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Human T-lymphotropic virus 1 (HTLV-1) is frequent in Peru; an estimated 1-2% of the Peruvian population carry this retrovirus. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling disease that affects about 1% of the carriers of HTLV-1. It is not yet known why some HTLV-1-infected people develop HAM/TSP while others do not. In this case report, we present a family with an unusually high burden of HAM/TSP: 5 (the 2 parents and 3 of their children) of 7 HTLV-1 carriers developed the same disease. We describe the clinical presentation and discuss the clustering of disease against the current knowledge of the pathogenesis of HAM/TSP. Families such as this may hold the key to discovering which factors trigger the development of HAM/TSP., (2015 BMJ Publishing Group Ltd.)

Background: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies., Methods/design: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies., Discussion: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics., Trial Registration: ClinicalTrials.gov; identifier: NCT02105714 .

Objectives: To evaluate the presence of human T-lymphotropic virus type 1 (HTLV-1) infection in isolated rural communities in the southern Andes of Peru., Methods: We conducted a cross-sectional study in five communities located in three provinces in Ayacucho, Peru. The five communities are located at >3000 meters above sea level and are mainly rural, and more than 85% of the population speaks Quechua. Volunteers aged 12 years and older were included. Clinical and epidemiological data were collected, along with a blood sample for serological testing., Results: We included 397 participants; their median age was 41 years (interquartile range 31-57 years) and 69% were women. According to our definitions, 98% were of Quechua origin. HTLV-1 was diagnosed in 11 people: 0/164 in Cangallo, 3/154 (2%) in Vilcashuaman, and 8/79 (10%) in Parinacochas. There were no cases of HTLV-2. All the HTLV-1-positive participants were born in Ayacucho and were of Quechua origin; they ranged in age from 29 to 87 years (median 56 years) and 10/11 were women. Ten were apparently healthy, and one woman was diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three out of 11 had a family member with a lower limb impairment compatible with HAM/TSP., Conclusion: The fact that HTLV-1 infection was present in two out of three provinces suggests that HTLV-1 could be highly endemic in the southern Andes in the Quechua population., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Impoverished populations carry a disproportionately high share of the burden of neglected tropical diseases, including dengue. The burden of dengue is high among poor people because they often live in communities where mosquito vectors are abundant, because they use less vector-human barrier methods, and because interventions tend to be less effective in disadvantaged populations. We believe that a better understanding and management of the "causes behind the causes" of dengue would lead to more equitable and more effective control strategies. Two main ideas are worked out. First, we propose targeted interventions in well-defined geographical areas with high risk of dengue transmission. The definition of these high-risk areas should be based on socio-economical, entomological, environmental as well as epidemiological information. Second, there is a need to adapt dengue control tools to local, context-specific factors, in active collaboration with the sectors involved in risk management as well as with the affected communities.

Objective: To assess the association between human T-lymphotropic virus type 1 (HTLV-1) infection and onychodystrophy., Methods: This was a cross-sectional study. At our institute, we provide HTLV-1 testing to relatives of HTLV-1-infected people and patients with suspected HTLV-1-associated diseases. The diagnosis of onychodystrophy was made clinically before testing for HTLV-1; the number and distribution of affected nails was registered. We assessed the association between onychodystrophy and HTLV-1 through bi- and multivariable analyses. Logistic regression was used to adjust for age, sex, and indication for HTLV-1 testing, using six affected nails (90(th) percentile) as the cut-off point., Results: Between April 2006 and March 2008, we included 893 subjects; their mean age was 38 years (standard deviation 19 years), and 527 (59%) were women. Onychodystrophy of one or more nails was observed in 323 participants (36%), and 236 subjects (26%) were HTLV-1-positive. The median number of affected nails was higher in HTLV-1-positive than in HTLV-1-negative subjects (Mann-Whitney test, p < 0.001). Thirty-eight of 97 subjects with six or more affected nails (39%) were HTLV-1-infected, compared to 198 of 796 subjects with fewer than six affected nails (25%) (crude OR 1.9, 95% confidence interval (CI) 1.2-3.1; p = 0.003). This association remained significant in the multiple logistic regression model (adjusted OR 2.0, 95% CI 1.2-3.3; p = 0.005)., Conclusions: There is an independent association between HTLV-1 infection and onychodystrophy. Patients with an HTLV-1 infection might have a higher risk for onychomycosis given the abnormal nail plate and a decreased T-cell-mediated immunologic response., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-γ enzyme-linked immunospot (ELISPOT) responses against the region spanning amino acids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP-associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6-h incubation IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMCs) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other proinflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185 and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801 allele, which is predicted to bind to the Tax 181-193 peptide, was overpresented in the HAM/TSP patients tested.

Research is a main element for human and social development. Under this point of view, it involves particular challenges and opportunities for the so-called "developing countries". An approach for those challenges and opportunities comes from the analysis of two interrelated activities; the training of new researchers and the research development with institutions or researchers which are external to the institution ("collaborative research"). Both activities are essential for the consolidation, widening and updating of the institutional capabilities for scientific production. We present here the experiences of the Instituto de Medicina Tropical "Alexander von Humboldt" of the Universidad Peruana Cayetano Heredia, in relation to the training of new researchers, we discuss the four elements we consider key for this process; the promotion of stimulating environments for research, the proactive identification of fellows, the complementary advice and networks consolidation; and we analyze three successful models of international collaboration for the training of new researchers under different institutional approaches.

Human T-lymphotropic virus 1 (HTLV-1) can cause HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study was to gain insight into the pathogenesis of HAM/TSP by focusing on the CD8(+) T-cell response. Twenty-three HTLV-1-seronegative controls (SC), 29 asymptomatic HTLV-1 carriers (AC) and 48 patients with HAM/TSP were enrolled in the study. We evaluated the production of interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells stimulated with Tax overlapping peptides, the expression of genes related to the CD8(+) cytotoxic T-cell response, the frequency of CD4(+) Foxp3(+) cells and of dendritic cells, and the HTLV-1 provirus load (PVL). The frequency of cells producing IFN-gamma in response to Tax 161-233, but not to Tax 11-19, discriminated patients with HAM/TSP from AC. The increased pro-inflammatory response observed in patients with HAM/TSP was shared by AC with a high PVL, who also exhibited lower levels of granzyme H mRNA in unstimulated CD8(+) T cells than AC with a low PVL. Patients with HAM/TSP showed higher frequencies of CD4(+) Foxp3(+) cells and lower frequencies of plasmacytoid dendritic cells (pDC) than AC. Our findings are consistent with a model in which HTLV-1, along with the host genetic background, drives quantitative and qualitative changes in pDC and CD4(+) Foxp3(+) cells that lead to a predominance of inflammatory responses over lytic responses in the CD8(+) T-cell response of individuals predisposed to develop HAM/TSP.

Objectives: Our aim was to investigate CD4+ cell recovery and adverse outcome after highly active antiretroviral therapy (HAART) under the Peruvian National Program for HIV., Methods: A prospective, observational study was conducted between May 2004 and September 2005. Data were collected from records of patients receiving HAART at a public hospital under the Peruvian National Program for HIV. Predictors of CD4+ cell count recovery and adverse outcome were analyzed by multiple regression., Results: Three hundred and twenty-six patients were included in the study. The mean increase in CD4+ cell count at six months was 114 cells/microl (95% confidence interval: 103-126). Patients with a lower CD4+ cell count at baseline and those starting HAART with a didanosine-based regimen had a higher increase in CD4+ cell count at six months. Patients starting HAART with a stavudine-based regimen had a lower increase in CD4+ cell count at six months. World Health Organization clinical stage IV at diagnosis of HIV infection, a low body weight at baseline, and starting HAART with a stavudine-based regimen were independently associated with an adverse outcome., Conclusions: The CD4+ cell response to HAART under Peruvian National Program for HIV was comparable with reports from other countries. However, the fact that advanced clinical disease predicted adverse outcome emphasizes the need for earlier access to HAART.

Human T-lymphotropic virus 1 (HTLV-1) has infected human beings for thousands of years, but knowledge about the infection and its pathogenesis is only recently emerging. The virus can be transmitted from mother to child, through sexual contact, and through contaminated blood products. There are areas in Japan, sub-Saharan Africa, the Caribbean, and South America where more than 1% of the general population is infected. Although the majority of HTLV-1 carriers remain asymptomatic, the virus is associated with severe diseases that can be subdivided into three categories: neoplastic diseases (adult T-cell leukaemia/lymphoma), inflammatory syndromes (HTLV-1-associated myelopathy/tropical spastic paraparesis and uveitis among others), and opportunistic infections (including Strongyloides stercoralis hyperinfection and others). The understanding of the interaction between virus and host response has improved markedly, but there are still no clear surrogate markers for prognosis and there are few treatment options.

To evaluate the human T-lymphotropic virus type 1 (HTLV-1) proviral DNA load in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 carriers, a SYBR Green-based real-time quantitative polymerase chain reaction (qPCR) assay was developed. HTLV-1 proviral DNA in peripheral blood mononuclear cells (PBMCs) was quantified using primers targeting the pX region and the HTLV-1 copy number normalized to the amount of ERV-3 (Endogenous Retrovirus 3) cellular DNA. Thirty-three asymptomatic HTLV-1 carriers (ACs) and 39 patients with HAM/TSP were enrolled. Some participants were relatives of HAM/TSP cases (16 ACs and 7 patients with HAM/TSP). On multiple linear regression analysis, the authors found a significant association between clinical status and HTLV-1 proviral load (P < .01), but only among women. ACs showed a median proviral load of 561 copies per 104 PBMCs (interquartile range: 251-1623). In HAM/TSP patients, the median proviral load was 1783 (1385-2914). ACs related to HAM/TSP patients presented a relatively high proviral load (median 1152); however, the association between relatedness to a HAM/TSP patient and proviral load was not significant (P = .1). In HAM/TSP patients, no association was found between proviral load and disease duration, progression or severity. The fact that the effect of HAM/TSP upon the HTLV-1 proviral load differed between sexes and the finding of a high proviral load among asymptomatic relatives of HAM/TSP patients suggest that not yet identified genetic or environmental factors influence the pathogenesis of HTLV-1 infection.

Unlabelled: Reports on the sensitivity of polymerase chain reaction (PCR) for the diagnosis of lymph node tuberculosis (TB) show divergent results. We evaluated the accuracy of the Roche Amplicor Mycobacterium tuberculosis PCR test with lymph node aspirate and biopsy samples., Methods: The study was conducted at a public reference hospital in Lima, Peru. From the period of January 2003 to January 2004, we included patients who had lymphadenopathy and in whom the attending physician suspected TB. Aspirate and biopsy samples were submitted for culturing in Lowenstein-Jensen medium, for histopathologic testing, and for PCR. The sensitivity and specificity of PCR were calculated against a reference standard based on histopathologic findings and culture., Results: Our study included 154 patients. Median age was 29 years (interquartile range, 21-40 years); 97 patients (62.9%) were men. Twenty-nine patients (18.8%) had acid fast bacilli-positive histopathologic findings, and 44 (28.6%) had a positive culture result. Using the combination of histopathologic findings and culture as reference standard, 55 patients (35.7%) had a diagnosis of tuberculous lymphadenitis. The sensitivity of the PCR test was 58.2%, and the specificity was 93.9%. For biopsy tissue only, the sensitivity of PCR was 52.7%, and the specificity was 97.0%. For aspirate samples only, the sensitivity of PCR was 47.3%, and the specificity was 96.0%., Conclusion: The Amplicor PCR test revealed low sensitivity and high specificity for the diagnosis of lymph node TB. The sensitivity was higher in cases in which the bacillary load was high--in acid fast bacilli-positive samples and among HIV-infected patients. Considering the results of microbiological and PCR tests together, there was still a patient group in whom no final diagnosis could be established.