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Background: The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3).Methods and Findings: In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28-36 weeks of gestation, age 26 (19-42), weight 67kg (45-119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3-8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum.Conclusion: Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy.Trial Registration: clinicaltrials.gov NCT02245022. [ABSTRACT FROM AUTHOR]

Background: Large numbers of young people die yearly due to homicide, but little is known about homicide during adolescence. Research primarily focuses on youth violence among young men and masks important gender-related factors inherent in the adolescent age group. Although young women are less likely to be victims of homicide, violence against women is an important form of violence experienced during adolescence. In this paper, we describe the prevalence of and gender difference in adolescent homicide in South Africa in 2009. Methods: We conducted a retrospective national mortuary-based study to identify all child homicides (boys and girls < 18 years) in 2009 in a proportionate sample of mortuaries. Victim, perpetrator and crime data were collected in three phases: cases were identified from the mortuary register, the autopsy report and from police interviews. In this paper we focus on the adolescent group, aged 10 to 17 years. Findings: We identified 674 (95% CI: 520–823) adolescent homicides for 2009, with more male (520) than female (154) homicides. This gender disparity increased as children aged, with the male homicide rate 27.9/100 000 population (95% CI: 20.3–35.5), nearly 5 times the female rate (4.5:1) of 6.5/ 100 000 population (95% CI: 4.7–8.2) in older adolescents (15–17 year old). Adolescent males were significantly more likely (61.2%) to die in a public space compared to female adolescents (39.3%) but more adolescent females (48.4%) died at home compared to adolescent males (32.9%). Adolescent females (42.1%) were mainly killed by a family member or intimate partner while adolescent males were predominantly (58%) killed by an acquaintance. Conclusion: We found a distinct gender pattern for adolescent homicide in South Africa. This pattern appears to be driven by gender norms that support violence. South Africa requires an investment in developing evidence informed interventions to reduce violence. [ABSTRACT FROM AUTHOR]

Background: Evidence on the association between breastfeeding and later childhood obesity and blood pressure (BP) is inconsistent, especially in HIV-prevalent areas where, until recently, HIV-infected women were discouraged from breastfeeding, but obesity is increasingly prevalent.Methods and Findings: The Siyakhula cohort (2012-2014), a population-based prospective cohort study, collected data over 3 visits on HIV-negative children ages 7 to 11 years in rural South Africa. We used weight (body mass index [BMI]), fat, and BP as outcome variables and incorporated early life (including mother's age at delivery and HIV status) and current life factors (including maternal education and current BMI). Our primary exposure was breastfeeding duration. We dichotomized 3 outcome measures using pre-established thresholds for clinical interpretability: (1) overfat: ≥85th percentile of body fat; (2) overweight: >1 SD BMI z score; and (3) prehypertension: ≥90th percentile for systolic BP (SBP) or diastolic BP (DBP). We modelled each outcome using multivariable logistic regression, including stopping breastfeeding, then early life, and finally current life factors. Of 1,536 children (mean age = 9.3 years; 872 girls; 664 boys), 7% were overfat, 13.2% overweight, and 9.1% prehypertensive. Over half (60%) of the mothers reported continued breastfeeding for 12+ months. In multivariable analyses, continued breastfeeding between 6 and 11 months was associated with approximately halved odds of both being overfat (adjusted odds ratio [aOR] = 0.43, 95% confidence interval [CI] 0.21-0.91, P = 0.027) and overweight (aOR = 0.46, CI 0.26-0.82, P = 0.0083), but the association with prehypertension did not reach statistical significance (aOR = 0.72, CI 0.38-1.37, P = 0.32). Children with a mother who was currently obese were 5 times more likely (aOR = 5.02, CI 2.47-10.20, P < 0.001) to be overfat and over 4 times more likely to be overweight (aOR = 4.33, CI 2.65-7.09, P < 0.001) than children with normal weight mothers. Differences between HIV-exposed and unexposed children on any of the outcomes were minimal and not significant. The main study limitation was that duration of breastfeeding was based on maternal recall.Conclusions: To our knowledge, this is the first study examining and quantifying the association between breastfeeding and childhood obesity in an African setting with high HIV prevalence. We observed that breastfeeding was independently associated with reduced childhood obesity for both HIV-exposed and unexposed children, suggesting that promoting optimal nutrition throughout the life course, starting with continued breastfeeding, may be critical to tackling the growing obesity epidemic. In the era of widespread effective antiretroviral treatment for HIV-infected women for life, these data further support the recommendation of breastfeeding for all women. [ABSTRACT FROM AUTHOR]

Uranium (U) measurements in water, soil, and food related to gold mining activities in populated areas in Gauteng Province, South Africa, suggest the possibility of exposure levels that may lead to adverse health consequences, including cancer. Theoretical considerations on pathways of human uptake of significant exposures are plausible, but few data on directly measured human exposure are available. A cross-sectional study was conducted using human measurements to compare U levels with other settings around the globe (based on literature review), to explore potential exposure variability within the province, and to test the feasibility of recruiting subjects partially coming from vulnerable and difficult-to-reach populations. Wards of potentially high (HE) and low exposure (LE) were identified. Composite hair samples representing the respective local populations were collected from regular customers of selected barber shops over a period of 1–2 months. A total of 70 U concentrations were determined in 27 composite samples from 1332 individuals. U concentrations ranged from 31 μg/kg to 2524 μg/kg, with an arithmetic mean of 192 μg/kg (standard deviation, 310 μg/kg) and a median of 122 μg/kg. Although HE wards collectively showed higher U levels than LE wards (184 vs 134 μg/kg), differences were smaller than expected. In conclusion, detected U levels were higher than those from most other surveys of the general public. The barber-based approach was an efficient hair collection approach. Composite hair samples are not recommended, due to technical challenges in measuring U, and individual hair samples are needed in follow-up studies to determine predictors of exposure. [ABSTRACT FROM AUTHOR]

Objective: To study the performance and cardiovascular function after a 3-week training camp in athletes competing in an anaerobically dominant sport. Methods: Twenty-three competitive 400-m athletes were enrolled in this non-randomized study, 17 took part in a 3-week training camp in South-Africa (intervention), but one declined follow-up assessment, while 6 pursued in-door winter training in Sweden and served as controls. Electrocardiography, transthoracic echocardiography, blood test analyses, maximal exercise tolerance test, and a 300-m sprint test with lactate measurements ([La]peak) were performed before and after the training camp period. Results: At baseline, there were no clinically significant pathological findings in any measurements. The training period resulted in improved 300m-sprint performance [n = 16; running time 36.71 (1.39) vs. 35.98 (1.13) s; p<0.01] and higher peak lactate values. Despite 48% more training sessions than performed on home ground (n = 6), myocardial biomarkers decreased significantly (NT-pro BNP -38%; p<0.05, troponin T -16%; p<0.05). Furthermore, resting heart rate (-7%; p<0.01) and left ventricular systolic and diastolic volumes decreased -6% (p<0.01) and -10% (p<0.05), respectively. Conclusions: Intense physical activity at training camp improved the performance level, likely due to improved anaerobic capacity indicated by higher [La]peak. There were no clinically significant adverse cardiac changes after this period of predominantly anaerobic training. [ABSTRACT FROM AUTHOR]

Background: Globally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics. Methods: This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates. Results: We enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6–8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1–5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS. Conclusion: Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment. Methods: This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics. Results: 101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ≥-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%). Conclusions: In this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight. [ABSTRACT FROM AUTHOR]

Background: Shuni virus (SHUV) is an orthobunyavirus that belongs to the Simbu serogroup. SHUV was isolated from diverse species of domesticated animals and wildlife, and is associated with neurological disease, abortions, and congenital malformations. Recently, SHUV caused outbreaks among ruminants in Israel, representing the first incursions outside the African continent. The isolation of SHUV from a febrile child in Nigeria and seroprevalence among veterinarians in South Africa suggests that the virus may have zoonotic potential as well. The high pathogenicity, extremely broad tropism, potential transmission via both biting midges and mosquitoes, and zoonotic features of SHUV require further investigation. This is important to accurately determine the risk for animal and human health, and to facilitate preparations for potential epidemics. To gain first insight into the potential involvement of biting midges and mosquitoes in SHUV transmission we have investigated the ability of SHUV to infect two species of laboratory-colonised biting midges and two species of mosquitoes. Methodology/Principal findings: Culicoides nubeculosus, C. sonorensis, Culex pipiens pipiens, and Aedes aegypti were orally exposed to SHUV by providing an infectious blood meal. Biting midges showed high infection rates of approximately 40%-60%, whereas infection rates of mosquitoes were only 0–2%. Moreover, successful dissemination in both species of biting midges and no evidence for transmission by orally exposed mosquitoes was found. Conclusions/Significance: The results of this study suggest that different species of Culicoides midges are efficient in SHUV transmission, while the involvement of mosquitoes has not been supported. [ABSTRACT FROM AUTHOR]

Background: HIV self-testing (HIVST) may increase HIV testing uptake, facilitating earlier treatment for key populations like MSM who experience barriers accessing clinic-based HIV testing. HIVST usability among African MSM has not been explored. Methods: We assessed usability of oral fluid (OF) and fingerstick (FS; blood) HIVST kits during three phases among MSM with differing degrees of HIVST familiarity in Mpumalanga, South Africa. In 2015, 24 HIVST-naïve MSM conducted counselor-observed OF and FS HIVST after brief demonstration. In 2016 and 2017, 45 and 64 MSM with experience using HIVST in a pilot study chose one HIVST to conduct with a counselor-observer present. In addition to written, the latter group had access to video instructions. We assessed frequency of user errors and reported test use ease, changes in error frequency by phase, and covariates associated with correct usage using log-Poisson and Gaussian generalized estimating equations. Results: Among OF users (n = 57), 15–30% committed errors in each phase; however, observers consistently rated participants as able to test alone. Among FS users (n = 100), observers noted frequent errors, most commonly related to blood collection and delivery. We found suggestive evidence (not reaching statistical significance) that user errors decreased, with 37.5%, to 28.1%, and 18.2% committing errors in phases I, II, and III, respectively (p-value:0.08), however observer concerns remained constant. Ease and confidence using HIVST increased with HIV testing experience. Participants using three HIVST were more likely (RR:1.92, 95% CI:1.32, 2.80) to report ease compared to those without prior HIVST experience. Never testers (RR:0.66, 95% CI:0.44–0.99) reported less ease performing HIVST compared to participants testing in the past six months. Conclusions: MSM were able to perform the OF test. Fingerstick test performance was less consistent; however preference for fingerstick was strong and performance may improve with exposure and instructional resources. Continued efforts to provide accessible instructions are paramount. [ABSTRACT FROM AUTHOR]

A new species of hermit crab, Pagurus fraserorum n. sp. (family Paguridae) is described from rocky subtidal reefs off KwaZulu-Natal, South Africa, and illustrated using both conventional drawings and colour photographs, and via three-dimensional (3D) X-ray micro-computed tomography (μCT). Because of the limitation μCT has in detecting very fine and soft structures, a novel approach of manually drawing setation and spinulation onto the two-dimensional images of the 3D visualizations was used to illustrate the pereopods. In addition, an interactive figure and rotation movie clips in the supplement section complement the species description, and the 3D raw data of the 3D type data are downloadable from the Gigascience Database repository. The new species is the sixth species of Pagurus Fabricius, 1775 reported from South Africa and is closely allied to the Indo-Pacific P. boriaustraliensis Morgen, 1990 and P. pitagsaleei McLaughlin, 2002, from which it differs by its shorter ocular peduncles, by the armature of the carpus of the right cheliped, and also in colouration. This study presents the first description of a hermit crab in which a majority of taxonomic details are illustrated through 3D volume-rendered illustrations. In addition, colour photographs and COI molecular barcodes are provided, and the latter compared to COI sequences of specimens from Western Australia previously identified as P. boriaustraliensis and of specimens of P. pitagsaleei from Taiwan, as well as to three additional South African members of the genus. The South African taxon was confirmed to be genetically distinct from all species tested. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. Methods: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. Results: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28–40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27–38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. Conclusions: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings. [ABSTRACT FROM AUTHOR]

Introduction: Disseminated intravascular coagulopathy (DIC) is a thrombotic microangiopathy arising from consumption of both coagulation factors and platelets. DIC is triggered by a number of clinical conditions including severe infection, trauma and obstetric complications. Early diagnosis and treatment of the underlying condition is paramount. A high clinical index of suspicion is needed to ensure that patients at risk of developing DIC are appropriately investigated. Methods: In order to establish the clinical conditions most frequently associated with DIC, we reviewed all DIC screens received at a tertiary hospital in Johannesburg, South Africa over a 1 year period. Results: The commonest clinical condition associated with DIC in our population was infection with 84% of patients infected with an identified pathogen. The most frequently diagnosed pathogen was HIV followed by Mycobacterium tuberculosis and other bacterial infections. In the majority of cases, bacteria were isolated from blood cultures. In 47 patients, HIV was the only pathogen which could be isolated. A relative risk ratio of 2.73 and an odds ratio of 29.97 was attributed to HIV for development of a DIC. A malignancy was present in 51 of the patients of which approximately 60% had co-existing infection. No cause could be attributed in 30 patients. Conclusion: Infection was identified in the majority of the patients diagnosed with DIC in this study. HIV showed the highest relative risk ratio of all pathogens although previous studies have not suggested that HIV was strongly associated with DIC. In almost half of the HIV infected patients, there was no other pathogen isolated despite extensive investigation. This suggests that HIV has a strong association with the development of DIC, warranting further research into the relationship between HIV and disseminated microvascular thrombosis. [ABSTRACT FROM AUTHOR]

Background: Urine microscopy is the standard diagnostic method for urogenital S. haematobium infection. However, this may lead to under-diagnosis of urogenital schistosomiasis, as the disease may present itself with genital symptoms in the absence of ova in the urine. Currently there is no single reliable and affordable diagnostic method to diagnose the full spectrum of urogenital S. haematobium infection. In this study we explore the classic indicators in the diagnosis of urogenital S. haematobium infection, with focus on young women. Methods: In a cross-sectional study of 1237 sexually active young women in rural South Africa, we assessed four diagnostic indicators of urogenital S. haematobium infection: microscopy of urine, polymerase chain reaction (PCR) of cervicovaginal lavage (CVL), urogenital symptoms, and sandy patches detected clinically in combination with computerised image analysis of photocolposcopic images. We estimated the accuracy of these diagnostic indicators through the following analyses: 1) cross tabulation (assumed empirical gold standard) of the tests against the combined findings of sandy patches and/or computerized image analysis and 2) a latent class model of the four indicators without assuming any gold standard. Results: The empirical approach showed that urine microscopy had a sensitivity of 34.7% and specificity of 75.2% while the latent class analysis approach (LCA) suggested a sensitivity of 81.0% and specificity of 85.6%. The empirical approach and LCA showed that Schistosoma PCR in CVL had low sensitivity (14.1% and 52.4%, respectively) and high specificity (93.0% and 98.0, respectively). Using LCA, the presence of sandy patches showed a sensitivity of 81.6 and specificity of 42.4%. The empirical approach and LCA showed that urogenital symptoms had a high sensitivity (89.4% and 100.0%, respectively), whereas specificity was low (10.6% and 12.3%, respectively). Conclusion: All the diagnostic indicators used in the study had limited accuracy. Using urine microscopy or Schistosoma PCR in CVL would only confirm a fraction of the sandy patches found by colposcopic examination. [ABSTRACT FROM AUTHOR]

Background: The extent and circumstances under which empiric tuberculosis (TB) treatment (treatment without microbiological confirmation at treatment initiation) is administered in primary health care settings in South Africa are not well described. Methods: We used data from a pragmatic evaluation of Xpert MTB/RIF in which persons undergoing TB investigations by PHC nurses were followed for six months. Following Xpert or smear-microscopy at enrolment, investigations for tuberculosis were undertaken at the discretion of health care workers. We identified persons whose TB treatment was initiated empirically (no microbiological confirmation at time of treatment initiation at a primary health care facility) and describe pathways to treatment initiation. Results: Of 4665 evaluable participants, 541 persons were initiated on treatment of whom 167 (31%) had negative sputum tests at enrolment. Amongst these 167, the median number of participant visits to health care providers prior to treatment initiation was 3 (interquartile range [IQR] 2–4). Chest radiography, sputum culture or hospital referral was done in 106/167 (63%). Reasons for TB treatment start were: 1) empiric (n = 82, 49%); 2) a positive laboratory test (n = 49, 29%); 3) referral and treatment start at a higher level of care (n = 28, 17%); and 4) indeterminable (n = 8, 5%). Empiric treatment accounted for 15% (82/541) of all TB treatment initiations and 1.7% (82/4665) of all persons undergoing TB investigations. Chest radiography findings compatible with TB (63/82 [77%]) were the basis for treatment initiation amongst the majority of empirically treated participants. Microbiological confirmation of TB was subsequently obtained for 11/82 (13%) empirically-treated participants. Median time to empiric treatment start was 3.9 weeks (IQR 1.4–11 weeks) after enrolment. Conclusion: Uncommon prescription of empiric TB treatment with reliance on chest radiography in a nurse-managed programme underscores the need for highly sensitive TB diagnostics suitable for point-of-care, and strong health systems to support TB diagnosis in this setting. [ABSTRACT FROM AUTHOR]

Background: The growing prevalence of overweight and obesity in low- or middle-income countries precipitates the need to examine early life predictors of adiposity. Objectives: To examine growth trajectories from birth, and associations with adult body composition in the Birth to Twenty Plus Cohort, Soweto, South Africa. Methods: Complete data at year 22 was available for 1088 participants (536 males and 537 females). Conditional weight and height indices were generated indicative of relative rate of growth between years 0–2, 2–5, 5–8, 8–18, and 18–22. Whole body composition was measured at year 22 (range 21–25 years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were recorded. Results: Birth weight was positively associated with FFSTM and fat mass at year 22 (β = 0.11, p<0.01 and β = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative linear growth from birth to year 22 was positively associated with FFSTM at year 22. Relative linear growth from birth to year 2 was positively associated with VAT at year 22. Being born small for gestational age and being stunted at age 2 years were inversely associated with FFSTM at year 22. Conclusions: The importance of optimal birth weight and growth tempos during early life for later life body composition, and the detrimental effects of pre- and postnatal growth restriction are clear; yet contemporary weight-gain most strongly predicted adult body composition. Thus interventions should target body composition trajectories during childhood and prevent excessive weight gain in early adulthood. [ABSTRACT FROM AUTHOR]

Introduction: Hospital-associated methicillin-resistant S. aureus (HA-MRSA) remains a significant cause of morbidity and mortality worldwide. We conducted a study to determine risk factors for HA-MRSA in order to inform control strategies in South Africa. Methods: We used surveillance data collected from five tertiary hospitals in Gauteng and Western Cape provinces during 2014 for analysis. A case of HA-MRSA was defined as isolation of MRSA from a blood culture 48 hours after admission and/or if the patient was hospitalised in the six months prior to the current culture. Multivariable logistic regression modelling was used to determine risk factors for HA-MRSA. Results: Of the 9971 patients with positive blood cultures, 7.7% (772) had S. aureus bacteraemia (SAB). The overall prevalence of MRSA among those with SAB was 30.9% (231/747; 95% confidence interval [CI] 27.6%– 34.3%). HA-MRSA infections accounted for 28.3% of patients with SAB (207/731; 95% CI 25.1%– 31.7%). Burns (adjusted odds ratio [aOR] 12.7; 95% CI 4.7–34.4), age ≤1 month (aOR 8.7; 95% CI 3.0–24.6), residency at a long-term care facility (aOR 5.2; 95% CI, 1.5–17.4), antibiotic use within two months of the current SAB episode (aOR 5.1; 95% CI 2.8–9.1), hospital stay of 13 days or more (aOR 2.8; 95% CI 1.3–5.6) and mechanical ventilation (aOR 2.2; 95% CI 1.07–4.6), were independent risk factors for HA-MRSA infection. Conclusion: The prevalence of MRSA remains high in South African tertiary public hospitals. Several identified risk factors of HA-MRSA infections should be considered when instituting infection and prevention strategies in public-sector hospitals, including intensifying the implementation of antimicrobial stewardship programmes. There is an urgent need to strengthen infection prevention and control in burn wards, neonatal wards, and intensive care units which house mechanically ventilated patients. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to lead (Pb) has been shown to have negative and irreversible health impacts on foetal and early childhood development, affecting morbidity and mortality in adulthood. This study aimed to assess in utero Pb exposure, examine birth outcomes, and identify confounding factors in the large cohort of South African population, following the legislated removal of Pb from petrol. Methods: Lead was measured in the maternal blood, urine and cord blood using Inductive Coupled Plasma Mass spectrometry (ICP-MS). The statistical analyses included Spearman’s correlation, Wilcoxon rank sum (Mann Whitney), Kruskal-Wallis rank tests and multivariate linear regression. Results: Overall, the geometric mean (GM) of Pb in maternal blood (PbB) was 1.32 μg/dL (n = 640; 95% CI, 1.24–1.40). In the subset cohort, the GM of paired maternal PbB and cord blood (PbC) was 1.73 μg/dL (n = 350; 95% CI, 1.60–1.86) and 1.26 μg/dL (n = 317; 95% CI, 1.18–1.35), respectively with a positive correlation between the log PbB and the log PbC (rho = 0.65, p = <0.001). Birth outcomes showed geographical differences in the gestational age (p<0.001), birth length (p = 0.028) and head circumference (p<0.001), Apgar score at 5 min (p<0.001) and parity (p<0.002). In female neonates, a positive association was found between PbC and head circumference (rho = 0.243; p<0.016). The maternal PbB levels were positively correlated with race, educational status, water sources, cooking fuels and use of pesticides at home. Conclusions: This study has demonstrated not only the positive impact that the introduction of unleaded petrol and lead-free paint has had on in utero exposure to Pb in South Africa, but has also contributed new data on the topic, in a region where such data and scientific investigations in this field are lacking. Future research should evaluate if similar effects can be detected in young children and the adult population. [ABSTRACT FROM AUTHOR]

Background: In South Africa, roughly half of the drug-resistant TB cases diagnosed are reported to have been started on treatment. We determined the proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated treatment in Johannesburg after the introduction of decentralized RR-TB care in 2011. Methods: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 with records of patients initiating RR-TB treatment at one of the city’s four public sector treatment sites (one centralized, three decentralized). Patients were followed from date of diagnosis until the earliest of RR-TB treatment initiation, death, or 6 months’ follow-up. We report diagnostic methods and outcomes, proportions initiating treatment, and median time from diagnosis to treatment initiation. Results: 594 patients were enrolled (median age 34 (IQR 29–42), 287 (48.3%) female). Diagnosis was by GenoType MTBDRplus (Hain-Life-Science) line probe assay (LPA) (281, 47.3%), Xpert MTB/RIF (Cepheid) (258, 43.4%), or phenotypic drug susceptibility testing (DST) (30, 5.1%) with 25 (4.2%) missing a diagnosis method. 320 patients (53.8%) had multi-drug resistant TB, 158 (26.6%) rifampicin resistant TB by Xpert MTB/RIF, 102 (17.2%) rifampicin mono-resistance, and 14 (2.4%) extensively drug-resistant TB. 256/594 (43.0%) patients initiated treatment, representing 70.7% of those who were referred for treatment (362/594). 338/594 patients (57.0%) did not initiate treatment, including 104 (17.5%) who died before treatment was started. The median time from sputum collection to treatment initiation was 33 days (IQR 12–52). Conclusion: Despite decentralized RR-TB treatment, fewer than half the patients diagnosed in Johannesburg initiated appropriate treatment. Offering treatment at decentralized sites alone is not sufficient; improvements in linking patients diagnosed with RR-TB to effective treatment is essential. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. Methods: We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005–2008) and post-PCV introduction (2012–2013) in children aged 0–59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. Results: In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000–140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000–50,000) severe pneumococcal disease cases were estimated in 2012–2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000–6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000–2500) in 2012–2013, a mortality rate difference of 61 per 100,000 child-years. Conclusions: While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0–59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden. [ABSTRACT FROM AUTHOR]

Background: Samples submitted for HIV PCR testing that fail to yield a positive or negative result represent missed diagnostic opportunities. We describe HIV PCR test rejections and indeterminate results, and the associated delay in diagnosis, within South Africa’s early infant diagnosis (EID) program from 2010 to 2015. Methods: HIV PCR test data from January 2010 to December 2015 were extracted from the National Health Laboratory Service Corporate Data Warehouse, a central data repository of all registered test-sets within the public health sector in South Africa, by laboratory number, result, date, facility, and testing laboratory. Samples that failed to yield either a positive or negative result were categorized according to the rejection code on the laboratory information system, and descriptive analysis performed using Microsoft Excel. Delay in diagnosis was calculated for patients who had a missed diagnostic opportunity registered between January 2013 and December 2015 by means of a patient linking-algorithm employing demographic details. Results: Between 2010 and 2015, 2 178 582 samples were registered for HIV PCR testing of which 6.2% (n = 134 339) failed to yield either a positive or negative result, decreasing proportionally from 7.0% (n = 20 556) in 2010 to 4.4% (n = 21 388) in 2015 (p<0.001). Amongst 76 972 coded missed diagnostic opportunities, 49 585 (64.4%) were a result of pre-analytical error and 27 387 (35.6%) analytical error. Amongst 49 694 patients searched for follow-up results, 16 895 (34.0%) had at least one subsequent HIV PCR test registered after a median of 29 days (IQR: 13–57), of which 8.4% tested positive compared with 3.6% of all samples submitted for the same period. Conclusions: Routine laboratory data provides the opportunity for near real-time surveillance and quality improvement within the EID program. Delay in diagnosis and wastage of resources associated with missed diagnostic opportunities must be addressed and infants actively followed-up as South Africa works towards elimination of mother-to-child transmission. [ABSTRACT FROM AUTHOR]

Background: Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert’s random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Method: Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Results: Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32–0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. Conclusion: The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services. [ABSTRACT FROM AUTHOR]

Introduction: Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. Methods: We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. Results: We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. Conclusions: In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines. [ABSTRACT FROM AUTHOR]

Background: We assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa. Methods: A systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever ≥3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss ≥10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as “confirmed” if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and “clinical” if tuberculosis treatment started without microbiological confirmation. Results: Amongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 ≥100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used. Conclusion: Sensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care. [ABSTRACT FROM AUTHOR]

Background: The BD-FACSPresto™ CD4 is a new, point-of-care (POC) instrument utilising finger-stick capillary blood sampling. This study evaluated its performance against predicate CD4 testing in South Africa. Methods: Phase-I testing: HIV+ patient samples (n = 214) were analysed on the Presto™ under ideal laboratory conditions using venous blood. During Phase-II, 135 patients were capillary-bled for CD4 testing on FACSPresto™, performed according to manufacturer instruction. Comparative statistical analyses against predicate PLG/CD4 method and industry standards were done using GraphPad Prism 6. It included Bland-Altman with 95% limits of agreement (LOA) and percentage similarity with coefficient of variation (%CV) analyses for absolute CD4 count (cells/μl) and CD4 percentage of lymphocytes (CD4%). Results: In Phase-I, 179/217 samples yielded reportable results with Presto™ using venous blood filled cartridges. Compared to predicate, a mean bias of 40.4±45.8 (LOA of -49.2 to 130.2) and %similarity (%CV) of 106.1%±7.75 (7.3%) was noted for CD4 absolute counts. In Phase-2 field study, 118/135 capillary-bled Presto™ samples resulted CD4 parameters. Compared to predicate, a mean bias of 50.2±92.8 (LOA of -131.7 to 232) with %similarity (%CV) 105%±10.8 (10.3%), and 2.87±2.7 (LOA of -8.2 to 2.5) with similarity of 94.7±6.5% (6.83%) noted for absolute CD4 and CD4% respectively. No significant clinical differences were indicated for either parameter using two sampling methods. Conclusion: The Presto™ produced remarkable precision to predicate methods, irrespective of venous or capillary blood sampling. A consistent, clinically insignificant over-estimation (5–7%) of counts against PLG/CD4 and equivalency to FACSCount™ was noted. Further field studies are awaited to confirm longer-term use. [ABSTRACT FROM AUTHOR]

Background: High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.Methods and Findings: RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study ("standard arm") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05-1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.Conclusions: Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa.Trial Registration: ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177. [ABSTRACT FROM AUTHOR]

Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7–89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06–1.43] vs. 1.50 [95%CI 1.30–1.71], respectively, rate ratio 0.82 [95%CI 0.67–1.01]; LOD 1.04 [95% CI 0.90–1.23] vs. 1.22 [95%CI 1.05–1.42], rate ratio 0.85 [95% CI 0.68–1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better quantify the burden of invasive GBS disease in low-middle resourced settings such as ours. From our study passive systems are important to monitor trends over time as long as they are interpreted with caution; active systems give better detailed information and will have greater representivity when expanded to other surveillance sites. [ABSTRACT FROM AUTHOR]

Edentulism can negatively affect both masticatory performance and dietary intake by altering the patterns of biomechanical stress and strain, which in turn modifies the morphology of the different regions of the mandible. The morphological changes in the mandible caused by these stressors are unknown when comparing mandibles across varying dentition states. This study investigated differences in the morphology of human mandibles across various states of the dentition. In total, 498 mandibles of individuals between 20 and 80 yr of age at death were sourced from the Raymond A. Dart Collection of Human Skeletons. These included fully dentate ( n = 95), partially edentulous ( n = 333), and fully edentulous ( n = 70) mandibles. Twelve linear anthropometric measurements of the mandible were derived from digitized landmarks located on its external surface. Data analysis included geometric morphometrics and multivariate analyses. Compared with dentate and partially edentulous mandibles, fully edentulous mandibles showed a shorter alveolar height (−0.4 mm), a shorter mandibular body length (−4 mm), a larger gonial angle (+4°), a more obtuse mental angle (+4.7°), a broader bicondylar width (+3.8 mm), and a taller ramus height (+1.6 mm). Thus, edentulous states are associated with an altered mandibular morphology, which may result from a reduction in jaw function. [ABSTRACT FROM AUTHOR]

Studies on the amphibian respiratory tract microvascular anatomy are few. Using scanning electron microscopy ( SEM) of vascular corrosion casts ( VCCs) and light microscopy of perfusion-fixed tissue sections, we studied the bronchial microvascular anatomy in the adult South African Clawed Toad, Xenopus laevis Daudin. Histomorphology showed that the bronchial wall consists (from luminal to abluminal) of squamous epithelium, subepithelial capillary bed, cartilage rings or cartilage plates, a layer of dense connective tissue, a layer of smooth muscle cells, and squamous epithelium (serosa). SEM of VCCs reveals that bilaterally a ventral, a dorsal (Ø 77.21 ± 7.61 μm), and a caudal bronchial artery supply the bronchial subepithelial capillary bed. The ventral bronchial artery has 3-4 branching orders (interbranching distances: 506.3 ± 392.12 μm; branching angles of first- and second-order bifurcations: 24.60 ± 10.24° and 29.59 ± 14.3°). Casts of bronchial arteries display imprints of flow dividers and sphincters. Cranial and caudal bronchial veins (Ø 154.78 ± 49.68 μm) drain into pulmonary veins. They lack microvenous valves. The location of the dense subepithelial capillary meshwork just beneath the thin squamous bronchial epithelium and its drainage into the pulmonary veins make it likely that in Xenopus, bronchi assist in aerial gas exchange. [ABSTRACT FROM AUTHOR]