Direct mosquito feedings on dengue-2 virus-infected people reveal dynamics of human infectiousness.

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.

Pleural empyema by Parvimonas micra in an immunocompetent patient: a case report. / Empiema pleural por Parvimonas micra en un paciente inmunocompetente: reporte de un caso.

We present the case of a young immunocompetent patient, with a history of pulmonary tuberculosis, who attended the hospital with a subacute clinical picture of persistent fever, weight loss, dyspnea and abolition of vesicular murmur. Chest CT scan showed an extensive empyema in the left hemithorax. Samples were taken for detection of common germs. Then, a chest drainage tube was placed and antibiotic therapy started. The MALDI-TOF MS test identified Parvimonas micra, an anaerobic bacterium, commensal to the oral flora, associated with severe periodontitis, but rarely reported in cases of pleural empyema, especially in immunocompetent patients. Gingivitis and pericoronaritis of the third molar were diagnosed during oral evaluation. The patient progressed favorably. Parvimonas micra should be considered as a possible etiological agent in cases of subacute or chronic pleural empyema, in addition to mycobacteria. Tests such as MALDI-TOF MS or 16S rRNA sequencing, chest tube placement, empirical antibiotic coverage and an adequate oral evaluation should be considered in these cases.

Se presenta el caso de un paciente joven inmunocompetente, con antecedente de tuberculosis pulmonar, que acude al hospital por un cuadro clínico subagudo de fiebre persistente, baja de peso, disnea y abolición del murmullo vesicular. La tomografía de tórax mostró un extenso empiema en hemitórax izquierdo. Se le toman muestras para detección de gérmenes comunes y se le colocan un tubo de drenaje torácico y se inicia antibioticoterapia. La prueba de MALDI-TOF MS identificó a Parvimonas micra, una bacteria anaerobia, comensal de la flora oral, asociado a periodontitis severa, escasamente reportado en empiema pleural, especialmente, en personas inmunocompetentes. En la evaluación odontológica se realizó el diagnóstico de gingivitis y pericoronaritis de la tercera molar. El paciente evolucionó favorablemente. Se sugiere que, en casos de empiemas pleurales subagudos o crónicos, se debe considerar, además de las micobacterias, como agente etiológico al Parvimonas micra, y optar por exámenes como MALDI-TOF MS o secuenciamiento del 16S rRNA, colocación de tubo de tórax, cobertura antibiótica empírica y evaluación odontológica.

Feasibility of Training Community Health Workers to Use Smartphone-Attached Microscopy for Point-of-Care Visualization of Soil-Transmitted Helminths in the Peruvian Amazon.

The prevalence of soil-transmitted helminths (STH) is high in communities within the Peruvian Amazon despite repeated mass-drug administration, demanding alternative strategies of control. Smartphone-attached microscopy (SAM) permits visualization of STH from a small portable microscope through a smartphone screen, potentially providing an inexpensive and rapid method of STH visualization in communities where diagnostic laboratories with microscopes are inaccessible. In this study, a total of 45 community health workers who work within the health systems of Loreto, Peru, attended a 1-day training session with lectures and practicums on STH and SAM. Participants received a pre- and post-intervention questionnaire. Post-intervention, participants were significantly more confident using SAM and identifying parasite images, symptoms, transmission, and treatment (P ≤ 0.0045). Post-intervention, participants correctly labeled a median of five of seven SAM apparatus components and five of eight steps of Kato-Katz technique, were less likely to choose taking medicine to prevent parasite infection (P = 0.0075), and were more likely to select Kato-Katz technique as a type of diagnostic test (P < 0.0001). Most participants felt ready to use SAM in their communities and stated that it could help rural communities far from health centers or laboratories (24%); provide faster identification, results, diagnosis (19%); permit at-home or on-the-spot visualization (14%); and save money (14%). Results show that community health workers show a high level of willingness and competency to learn about both STH and SAM and may be a yet-unexplored practical method of augmenting STH visualization, bringing healthcare to communities in Loreto with poor access to diagnostic laboratories and clinics.

Empiema pleural por Parvimonas micra en un paciente inmunocompetente: reporte de un caso / Pleural empyema by Parvimonas micra in an immunocompetent patient: a case report

Se presenta el caso de un paciente joven inmunocompetente, con antecedente de tuberculosis pulmonar, que acude al hospital por un cuadro clínico subagudo de fiebre persistente, baja de peso, disnea y abolición del murmullo vesicular. La tomografía de tórax mostró un extenso empiema en hemitórax izquierdo. Se le toman muestras para detección de gérmenes comunes y se le colocan un tubo de drenaje torácico y se inicia antibioticoterapia. La prueba de MALDI-TOF MS identificó a Parvimonas micra, una bacteria anaerobia, comensal de la flora oral, asociado a periodontitis severa, escasamente reportado en empiema pleural, especialmente, en personas inmunocompetentes. En la evaluación odontológica se realizó el diagnóstico de gingivitis y pericoronaritis de la tercera molar. El paciente evolucionó favorablemente. Se sugiere que, en casos de empiemas pleurales subagudos o crónicos, se debe considerar, además de las micobacterias, como agente etiológico al Parvimonas micra, y optar por exámenes como MALDI-TOF MS o secuenciamiento del 16S rRNA, colocación de tubo de tórax, cobertura antibiótica empírica y evaluación odontológica.

We present the case of a young immunocompetent patient, with a history of pulmonary tuberculosis, who attended the hospital with a subacute clinical picture of persistent fever, weight loss, dyspnea and abolition of vesicular murmur. Chest CT scan showed an extensive empyema in the left hemithorax. Samples were taken for detection of common germs. Then, a chest drainage tube was placed and antibiotic therapy started. The MALDI-TOF MS test identified Parvimonas micra, an anaerobic bacterium, commensal to the oral flora, associated with severe periodontitis, but rarely reported in cases of pleural empyema, especially in immunocompetent patients. Gingivitis and pericoronaritis of the third molar were diagnosed during oral evaluation. The patient progressed favorably. Parvimonas micra should be considered as a possible etiological agent in cases of subacute or chronic pleural empyema, in addition to mycobacteria. Tests such as MALDI-TOF MS or 16S rRNA sequencing, chest tube placement, empirical antibiotic coverage and an adequate oral evaluation should be considered in these cases.

Challenges of design, implementation, acceptability, and potential for, biomedical technologies in the Peruvian Amazon.

BACKGROUND: Biomedical technologies have the potential to be advantageous in remote communities. However, information about barriers faced by users of technology in general and in remote Indigenous communities is scarce. The purpose of this study was to characterize the leading challenges faced by researchers who have used biomedical technologies in the Peruvian Amazon. METHODS: This exploratory, qualitative study with a phenomenological approach depicts the lived experience of participants who were researchers with experience working with biomedical technologies in the Peruvian Amazon in the past five years. Analysis was based on three core themes: design, implementation, and acceptability. Sub-themes included environment, community, and culture. Of the 24 potential participants identified and contacted, 14 agreed to participate, and 13 met inclusion criteria and completed semi-structured interviews. Results were sent to each participant with the opportunity to provide feedback and partake in a 30-minute validation meeting. Five participants consented to a follow-up meeting to validate the results and provide further understanding. RESULTS: Participants recognized significant challenges, including technologies designed out-of-context, difficulty transporting the technologies through the Amazon, the impact of the physical environment (e.g., humidity, flooding), and limited existing infrastructure, such as electricity and appropriately trained health personnel. Participants also identified cultural factors, including the need to address past experiences with technology and health interventions, understand and appropriately communicate community benefits, and understand the effect of demographics (e.g., age, education) on the acceptance and uptake of technology. Complementary challenges, such as corruption in authority and waste disposal, and recommendations for technological and health interventions such as co-design were also identified. CONCLUSIONS: This study proposes that technological and health interventions without efforts to respect local cultures and health priorities, or understand and anticipate contextual challenges, will not meet its goal of improving access to healthcare in remote Amazon communities. Furthermore, the implications of corruption on health services, and improper waste disposal on the environment may lead to more detrimental health inequities.

[Brain abscess due to Nocardia sp. In an immunocompetent patient in Peru: a case report]. / Absceso cerebral por Nocardia sp. En un paciente inmunocompetente en el Perú: reporte de caso.

Cerebral nocardia infections is a rare entity, which has been mainly reported in immunosuppressed patients. Currently, there are no clinical guidelines for first-line treatment. Our case refers to an older immunocompetent adult, with encephalopathy and left hemiparesis, associated with lesions compatible with multiple brain abscess and suggestive of infectious etiology. He initially received treatment for tuberculosis, bacterial abscess, and toxoplasmosis, without a favorable clinical response. An empirical treatment for nocardiosis started, by using meropenem and trimethoprim / sulfamethoxazole, and clinical and imaging improvement was achieved. The occurrence of adverse events forces the temporary use of alternative medications. We highlight some criteria for including nocardiosis in the differential diagnosis in cases of multiple brain abscess and mention laboratory diagnostic methods and drugs to initiate empirical treatment.

La nocardiosis cerebral es una entidad rara que ha sido reportada principalmente en inmunosuprimidos, y en la actualidad no se dispone de guías clínicas que recomienden un tratamiento de primera línea. Presentamos el caso de un adulto mayor, inmunocompetente, con cuadro de encefalopatía y hemiparesia izquierda, asociado a lesiones compatibles con absceso cerebral múltiple y sugerente de etiología infecciosa. Recibió, inicialmente, tratamiento para la tuberculosis, absceso bacteriano y toxoplasmosis, sin respuesta clínica favorable. Se inició un tratamiento empírico para la nocardiosis con meropenem y trimetoprim/sulfametoxazol, y se logró mejoría clínica e imagenológica. La ocurrencia de eventos adversos obliga el uso temporal de medicamentos alternativos. Se resaltan algunos criterios a considerar para incluir la nocardiosis en el diagnóstico diferencial en los casos de absceso cerebral múltiple y se mencionan los métodos diagnósticos de laboratorio y los fármacos para iniciar un tratamiento empírico.

Serological Responses in Patients Infected with Mayaro Virus and Evaluation of Cross-Protective Responses against Chikungunya Virus.

Mayaro virus (MAYV) is an alphavirus endemic to both Latin America and the Caribbean. Recent reports have questioned the ability of MAYV and its close relative, Chikungunya virus (CHIKV), to generate cross-reactive, neutralizing antibodies to one another. Since CHIKV was introduced to South America in 2013, discerning whether individuals have cross-reactive antibodies or whether they have had exposures to both viruses previously has been difficult. Using samples obtained from people infected with MAYV prior to the introduction of CHIKV in the Americas, we performed neutralizing assays and observed no discernable neutralization of CHIKV by sera from patients previously infected with MAYV. These data suggest that a positive CHIKV neutralization test cannot be attributed to prior exposure to MAYV and that previous exposure to MAYV may not be protective against a subsequent CHIKV infection.

Absceso cerebral por Nocardia sp. En un paciente inmunocompetente en el Perú: reporte de caso / Brain abscess due to Nocardia sp. In an immunocompetent patient in Peru: a case report

RESUMEN La nocardiosis cerebral es una entidad rara que ha sido reportada principalmente en inmunosuprimidos, y en la actualidad no se dispone de guías clínicas que recomienden un tratamiento de primera línea. Presentamos el caso de un adulto mayor, inmunocompetente, con cuadro de encefalopatía y hemiparesia izquierda, asociado a lesiones compatibles con absceso cerebral múltiple y sugerente de etiología infecciosa. Recibió, inicialmente, tratamiento para la tuberculosis, absceso bacteriano y toxoplasmosis, sin respuesta clínica favorable. Se inició un tratamiento empírico para la nocardiosis con meropenem y trimetoprim/sulfametoxazol, y se logró mejoría clínica e imagenológica. La ocurrencia de eventos adversos obliga el uso temporal de medicamentos alternativos. Se resaltan algunos criterios a considerar para incluir la nocardiosis en el diagnóstico diferencial en los casos de absceso cerebral múltiple y se mencionan los métodos diagnósticos de laboratorio y los fármacos para iniciar un tratamiento empírico.

ABSTRACT Cerebral nocardia infections is a rare entity, which has been mainly reported in immunosuppressed patients. Currently, there are no clinical guidelines for first-line treatment. Our case refers to an older immunocompetent adult, with encephalopathy and left hemiparesis, associated with lesions compatible with multiple brain abscess and suggestive of infectious etiology. He initially received treatment for tuberculosis, bacterial abscess, and toxoplasmosis, without a favorable clinical response. An empirical treatment for nocardiosis started, by using meropenem and trimethoprim / sulfamethoxazole, and clinical and imaging improvement was achieved. The occurrence of adverse events forces the temporary use of alternative medications. We highlight some criteria for including nocardiosis in the differential diagnosis in cases of multiple brain abscess and mention laboratory diagnostic methods and drugs to initiate empirical treatment.

Heterogeneity of Dengue Illness in Community-Based Prospective Study, Iquitos, Peru.

Measuring heterogeneity of dengue illness is necessary to define suitable endpoints in dengue vaccine and therapeutic trials and will help clarify behavioral responses to illness. To quantify heterogeneity in dengue illness, including milder cases, we developed the Dengue Illness Perceptions Response (IPR) survey, which captured detailed symptom data, including intensity, duration, and character, and change in routine activities caused by illness. During 2016-2019, we collected IPR data daily during the acute phase of illness for 79 persons with a positive reverse transcription PCR result for dengue virus RNA. Most participants had mild ambulatory disease. However, we measured substantial heterogeneity in illness experience, symptom duration, and maximum reported intensity of individual symptoms. Symptom intensity was a more valuable predicter of major activity change during dengue illness than symptom presence or absence alone. These data suggest that the IPR measures clinically useful heterogeneity in dengue illness experience and its relation to altered human behavior.

Guaroa Virus and Plasmodium vivax Co-Infections, Peruvian Amazon.

During April-June 2014 in a malaria-endemic rural community close to the city of Iquitos in Peru, we detected evidence of Guaroa virus (GROV) infection in 14 febrile persons, of whom 6 also had evidence of Plasmodium vivax malaria. Cases were discovered through a long-term febrile illness surveillance network at local participating health facilities. GROV cases were identified by using a combination of seroconversion and virus isolation, and malaria was diagnosed by thick smear and PCR. GROV mono-infections manifested as nonspecific febrile illness and were clinically indistinguishable from GROV and P. vivax co-infections. This cluster of cases highlights the potential for GROV transmission in the rural Peruvian Amazon, particularly in areas where malaria is endemic. Further study of similar areas of the Amazon may provide insights into the extent of GROV transmission in the Amazon basin.

Feasibility of feeding Aedes aegypti mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, 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 × 10(2) to 2.9 × 10(6) 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.

[Resistance to ganciclovir in cytomegalovirus infection after heart transplant: case report]. / Reporte de caso de resistencia al ganciclovir en enfermedad por citomegalovirus postrasplante cardiaco.

Cytomegalovirus infection after a heart transplant is a recurrent medical condition. Its frequency increases when the donors are serum-positive, and the recipients are serum-negative to this virus. In the pediatric population, the infection only develops in a small percentage and the patients rarely present resistance to conventional treatment with ganciclovir and valganciclovir. We presented the first report of a pediatric case of the cytomegalovirus infection resistant to ganciclovir and valganciclovir after a heart transplant in a Peruvian public hospital with an unusual presentation. The resistance to these drugs was evident after 277 days of evolution of the disease considering the non-remission of the symptomatology and the persistence of an elevated viral load. The administration of foscarnet led to a clinical and laboratory improvement until remission of the disease.

La infección por citomegalovirus postrasplante cardiaco es una condición médica recurrente. Su frecuencia se incrementa cuando los donantes poseen serología positiva y los receptores presentan serología negativa para el virus. En la población pediátrica, la enfermedad solo se desarrolla en un porcentaje pequeño y raramente presentan resistencia al tratamiento convencional con ganciclovir y valganciclovir. Presentamos el primer reporte de caso pediátrico de enfermedad por citomegalovirus resistente a ganciclovir y valganciclovir postrasplante cardiaco en un hospital público peruano, con una presentación inusual. La resistencia a estos fármacos fue evidente luego de 277 días de evolución de la enfermedad, ante la no remisión de la sintomatología y la persistencia de una carga viral elevada. La posterior administración de foscarnet condujo a una mejora clínica y de laboratorio, hasta la remisión de la enfermedad.