Outbreak of invasive Group A streptococcus disease in a nursing home in Ireland in February 2023 caused by emm type 18.

An out-of-season increase in cases of invasive Group A streptococcus (iGAS) was observed in Ireland between October 2022 and August 2023. We describe the management of an iGAS outbreak involving three nursing home residents in Ireland in early 2023. A regional Department of Public Health was notified of an iGAS case in a nursing home resident in January 2023. When two further cases among residents were notified 7 days later, an outbreak was declared. Surveillance for GAS/iGAS infection in residents and staff was undertaken. The site was visited to provide infection prevention and control (IPC) support. Isolates were emm typed. A total of 38 residents and 29 staff in contact with resident cases were provided with antibiotic chemoprophylaxis. Seven additional staff with no direct resident contact also received chemoprophylaxis after finding one probable localised GAS infection among them. No more iGAS cases subsequently occurred.Site visit recommendations included advice on terminal cleaning and cleaning of shared equipment, as well as strengthening staff education on hand hygiene and masking. All isolates were of emm subtype 18.12, a subtype not previously detected in Ireland. Key outbreak control measures were rapid delivery of IPC support and chemoprophylaxis. Emm18 is infrequently associated with GAS infections.

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis.

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Genomic epidemiology of group B streptococci spanning 10 years in an Irish maternity hospital, 2008-2017.

OBJECTIVES: The genomic epidemiology of group b streptococcal (GBS) isolates from the Rotunda maternity hospital, Dublin, 2008-2017, was investigated. METHODS: Whole genome sequences of isolates (invasive, n = 114; non-invasive, n = 76) from infants and women were analysed using the PubMLST database (https://pubmlst.org/sagalactiae/). RESULTS: Serotypes III (36%), Ia (18%), V (17%), II (11%) and Ib, (9%) and sequence types (ST) 17 (23%), ST-23 (14%), ST-1 (12%) and ST-19 (7%) were most common. Core genome MLST (cgMLST) differentiated isolates of the same ST, grouped STs into five lineages congruent with known clonal complexes and identified known mother-baby pairs and suspected linked infant cases. Clonal complex (CC) 17 accounted for 40% and 22% of infant and maternal invasive cases, respectively and 21% of non-invasive isolates. CC23 and CC19 were associated with maternal disease (30%) and carriage (24%), respectively. Erythromycin (26%) and clindamycin (18%) resistance increased over the study period and was associated with presence of the erm(B) gene (55%), CC1 (33%) and CC19 (24%). A multi-resistant integrative conjugative element incorporated in the PI-1 locus was detected in CC17, an ST-12 and ST-23 isolate confirming the global dissemination of this element. All isolates possessed one or more pilus islands. Genes encoding other potential protective proteins including Sip, C5a peptidase and Srr1 were present in 100%, 99.5% and 65.8% of isolates, respectively. The srr2 gene was unique to CC17. CONCLUSIONS: The PubMLST.org website provides a valuable framework for genomic GBS surveillance to inform on local and global GBS epidemiology, preventive and control measures.

Uncovering Infant Group B Streptococcal (GBS) Disease Clusters in the United Kingdom and Ireland Through Genomic Analysis: A Population-based Epidemiological Study.

BACKGROUND: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. METHODS: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. RESULTS: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days. CONCLUSIONS: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

The role of real-time PCR testing in the investigation of paediatric patients with community-onset osteomyelitis and septic arthritis.

BACKGROUND: Culture yield in osteomyelitis and septic arthritis is low, emphasising the role for molecular techniques. AIMS: The purpose of this study was to review the laboratory investigation of childhood osteomyelitis and septic arthritis. METHODS: A retrospective review was undertaken in an acute tertiary referral paediatric hospital from January 2010 to December 2016. Cases were only included if they had a positive culture or bacterial PCR result from a bone/joint specimen or blood culture, or had radiographic evidence of osteomyelitis. RESULTS: Seventy-eight patients met the case definition; 52 (66%) were male. The median age was 4.8 years. Blood cultures were positive in 16 of 56 cases (29%), with 11 deemed clinically significant (Staphylococcus aureus = 8, group A Streptococcus = 3). Thirty-seven of 78 (47%) bone/joint samples were positive by culture with S. aureus (n = 16), coagulase-negative Staphylococcus (n = 9) and group A Streptococcus (n = 4), being the most common organisms. Sixteen culture-negative samples were sent for bacterial PCR, and four were positive (Kingella kingae = 2, Streptococcus pneumoniae = 1, group A Streptococcus = 1). CONCLUSIONS: Sequential culture and PCR testing can improve the detection rate of causative organisms in paediatric bone and joint infections, particularly for fastidious microorganisms such as K. kingae. PCR testing can be reserved for cases where culture is negative after 48 h. These results have been used to develop a standardised diagnostic test panel for bone and joint infections at our institution.

Group B streptococcal disease in UK and Irish infants younger than 90 days, 2014-15: a prospective surveillance study.

BACKGROUND: Group B streptococcus is a leading cause of serious infection in young infants in many countries worldwide. We aimed to define the burden and clinical features of invasive group B streptococcal disease in infants younger than 90 days in the UK and Ireland, together with the characteristics of disease-causing isolates. METHODS: Prospective, active national surveillance of invasive group B streptococcal disease in infants younger than 90 days was done from April 1, 2014, to April 30, 2015, through the British Paediatric Surveillance Unit, microbiology reference laboratories, and national public health agencies in the UK and Ireland. Early onset was defined as disease in the first 6 days of life and late onset was defined as 7-89 days of life. Incidence was calculated using livebirths in 2014 (after adjustment for the 13-month surveillance period). Isolates were characterised by serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. FINDINGS: 856 cases of group B streptococcus were identified in 2014-15, an incidence of 0·94 per 1000 livebirths (95% CI 0·88-1·00). Incidence for early-onset disease (n=517) was 0·57 per 1000 livebirths (95% CI 0·52-0·62), and for late-onset disease (n=339) was 0·37 per 1000 livebirths (0·33-0·41). 53 infants died (case fatality rate 6·2%), of whom 27 had early-onset disease (case fatality rate 5·2%) and 26 had late-onset disease (case fatality rate 7·7%). The predominant serotypes were III (241 [60%] of 402 serotyped isolates) and Ia (69 [17%]); five serotypes (Ia, Ib, II, III, V) accounted for 377 (94%) of all serotyped isolates. INTERPRETATION: The incidence of invasive infant group B streptococcal disease in the UK and Ireland has increased since a comparable study done in 2000-01. The burden of early-onset disease has not declined despite the introduction of national prevention guidelines. New strategies for prevention are required. FUNDING: Meningitis Now.

Epidemiology of an upsurge of invasive group A streptococcal infections in Ireland, 2012-2015.

OBJECTIVES: Group A streptococcus (GAS) is responsible for mild to very severe disease. The epidemiology of an upsurge in invasive GAS (iGAS) infections in Ireland, 2012-2015 was investigated. METHODS: Epidemiological typing of iGAS (n = 473) isolates was performed and compared to non-invasive (n = 517) isolates. Clinical data of notified iGAS was obtained from the national infectious disease information system. RESULTS: Annual incidences of iGAS cases (n = 561) were 2.33-3.66 per 100,000 population. Bacteraemia was the most common clinical presentation (75%) followed by focus without bacteraemia (19%) and necrotizing faciitis (7%). Streptococcal toxic shock syndrome occurred in 19% of presentations. The main invasive emm types in rank order were emm1, emm3, emm28, emm12 and emm89 whereas emm4, emm28, emm3, emm12, emm89 and emm1 predominated in non-invasive infections. Invasive emm1 and emm3 showed annual fluctuations (15-48% and 4-37%, respectively) and predominated in most clinical presentations of iGAS. Superantigens speA, speG, speJ was associated with iGAS disease and, speC, speI and ssa with non-invasive infections. There was 4.3% erythromycin and 5.6% tetracycline resistance. The main resistant types were emm11, emm28 and emm77. CONCLUSIONS: Cyclic increases in emm1 and emm3 occurred during the iGAS upsurge. Continued surveillance of GAS is therefore essential given the epidemiological changes that occur in a short time period.

An Outbreak of Streptococcus pyogenes in a Mental Health Facility: Advantage of Well-Timed Whole-Genome Sequencing Over emm Typing.

OBJECTIVEWe report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.SETTINGA 2,000-bed tertiary-care psychiatric hospital.METHODSActive surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)-based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.RESULTSThe study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1-C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0-5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21-45 and 26-58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.CONCLUSIONSWGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.Infect Control Hosp Epidemiol 2018;852-860.

Screening for early-onset invasive group B Streptococcal disease in neonates in an Irish hospital (2001-2014): a retrospective audit.

Group B Streptococcus (GBS) is the most common cause of early-onset neonatal sepsis and meningitis. In babies with no clinical suspicion of infection, who are at risk of early-onset invasive disease based on maternal risk factors, blood cultures are taken to detect bacteraemia. In our institution, lumbar punctures are performed in infants with clinical signs of sepsis but not in infants who are well at the time of screening. Between 2001 and 2014, there were 112,361 live births weighing >500 g, of whom 13,959 (12.4%) infants had a blood culture taken on the first or second day of life, and 1971 (14.1%) of these infants had lumbar punctures on these first two days of life. Fifty-three cases of early-onset GBS disease were identified. Only three patients with invasive GBS disease had no clinical suspicion for sepsis at the time of testing. Thus, the number of blood cultures taken to detect one case of GBS bacteraemia in an infant who is well at the time of testing was 3996.

Noninvasive pneumococcal clones associated with antimicrobial nonsusceptibility isolated from children in the era of conjugate vaccines.

Carriage and noninvasive pneumococcal isolates frequently have a higher prevalence of antimicrobial nonsusceptibility than invasive isolates. From 2009 to 2014, we determined the associated clones in 169 pediatric noninvasive nonsusceptible pneumococci from a total of 506 isolates collected after 7- and 13-valent conjugate vaccine introduction (PCV7/13) to the Irish childhood immunization schedule in 2008 and 2010, respectively. We compared our results to those from 25 noninvasive pediatric pneumococcal isolates collected in 2007, the year before introduction of conjugate vaccines. In 2007, England(14)-9 and Spain(9V)-3 accounted for 12% and 32% of nonsusceptible clones, respectively, but in 2009 to 2014, their prevalence fell to 0% and 2.4%. Furthermore, there was a significant decline in Spain(6B)-2 and its variants from 2009 to 2014 (P = 0.0024). Fluctuations occurred in clonal complex 320 associated with serotype 19A. The prevalence of Sweden(15A)-25 and its variants and ST558 (a single-locus variant of Utah(35B)-24) associated with nonvaccine serotypes (NVT) 15A and 35B increased from 0% and 8% in 2007 to 19% and 16% in 2013 to 2014, respectively. Pilus locus 1 (PI-1) is associated with the spread of some nonsusceptible pneumococcal clones. PI-1 was more frequently associated with PCV7/13 serotypes than NVT (P = 0.0020). Our data highlight the value of surveillance of noninvasive pneumococci following conjugate vaccine introduction. Importantly, emerging clones associated with NVT may limit the effectiveness of PCV7/13 in reducing the high rate of nonsusceptibility among pediatric noninvasive pneumococci, with implications for empirical treatment strategies.

Molecular epidemiology of group B streptococci in Ireland reveals a diverse population with evidence of capsular switching.

The molecular epidemiology of group B Streptococcus (GBS) in Ireland was investigated. Invasive (n = 132) and non-invasive (n = 45) isolates, collected in 2007-2011, were analysed by multilocus locus sequence typing, capsular polysaccharide (CPS) serotyping, profiling of surface proteins, pilus islands (PI), and antimicrobial susceptibility. Isolates grouped into 45 sequence types and five main clonal complexes (CC). CC1, CC17 and CC23 represented 67.2 % of isolates and the most prevalent serotypes Ia, III and V. Serotype and surface protein genes were largely predictive of CC. Accordingly, CPS V/alp3, CPS Ib/CPS II/bca + bac, and CPS Ia/eps predominated in CC1, CC12 and CC23, respectively, and CPS III/rib in CC17 and CC19. Supporting their vaccine potential, all isolates harboured at least one PI, of which the PI-1 + PI-2a combination was most prevalent. Macrolide resistance was found in 18.6 % of isolates. erm(B) and the globally disseminated CC1/CPS V were the most common resistance mechanism and CC/CPS type, respectively. CC17, significantly associated with neonatal disease, was also prevalent in pregnant adults, but was underrepresented among non-pregnant adults. Two of 46 CC17 isolates (typically CPS III) were CPS IV. Sequence analysis confirmed capsular switching and their relatedness to CC17/CPS IV strains recently characterized in France. CPS IV, detected only in invasive isolates (6.8 %), was most prevalent in adults (12 %) and showed an increase in prevalence to that reported (1.4 %) for invasive isolates in Ireland 1997-1999. Increases in serotype IV and evidence of capsular switching in CC17 highlights the importance of ongoing surveillance of GBS and may have implications for vaccine development strategies.

Development of a diagnostic real-time polymerase chain reaction assay for the detection of invasive Haemophilus influenzae in clinical samples.

Since the introduction of the Haemophilus influenzae serotype b vaccine, invasive H. influenzae disease has become dominated by nontypeable (NT) strains. Several widely used molecular diagnostic methods have been shown to lack sensitivity or specificity in the detection of some of these strains. Novel real-time assays targeting the fucK, licA, and ompP2 genes were developed and evaluated. The fucK assay detected all strains of H. influenzae tested (n = 116) and had an analytical sensitivity of 10 genome copies/polymerase chain reaction (PCR). This assay detected both serotype b and NT H. influenzae in 12 previously positive specimens (culture and/or bexA PCR) and also detected H. influenzae in a further 5 of 883 culture-negative blood and cerebrospinal fluid (CSF) samples. The fucK assay has excellent potential as a diagnostic test for detection of typeable and nontypeable strains of invasive H. influenzae in clinical samples of blood and CSF.

Characterization of the haem-uptake system of the equine pathogen Streptococcus equi subsp. equi.

Streptococcus equi possesses a haem-uptake system homologous to that of Streptococcus pyogenes and Streptococcus zooepidemicus. The system consists of two ligand-binding proteins (Shr and Shp) and proteins (HtsA-C) with homology to an ABC transporter. The haem-uptake system of S. equi differs from that of S. pyogenes and S. zooepidemicus in that Shr is truncated by two-thirds. This study focused on the SeShr, SeShp and SeHtsA proteins of S. equi. Analysis of shr, shp and shphtsA knockout mutants showed that all three proteins were expressed in vitro and that expression was upregulated under conditions of iron limitation. SeShr possesses no membrane-/cell wall-spanning sequences and was shown to be secreted. Both SeShp and SeHtsA were confirmed to be envelope-associated. Recombinant SeShp and SeHtsA proteins have been previously shown to bind haem and SeHtsA could capture haem from SeShp. This report extends these studies and shows that both SeShp and SeHtsA can sequester haem from haemoglobin but not from haemoglobin-haptoglobin complexes. Like full-length Shr, SeShr possesses haemoglobin and haemoglobin-haptoglobin binding ability but unlike full-length Shr, it lacks haem- or fibronectin-binding capabilities. Analysis of SeShr truncates showed that residues within and upstream of the near transporter (NEAT) domain are required for this ligand binding. Structural predictions suggest that truncation of NEAT1 in SeShr accounts for its impaired ability to bind haem. Haem and haemoglobin restored to almost normal the impaired growth rates of wild-type S. equi cultured under iron-limiting conditions. However, no difference in the growth rates of wild-type and mutants could be detected under the in vitro growth conditions tested.

Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi.

Fibrinogen-binding protein (FgBP, also termed SeM) is a cell-wall-associated anti-phagocytic M-like protein of the equine pathogen Streptococcus equi subsp. equi, and binds fibrinogen (Fg) and IgG. FgBP binds Fg avidly through residues located at the extreme N terminus of the molecule, whereas the IgG-binding site is more centrally located between the A and B repeats. FgBP binds equine IgG4 and IgG7 subclasses through interaction with the CH2-CH3 interdomain region of IgG-Fc, and possesses overlapping Fc-binding sites with protein A and protein G. In this study, FgBP truncates containing defined internal deletions were used to identify a stretch of 14 aa (residues 335-348) critical for IgG binding. Protein chimeras consisting of the non-IgG-binding alpha-helical coiled-coil M5 protein fused to FgBP sequences were used to identify a minimal equine IgG-binding domain consisting of residues 329-360. Competition ELISA tests suggested that IgG does not compromise Fg binding and vice versa.

Lack of correlation between antibody titers to fibrinogen-binding protein of Streptococcus equi and persistent carriers of strangles.

Previously published studies have neither used nor reported the results of an indirect enzyme-linked immunosorbent assay (iELISA) to measure serologic responses in natural outbreaks of strangles. The concept of using serologic responses to identify persistent carriers of Streptococcus equi has been proposed but not scientifically evaluated. The specific aims of the current study were to determine the duration and level of truncated fibrinogen-binding protein-specific (SeM allele 1) antibody production in ponies involved in a natural outbreak of strangles and to determine if test results from this serologic iELISA could predict persistent carrier status. Serologic samples were obtained before and after an outbreak of naturally occurring strangles infection. Persistent carriers of S. equi were identified via culture and polymerase chain reaction (PCR) testing of lavage fluid collected from the guttural pouches and nasopharynx or swabs of the nasopharynx after recovery from acute disease and at postmortem examination. Logistic regression analysis was used to determine if an association existed between serologic response and persistent carrier state. The ELISA reported in the current study definitively confirmed a recent exposure to S. equi. However, the measured serologic response did not predict carrier status in this strangles outbreak. Therefore, a guttural-pouch endoscopy with subsequent culture or PCR testing to detect S. equi remains the most accurate method available for the identification of persistent carriers.

A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system.

The M protein of Streptococcus equi subsp. equi known as fibrinogen-binding protein (FgBP) is a cell wall-associated protein with antiphagocytic activity that binds IgG. Recombinant versions of the seven equine IgG subclasses were used to investigate the subclass specificity of FgBP. FgBP bound predominantly to equine IgG4 and IgG7, with little or no binding to the other subclasses. Competitive binding experiments revealed that FgBP could inhibit the binding of staphylococcal protein A and streptococcal protein G to both IgG4 and IgG7, implicating the Fc interdomain region in binding to FgBP. To identify which of the two IgG Fc domains contributed to the interaction with FgBP, we tested two human IgG1/IgA1 domain swap mutants and found that both domains are required for full binding, with the CH3 domain playing a critical role. The binding site for FgBP was further localized using recombinant equine IgG7 antibodies with single or double point mutations to residues lying at the CH2-CH3 interface. We found that interaction of FgBP with equine IgG4 and IgG7 was able to disrupt C1q binding and antibody-mediated activation of the classical complement pathway, demonstrating an effective means by which S. equi may evade the immune response. The mode of interaction of FgBP with IgG fits a common theme for bacterial Ig-binding proteins. Remarkably, for those interactions studied in detail, it emerges that all the Ig-binding proteins target the CH2-CH3 domain interface, regardless of specificity for IgG or IgA, streptococcal or staphylococcal origin, or host species (equine or human).

Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda.

BACKGROUND: We estimated rates of human immunodeficiency virus (HIV)-1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner. METHODS: We retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner's stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression. RESULTS: The average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039-0.0150) within approximately 2.5 months after seroconversion of the index partner; 0.0015/coital act within 6-15 months after seroconversion of the index partner (95% CI, 0.0002-0.0055); 0.0007/coital act (95% CI, 0.0005-0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015-0.0041) 6-25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission. CONCLUSIONS: The rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission.

Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda.

Human immunodeficiency virus (HIV) type 1 RNA loads were determined for 256 subjects with early (incident) HIV infection and for 1293 subjects with later (prevalent) HIV infection, in a Ugandan cohort. Prevalent infections were classified as latent (0-1 symptoms) and midstage disease (>/=2 symptoms), and deaths were ascribed to acquired immunodeficiency syndrome. Among subjects with incident HIV infection, HIV load did not differ by sex, but, among subjects with prevalent HIV infection, it was higher in males than in females. HIV load was highest in subjects (25-29 years old) with incident HIV infection but increased with age in subjects with prevalent HIV infection. Viremia was higher after serconversion than in latency and increased with more advanced disease. Viremia was increased with genital ulcer disease (GUD) in both subjects with incident infection and in those with prevalent infection, and with herpes simplex virus type 2 seropositivity in subjects with incident HIV infection. GUD was consistently associated with higher HIV loads in subjects with incident and those with prevalent HIV infection, suggesting that treatment of GUD might reduce HIV viremia.