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Some centers prefer CMV-IVIG over IVIG for the prophylaxis of EBV-related PTLD in solid organ transplant patients. Our objective was to compare the relative dose-related EBV ELISA antibody concentrations and cost of standard IVIG and CMV-IVIG. The concentration of EBV IgG to VCA was analyzed via ELISA in four lots of IVIG and four lots of CMV-IVIG. Relative EBV ELISA antibody concentrations and cost were compared assuming an IVIG dose of 0.5 gm/kg and CMV-IVIG dose of 0.15 gm/kg in a 50-kg patient. The price of IVIG was $70/gm and CMV-IVIG $430/gm. IVIG contains the same EBV antibody concentrations (20 790 ELISA antibody units/mL) than CMV-IVIG (17 430 ELISA antibody units/mL, p > 0.2) in the four lots of each product sampled. When factoring in the dosing scheme for a 50-kg patient, IVIG contains two times more EBV antibody than CMV-IVIG. Yet, CMV-IVIG is 1.8 times more expensive than IVIG ($3225 vs. $1750). In the four lots of each product sampled, IVIG contains more EBV antibodies and costs less than CMV-IVIG when factoring in the dosing scheme. Studies are needed to determine whether there is clinical efficacy of immunoglobulin products for EBV-related PTLD prophylaxis.

We investigated whether and how infection prevention programs monitor for health disparities as part of healthcare-associated infection (HAI) surveillance through a survey of healthcare epidemiology leaders. Most facilities are not assessing for disparities in HAI rates. Professional society and national guidance should focus on addressing this gap.

Two independent temporal-spatial clusters of hospital-onset Rhizopus infections were evaluated using whole-genome sequencing (WGS). Phylogenetic analysis confirmed that isolates within each cluster were unrelated despite epidemiological suspicion of outbreaks. The ITS1 region alone was insufficient for accurate analysis. WGS has utility for rapid rule-out of suspected nosocomial Rhizopus outbreaks.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that confers significant morbidity and mortality., Objective: Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority., Methods: We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP)., Results: Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events., Conclusions: Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.

Candida auris is an emerging multidrug-resistant yeast with high mortality. We report the sentinel C. auris case on the United States West Coast in a patient who relocated from India. We identified close phylogenetic relatedness to the South Asia clade and ERG11 Y132F and FKS1 S639Y mutations potentially explaining antifungal resistance.

During August 2017, two separate clusters of platelet transfusion-associated bacterial sepsis were reported in Utah and California. In Utah, two patients died after platelet transfusions from the same donation. Clostridium perfringens isolates from one patient's blood, the other patient's platelet bag, and donor skin swabs were highly related by whole genome sequencing (WGS). In California, one patient died after platelet transfusion; Klebsiella pneumoniae isolates from the patient's blood and platelet bag residuals and a nontransfused platelet unit were matched using WGS. Investigation revealed no deviations in blood supplier or hospital procedures. Findings in this report highlight that even when following current procedures, the risk for transfusion-related infection and fatality persists, making additional interventions necessary. Clinicians need to be vigilant in monitoring for platelet-transmitted bacterial infections and report adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers and hospitals could consider additional evidence-based bacterial contamination risk mitigation strategies, including pathogen inactivation, rapid detection devices, and modified screening of bacterial culture protocols., Competing Interests: No conflicts of interest were reported.

HIV clinics formerly supported by the President's Emergency Plan for AIDS Relief are transferring patients to public-sector clinics. We evaluated adolescent linkage to care after a large-scale transfer from a President's Emergency Plan for AIDS Relief-subsidized pediatric HIV clinic in Durban, South Africa. All adolescents (11-18 years) in care at a pediatric state-subsidized, hospital-based clinic (HBC) were transferred, from May to June 2012, to government sites [primary health care (PHC) clinic; community health center (CHC); and HBCs] or private clinics. Caregivers were surveyed 7-8 months after transfer to assess their adolescents' linkage to care and their reports were validated by clinic record audits in a subset of randomly selected clinics. Of the 309 (91%) caregivers reached, only 5 (2%) reported that their adolescent did not link. Of the 304 adolescents who linked, 105 (35%) were referred to a PHC, 73 (24%) to a CHC and 106 (35%) to a HBC. A total of 146 (48%) linked adolescents attended a different clinic than that assigned. Thirty-five (20%) of the 178 who linked and were assigned to a PHC or CHC ultimately attended a HBC. Based on clinic validation, the estimated transfer success was 88% (95% confidence interval: 77%-97%). The large majority of adolescents successfully transferred to a new HIV clinic, although nearly half attended a clinic other than that assigned., Competing Interests: The authors have no conflicts of interest to disclose.

Invasive aspergillosis (IA) is a disease of increasing importance in pediatrics due to growth of the immunocompromised populations at risk and improvements in long-term survival for many of these groups. While general principles of diagnosis and therapy apply similarly across the age spectrum, there are unique considerations for clinicians who care for children and adolescents with IA. This review will highlight important differences in the epidemiology, clinical manifestations, diagnosis, and therapy of pediatric IA.

The HIV public health messages in South Africa have increased. Our objective was to evaluate changes over time in HIV testing behaviour, prevalence and knowledge. We prospectively enrolled adults (≥18 years) prior to HIV testing at one urban and one peri-urban outpatient department in Durban, South Africa. A baseline questionnaire administered before testing included the number of prior HIV tests and four knowledge items. We used test results to estimate previously undiagnosed HIV prevalence among those tested. We assessed linear trends over enrollment. From November 2006 to August 2010, 5229 subjects enrolled and 4877 (93%) were HIV tested and had results available. Subjects reporting prior testing over time increased, from 13% in study year 1 to 42% in year 4 (linear trend p < 0.001). The HIV prevalence among those tested declined steadily and significantly over time, from 64% of enrollees in study year 1 to 39% in the final year (linear trend p < 0.001). The percentage of subjects who recognised that medicine can help people with HIV live longer increased from 80% in study year 1 to 96% in study year 4. Rates of HIV testing have increased and prevalence among those tested has decreased in outpatients in Durban, South Africa., (© The Author(s) 2014.)

Progressive multifocal leukoencephalopathy is a rare, demyelinating disease of the central nervous system caused by JC virus. Fewer than 30 cases have been reported in HIV- and non-infected children. We report the case of a 15-year-old girl with progressive multifocal leukoencephalopathy and AIDS who presented with nystagmus, dysarthria and ataxia. Following combined antiretroviral therapy, she developed immune reconstitution inflammatory syndrome, which proved fatal.

Background: Computer simulation models can project long-term patient outcomes and inform health policy. We internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to provide a framework against which to compare the impact of pediatric HIV treatment strategies., Methods: We developed a patient-level (Monte Carlo) model of HIV progression among untreated children <5 years of age, using the Cost-Effectiveness of Preventing AIDS Complications model framework: the CEPAC-Pediatric model. We populated the model with data on opportunistic infection and mortality risks from the International Epidemiologic Database to Evaluate AIDS (IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/month) from the Women and Infants' Transmission Study (WITS). We internally validated the model by varying WITS-derived CD4% data, comparing the corresponding model-generated survival curves to empirical survival curves from IeDEA, and identifying best-fitting parameter sets as those with a root-mean square error (RMSE) <0.01. We then calibrated the model to other African settings by systematically varying immunologic and HIV mortality-related input parameters. Model-generated survival curves for children aged 0-60 months were compared, again using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African children., Results: In internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4% parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages >3 months). In calibration analyses, increases in IeDEA-derived mortality risks were necessary to fit UNAIDS survival data., Conclusions: The CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric cohort studies.

Background: Limited access to HIV testing of children impedes early diagnosis and access to antiretroviral therapy. Our objective was to evaluate the feasibility and acceptability of routine pediatric HIV testing in an urban, fee-for-service, outpatient clinic in Durban, South Africa., Methods: We assessed the number of patients (0-15 years) who underwent HIV testing upon physician referral during a baseline period. We then established a routine, voluntary HIV testing study for pediatric patients, regardless of symptoms. Parents/caretakers were offered free rapid fingerstick HIV testing of their child. For patients <18 months, the biological mother was offered HIV testing and HIV DNA polymerase chain reaction was used to confirm the infant's status. The primary outcome was the HIV testing yield, defined as the average number of positive tests per month during the routine compared with the baseline period., Results: Over a 5-month baseline testing period, 931 pediatric patients registered for outpatient care. Of the 124 (13%) patients who underwent testing on physician referral, 21 (17%, 95% confidence interval: 11-25%) were HIV infected. During a 13-month routine testing period, 2790 patients registered for care and 2106 (75%) were approached for participation. Of these, 1234 were eligible and 771 (62%) enrolled. Among those eligible, 637 (52%, 95% confidence interval: 49-54%) accepted testing of their child or themselves (biological mothers of infants <18 months). There was an increase in the average number of HIV tests during the routine compared with the baseline HIV testing periods (49 versus 25 tests/month, P = 0.001) but no difference in the HIV testing yield during the testing periods (3 versus 4 positive HIV tests/month, P = 0.06). However, during the routine testing period, HIV prevalence remains extraordinarily high with 39 (6%, 95% confidence interval: 4-8%) newly diagnosed HIV-infected children (median 7 years, 56% female)., Conclusions: Targeted and symptom-based testing referral identifies an equivalent number of HIV-infected children as routine HIV testing. Routine HIV testing identifies a high burden of HIV and is a feasible and moderately acceptable strategy in an outpatient clinic in a high prevalence area.

We evaluated the prevalence and correlates of depressive symptoms prior to HIV diagnosis and determined the effect of these symptoms on seeking HIV care at an urban and rural clinic in Durban, South Africa. Adults were administered a questionnaire which included the 5-item Mental Health Index (MHI-5) before HIV testing. We determined the depressive symptoms among HIV-infected subjects. Of 1,545 newly-diagnosed HIV-infected subjects, 55% had depressive symptoms by MHI-5 score. Enrolling at the urban clinic and decreasing functional activity score were associated with depressive symptoms. Subjects with depressive symptoms who were referred for HIV testing by a healthcare provider were less likely to obtain a CD4 count than those without depressive symptoms who self-referred for testing. Depressive symptoms were common among newly-diagnosed HIV-infected participants and impacted CD4 uptake. Depression screening at the time of HIV diagnosis is critical for improving linkage to mental health and HIV services in South Africa.

Objectives: Although youth (12-24 years) in Sub-Saharan Africa have a high HIV risk, many have poor access to HIV testing services and are unaware of their status. Our objective was to evaluate the proportion of adolescents (12-17 years) and young adults (18-24 years) who underwent HIV testing and the prevalence among those tested in an urban adult outpatient clinic with a routine HIV testing program in Durban, South Africa., Design: We conducted a retrospective cross-sectional analysis of adolescent and young adult outpatient records between February 2008 and December 2009., Methods: We determined the number of unique outpatient visitors, HIV tests, and positive rapid tests among those tested., Results: During the study period, 956 adolescents registered in the outpatient clinic, of which 527 (55%) were female. Among adolescents, 260/527 (49%, 95% CI 45-54%) females underwent HIV testing compared to 129/429 (30%, 95% CI 26-35%) males (p<0.01). The HIV prevalence among the 389 (41%, 95% CI 38-44%) adolescents who underwent testing was 16% (95% CI 13-20%) and did not vary by gender (p = 0.99). During this period, there were 2,351 young adult registrations, and of these 1,492 (63%) were female. The proportion consenting for HIV testing was similar among females 980/1,492 (66%, 95% CI 63-68%) and males 543/859 (63%, 95% CI 60-66%, p = 0.25). Among the 1,523 (65%, 95% CI 63-67%) young adults who underwent testing, the HIV prevalence was 22% (95% CI 19-24%) in females versus 14% in males (95% CI 11-17%, p<0.01)., Conclusions: Although the HIV prevalence is high among youth participating in an adult outpatient clinic routine HIV program, the uptake of testing is low, especially among 12-17 year old males. There is an urgent need to offer targeted, age-appropriate routine HIV testing to youth presenting to outpatient clinics in epidemic settings.

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings.

Eosinophilic meningitis can be the result of noninfectious causes and infectious agents. Among the infectious agents, Angiostrongylus cantonensis and Gnathostoma spinigerum are the most common. Although angiostrongyliasis and gnathostomiasis are not common in the United States, international travel and immigration make these diseases clinically relevant. Both A. cantonensis and G. spinigerum infection can present as severe CNS compromise. Diagnoses of both infections can be challenging and are often clinical because of a paucity of serological assays readily available in the United States. Furthermore, there are conflicting recommendations about treatment for angiostrongyliasis and gnathostomiasis. To further explore the emerging nature of these helminthic infections, a case description and review of A. cantonensis and G. spinigerum infections are presented. The clinical severity of eosinophilic meningitis and diagnosis of these infections are highlighted.

Balantidium coli is a cosmopolitan parasitic-opportunistic pathogen that can be found throughout the world. Pigs are its reservoir hosts, and humans become infected through direct or indirect contact with pigs. In rural areas and in some developing countries where pig and human fecal matter contaminates the water supply, there is a greater likelihood that balantidiosis may develop in humans. The infection may be subclinical in humans, as it mostly is in pigs, or may develop as a fulminant infection with bloody and mucus-containing diarrhea; this can lead to perforation of the colon. The disease responds to treatment with tetracycline or metronidazole. Balantidiosis is a disease that need never exist given access to clean water and a public health infrastructure that monitors the water supply and tracks infections. Its spread can be limited by sanitary measures and personal hygiene, but it is a disease that will be around as long as there are pigs. Immunocompromised individuals have developed balantidiosis without any direct contact with pigs, perhaps with rats or contaminated produce as a possible source of infection. For the clinician, balanatidiosis should be included in the differential diagnosis for persistent diarrhea in travelers to or from Southeast Asia, the Western Pacific islands, rural South America, or communities where close contact with domestic swine occurs. Warming of the earth's surface may provide a more favorable environment, even in the now-temperate areas of the world, for survival of trophic and cystic stages of Balantidium, and its prevalence may increase. Effective sanitation and uncontaminated water are the most useful weapons against infection. Fortunately, balantidiosis responds to antimicrobial therapy, and there have been no reports of resistance to the drugs of choice.

Entamoeba histolytica causes amebic colitis and liver abscess in developing countries such as Mexico and India. Entamoeba dispar is morphologically identical but is not associated with disease. Here we determined the ploidy of E. histolytica and developed PCR-based methods for distinguishing field isolates of E. histolytica or E. dispar. Fluorescence in situ hybridization showed that E. histolytica trophozoites are diploid for five "single-copy" probes tested. Intergenic sequences between superoxide dismutase and actin 3 genes of clinical isolates of E. histolytica from the New and Old Worlds were identical, as were those of E. dispar. These results suggest a bottleneck or demographic sweep in entamoebae which infect humans. In contrast, E. histolytica and E. dispar genes encoding repeat antigens on the surface of trophozoites (Ser-rich protein) or encysting parasites (chitinase) were highly polymorphic. chitinase alleles suggested that the early axenized strains of E. histolytica, HM-1 from Mexico City, Mexico, and NIH-200 from Calcutta, India, are still present and that similar E. dispar parasites can be identified in both the New and Old Worlds. Ser-rich protein alleles, which suggested the presence of the HM-1 strain in Mexico City, included some E. histolytica genes that predicted Ser-rich proteins with very few repeats. These results, which suggest diversifying selection at chitinase and Ser-rich protein loci, demonstrate the usefulness of these alleles for distinguishing clinical isolates of E. histolytica and E. dispar.