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BACKGROUND: The National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas. METHODS AND FINDINGS: We conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects. To evaluate each individual's treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive). Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months' time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment. CONCLUSIONS: Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation., PLoS neglected tropical diseases, 13(9), e0007715; 2019

Comparison of VNT (threshold set at 80) and PRNT assays for a panel of 142 samples. (DOCX 14 kb)

Dengue fever represents a major public health problem. Both viral and host immune factors are involved in severe infections. Humans and mosquito-vectors are infected with diverse viral populations that may play a role in viral adaptation and disease pathogenesis. Our objective was to analyse the intra-host genetic variability of dengue virus type 1 (DENV-1) in the venous and capillary blood and its relationships with the clinical presentation of dengue fever. Early serum samples were collected in 2009 from ten DENV-1-infected patients hospitalized in Santa Cruz de la Sierra, Bolivia. Partial viral envelope sequences were analysed at the inter-host and intra-host level. For each patient, an average of 56 clone sequences was analysed both in the venous sector and the capillary sector (from right and left hands). The ten consensus sequences were highly similar. The intra-host DENV-1 genetic variability was significantly lower in the venous sector than in the capillary sector, and in patients with haemorrhagic symptoms than in those without haemorrhagic symptoms, particularly in capillary samples. No relation was found with sex, age, dengue IgG-serological status, day of serum sampling, or viral load. Significant relationships were found between the clinical presentation of dengue fever and the variability of viral populations within hosts, particularly in capillary samples. The observed variability of envelope sequences at the early phase of dengue infection was not critically influenced by the previous dengue serological status of patients. An important part of viral microevolution may occur in the capillary sector and influence the mechanisms of severe forms.

La dengue, maladie transmise par un vecteur du genre aedes, est largement infeodee aux milieux urbains en raison des exigences ecologiques de son vecteur qui se reproduit dans les multiples collections d’eau generees par la ville et ses habitants. Cependant la diversite des paysages urbains semble entrainer des heterogeneites importantes de distribution de la maladie au sein meme de la ville. Si la diffusion de la maladie a l’echelle du globe s’appuie sur le developpement du fait urbain et notamment ses formes mal controlees, ainsi que sur l’acceleration des deplacements de populations, peut-on expliquer l’heterogeneite de la transmission en ville par les memes phenomenes mais dans leurs manifestations a grande echelle ? L’etude du cas de Santa Cruz de la Sierra, ville en pleine croissance d’un million et demi d’habitants, carrefour de circulation et « epicentre » de la maladie en Bolivie doit nous permettre de discuter de l’interaction entre les differents niveaux de determinants pour une meilleure prise en compte du risque sanitaire dans les politiques de developpement urbain. Une analyse critique de l’information et des resultats nous permet de mieux comprendre quelles inegalites sont revelees par la dengue pour une meilleure prise en charge de celles-ci.

Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0・046 for human, 1/11, P = 0・0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease., Parasite Immunology, 38(10), pp.609-617; 2016

To the Editor: Bolivian hemorrhagic fever (BHF) was first described in 1959 during outbreaks affecting isolated human communities in eastern Bolivia. However, it was not until 1963 that the etiologic agent, Machupo virus, was isolated from the spleen of a patient who died from this disease (1). Although no cases were reported between 1976 and 1993, an outbreak occurred in 1994 and sporadic cases have been observed since then.

La dengue, maladie transmise par un vecteur du genre aedes, est largement inféodée aux milieux urbains en raison des exigences écologiques de son vecteur qui se reproduit dans les multiples collections d’eau générées par la ville et ses habitants. Cependant la diversité des paysages urbains semble entraîner des hétérogénéités importantes de distribution de la maladie au sein même de la ville. Si la diffusion de la maladie à l’échelle du globe s’appuie sur le développement du fait urbain et notamment ses formes mal contrôlées, ainsi que sur l’accélération des déplacements de populations, peut-on expliquer l’hétérogénéité de la transmission en ville par les mêmes phénomènes mais dans leurs manifestations à grande échelle ? L’étude du cas de Santa Cruz de la Sierra, ville en pleine croissance d’un million et demi d’habitants, carrefour de circulation et « épicentre » de la maladie en Bolivie doit nous permettre de discuter de l’interaction entre les différents niveaux de déterminants pour une meilleure prise en compte du risque sanitaire dans les politiques de développement urbain. Une analyse critique de l’information et des résultats nous permet de mieux comprendre quelles inégalités sont révélées par la dengue pour une meilleure prise en charge de celles-ci. Between Spaces at Risk and Mobilities : Appreciation of the Inequalities and Risk Management Dengue fever, transmitted by the aedes vector, is most prevalent in urban environments because of the ecological requirements of its vectors that reproduce in the multiple water collections generated by the city and its inhabitants. However the diversity of urban landscapes seems to determine the heterogeneous distribution of the disease across the urban landscape. Across the world, the diffusion of the disease is due in part to urban development, especially to uncontrolled development, and on the acceleration of population displacements. This study explores whether these large-scale processes are also at play at a more local scale, using the city of Santa Cruz de la Sierra, in Bolivia, as a case study. This city of a million and half of inhabitants is rapidly growing and is at the crossroads of circulation ; it is the epicentre of the disease in Bolivia. We examine the interaction between the various levels of risk factors influencing the disease and inequalities in its distribution. We discuss implications of the results for the development and implementation of urban policies, highlighting the importance of considering health hazards in their formulation.

Background The spread of Aedes albopictus, a vector for re-emergent arbovirus diseases like chikungunya and dengue, points up the need for better control strategies and new tools to evaluate transmission risk. Human antibody (Ab) responses to mosquito salivary proteins could represent a reliable biomarker for evaluating human-vector contact and the efficacy of control programs. Methodology/Principal Findings We used ELISA tests to evaluate specific immunoglobulin G (IgG) responses to salivary gland extracts (SGE) in adults exposed to Aedes albopictus in Reunion Island. The percentage of immune responders (88%) and levels of anti-SGE IgG Abs were high in exposed individuals. At an individual level, our results indicate heterogeneity of the exposure to Aedes albopictus bites. In addition, low-level immune cross-reactivity between Aedes albopictus and Aedes aegypti SGEs was observed, mainly in the highest responders. Conclusion/Significance Ab responses to saliva could be used as an immuno-epidemiological tool for evaluating exposure to Aedes albopictus bites. Combined with entomological and epidemiological methods, a “salivary” biomarker of exposure to Aedes albopictus could enhance surveillance of its spread and the risk of arbovirus transmission, and could be used as a direct tool for the evaluation of Aedes albopictus control strategies., Author Summary Aedes-borne viruses like dengue and chikungunya are a major problem in Reunion Island. Assessing exposure to Aedes bites is crucial to estimating the risk of pathogen transmission. Currently, the exposure of populations to Aedes albopictus bites is mainly evaluated by entomological methods which are indirect and difficult to apply on a large scale. Recent findings suggest that evaluation of human antibody responses against arthropod salivary proteins could be useful in assessing exposure to mosquito bites. The results indicate that 88% of the studied population produce IgG to Ae. albopictus saliva antigens in Reunion Island and show that this biomarker can detect different levels of individual exposure. In addition, little cross-reactivity is observed with Aedes aegypti saliva, suggesting that this could be a specific marker for exposure to Aedes albopictus bites. Taken together, these results suggest that antibody responses to saliva could constitute a powerful immuno-epidemiological tool for evaluating exposure to Aedes albopictus and therefore the risk of arbovirus infection.

Dengue fever was first recognized in Bolivia in 1931. However, very limited information was available to date regarding the genetic characterization and epidemiology of Bolivian dengue virus strains. Here, we performed genetic characterization of the full-length envelope gene of 64 Bolivian isolates from 1998 to 2008 and investigated their origin and evolution to determine whether strains circulated simultaneously or alternatively, and whether or not multiple introductions of distinct viral variants had occurred during the period studied. We determined that, during the last decade, closely related viruses circulated during several consecutive years (5, 6, and 6 years for DENV-1, DENV-2, and DENV-3, respectively) and the co-circulation of two or even three serotypes was observed. Emergence of new variants (distinct from those identified during the previous episodes) was identified in the case of DENV-1 (2007 outbreak) and DENV-2 (2001 outbreak). In all cases, it is likely that the viruses originated from neighboring countries.

BACKGROUND: The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. METHODS AND FINDINGS: Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. CONCLUSIONS: None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia., PLoS Neglected Tropical Diseases, 4(5), pp.e687; 2010

Objective To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. Design Case-control study. Setting Six hospitals in Bolivia, between March 2010 and June 2011. Participants 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. Main outcome measures Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1–adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. Results In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. Conclusion The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against diverse serotypes different from the vaccine strain.

Venezuelan equine encephalitis virus (VEEV) has been responsible for hundreds of thousands of human and equine cases of severe disease in the Americas. A passive surveillance study was conducted in Peru, Bolivia and Ecuador to determine the arboviral etiology of febrile illness. Patients with suspected viral-associated, acute, undifferentiated febrile illness of, Author Summary Venezuelan equine encephalitis virus (VEEV) has been responsible for hundreds of thousands of human and equine cases of severe disease in the Americas. In 2005–2007, cases of Venezuelan equine encephalitis (VEE) were diagnosed for the first time in residents of Bolivia; the patients did not report traveling, suggesting endemic circulation of VEEV in Bolivia. In 2001 and 2003, VEE cases were also identified in Ecuador. We characterize recent VEEV from Bolivia, Ecuador and Peru and compared their relationships to strains from other parts of South America. We found that most VEEV from Peru grouped within a particular genetic lineage known to circulate in Panama and Peru whereas the VEEV circulating in Ecuador belong to a genetic lineage that circulates in Colombia and Venezuela. Importantly, the VEEV from Madre de Dios, Peru and Cochabamba, Bolivia belong to a new genetic lineage. This finding could aid in the understanding of the emergence and evolution of VEEV in South America and underscores the need for continuous monitoring for VEEV activity.

Light microscopy image of a VNT assay at day 5 pi. (DOCX 3995 kb)

Comparison of CPE-based Virus Neutralization Titre100 and PRNT90 titres. (DOCX 168 kb)

Specificity and sensitivity of VNT in low ZIKV seropositivity (titre 40â 80) and strong ZIKV positivity (titre â Ľ160) compared to the PRNT90. (DOCX 14 kb)

Plaque Reduction Neutralisation Test of ZIKV at day 5 pi. (DOCX 9182 kb)

Specificity and sensitivity of VNT in DENGUE ELISA negative and positive samples. (DOCX 14 kb)

Light microscopy image of a VNT assay at day 5 pi. (DOCX 3995 kb)

Comparison of VNT (threshold set at 80) and PRNT assays for a panel of 142 samples. (DOCX 14 kb)

Comparison of VNT (threshold set at 20) and PRNT assays for a panel of 142 samples. (DOCX 12 kb)

Comparison of VNT (threshold set at 20) and PRNT assays for a panel of 142 samples. (DOCX 12 kb)

Comparison of CPE-based Virus Neutralization Titre100 and PRNT50 titres. (DOCX 172 kb)

Specificity and sensitivity of VNT in low ZIKV seropositivity (titre 40â 80) and strong ZIKV positivity (titre â Ľ160) compared to the PRNT90. (DOCX 14 kb)

Comparison of CPE-based Virus Neutralization Titre100 and PRNT50 titres. (DOCX 172 kb)

Sensitivity and specificity comparison of VNT and PRNT (threshold was set as 10 and 20) for a panel of 142 samples. (DOCX 15 kb)

Comparison of CPE-based Virus Neutralization Titre100 and PRNT90 titres. (DOCX 168 kb)

Sensitivity and specificity comparison of VNT and PRNT (threshold was set as 10 and 20) for a panel of 142 samples. (DOCX 15 kb)