Kristien Verdonck

Sexual behavior in travelers visiting Cuzco.

BACKGROUND In South America, little is known about sexual behavior and risk factors for acquiring sexually transmitted diseases (STDs) among travelers and among local people sexually interacting with travelers. There is evidence that, in Peru, significant sexual interaction between these groups exists. METHOD An anonymous written questionnaire was administered to travelers in the airport and bus stations before they left Cuzco. RESULTS Of the travelers,5.6% engaged in sexual activity with a new partner during their stay in Cuzco. Sexual intercourse with other travelers was most common (76/140, 54.3%), followed by sex with local partners (57/140, 40.7%), and with commercial sex workers (3/140, 2.15%). Consistent condom use was reported by 97/140 (69.3%). In the multivariate analysis, the following variables were independently associated with casual sex: male gender, single marital status, age between 15 and 35 years, non-United States travelers (NUSTs), traveling alone or with friends, length of stay more than 30 days, homosexual or bisexual orientation, and expectation of having sex before traveling. Homosexual and bisexual travelers had 3 or more new sexual partners more frequently than heterosexual travelers (4/8, 18/129, OR=6.17 (1.16<OR<33.5)). NUSTs received more pretravel advice (698/1587, 210/718, OR=1.86 (1.54<OR<2.24)) and engaged in more sexual activity (100/1,587, 25/722, OR=1.86 (1.20<OR<2.93)) than United States travelers (USTs). CONCLUSION Travelers visiting Cuzco engage in sexual activities that put them at risk of acquiring STD and transmitting it, both in their home country and in Peru. We recommend the inclusion of Peru and possibly other Latin American countries in the list of destinations where there is substantial risk of transmission of STD and the provision of pretravel advice regarding this issue to travelers to Peru.

Proviral load and immune markers associated with human T‐lymphotropic virus type 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru

Human T‐lymphotropic virus type 1 (HTLV‐1) is the aetiological agent of HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study is to identify which ex vivo and in vivo markers are associated independently with HAM/TSP in a Peruvian population. Eighty‐one subjects (33 men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV‐1 carriers (ACs) and 13 were HTLV‐1‐seronegative controls (SCs). Ex vivo markers included T cell proliferation and Th1 [interferon (IFN)‐γ], Th2 [interleukin (IL)‐4, IL‐5], proinflammatory [tumour necrosis factor (TNF)‐α] and anti‐inflammatory (IL‐10) cytokine production in non‐stimulated peripheral blood mononuclear cell (PBMC) cultures. In vivo CD4+ T cell count, markers of Th1 [interferon‐inducible protein (IP)‐10] and Th2 (sCD30) activity in plasma and HTLV‐1 proviral load in PBMCs were also evaluated. In univariate analysis, several markers, including T cell proliferation, IFN‐γ, IP‐10, sCD30 and proviral load were associated with HAM/TSP, but in a multiple logistic regression analysis only the proviral load remained associated significantly with disease manifestation [adjusted OR 9·10 (1·24–66·91)]. Our findings suggest that HAM/TSP is associated primarily with proviral load, whereas the observed association with some immune markers seems secondary.

Pretravel Health Advice among International Travelers Visiting Cuzco, Peru

BACKGROUND Cuzco, a Peruvian city of historical interest located 3,326 m above sea level, is a frequent destination for tourists. We conducted a descriptive study to assess the extent and sources of pretravel health advice received by international travelers before their arrival to Cuzco. METHODS Data were collected as part of a health survey among travelers. Between August and November 2002, travelers between 15 and 65 years old were invited to fill out a questionnaire in the departing area of Cuzcos international airport. RESULTS A total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr); 50.6% were female and 50.8% were single. Tourism was the reason for traveling in 90.2% of the participants, and 89.3% of them were traveling with companions. Pretravel health information was received by 93.6%. The median number of information sources was two, with books (41.5%), travel medicine clinics (38.8%), the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most frequently received recommendations were about safe food and water consumption (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2% took medication to prevent travelers diarrhea. Variables independently associated with receiving pretravel health information from a health care professional were female gender, country of residence other than the United States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities > 7 days, tourism as the main reason for visiting Cuzco, traveling with companions, and consulting of more than one source of information. CONCLUSIONS Most travelers arriving to Cuzco had received pretravel health information, and the majority obtained it from more than one source. Recommendations addressed for specific health risks, such as altitude sickness prophylaxis, were received by few travelers.

Strongyloidiasis and infective dermatitis alter human T lymphotropic virus-1 clonality in vivo.

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called “DivE” was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1+ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1+ clones.

Development and Validation of a Multiplex Real-Time PCR Assay for Simultaneous Genotyping and Human T-Lymphotropic Virus Type 1, 2, and 3 Proviral Load Determination

ABSTRACT The human T-lymphotropic virus (HTLV) proviral load remains the best surrogate marker for disease progression. Real-time PCR techniques have been developed for detection and quantification of cosmopolitan HTLV type 1a (HTLV-1a) and HTLV-2. Since a growing level of diversity in subtypes and genotypes is observed, we developed a multiplex quantitative PCR for simultaneous detection, genotyping, and quantification of proviral loads of HTLV-1, 2, and 3. Our assay uses tax type-specific primers and dually labeled probes and has a dynamic range of 105 to 10 HTLV copies. One hundred sixty-three samples were analyzed, among which all of the different subtypes within each HTLV genotype could be detected. The performance of proviral load determination of our multiplex assay was compared with that of a previously published HTLV-1 singleplex quantitative PCR based on SYBR green detection, developed at a different institute. Linear regression analysis showed a statistically significant (P < 0.0001) and strong (r2 = 0.87) correlation between proviral load values measured with the two distinct real-time PCR assays. In conclusion, our novel assay offers an accurate molecular diagnosis and genotyping, together with the determination of the proviral load of HTLV-infected individuals, in a single amplification reaction. Moreover, our molecular assay could offer an alternative when current available serological assays are insufficient.

IFN‐γ production in response to Tax 161–233, and frequency of CD4+ Foxp3+ and Lin− HLA‐DRhigh CD123+ cells, discriminate HAM/TSP patients from asymptomatic HTLV‐1‐carriers in a Peruvian population

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‐γ (IFN‐γ) 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‐γ 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.

Clinical Evaluation of a 16S Ribosomal RNA Polymerase Chain Reaction Test for the Diagnosis of Lymph Node Tuberculosis

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.

Impact of new developments in antiretroviral treatment on AIDS prevention and care in resource-poor countries.

Combination antiretroviral treatment (ARV) including protease inhibitors, decreased the morbidity and mortality due to AIDS in the industrialized world. Many obstacles remain before ARVs can be introduced in resource-poor countries: high treatment costs, lack of laboratories to monitor the treatment, weak healthcare systems, and many other competing healthcare needs. The introduction of ARVs in resource-poor countries should be closely monitored. The first priority for the use of ARVs in resource-poor countries is the prevention of mother-to-child transmission of HIV. News about the success of ARV treatment may lead to an increase in unsafe behaviors including a decreased use of condoms. Therefore, prevention efforts should be strengthened; especially the development of an HIV vaccine needs to become a top priority. Funds for ARV treatment cannot come from the already strained healthcare budgets of resource-poor countries. The pressure on politicians and international donor agencies to provide ARVs to resource-poor countries should be used to increase overall healthcare budgets and to improve healthcare services in general.

Defining micro-epidemiology for malaria elimination: systematic review and meta-analysis

BackgroundMalaria risk can vary markedly between households in the same village, or between villages, but the determinants of this “micro-epidemiological” variation in malaria risk remain poorly understood. This study aimed to identify factors that explain fine-scale variation in malaria risk across settings and improve definitions and methods for malaria micro-epidemiology.MethodsA systematic review of studies that examined risk factors for variation in malaria infection between individuals, households, clusters, hotspots, or villages in any malaria-endemic setting was conducted. Four databases were searched for studies published up until 6th October 2015. Crude and adjusted effect estimates for risk factors for malaria infection were combined in random effects meta-analyses. Bias was assessed using the Newcastle–Ottawa Quality Assessment Scale.ResultsFrom 743 retrieved records, 51 studies were selected, representing populations comprising over 160,000 individuals in 21 countries, in high- and low-endemicity settings. Sixty-five risk factors were identified and meta-analyses were conducted for 11 risk factors. Most studies focused on environmental factors, especially increasing distance from a breeding site (OR 0.89, 95% CI 0.86–0.92, 10 studies). Individual bed net use was protective (OR 0.63, 95% CI 0.52–0.77, 12 studies), but not household bed net ownership. Increasing household size (OR 1.08, 95% CI 1.01–1.15, 4 studies) and household crowding (OR 1.79, 95% CI 1.48–2.16, 4 studies) were associated with malaria infection. Health seeking behaviour, medical history and genetic traits were less frequently studied. Only six studies examined whether individual-level risk factors explained differences in malaria risk at village or hotspot level, and five studies reported different risk factors at different levels of analysis. The risk of bias varied from low to high in individual studies. Insufficient reporting and comparability of measurements limited the number of meta-analyses conducted.ConclusionsSeveral variables associated with individual-level malaria infection were identified, but there was limited evidence that these factors explain variation in malaria risk at village or hotspot level. Social, population and other factors may confound estimates of environmental risk factors, yet these variables are not included in many studies. A structured framework of malaria risk factors is proposed to improve study design and quality of evidence in future micro-epidemiological studies.

Duration of cough, TB suspects’ characteristics and service factors determine the yield of smear microscopy

Objective  To determine the efficiency of routine tuberculosis (TB) case detection by examining sputum smear positivity for acid‐fast bacilli in relation to duration of cough, characteristics of TB suspects examined and health service factors.