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Background There is a need to evaluate antibiotic use, duration of therapy, and stewardship in low- and middle-income countries to guide the development of appropriate stewardship programs that are global in scope and effectively decrease unnecessary antibiotic use. Methods We prospectively collected information on illness occurrence and antibiotic use from a cohort of 303 children. We evaluated the incidence, duration of therapy, and appropriateness of antibiotic prescriptions by 5 main antibiotic prescribers (physicians and nurses, pharmacists, nursing assistants, self-prescriptions, and neighbors or family members). Results Ninety percent of children received an antibiotic during follow-up, and on average, by the end of follow-up a child had spent 4.3% of their first 5 years of life on antibiotics. The most frequent prescribers were physicians/nurses (79.4%), followed by pharmacists (8.1%), self-prescriptions (6.8%), nursing assistants (3.7%), and family or neighbors (1.9%). Of the 3702 courses of antibiotics prescribed, 30.9% were done so for the occurrence of fever, 25.3% for diarrhea, 2.8% for acute lower respiratory disease, 2.7% for dysentery, and 38.2% for an undetermined illness. Courses exceeding the recommended duration were common for the principal diseases for which treatment was initiated, with 27.3% of courses exceeding the recommended length duration, representing a potential reduction in 13.2% of days on which this cohort spent on antibiotics. Conclusions Stewardship programs should target medical personnel for a primary care stewardship program even in a context in which antibiotics are available to the public with little or no restrictions and appropriate duration should be emphasized in this training.

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.

Health-care–associated infections (HAI) and antimicrobial resistance are of great public health concern worldwide.1 Bacterial pathogens causing HAI have become increasingly more resistant over the past 10–15 years as a result of various mechanisms, including gene-mediated enzymes such as class A, B, and D β-lactamases.2 Numerous factors, from the horizontal transfer of gene-encoded enzymes to global travel, have allowed resistance and resistant organisms to rapidly spread with great clinical and epidemiological impact.3,4 The recently described carbapenemase, New Delhi metallo-β-lactamase (NDM-1) class B, is of particular epidemiological and clinical concern. Since its discovery in 2008, NDM-1 has rapidly spread worldwide and confers resistance to almost all lactams, with the exception of aztreonam, leaving limited therapeutic options against pathogens harboring NDM-1, typically colistin, tigecycline, and fosfomycin.2,5,6 In Latin America, the blaNDM-1 gene was first reported in 2011 from Guatemala and Colombia, and later from Mexico in 2012, Brazil in 2013, and Uruguay in 2013, with all instances from Enterobacteriaceae.5 The blaNDM-1 gene in non-fermentative pathogens was first reported in Latin America from Honduras (Acinetobacter baumannii) and Paraguay (Acinetobacter pittii) in 2012, and later from Brazil (A. baumannii) in 2014, Cuba (Acinetobacter soli) in 2015, Argentina (Acinetobacter junii) in 2016, and Colombia (A. baumannii) in 2017.5–8 In Peru, the first report of blaNDM-1 was in May 2017 in a set of nine Klebsiella pneumoniae infecting or colonizing critically ill neurological patients from one hospital in Lima.9 Here, we describe the identification of the first three strains of A. baumannii harboring blaNDM-1 in Peru as part of a strain-based surveillance project carried out by the Naval Medical Research Unit No Six (NAMRU-6) in Lima, Peru.

Background Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru. Methodology/Principal findings Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 102 to 2.9 × 106 focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were similar across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity. Conclusions/Significance Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability., Author summary In the context of ongoing clinic- and field-based epidemiological studies on dengue virus (DENV), we compared methods of feeding mosquitoes on blood from naturally infected humans. Participants chose to participate in direct (uninfected mosquitoes applied directly to skin) and/or indirect (uninfected mosquitoes fed on a membrane feeder in the laboratory with blood drawn from a participant) methods. Overall, rates of DENV infection and dissemination were lower in mosquitoes fed indirectly on blood with no additive than in mosquitoes fed directly on a participant. Rates of DENV infection and dissemination were similar between mosquitoes fed directly and indirectly when anticoagulant (EDTA) was added. The indirect-EDTA method resulted in more variable infection rates than the direct method. Our results demonstrate the feasibility of using either direct or indirect feeding methods to study DENV-human infectiousness to mosquito vectors. In our experience, however, direct feeding is preferable to indirect feeding in terms of logistical ease, biosecurity, and reliability.

Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine–tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11–0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03–0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 μM was associated with a 1.63 (95% CI = 1.13–2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines.

Probiotics are increasingly used for diarrhea, but studies under the Food and Drug Administration and Investigational New Drug program are few. We conducted a phase-one placebo-controlled study of Lactobacillus reuteri DSM 17938 under Investigational New Drug program in 60 children 2-5 years of age (41 L. reuteri, 19 placebos) in a resource-constrained community in Peru. No differences in objective data on adverse events were noted, although some differences based on subjective parental reports for fever and diarrhea were seen.

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study communities in Peru are located in Loreto province, in a rural area 15 km from the city of Iquitos. This riverine population of approximately 5000 individuals is fairly representative of Loreto. The province lags behind the rest of the country in access to water and sanitation, per capita income, and key health indicators including infant mortality (43.0 vs 16.0 per 1000 nationwide) and under-5 mortality (60.6 vs 21.0 per 1000). Total fertility rates are higher than elsewhere in the country (4.3 vs 2.6). Nationwide, the prevalence of human immunodeficiency virus is estimated at 0.45%, the prevalence of tuberculosis is 117 per 100 000, and the incidence of malaria is 258 per 100 000. Stunting in this community is high, whereas acute undernutrition is relatively uncommon. The population suffers from high rates of diarrheal disease. Prevalent enteric pathogens include Ascaris, Giardia, enterotoxigenic Escherichia coli, Shigella, and Campylobacter.

Introduction Long-term disease surveillance data provide a basis for studying drivers of pathogen transmission dynamics. Dengue is a mosquito-borne disease caused by four distinct, but related, viruses (DENV-1-4) that potentially affect over half the world's population. Dengue incidence varies seasonally and on longer time scales, presumably driven by the interaction of climate and host susceptibility. Precise understanding of dengue dynamics is constrained, however, by the relative paucity of laboratory-confirmed longitudinal data. Methods We studied 10 years (2000–2010) of laboratory-confirmed, clinic-based surveillance data collected in Iquitos, Peru. We characterized inter and intra-annual patterns of dengue dynamics on a weekly time scale using wavelet analysis. We explored the relationships of case counts to climatic variables with cross-correlation maps on annual and trimester bases. Findings Transmission was dominated by single serotypes, first DENV-3 (2001–2007) then DENV-4 (2008–2010). After 2003, incidence fluctuated inter-annually with outbreaks usually occurring between October and April. We detected a strong positive autocorrelation in case counts at a lag of ∼70 weeks, indicating a shift in the timing of peak incidence year-to-year. All climatic variables showed modest seasonality and correlated weakly with the number of reported dengue cases across a range of time lags. Cases were reduced after citywide insecticide fumigation if conducted early in the transmission season. Conclusions Dengue case counts peaked seasonally despite limited intra-annual variation in climate conditions. Contrary to expectations for this mosquito-borne disease, no climatic variable considered exhibited a strong relationship with transmission. Vector control operations did, however, appear to have a significant impact on transmission some years. Our results indicate that a complicated interplay of factors underlie DENV transmission in contexts such as Iquitos., Author Summary Description of long-term temporal patterns in disease occurrence improves our understanding of pathogen transmission dynamics and facilitates predicting new epidemics. Dengue, the most prevalent mosquito-borne, viral disease of humans, typically varies seasonally and on longer, inter-annual time scales. In most studies of these patterns, however, only a fraction of putative dengue cases are confirmed with laboratory diagnostics. Here we analyzed 10 years of fully confirmed dengue cases reported to a sentinel surveillance system in Iquitos, Peru. We describe the inter and intra-annual patterns of weekly case counts and relate these to climate and local vector control efforts. We show that dengue case counts vary seasonally in Iquitos despite very little variation in key climatic conditions, such as temperature and humidity. Overall, transmission correlated poorly with climate regardless of time lag. In seasons when vector control was conducted early, there was an apparent decline in cases later that season. We speculate that the relationships between climatic conditions and transmission of DENV in Iquitos are complex and non-linear, and that other factors, such as herd immunity, virus diversity, and vector control efforts, play key roles determining the timing and intensity of transmission.

El dengue es la arbovirosis mas importante del mundo y causa un amplio espectro clinico. Presentamos el primer caso de dengue causado por el serotipo 4 (DENV-4) en Peru con compromiso gastrointestinal (colecistitis aguda alitiasica y hepatitis aguda moderada). Se presenta una revision de la literatura medica sobre este tipo de presentacion, enfatizando la importancia y caracteristicas del dolor abdominal (hipocondrio derecho), el signo de Murphy, los hallazgos ultrasonograficos y la medicion de las enzimas hepaticas para establecer el diagnostico y manejo adecuado.

An 8-year-old girl from the rural eastern Amazon department of Loreto presented to her local health post with a 1-week history of fever, headache, and poorly localized abdominal discomfort. At the health post, the child had a temperature of 39°C. A thick smear was obtained, and the patient was started on chloroquine after parasites were observed on the thick smear. The smear was referred to a regional diagnostic center for further evaluation. There the smear was found to be negative for Plasmodium species but positive for