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Background: The prevalence of obesity rises gradually worldwide and it is a chronic metabolic disease, which is defined by an excessive accumulation of body fat resulting from an imbalance between energy intake and expenditure. Some studies suggested that the level of serum 25(OH)D was associated with obesity. Vitamin D insufficiency or deficiency is closely associated with chronic diseases, such as tumours, cardiovascular diseases, and diabetes. Vitamin D is fat soluble that can be stored in body fat tissues and excessive body fat can reduce 25(OH) D levels in the blood, especially in obese individuals. Many studies revealed that young women are at a high risk of vitamin D deficiency. Objective: To evaluate the relationship between serum 25(OH)D level and obesity among young women. Methods: This cross-sectional analytical study was carried out in the Department of Biochemistry of Sir Salimullah Medical College & Mitford Hospital, during July 20- June 21. 100 female subjects aged belongs to 19-29 yrs were selected by purposive sampling. Among them 50 women were obese (BMI ≥25 kg/m²) and 50 women were non-obese (BMI< 25 kg/m²). Initial evaluation was done by history taking and anthropometric indices were measured. Here, used student unpaired t-test, chi square test and Pearson's correlation test to determine the association between vitamin D statuses with different variables. Lipid profile assay were carried out by a semi auto biochemistry analyzer and Vitamin D was estimated by immunoanalyzer. SPSS (22) was used for test of significance and p value

Supplemental Digital Content is Available in the Text., Background: Although differentiated service delivery (DSD) models for stable patients on antiretroviral therapy (ART) offer a range of health systems innovations, their comparative desirability to patients remains unknown. We conducted a discrete choice experiment to quantify service attributes most desired by patients to inform model prioritization. Methods: Between July and December 2016, a sample of HIV-positive adults on ART at 12 clinics in Zambia were asked to choose between 2 hypothetical facilities that differed across 6 DSD attributes. We used mixed logit models to explore preferences, heterogeneity, and trade-offs. Results: Of 486 respondents, 59% were female and 85% resided in urban locations. Patients strongly preferred infrequent clinic visits [3- vs. 1-month visits: β (ie, relative utility) = 2.84; P < 0.001]. Milder preferences were observed for waiting time for ART pick-up (1 vs. 6 hours.; β = −0.67; P < 0.001) or provider (1 vs. 3 hours.; β = −0.41; P = 0.002); “buddy” ART collection (β = 0.84; P < 0.001); and ART pick-up location (clinic vs. community: β = 0.35; P = 0.028). Urban patients demonstrated a preference for collecting ART at a clinic (β = 1.32, P < 0.001), and although most rural patients preferred community ART pick-up (β = −0.74, P = 0.049), 40% of rural patients still preferred facility ART collection. Conclusions: Stable patients on ART primarily want to attend clinic infrequently, supporting a focus in Zambia on optimizing multimonth prescribing over other DSD features—particularly in urban areas. Substantial preference heterogeneity highlights the need for DSD models to be flexible, and accommodate both setting features and patient choice in their design.

Differentiated service delivery (DSD) models were initially developed as a means to combat suboptimal long-term retention in HIV care, and to better titrate limited health systems resources to patient needs, primarily in low-income countries. The models themselves are designed to streamline care along the HIV care cascade and range from individual to group-based care and facility to community-based health delivery systems. However, much remains to be understood about how well and for whom DSD models work and whether these models can be scaled, are sustainable, and can reach vulnerable and high-risk populations. Implementation science is tasked with addressing some of these questions through systematic, scientific inquiry. We review the available published evidence on the implementation of DSD and suggest further health systems innovations needed to maximize the public health impact of DSD and future implementation science research directions in this expanding field. While early observational data supported the effectiveness of various DSD models, more recently published trials as well as evaluations of national scale-up provide more rigorous evidence for effectiveness and performance at scale. Deeper understanding of the mechanism of effect of various DSD models and generalizability of studies to other countries or contexts remains somewhat limited. Relative implementability of DSD models may differ based on patient preference, logistical complexity of model adoption and maintenance, human resource and pharmacy supply chain needs, and comparative cost-effectiveness. However, few studies to date have evaluated comparative implementation or cost-effectiveness from a health systems perspective. While DSD represents an exciting and promising “next step” in HIV health care delivery, this innovation comes with its own set of implementation challenges. Evidence on the effectiveness of DSD generally supports the use of most DSD models, although it is still unclear which models are most relevant in diverse settings and populations and which are the most cost-effective. Challenges during scale-up highlight the need for accurate differentiation of patients, sustainable inclusion of a new cadre of health care worker (the community health care worker), and substantial strengthening of existing pharmacy supply chains. To maximize the public health impact of DSD, systems need to be patient-centered and adaptive, as well as employ robust quality improvement processes.

Background Current models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design. Methods and findings Using a matched-pair cluster randomized study design (ClinicalTrials.gov: NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not 7 days late). Intervention effect was estimated using unadjusted Kaplan–Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15–0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period. Conclusions ACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective. Trial registration ClinicalTrials.gov NCT02776254., Monika Roy and colleagues study methods to streamline delivery of antiretrovirals to people with HIV infection in Zambia., Author summary Why was this study done? The adherence club intervention was designed to decrease burden on the health system and improve retention in care among treatment-experienced, clinically stable HIV-infected adults by providing off-hours facility access and streamlined (group-based, pharmacist-led) drug delivery. To date, published data on adherence clubs have been primarily limited to observational data from a similar intervention in South Africa. This study was done to learn about the effectiveness of the intervention and challenges with implementation in other settings in sub-Saharan Africa. What did the researchers do and find? We conducted a matched-pair cluster randomized study to estimate the effect of participating in adherence clubs on on-time drug pickup in Zambia. We additionally used a mixed-methods approach to evaluate the implementation of the intervention. We found that participation in the adherence club led to a reduction in the occurrence and rate of experiencing a late drug pickup. However, on-time drug pickups outside of adherence club meetings were relatively common. Both patients and providers found the intervention to be acceptable, but while patients embraced the patient-centered aspects of adherence clubs, some providers questioned the appropriateness and feasibility of the model. What do these findings mean? The urban adherence club intervention decreased late drug pickup among treatment-experienced adults living with HIV in Zambia. However, patients commonly missed their club meeting, seeking alternative means to pick up their medication on time. While club participation was associated with greater retention in care, flexibility in drug pickup and patient-centeredness were likely important factors.

To synthesize published literature on noncommunicable disease (NCD) behavior change communication (BCC) interventions in sub-Saharan Africa (SSA) among persons living with HIV (PLHIV) and in the general population to inform efforts to adopt similar HIV and NCD BCC intervention activities.We conducted a literature review of NCD BCC interventions and included 20 SSA-based studies. Inclusion criteria entailed describing a BCC intervention targeting any four priority NCDs (cardiovascular disease, type 2 diabetes, cervical cancer, and depression) or both HIV and any of the NCDs. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was used to assess potential public health impact of these studies. We also solicited expert opinions from 10 key informants on the topic of HIV/NCD health promotion in five SSA countries.The BCC interventions reviewed targeted multiple parts of the HIV and NCD continuum at both individual and community levels. Various strategies (i.e. health education, social marketing, motivational interviewing, mobile health, and peer support) were employed. However, few studies addressed more than one dimension of the RE-AIM framework. Opinions solicited from the key informants supported the feasibility of integrating HIV and NCD BCC interventions in SSA potentially improving access, service provision and service demand, especially for marginalized and vulnerable populations.Although HIV/NCD integration can improve effectiveness of preventive services at individual and community levels, potential public health impact of such approaches remain unknown as reach, adoptability, and sustainability of both integrated and nonintegrated NCD BCC approaches published to date have not been well characterized.

BACKGROUND: Differentiated service delivery (DSD) for human immunodeficiency virus (HIV)–infected persons who are clinically stable on antiretroviral therapy (ART) has been embraced as a solution to decrease access barriers and improve quality of care. However, successful DSD implementation is dependent on understanding the prevalence, incidence, and durability of clinical stability. METHODS: We evaluated visit data in a cohort of HIV-infected adults who made at least 1 visit between 1 March 2013 and 28 February 2015 at 56 clinics in Zambia. We described visit frequency and appointment intervals using conventional stability criteria and used a mixed-effects linear regression model to identify predictors of appointment interval. We developed a multistate model to characterize patient stability over time and calculated incidence rates for transition between states. RESULTS: Overall, 167819 patients made 3418018 post–ART initiation visits between 2004 and 2015. Fifty-four percent of visits were pharmacy refill-only visits, and 24% occurred among patients on ART for >6 months and whose current CD4 was >500 cells/mm(3). Median appointment interval at clinician visits was 59 days, and time on ART and current CD4 were not strong predictors of appointment interval. Cumulative incidence of clinical stability was 66.2% at 2 years after enrollment, but transition to instability (31 events per 100 person-years) and lapses in care (41 events per100 person-years) were common. CONCLUSIONS: Current facility-based care was characterized by high visit burden due to pharmacy refills and among treatment-experienced patients. Differentiated service delivery models targeted toward stable patients need to be adaptive given that clinical stability was highly transient and lapses in care were common.

BACKGROUND The uptake of intensified active TB case-finding among HIV-infected patients using symptom screening is not well understood. We evaluated the rate and completeness of each interim step in the TB pulmonary "diagnostic cascade" to understand real-world barriers to active TB case detection. METHODS We conducted a cohort analysis of new, antiretroviral therapy-naive, HIV-infected patients who attended a large HIV clinic in Mbarara, Uganda (March 1, 2012-September 30, 2013). We used medical records to extract date of completion of each step in the diagnostic cascade: symptom screen, order, collection, processing, and result. Factors associated with lack of sputum order were evaluated using multivariate Poisson regression and chart review of 50 screen-positive patients. RESULTS Of 2613 patients, 2439 (93%) were screened for TB and 682 (28%) screened positive. Only 90 (13.2%) had a sputum order. Of this group, 83% completed the diagnostic cascade, 13% were diagnosed with TB, and 50% had a sputum result within 1 day of their visit. Sputum ordering was associated with WHO stage 3 or 4 HIV disease and greater number of symptoms. The main identifiable reasons for lack of sputum order in chart review were treatment of presumed malaria (51%) or bacterial infection (43%). CONCLUSIONS The majority of newly enrolled HIV-infected patients who screened positive for suspected TB did not have a sputum order, and those who did were more likely to have more symptoms and advanced HIV disease. Further evaluation of provider behavior in the management of screen-positive patients could improve active TB case detection rates.

Sustained retention represents an enduring and evolving challenge to HIV treatment programs in Africa. We present a theoretical framework for sustained retention borrowing from ecologic principles of sustainability and dynamic adaptation. We posit that sustained retention from the patient perspective is dependent on three foundational principles: (1) patient activation: the acceptance, prioritization, literacy, and skills to manage a chronic disease condition, (2) social normalization: the engagement of a social network and harnessing social capital to support care and treatment, and (3) livelihood routinization: the integration of care and treatment activities into livelihood priorities that may change over time. Using this framework, we highlight barriers specific to sustained retention and review interventions addressing long-term, sustained retention in HIV care with a focus on Sub-Saharan Africa.

Background Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia’s HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. Methods and findings We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28–41], median CD4 268 cells/μL [IQR 134–430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%–16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%–6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%–13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%–49.9%), 13.6% increase in retention at six months (95% CI, 7.3%–20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%–41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%–46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. Conclusions In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards., In a regression discontinuity analysis, Aaloke Mody and colleagues assess the implications for treatment initiation and retention of expanded eligibility for antiretroviral therapy in Zambia., Author summary Why was this study done? Universal treatment with ART regardless of CD4 count (i.e., treat-all) is based on randomized controlled trials showing the biologic efficacy of ART, but the public impact of expanding ART eligibility also depends on the behavior of patients and the capacity of health systems to absorb an influx of new patients. Direct effects of expanding ART eligibility include increased ART initiation, but it may also indirectly affect patient behavior (i.e., retention) or create negative spillover effects through increased clinic congestion and crowding out of patients already eligible for ART. We leveraged a 2014 change to Zambia’s national ART guidelines that expanded ART eligibility to those with a CD4 between 350 and 500 cells/μL and pregnant or breastfeeding women to anticipate the effects of expanding treatment to those with CD4 above 500 cells/μL under treat-all. What did the researchers do and find? We used a regression discontinuity design to compare patients enrolling just before and after this 2014 change to Zambia’s national ART guidelines expanding the CD4 treatment threshold from 350 to 500 cells/μL to estimate the effects of the guideline change on ART initiation and retention in care in the entire patient population. Among 34,587 patients who newly enrolled in HIV care between August 1, 2013, and November 1, 2014, Zambia’s 2014 guideline change was associated with a 13.6% increase in the proportion initiating treatment within 3 months of enrollment, a 4.1% increase in retention in care at 6 months, and a 10.8% increase in the percentage of patients in care and on ART at 6 months in the entire clinic population. These effects were most pronounced in those patients who would have become newly eligible with the guideline, but ART initiation also increased without evidence of decreased retention in those who remained eligible as well as those who were not yet eligible for ART. We estimated that initiating ART in response to the change in guidelines led to a 37.9% increase in retention in care, indicating that 2.6 patients would need to be initiated on ART to prevent one episode of LTFU. What do these findings mean? Expanding ART eligibility to patients with higher CD4 counts in a real-world setting was associated with marked changes in patient behavior that were not observed in the more tightly controlled settings of randomized trials. Expanding treatment eligibility was associated with modest increases in ART initiation, overall retention in care, and the percentage of patients in care and on ART, without increasing clinic congestion or negatively impacting those who were already eligible for treatment before the 2014 guideline change (i.e., those with a CD4 less than 350 cells/μL at the time of enrollment). Adopting treat-all may lead to similar improvements in ART initiation and retention without associated negative effects; further research regarding the real-world effects of implementing treat-all is needed. Although expanding treatment eligibility improved ART initiation and retention in care, the overall HIV care cascade remained suboptimal. Further innovations in health systems are needed to increase early diagnosis and linkage and improve overall ART initiation and retention in care.

Introduction Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. Methods We conducted active population-based candidemia surveillance in 4 US metropolitan areas between 2009 and 2015. We calculated incidences among neonates (0-30 days old), infants (0-364 days old), and noninfant children (1-19 years old), documented their clinical features and antifungal drug resistance. Results We identified 307 pediatric candidemia cases. Incidence trends varied according to site, but overall, the incidence in neonates decreased from 31.5 cases/100000 births in 2009 to 10.7 to 11.8 cases/100000 births between 2012 and 2015, the incidence in infants decreased from 52.1 cases/100000 in 2009 to 15.7 to 17.5 between 2012 and 2015, and the incidence in noninfant children decreased steadily from 1.8 cases/100000 in 2009 to 0.8 in 2014. Common underlying conditions were prematurity in neonates (78%), surgery in nonneonate infants (38%), and malignancy in noninfant children (28%). Most neonate cases were caused by C albicans (67%), whereas non-C. albicans species accounted for 60% of cases in nonneonate infants and noninfant children. Fluconazole and echinocandin resistance rates were low overall. Thirty-day crude mortality was 13%. Conclusions The incidence of candidemia among neonates and infants declined after 2009 but remained stable from 2012 to 2015. Antifungal drug resistance is uncommon. Reasons for the lack of recent declines in neonatal and infant candidemia deserve further exploration. In this article, we describe the epidemiology of candidemia in children in the United States and on the basis of data collected as part of US Centers for Disease Control and Prevention active population-based surveillance. Trends in incidence, clinical characteristics, species distribution, and resistance rates are presented.

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases. and copy; 2017 by The American Society of Tropical Medicine and Hygiene.

Background Extending appointment intervals for stable HIV-infected patients in sub-Saharan Africa can reduce patient opportunity costs and decongest overcrowded facilities. Methods We analyzed a cohort of stable HIV-infected adults (on treatment with CD4 >200 cells/μL for more than 6 months) who presented for clinic visits in Lusaka, Zambia. We used multilevel, mixed-effects logistic regression adjusting for patient characteristics, including prior retention, to assess the association between scheduled appointment intervals and subsequent missed visits (>14 days late to next visit), gaps in medication (>14 days late to next pharmacy refill), and loss to follow-up (LTFU; >90 days late to next visit). Results A total of 62084 patients (66.6% female, median age 38, median CD4 438 cells/μL) made 501281 visits while stable on antiretroviral therapy. Most visits were scheduled around 1-month (25.0% clinical, 44.4% pharmacy) or 3-month intervals (49.8% clinical, 35.2% pharmacy), with fewer patients scheduled at 6-month intervals (10.3% clinical, 0.4% pharmacy). After adjustment and compared to patients scheduled to return in 1 month, patients with six-month clinic return intervals were the least likely to miss visits (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.17-0.24); miss medication pickups (aOR, 0.47; 95% CI 0.39-0.57), and become LTFU prior to the next visit (aOR, 0.41; 95% CI, 0.31-0.54). Conclusions Six-month clinic return intervals were associated with decreased lateness, gaps in medication, and LTFU in stable HIV-infected patients and may represent a promising strategy to reduce patient burdens and decongest clinics.

Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off -patent antifungal drugs: amphotericin B deoxycholate, fl ucytosine, and fl uconazole. Widely accepted treatment guidelines recommend amphotericin B and fl ucytosine as fi rst-line induction treatment for cryptococcal meningitis. However, fl ucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common sideeff ects. Therefore, fl uconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with signifi cantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical eff ectiveness and access issues specifi c to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic eff ects, and insuffi ciently coordinated distribution; fl ucytosine through cost and scarcity of registration; and fl uconazole through challenges in maintenance of local stocks—eg, sustainability of donations or insuffi cient generic supplies. We advocate ten steps that need to be taken to improve access to safe and eff ective antifungal therapy for cryptococcal meningitis.

Background. Blastomycosis is a potentially life-threatening infection caused by the soil-based dimorphic fungus Blastomyces dermatitidis, which is endemic throughout much of the Midwestern United States. We investigated an increase in reported cases of blastomycosis that occurred during 2009–2010 in Marathon County, Wisconsin. Methods. Case detection was conducted using the Wisconsin Electronic Disease Surveillance System (WEDSS). WEDSS data were used to compare demographic, clinical, and exposure characteristics between outbreak-related and historical case patients, and to calculate blastomycosis incidence rates. Because initial mapping of outbreak case patients’ homes and recreational sites demonstrated unusual neighborhood and household case clustering, we conducted a 1:3 matched case-control study to identify factors associated with being in a geographic cluster. Results. Among the 55 patients with outbreak-related cases, 33 (70%) were hospitalized, 2 (5%) died, 30 (55%) had cluster-related cases, and 20 (45%) were Hmong. The overall incidence increased significantly since 2005 (average 11% increase per year, P< .001), and incidence during 2005–2010 was significantly higher among Asians than non-Asians (2010 incidence: 168 vs 13 per 100 000 population). Thirty of the outbreak cases grouped into 5 residential clusters. Outdoor activities were not risk factors for blastomycosis among cluster case patients or when comparing outbreak cases to historical cases. Conclusions. This outbreak of blastomycosis, the largest ever reported, was characterized by unique household and neighborhood clustering likely related to multifocal environmental sources. The reasons for the large number of Hmong affected are unclear, but may involve genetic predisposition.

We investigated an increase in Trichosporon asahii isolates among inpatients. We identified 63 cases; 4 involved disseminated disease. Trichosporon species was recovered from equipment cleaning rooms, washbasins, and fomites, which suggests transmission through washbasins. Patient washbasins should be single-patient use only; adherence to appropriate hospital disinfection guidelines was recommended.

Blastomycosis is a potentially fatal infection caused by Blastomyces dermatitidis, a fungus endemic to North America in areas surrounding the Ohio and Mississippi River valleys and the Great Lakes. The clinical manifestations, diagnostic techniques, and treatment strategies for blastomycosis are relatively well-described in the literature; however, the epidemiologic features of disease are not as clearly defined as those of other endemic mycoses, such as histoplasmosis and coccidioidomycosis. We review the ecologic and epidemiologic aspects of B. dermatitidis and blastomycosis, including geographic distribution, environmental niche, seasonality, and possible risk factors.

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus species, is one of the most common opportunistic infections among persons with HIV/AIDS. The highest burden of disease is in sub-Saharan Africa and Southeast Asia, where limited access to antiretroviral treatment and appropriate antifungal therapy contributes to high mortality rates. Increasing focus has been placed on earlier detection and prevention of disease. Primary prophylaxis and screening may provide a survival benefit and can be cost-effective in settings where CM prevalence is high. The development of a new point-of-care cryptococcal antigen assay has the potential to transform both disease prevention and diagnosis.

Fungal infection can occur in transplant patients via one of four mechanisms: donor-derived infections, contamination during the transplantation period, reactivation of latent infection in the host, or new infection during the posttransplantation period. Distinguishing between these mechanisms is often difficult and as a result, donor-derived fungal infections may be under-recognized with few data on its prevalence. We review published reports of donor-derived fungal infections and discuss the role of donor screening and the importance of establishing a national reporting, tracking, and notification system for transplant-transmitted infections.

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is present several weeks before overt signs of meningitis develop, provides an opportunity to detect infection early. Screening persons with HIV for cryptococcal infection when they access healthcare can identify asymptomatic infected patients allowing for prompt treatment and prevention of death. A newly developed point-of-care assay for cryptococcal antigen, as well as growing evidence supporting the utility and cost-effectiveness of screening, are further reasons to consider broad implementation of cryptococcal screening in countries with a high burden of cryptococcal disease.

During September 2009, we performed a rapid cross-sectional study to investigate the extent of aflatoxin contamination among common Bangladeshi foods. We collected eight common human food commodities (rice, lentils, wheat flour, dates, betelnut, red chili powder, ginger and groundnuts) and poultry feed samples from two large markets in each of three cities in Bangladesh. We quantified aflatoxin levels from pooled subsamples using fluorescence high-performance liquid chromatography. Aflatoxin levels were highest in dates and groundnuts (maximum 623 and 423 ng/g), respectively. Samples of betelnut (mean 30.6 ng/g), lentils (mean 21.2 ng/g) and red chili powder (>20 ng/g) also had elevated levels. The mean aflatoxin level among poultry feed samples was 73.0 ng/g. Aflatoxin levels were above the US maximum regulatory levels of 20 ng/g in five of eight commonly ingested human food commodities tested.

Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections.We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification.Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P0.001), and such infections developed in patients with and in those without meningitis.The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).

Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana. Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana. Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. National AIDS Program. Georgetown, Guyana. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. Laborat?rio Central de Sa?de P?blica do Amap?. Macap?, AP, Brazil. Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname. Public Health Central Laboratory of Suriname. Paramaribo, Suriname. Diakonessenhuis Hospital. Paramaribo, Suriname. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Hospital de Clinicas Dr. Alberto Lima. Macap?, AP, Brazil. Hospital de Clinicas Dr. Alberto Lima. Macap?, AP, Brazil. Universidade Federal do Cear? - Faculdade de Medicina - Departamento de Sa?de Comunitaria. Fortaleza, CE, Brazil. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia. Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia Corporaci?n para Investigaciones Biol?gicas. Medell?n, Colombia INEI-ANLIS "Dr. Carlos G. Malbr?n". Buenos Aires, Argentina Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centre Hospitalier de l'Ouest Guyanais. Saint Laurent du Maroni, French Guiana, France Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Centers for Disease Control and Prevention. Mycotic Diseases Branch. Atlanta, Georgia, United States of America Institut Pasteur. National Reference Center for Mycoses and Antifungals. Molecular Mycology Unit. Paris, France Centre Hospitalier de Cayenne. Centre d Investigation Clinique Epid?miologie Clinique Antilles Guyane. Cayenne, French Guiana, France. / Universite? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Universit? Antilles Guyane. Epidemiologie Parasitoses et Mycoses Tropicales. Cayenne, French Guiana Academisch Ziekenhuis Paramaribo Hospital. Paramaribo, Suriname

In South Africa, the incidence of HIV-associated cryptococcal meningitis remains high despite the increased coverage of antiretroviral treatment, and in routine care settings, the disease is associated with a case-fatality ratio of more than 50%. Laboratory-based screening and pre-emptive antifungal treatment of cryptococcal disease have been suggested for routine implementation as part of the National Strategic Plan for HIV, STIs and TB, 2012 - 2016. In the first phase of a national screening programme, screening will begin at almost 500 healthcare facilities in the Gauteng and Free State provinces, and NHLS laboratories will reflexively test the remnant specimen of any blood sample with a CD4+ T-lymphocyte count

Department of Chemistry, Government College, Sundergarh Manuscript received 4 April 1977, revised 7 September 1971. accepted 24 February 1978 A number of polymethin dyes derived from 6-methyl-phenaothridine as the fixed basic nucleus have been prepared and their absorption maxima data were determined. The absorption maxima data have been utilised for determination of relative basicities of different basic nuclei as well as for determination of relative acidities of different acidic nuclei. These dyes are expected to be good photographic sensitisers.