Search

Background The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21–28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. Study Registration Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Background HIV-related incidence and mortality is increasing across Peru, with highest mortality rates recorded in the Amazonian region of Loreto. This epidemic is concentrated in men who have sex with men, a population with 14% HIV treatment adherence despite free national provision. This study investigates barriers and facilitators to following healthcare advice through experiences and perceptions of HIV-positive men who have sex with men and healthcare professionals in Loreto. Methods Twenty qualitative interviews with HIV-positive men who have sex with men and one focus group with HIV-specialist healthcare professionals were conducted in Loreto, January–February 2019. Interviews were transcribed per verbatim. Thematic content analysis and deviant case analysis were used. Results A culture of isolation and discrimination was identified, propagated by poor public knowledge surrounding HIV transmission and treatment. Employment potential was hampered and 7/20 patients had suicidal thoughts post-diagnosis. Barriers to care included: shame, depression, travel cost/times, a preference for traditional plant-based medicine and side-effects of antiretroviral therapy. Facilitators included: education, family and clinic support, disease acceptance and lifestyle changes. Conclusion More effective, focussed community education and workplace discrimination investigations are recommended to reduce stigma and increase adherence to treatment in this population.

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.

Se presentan dos casos de pacientes, naturales de Requena, ciudad a 160 Km al suroeste de Iquitos, departamento de Loreto, selva baja, con síntomas moderados de COVID-19, quienes fueron inyectados con ivermectina de uso veterinario por vía subcutánea en el hombro, como parte de un tratamiento que pudiera tener cierto efecto benéfico sobre la enfermedad. Cinco a ocho días después, en las zonas de inoculación, notaron un nódulo eritematoso que se tornó necrótico, dejando una úlcera redondeada con levessignos inflamatorios. La cicatrización fue lenta.

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.

Background Delays in receiving adequate care for children suffering from pneumonia can be life threatening and have been described associated with parents’ limited education and their difficulties in recognizing the severity of the illness. The “three delays” was a model originally proposed to describe the most common determinants of maternal mortality, but has been adapted to describe delays in the health seeking process for caregivers of children under five. This study aims to explore the caregivers’ perceived barriers for seeking and receiving health care services in children under five years old admitted to a referral hospital for community-acquired pneumonia in the Peruvian Amazon Region using the three-delays model framework. Methods There were two parts to this mixed-method, cross-sectional, hospital-based study. First, medical charts of 61 children (1 to 60 months old) admitted for pneumonia were reviewed, and clinical characteristics were noted. Second, to examine health care-seeking decisions and actions, as well as associated delays in the process of obtaining health care services, we interviewed 10 of the children’s caregivers. Results Half of the children in our study were 9 months old or less. Main reasons for seeking care at the hospital were cough (93%) and fever (92%). Difficulty breathing and fast breathing were also reported in more than 60% of cases. In the interviews, caregivers reported delays of 1 to 14 days to go to the closest health facility. Factors perceived as causes for delays in deciding to seek care were apparent lack of skills to recognize signs and symptoms and of confidence in the health system, and practicing self-medication. No delays in reaching a health facility were reported. Once the caregivers reached a health facility, they perceived lack of competence of medical staff and inadequate treatment provided by the primary care physicians. Conclusion According to caregivers, the main delays to get health care services for pneumonia among young children were identified in the initial decision of caregivers to seek healthcare and in the health system to provide it. Specific interventions targeted to main barriers may be useful for reducing delays in providing appropriate health care for children with pneumonia.

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.

Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon. El dengue ha afectado a Iquitos desde 1990 causando varios brotes de gran impacto en la salud pública y por el que se desplegaron grandes esfuerzos para su control temporal. Actualmente, ante la expansión del virus chikungunya en las Américas y la amenaza de la emergencia del virus en Iquitos, reflexionamos a modo de lecciones aprendidas las actividades emprendidas en el área del control vectorial; la vigilancia epidemiológica; el diagnóstico y el manejo clínico durante los periodos de brotes de dengue, de modo que nos permita enfrentar mejor la amenaza de un brote del virus chikunguña en la ciudad más grande de la Amazonía peruana.

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.

Se describe el caso de un paciente varón, de 13 años de edad, procedente de la ciudad de Iquitos con cuadro clínico de Dengue y que cumplía con los criterios de dengue hemorrágico. La gravedad de este caso de dengue hemorrágico fue de grado II. El diagnóstico fue confirmado por serología. El serotipo encontrado fue el tres. Este es el primer caso de dengue hemorrágico documentado ocurrido el Hospital Regional de Loreto. (Rev Med Hered 2008;19:). We report a case of a 13 year old male patient, well nourished, from Iquitos city with signs of dengue fever who also fulfills definitive criteria for dengue hemorrhagic fever. Classification of the gravity was degree II. Diagnosis was confirmed by serologic studies, showing serotype 3. This could be the first case of dengue hemorrhagic fever at the Hospital Regional de Loreto, although it is probable that in the past there might have been cases that could not be suitably documented. (Rev Med Hered 2008;19:).

Dengue fever is the world's most important arboviral disease, presenting a wide clinical spectrum. We report for the first time in Peru, a case caused by dengue virus serotype 4 with significant gastrointestinal involvement (acute acalculous cholecystitis and acute hepatitis). In addition we carried out a review of the literature atypical presentation illustrating the importance of the characteristics of abdominal pain (right upper quadrant); presence of Murphy's sign, ultrasound, and liver enzymes levels, for appropriate diagnosis and clinical management.

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

Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.