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The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi–specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1–3.6) and 2.27 (95% CI: 0.9–5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3–21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.

The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks.

Background Vertical transmission of Trypanosoma cruzi infection from mother to infant accounts for a growing proportion of new cases of Chagas disease. However, no systematic reviews of risk factors for T. cruzi vertical transmission have been performed. Methods We performed a systematic review of the literature in PubMed, LILACS, and Embase databases, following PRISMA guidelines. Studies were not excluded based on language, country of origin, or date of publication. Results Our literature review yielded 27 relevant studies examining a wide variety of risk factors, including maternal age, parasitic load, immunologic factors, vector exposure, and more. Several studies suggested that mothers with higher parasitic loads may have a greater risk of vertical transmission, and a meta-analysis of two studies found a significantly higher parasitic load among transmitting than non-transmitting mothers with T. cruzi infection. A second meta-analysis of ten studies demonstrated that maternal age was not significantly associated with vertical transmission risk. Conclusions The current literature suggests that high maternal parasitic load may be a risk factor for congenital Chagas disease among infants of T. cruzi seropositive mothers. Given the considerable heterogeneity and risk of bias among current literature, additional studies are warranted to assess potential risk factors for vertical transmission of T. cruzi infection.

Background: Sapovirus is increasingly recognized as an important cause of acute gastroenteritis (AGE) in children. We identified risk factors and characterized the clinical profile of sapovirus AGE in a birth cohort in León, Nicaragua. Methods: We conducted a case-control study nested within a birth cohort (n = 444). Fieldworkers conducted weekly household AGE surveillance. AGE stools were tested for sapovirus by reverse transcriptase quantitative polymerase chain reaction. For each first sapovirus episode, we selected 2 healthy age-matched controls and estimated independent risk factors of sapovirus AGE using conditional logistic regression. We compared clinical characteristics of sapovirus AGE episodes with episodes associated with other etiologies and identified co-infections with other enteric pathogens. Results: From June 2017 to July 2019, we identified 63 first sapovirus AGE episodes and selected 126 controls. Having contact with an individual with AGE symptoms and vaginal delivery were independent risk factors for sapovirus AGE. All cases experienced diarrhea, lasting a median 6 days; 23% experienced vomiting. Compared with children with AGE due to another etiology, sapovirus AGE was similar in severity, with less reported fever. Most cases experienced co-infections and were more likely than controls to be infected with diarrheagenic Escherichia coli or astrovirus. Conclusions: Sapovirus was a commonly identified AGE etiology in this Central American setting, and symptoms were similar to AGE associated with other etiologies. The association between vaginal delivery and sapovirus is a novel finding. Gut microbiome composition might mediate this relationship, or vaginal delivery might be a proxy for other risk factors. Further investigation into more specific biological mechanisms is warranted.

Background Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. Methods We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants’ homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. Results Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (, Children with in utero Zika virus exposure and without congenital Zika syndrome in Nicaragua had lower neurocognitive scores at 24 months. Our study includes multiple evaluations over time and a contemporary nonexposed comparator group of children, which is currently lacking in the literature.

Summary: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans.

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence reached 28% in the first 6 months of the country's epidemic and reached 35% 6 months later. Immune waning was uncommon. Individuals with a seropositive household member were over three times as likely to be seropositive themselves, suggesting the importance of household transmission.

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence was 34%, with higher prevalence in children compared to adults. Having a seropositive household member was associated with a two-fold probability of individual seropositivity, suggesting a role for household transmission. Co-morbidities and preventive behaviors were not associated with SARS-CoV-2 seroprevalence.

Background Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. Methology/principle findings Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. Conclusion/significances Our results demonstrate nanoparticle technology’s potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE., Author summary Toxoplasmic Encephalitis is a debilitating, yet highly treatable illness, classically seen in person living with HIV lacking treatment. Prompt diagnosis ensures the best outcome possible for patients, but remains a challenge: requiring invasive specimen collection, lacking necessary clinical sensitivity, demanding significant technical skills, and substantial infrastructure. Here we offer proof of concept of a diagnostic approach that is minimally invasive, using a urine-based approach that concentrates T. gondii antigens with hydrogel mesh nanoparticles to improve analytical sensitivity for detection by western blot.

Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in Le&oacute, n to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (&ge, 18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 &times, 106/mL vs. 63.5 &times, 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.

Campylobacteriosis is an important contributor to the global burden of acute gastroenteritis (AGE). In Nicaragua, the burden, risk factors, and species diversity for infant campylobacteriosis are unknown. Between June 2017 and December 2018, we enrolled 444 infants from León, Nicaragua, in a population-based birth cohort, conducting weekly household AGE surveillance. First, we described clinical characteristics of symptomatic Campylobacter infections, and then compared clinical characteristics between Campylobacter jejuni/coli and non-jejuni/coli infections. Next, we conducted a nested case–control analysis to examine campylobacteriosis risk factors. Finally, we estimated the population attributable fraction of campylobacteriosis among infants experiencing AGE. Of 296 AGE episodes in the first year of life, Campylobacter was detected in 59 (20%), 39 were C. jejuni/coli, and 20 were non-jejuni/coli species, including the first report of Campylobacter vulpis infection in humans. Acute gastroenteritis symptoms associated with C. jejuni/coli lasted longer than those attributed to other Campylobacter species. In a conditional logistic regression model, chickens in the home (odds ratio [OR]: 3.8, 95% CI: 1.4–9.8), a prior AGE episode (OR: 3.3; 95% CI: 1.4–7.8), and poverty (OR: 0.4; 95% CI: 0.2–0.9) were independently associated with campylobacteriosis. Comparing 90 infants experiencing AGE with 90 healthy controls, 22.4% (95% CI: 11.2–32.1) of AGE episodes in the first year of life could be attributed to Campylobacter infection. Campylobacter infections contribute substantially to infant AGE in León, Nicaragua, with non-jejuni/coli species frequently detected. Reducing contact with poultry in the home and interventions to prevent all-cause AGE may reduce campylobacteriosis in this setting.

Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

Acute Chagas disease reactivation (CDR) after cardiac transplantation is a well-known phenomenon in endemic countries of Central and South America and Mexico, but is rare outside of those countries. In this report, we describe a case of a 49 year old male who presented 25 weeks after heart transplant with clinical features concerning for acute rejection, including malaise, anorexia, weight loss, and fever. His immunosuppression therapy included tacrolimus, mycophenolate, and prednisone. An endomyocardial biopsy revealed lymphocytic and eosinophilic inflammation, myocyte damage, and rare foci of intracellular organisms consistent with Trypanosoma cruzi amastigotes. The patient had no known history of Chagas disease. Upon additional questioning, the patient endorsed bites from reduviid bugs during childhood in El Salvador. Follow-up serum PCR testing was positive for T. cruzi DNA. Tests for other infectious organisms and donor specific antibodies were negative. This case illustrates the striking clinical and histologic similarities between acute cellular rejection and acute CDR with cardiac involvement in heart transplant patients, and thus emphasizes the importance of pre-transplant testing for Chagas in patients with epidemiologic risk factors.

Norovirus is a leading cause of pediatric gastroenteritis. Understanding norovirus epidemiology is essential for reducing disease burden. We conducted a case–control study to describe the distribution, clinical features, and risk factors of norovirus gastroenteritis among children < 5 years of age in León, Nicaragua. Cases were children testing positive for norovirus and controls were children living in the cases’ communities. Study staff interviewed mothers of enrolled cases and controls to obtain detailed exposure information including food, water, and sanitation sources; recent exposures; household characteristics; and handwashing practices. In addition, study staff requested stool samples to be tested for norovirus from select household members. We used descriptive statistics to understand the epidemiologic and clinical features of gastroenteritis episodes. To analyze potential risk factors, we used Firth’s penalized logistic regression to estimate crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). There were 102 children with gastroenteritis, 18 cases of norovirus and 31 controls. Norovirus cases occurred later in the year, corresponding to a delay in the rainy season. Cases were more likely to have a household member with norovirus in their stool as compared with controls [crude OR: 13.3 (95% CI: 2.5, 136.2) and adjusted OR: 11.5 (95% CI: 1.6, 223.2)]. In addition, alcohol-based hand sanitizer use among household members was reported for 10 (32%) of controls and but never for cases. Further research is needed to understand household transmission of norovirus in low- and middle-income countries and the potential impact of hand sanitizer use.

Background Several health agencies define microcephaly for surveillance purposes using a single criterion, a percentile or Z-score cut-off for newborn head circumference. This definition, however, conflicts with the reported prevalence of microcephaly even in populations with endemic Zika virus. Objective We explored possible reasons for this conflict, hypothesising that the definition of microcephaly used in some studies may be incompletely described, lacking the additional clinical criteria that clinicians use to make a formal diagnosis. We also explored the potential for misclassification that can result from differences in these definitions, especially when applying a percentile cut-off definition in the presence of the much lower observed prevalence estimates that we believe to be valid. Methods We conducted simulations under a theoretical bimodal distribution of head circumference. For different definitions of microcephaly, we calculated the sensitivity and specificity using varying cut-offs of head circumference. We then calculated and plotted the positive predictive value for each of these definitions by prevalence of microcephaly. Results Simple simulations suggest that if the true prevalence of microcephaly is approximately what is reported in peer-reviewed literature, then relying on cut-off-based definitions may lead to very poor positive predictive value under realistic conditions. Conclusions While a simple head circumference criterion may be used in practice as a screening or surveillance tool, the definition lacks clarification as to what constitutes true pathological microcephaly and may lead to confusion about the true prevalence of microcephaly in Zika-endemic areas, as well as bias in aetiologic studies.

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients.

Members of the Chagas Disease Working Group in Peru and Bolivia include Edith Hinojosa, Clariza Chavez, Jean Karla Velarde, Carla Chavarria, Victoria Serrudo, Roberto Araya, Alcides Buitron, Rita Mendieta, Holger Mayta, Maritza Calderon, Holger Mayta and Yagahira Castro. Background Vertical transmission of Trypanosoma cruzi infection accounts for a growing proportion of new cases of Chagas disease. Congenital infection is curable if treated promptly, but the majority of infected infants do not receive timely diagnosis or treatment. Better risk stratification is needed to predict which women are more likely to transmit the infection. Methods This study enrolled women who presented for delivery and their infants at the Percy Boland Women’s Hospital in Santa Cruz, Bolivia. Pregnant women were screened for Chagas disease by rapid test. The infants of seropositive mothers underwent diagnostic testing with microscopy (“micromethod”) and quantitative polymerase chain reaction (qPCR) as newborns and at one- and nine-month follow-up. Mothers completed surveys about demographics and medical history. Results Among 5,828 enrolled women, 1,271 (21.8%) screened positive for Chagas disease. Of the 1,325 infants of seropositive mothers, 113 (8.5%) were diagnosed with congenital Chagas disease by microscopy or qPCR. Cesarean delivery was significantly associated with lower odds of vertical transmission (adjusted OR: 0.63, 95% CI: 0.41–0.98, p=0.040). Congenital infection was more common in twins (adjusted OR: 3.30, 95% CI: 1.97–5.54, p< 0.001) and male infants (adjusted OR: 1.50, 95% CI: 1.01–1.22, p=0.045). Conclusion Our findings suggest that Cesarean delivery may be protective against vertical transmission of T. cruzi, while twins and male infants may have an increased risk. A better understanding of risk stratification for congenital Chagas disease may help improve regional initiatives to reduce disease burden. Disclosures All Authors: No reported disclosures

Limited information is available on health outcomes related to Zika virus infection acquired during childhood. Zika virus can cause severe central nervous system malformations in congenitally exposed fetuses and neonates. In vitro studies show the capacity of Zika virus to infect neural progenitor cells, induce central and peripheral neuronal cell deaths, and target different brain cells over the course of brain development. Studies of postnatally infected mice and nonhuman primates have detected degradation of neural cells and morphologic brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and in adolescents secondary to Zika virus infection suggest that Zika virus may have a broader impact on neurological health beyond that observed in congenitally exposed newborns. Long-term neurological complications have been observed with other acquired flaviviral infections, with clinical symptoms manifesting for years after primary infection. The extent to which postnatal Zika virus infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage or cognitive effects is currently unknown. To better understand the potential for neurological sequelae associated with acquired Zika virus infection in children, we reviewed the biological, clinical, and epidemiologic literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of Zika virus infection in experimental studies. Second, we review observational studies of congenital Zika virus infection and case studies and surveillance reports of neurological sequelae of Zika virus infection in adults and in children. Lastly, we discuss the challenges of conducting Zika virus-neurological sequela studies and future directions for pediatric Zika virus research.

Human immunodeficiency virus (HIV) is common in pregnant women in many malaria-endemic regions and may increase risk of placental parasitemia. Placental malaria is more common in primigravidae than multigravidae, but the relationship between HIV and malaria across gravidities is not well characterized. We recruited pregnant Malawian women during the second trimester and followed them until delivery. Parasitemia was assessed at enrollment, follow-up visits, and delivery, when placental blood was sampled. There was no difference in risk of parasitemia between HIV-positive and HIV-negative primigravidae. Among multigravidae, HIV-infected women had greater than twice the risk of parasitemia as HIV-uninfected women throughout follow-up. Human immunodeficiency virus was also associated with more frequent peripheral parasitemia in multigravidae but not primigravidae. Both HIV and primigravid status were independently associated with higher peripheral and placental parasite densities. Although risk of parasitemia is lower in multigravidae than primigravidae, the HIV effect on risk of malaria is more pronounced in multigravidae.

The purpose of the study was to identify the predictors of short-term mortality in patients undergoing percutaneous dilatational tracheostomy (PDT).Retrospective analysis of data pertaining to adult patients who underwent PDT between July 2005 and June 2008 in an urban, academic, tertiary care medical center was done. Clinical and demographic data were analyzed for 483 patients undergoing PDT via multivariate logistic regression.Mortality data were examined at in-hospital, 14, 30, and 180 days postprocedure. Overall mortality rates were 11% at 14 days, 19% at 30 days, and 40% at 180 days. In-hospital mortality was 30%.Patients undergoing PDT have significant short-term mortality with 11% dying within 14 days and an in-hospital mortality rate of 30%. We identified an index diagnosis of ventilator-associated pneumonia and trauma to be associated with a higher survival rate, whereas older age, oncological diagnosis, cardiogenic shock, and ventricular-assist devices were associated with higher mortality. There is significant heterogeneity in both underlying diagnosis and patient outcomes, and these factors should be considered when deciding to perform this procedure and discussed with patients/family members to provide a realistic expectation of potential prognosis.

Background. Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones. Methods. We conducted a serosurvey of 1615 children

To the Editor—In their recent article, Shorr and colleagues present a new clinical tool to predict risk of drug-resistant bacterial pneumonia in patients presenting to emergency departments [1]. Improving risk assessment and minimizing inappropriate antibiotic use are necessary given the increasing prevalence of resistant pathogens and the risk of selecting for further resistance through overuse of broad-spectrum antibiotics, but this new risk score has several weaknesses. A weighted risk score is an attractive strategy to improve clinical decision making, but the authors overstate its advantages over the existing healthcare-associated pneumonia (HCAP) definition. Although the authors assert that their new risk score is superior to HCAP criteria because it incorporates weighting of risk factors, the cutoff of 0 turns the risk score into a dichotomous tool by which the presence of any risk factor yields a score considered positive rather than a stratified risk score. Under this conclusion, the predictive ability of the new tool is comparable (but not superior) to the current HCAP definition. Using a dichotomous risk tool ignores the information contained in a scoring system, and such a tool cannot be compared directly with the HCAP criteria. To compare the two, cutoff points should be contrasted for persons meeting 1, 2, or more HCAP or risk score criteria. The authors could further improve the predictive ability of their score by presenting likelihood ratios for each of the risk scores of the new tool. The authors present single positive and negative predictive values based on a risk score of 0, but these statistics could be calculated for other scores as well. Because of the effect of prevalence on the performance of diagnostic tests, we are concerned that the prevalence of drug-resistant pathogens reported in the study is inaccurate due to verification bias that occurs when the action of performing a test is affected by the pretest probability of disease [2]. The authors report a 47% prevalence of drug-resistant pathogens, likely an overestimation. A medical history suggesting a person had high risk for drug-resistant bacterial infection might influence physicians’ decisions to obtain cultures, a criterion for inclusion in the study. Persons without significant healthcare exposure might be deemed low-risk by clinicians, who would not order cultures, leading to underrepresentation of these patients in this study. Verification bias results in overestimation of the sensitivity and underestimation of the specificity of the new risk score. Unfortunately it is difficult to confirm that verification bias has occurred; however, the authors could have performed sensitivity analyses or controlled for culture collection to assess this problem. Finally, the most appropriate cutoff for risk score is determined by weighing the costs of further testing or broad-spectrum antibiotic use in patients who do not need them against benefits of appropriate early therapy in those infected with drug-resistant pathogens. This balance will depend on the clinical characteristics and risk factors of the patients, societal views of medical care, and economic considerations. Although the HCAP definition reaches an imperfect balance, the authors’ clinical risk score fails to improve upon that standard.