL) and a constant plasma threshold of ≥1000 copies/mL. RESULTS: On the Abbott platform, at ≥1000-copies/mL threshold, sensitivities, specificities, and kappa values for VF determination were ≥88.1%, ≥93.1%, and ≥0.82%, respectively, for all DBS methods, and it had the lowest percentage of downward misclassification compared with higher thresholds. V-DBS performance on CAP/CTM had significantly poorer specificity at all thresholds (1000%-33.0%, 3000%-60.9%, and 5000%-77.0%). No significant differences were found between adults and children. CONCLUSIONS: VL results from V-DBS, M-DBS, and D-DBS were comparable with those from plasma for determining VF using the Abbott platform but not with CAP/CTM. A 1000-copies/mL threshold was optimal and should be considered for VF determination using DBS in adults and children.

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

Decreased Ebola Transmission after Rapid Response to Outbreaks in Remote Areas, Liberia, 2014.

We measured the reproduction number before and after interventions were implemented to reduce Ebola transmission in 9 outbreaks in Liberia during 2014. We evaluated risk factors for secondary cases and the association between patient admission to an Ebola treatment unit (ETU) and survival. The reproduction number declined 94% from 1.7 (95% CI 1.1-2.6) to 0.1 (95% CI 0.02-0.6) after interventions began. The risk for secondary infections was 90% lower for patients admitted to an ETU (risk ratio 0.1, 95% CI 0.04-0.3) than for those who died in the community. The case-fatality rate was 68% (95% CI 60-74), and ETU admission was associated with a 50% reduction in death (hazard ratio 0.5, 95% CI 0.4-0.8). Isolation and treatment of Ebola patients had the dual benefit of interrupting community transmission and improving survival.

Rapid intervention to reduce Ebola transmission in a remote village - Gbarpolu County, Liberia, 2014.

As late as September 14, 2014, Liberia's Gbarpolu County had reported zero cases of Ebola virus disease (Ebola). On October 25, the Bong County Health Team, a local health department in the Liberian Ministry of Health and Social Welfare (MOHSW), received confirmation of Ebola in a man who had recently left Geleyansiesu, a remote village of approximately 800 residents, after his wife and daughter had died of illnesses consistent with Ebola. MOHSW requested assistance from CDC, the World Health Organization, and other international partners to investigate and confirm the outbreak in Geleyansiesu and begin interventions to interrupt transmission. A total of 22 cases were identified, of which 18 (82%) were laboratory confirmed by real-time polymerase chain reaction. There were 16 deaths (case-fatality rate = 73%). Without road access to or direct telecommunications with the village, interventions had to be tailored to the local context. Public health interventions included 1) education of the community about Ebola, transmission of the virus, signs and symptoms, the importance of isolating ill patients from family members, and the potential benefits of early diagnosis and treatment; 2) establishment of mechanisms to alert health authorities of possibly infected persons leaving the village to facilitate safe transport to the closest Ebola treatment unit (ETU); 3) case investigation, contact tracing, and monitoring of contacts; 4) training in hygienic burial of dead bodies; 5) active case finding and diagnosis; and 6) isolation and limited no-touch treatment in the village of patients unwilling or unable to seek care at an ETU. The findings of this investigation could inform interventions aimed at controlling focal outbreaks in difficult-to-reach communities, which has been identified as an important component of the effort to eliminate Ebola from Liberia.

Rapid response to Ebola outbreaks in remote areas - Liberia, July-November 2014.

West Africa is experiencing its first epidemic of Ebola virus disease (Ebola). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16-November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfully reduce transmission and improve outcomes.

Genetic relationships deduced from emm and multilocus sequence typing of invasive Streptococcus dysgalactiae subsp. equisimilis and S. canis recovered from isolates collected in the United States.

Beta-hemolytic group C and G streptococci cause a considerable invasive disease burden and sometimes cause disease outbreaks. Little is known about the critical epidemiologic parameter of genetic relatedness between isolates. We determined the emm types of 334 Streptococcus dysgalactiae subsp. equisimilis isolates, and attempted emm typing of 5 Streptococcus canis isolates from a recent population-based surveillance for invasive isolates. Thirty-four emm types were observed, including one from S. canis. We formulated multilocus sequence typing (MLST) primers with six of the seven loci corresponding to the Streptococcus pyogenes MLST scheme. We performed MLST with 65 of the 334 surveillance isolates (61 S. dysgalactiae subsp. equisimilis isolates, 4 S. canis isolates) to represent each emm type identified, including 2 to 3 isolates for each of the 25 redundantly represented emm types. Forty-one MLST sequence types (STs) were observed. Isolates within 16 redundantly represented S. dysgalactiae subsp. equisimilis emm types shared identical or nearly identical STs, demonstrating concordance between the emm type and genetic relatedness. However, seven STs were each represented by two to four different emm types, and 7 of the 10 S. dysgalactiae subsp. equisimilis eBURST groups represented up to six different emm types. Thus, S. dysgalactiae subsp. equisimilis isolates were similar to S. pyogenes isolates, in that strains of the same emm type were often highly related, but they differed from S. pyogenes, in that S. dysgalactiae subsp. equisimilis strains with identical or closely similar STs often exhibited multiple unrelated emm types. The phylogenetic relationships between S. dysgalactiae subsp. equisimilis and S. pyogenes alleles revealed a history of interspecies recombination, with either species often serving as genetic donors. The four S. canis isolates shared highly homologous alleles but were unrelated clones without evidence of past recombination with S. dysgalactiae subsp. equisimilis or S. pyogenes.

Population-based study of invasive disease due to beta-hemolytic streptococci of groups other than A and B.

BACKGROUND: Beta-hemolytic streptococci of groups other than A and B (NABS) are increasingly recognized as causes of clinically significant disease, but precise information about this heterogeneous group is lacking. We report the incidence of NABS infection and describe the epidemiologic and clinical characteristics. METHODS: Active, population-based surveillance for invasive NABS was performed over a 2-year period in the 8-county metropolitan Atlanta, Georgia, area and the 3-county San Francisco Bay, California, area. Clinical records were reviewed, and available isolates were sent to the Centers for Disease Control and Prevention (Atlanta) for additional microbiologic characterization. Incidences were calculated using year-appropriate US Census Bureau data. RESULTS: A total of 489 cases of invasive NABS infection were identified (3.2 cases per 100,000 population). The median age of patients was 55 years; 64% of patients were males, and 87% had underlying diseases. The incidence was higher among black persons than white persons (4.0 vs. 2.5 cases per 100,000 population; P < .01) and increased with age among all races. Infections were community acquired in 416 cases (85%). Among the 450 patients (94%) with NABS infection who were hospitalized, 55 (12%) died. Of 266 isolates (54%) speciated at the Centers for Disease Control and Prevention, 212 (80%) were Streptococcus dysgalactiae subspecies equisimilis; 46 (17%) were members of the Streptococcus anginosus group. S. dysgalactiae subspecies equisimilis primarily presented as skin and soft-tissue infection in older patients, whereas individuals with invasive S. anginosus group infections were more likely to be younger patients with intra-abdominal infections. CONCLUSIONS: NABS comprise multiple distinct species that cause a significant number of community-acquired invasive infections. Clinical manifestations differ by species. Thus, speciation of invasive NABS may be warranted in clinical settings.