Short-Term Malaria Reduction by Single-Dose Azithromycin during Mass Drug Administration for Trachoma,Tanzania

Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%–89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.     

Prevalence and density-related concordance of three diagnostic tests for malaria in a region of Tanzania with hypoendemic malaria

Accurate malaria diagnosis has dual roles in identification of symptomatic persons for effective malaria treatment and also enumeration of asymptomatic persons who contribute to the epidemiologic determinants of transmission. Three currently used diagnostic tests, microscopy, rapid diagnostic tests (RDTs), and real-time PCR, all have different sensitivities and specificities, which are parasite density dependent. Here, we compare their concordance among 451 febrile episodes in a cohort of 2,058 children and adults followed over 6 months in a region in central Tanzania with hypoendemic malaria. Microscopy, a histidine-rich protein-based RDT, and two different real-time PCR gene probes detected Plasmodium falciparum in 20, 54, 41, and 78 episodes of fever, respectively. They had complete concordance in only 9 episodes. Real-time PCR with an 18S probe was more sensitive than with a mitochondrial probe for cytochrome b despite higher copy numbers of mitochondrial DNA. Both PCR yields were increased 4-fold by glycogen/acetate precipitation with low-speed centrifugation. Duplicate PCR increases low-density malaria detection. RDT had the highest number of unique positives, presumably from persistent antigen despite the absence of parasites, although RDT did not detect 3 parasitemias with over 1,000 parasites/μl. In a latent class analysis, real-time PCR had significantly higher sensitivity than did microscopy or RDT. Agreement between real-time PCR, RDT, and microscopy was highest in March and April, when both the P. falciparum parasite rate and parasite densities are highest. Real-time PCR is more sensitive and specific than RDT and microscopy in low-prevalence, low-parasite-density settings.     

Differentiating ZIP Codes in Syndromic Data; What Can They Tell Us?

Objective

To classify visits to NYC emergency departments (ED) into NYC residential, NYC PO Box or commercial building, commuters to NYC, and out-of-town visitors. To describe patterns in each group, to evaluate how they differ, and to consider how the differences can affect syndromic surveillance analyses and results.

Introduction

The NYC Department of Health and Mental Hygiene (DOHMH) ED syndromic surveillance system receives data from 95% of all ED visits in NYC totaling 4 million visits each year. The data include residential ZIP code as reported by the patient. ZIP code information has been used by the DOHMH to separate visits into NYC and non-NYC for analysis; and, a closer examination of non-NYC visits may further inform disease surveillance.

Methods

Visits were initially differentiated into six home ZIP code types. NYC residential ZIP codes, PO Boxes and commercial buildings were identified with 2010 US Census and data from the SAS institute (SAS Institute Inc., Cary, NC, USA). Commuter visits to the EDs were classified as any ZIP codes from the NYC Core Based Statistical Area (CBSA; United States Office of Management and Budget). Out of town visits were identified using with the 2010 US Census. Unknown ZIP codes included all of those ZIP codes that were not identified by any of the previous methods, and missing ZIP codes were those that were blank. ZIP codes were verified with the United States Postal Service website (www.usps.com).Once ZIP codes were categorized, spatial and temporal trends in total ED visits by home ZIP code type were analyzed.

Results

Of the approximately 4 million ED visits in NYC during 2011, the number of visits by commuters and out-of-town visitors were 125,236 (3.1%) and 45,158 (1.1%) respectively (Figure 1). There were 4,676 (0.1%) visits with a NYC PO Box or building ZIP codes and 48,077 (1.2%) visits with a missing or non-interpretable ZIP codes. The majority of commuter and out-of-town ED visits occur at a smaller set of hospitals. Out-of town visitors mostly visited hospitals in Manhattan rather than hospitals in the outer boroughs. While the seasonal trends and day-of-week patterns for the NYC residents and the commuters appear to be fairly similar, this is not the case for out-of-town visitors. For example, total ED visit trends correlated well for NYC residents and commuters (r=0.77), but there was no correlation between NYC residents and out-of-town visitors (r=−0.18) over time. The number of ED visits among out-of-town visitors was higher during summer months and the winter holiday season, and this trend may have reflected the larger number of visitors during these periods. Day-of-week patterns were similar for NYC residents and commuters with weekdays associated with larger numbers of visits compared to weekends. However, the opposite was found true for out-of-town visitors with larger number of visits occurring over the weekends compared to weekdays.Open in a separate windowFigure 1:Total ED visits from the NYC Core Based Statistical Area (CBSA) and the surrounding region.

Conclusions

Considerable differences in temporal trends were found among out-of-town visitors, NYC residents, and commuters to NYC. Out-of-town visitors also tend to visit EDs located in Manhattan rather than in the outer boroughs. These results suggest that out-of-town visitors represent a unique population ED visitors. Analyzing NYC residents, commuters, and out-of-town visitors separately may provide additional information that could prove useful to daily syndromic surveillance activities.     

Long-Term Asthma Trend Monitoring in New York City: A Mixed Model Approach

Objective

Show the benefits of using a generalized linear mixed model (GLMM) to examine long-term trends in asthma syndrome data.

Introduction

Over the last decade, the application of syndromic surveillance systems has expanded beyond early event detection to include long-term disease trend monitoring. However, statistical methods employed for analyzing syndromic data tend to focus on early event detection. Generalized linear mixed models (GLMMs) may be a useful statistical framework for examining long-term disease trends because, unlike other models, GLMMs account for clustering common in syndromic data, and GLMMs can assess disease rates at multiple spatial and temporal levels (1). We show the benefits of the GLMM by using a GLMM to estimate asthma syndrome rates in New York City from 2007 to 2012, and to compare high and low asthma rates in Harlem and the Upper East Side (UES) of Manhattan.

Methods

Asthma related emergency department (ED) visits, and patient age and ZIP code were obtained from data reported daily to the NYC Department of Health and Mental Hygiene. Demographic data were obtained from 2010 US Census. ZIP codes that represented high and low asthma rates in Harlem and the UES of Manhattan were chosen for closer inspection. The ratio of weekly asthma syndrome visits to total ED visits was modeled with a Poisson GLMM with week and ZIP code random intercepts (2). Age and ethnicity were adjusted for because of their association with asthma rates (3).

Results

The GLMM showed citywide asthma rates remained stable from 2007 to 2012, but seasonal differences and significant inter-ZIP code variation were present. The Harlem ZIP code asthma rate that was estimated with the GLMM was significantly higher (5.83%, 95% CI: 3.65%, 9.49%) than the asthma rate in UES ZIP code (0.78%, 95% CI: 0.50%, 1.21%). A linear time component to the GLMM showed no appreciable change over time despite the seasonal fluctuations in asthma rate. GLMM based asthma rates are shown over time (Figure 1).Open in a separate windowFigure 1:Harlem ZIP code (red), the Upper East Side ZIP code (blue), and citywide (black) estimates are shown as dotted lines surrounded by 30% credibility bands in solid lines.

Conclusions

GLMMs have several strengths as statistical frameworks for monitoring trends including:

1. Disease rates can be estimated at multiple spatial and temporal levels,
2. Standard error adjustment for clustering in syndromic data allows for accurate, statistical assessment of changes over time and differences between subgroups,
3. “Strength borrowed” (4) from the aggregated data informs small subgroups and smooths trends,
4. Integration of covariate data reduces bias in estimated rates.

GLMMs have previously been suggested for early event detection with syndromic surveillance data (5), but the versatility of GLMM makes them useful for monitoring long-term disease trends as well. In comparison to GLMMs, standard errors from single level GLMs do not account for clustering and can lead to inaccurate statistical hypothesis testing. Bayesian hierarchical models (6), share many of the strengths of GLMMS, but are more complicated to fit. In the future, GLMMs could provide a framework for grouping similar ZIP codes based on their model estimates (e.g. seasonal trends and influence on overall trend), and analyzing long-term disease trends with syndromic data.     

Multiplex 5' nuclease-quantitative PCR for diagnosis of relapsing fever in a large Tanzanian cohort

Relapsing fever (RF) is caused by tick- and louse-borne Borrelia spp., is characterized by recurrent fever, and is often misdiagnosed as malaria. Because of submicroscopic bacteremia, microscopy can be insensitive between febrile bouts. We designed a multiplex quantitative PCR (qPCR) assay to distinguish RF Borrelia from Plasmodium falciparum and P. vivax. The assay specifically (100%) amplified pathogenic RF Borrelia (1 copy/reaction). We then tested blood from participants within a Tanzanian cohort assessed at scheduled intervals and with fever. Among 8,617 blood samples from 2,057 participants surveyed routinely, 7 (0.08%) samples and 7 (0.3%) participants had RF DNA (median, 4.4 × 10(3) copies/ml). Of 382 samples from 310 febrile persons, 15 (3.9%) samples from 13 (4.2%) participants had RF DNA (median, 7.9 × 10(2) copies/ml). Five (1.3%) samples from 4 (1.3%) participants were found to harbor Borrelia by microscopy. We conclude that multiplex qPCR holds promise for improved clinical diagnosis and epidemiologic assessment of RF.     

Lack of functionally active Melan-A(26-35)-specific T cells in the blood of HLA-A2+ vitiligo patients

Vitiligo, a skin disorder characterized by the spontaneous destruction of melanocytes, is believed to be of autoimmune origin. We investigated the presence and functionality of CD8(+) T-cells specific for the melanocyte-associated antigens Melan-A, gp100, tyrosinase, and TRP-2 in the blood of HLA-A2(+) vitiligo patients. We enumerated antigen-specific CD8(+) T cells by major histocompatibility complex multimer staining directly ex vivo, as well as after 9 days of in vitro stimulation and assessed IFN-gamma secretion by enzyme-linked immunospot (Elispot) assay. Tyrosinase-, gp100-, or TRP-2-specific CD8(+) T cells could not be identified in the peripheral blood of individuals with vitiligo. Although Melan-A-specific T cells were detectable at levels comparable to Flu-MP-specific T cells by multimer staining, these lymphocytes did not express the skin-homing receptor cutaneous lymphocyte antigen, were phenotypically na?ve (CD45RA(+)), and were unresponsive in the IFN-gamma Elispot assay, suggesting that they are unlikely to be involved in the etiopathogenesis of vitiligo.