A pragmatic stepped-wedge cluster randomized trial to evaluate the effectiveness and cost-effectiveness of active case finding for household contacts within a routine tuberculosis program, San Juan de Lurigancho, Lima, Peru.

BACKGROUND: Active case finding (ACF) in household contacts of tuberculosis (TB) patients is now recommended for National TB Programs (NTP) in low- and middle-income countries. However, evidence supporting these recommendations remains limited. This study evaluates the effectiveness and cost-effectiveness of ACF for household contacts of TB cases in a large TB endemic district of Lima, Peru. METHODS: A pragmatic stepped-wedge cluster randomized controlled trial was conducted in 34 health centers of San Juan de Lurigancho district. Centers were stratified by TB rate and randomly allocated to initiate ACF in groups of eight or nine centers at four-month intervals. In the intervention arm, NTP providers visited households of index patients to screen contacts for active TB. The control arm was routine passive case finding (PCF) of symptomatic TB cases. The primary outcomes were the crude and adjusted active TB case rates among household contacts. Program costs were directly measured, and the cost-effectiveness of the ACF intervention was determined. FINDINGS: 3222 index TB cases and 12,566 household contacts were included in the study. ACF identified more household contact TB cases than PCF, 199.29/10,000 contacts/year vs. 132.13 (incidence rate ratio of 1.51 (95% CI 1.21-1.88)). ACF was associated with an incremental cost-effectiveness ratio of US $16,400 per disability-adjusted life year averted and not cost-effective assuming a willingness-to-pay threshold for Peru of US $6360. CONCLUSION: ACF of TB case household contacts detected significantly more secondary TB cases than PCF alone, but was not cost-effective in this setting. In threshold analyses, ACF becomes cost-effective if associated with case detection rates 2.5 times higher than existing PCF programs.

Socioeconomic Factors Associated with Fasciola hepatica Infection Among Children from 26 Communities of the Cusco Region of Peru.

Fasciola hepatica is the most widely distributed trematode-affecting humans. The Andes Mountains are highly endemic for fascioliasis. We report results of a cross-sectional study evaluating the epidemiology of Fasciola among children in 26 agricultural communities in the Cusco region of Peru. Children 3 to 16 years old were enrolled in preschools and schools. Blood from participants was tested for complete blood counts, transaminases, and Fasciola antibodies. Stool samples were tested for Fasciola and other parasites. A total of 2,515 children were included in the analysis and the mean age was 9.6 years (±3.6). Ten percent (253) of the children had at least one positive test for Fasciola, 6% had chronic infection, and 0.4% acute infection. The rest of the subjects had only antibodies against Fasciola. The prevalence of infection varied from 0% to 20% between communities. Children with evidence of Fasciola exposure were older, lived at higher altitudes, and had a lower socioeconomic status than children without infection. The logistic regression analysis showed that children from Ancahuasi district, older children, and children with higher measures of poverty were more likely to have Fasciola exposure. Fascioliasis is common in the Cusco region and associated with poverty. However, the distribution varies markedly between communities.

Reducing the global burden of HTLV-1 infection: An agenda for research and action.

Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines.

A scoping review of cost-effectiveness of screening and treatment for latent tubercolosis infection in migrants from high-incidence countries.

BACKGROUND: In low-incidence countries, most tuberculosis (TB) cases occur among migrants and are caused by reactivation of latent tuberculosis infection (LTBI) acquired in the country of origin. Diagnosis and treatment of LTBI are rarely implemented to reduce the burden of TB in immigrants, partly because the cost-effectiveness profile of this intervention is uncertain. The objective of this research is to perform a review of the literature to assess the cost-effectiveness of LTBI diagnosis and treatment strategies in migrants. METHODS: Scoping review of economic evaluations on LTBI screening strategies for migrants was carried out in Medline. RESULTS: Nine studies met the inclusion criteria. LTBI screening was cost-effective according to seven studies. Findings of four studies support interferon gamma release assay as the most cost-effective test for LTBI screening in migrants. Two studies found that LTBI screening is cost-effective only if carried out in immigrants who are contacts of active TB cases. DISCUSSION AND CONCLUSIONS: Our findings support the cost-effectiveness of LTBI diagnostic and treatment strategies in migrants especially if they are focused on young subjects from high incidence countries. These strategies could represent and adjunctive and synergistic tool to achieve the ambitious aim of TB elimination.

HIV stigma as a barrier to retention in HIV care at a general hospital in Lima, Peru: a case-control study.

HIV stigma as a barrier to retention in HIV care has not been well-studied outside the United States. We conducted a case-control study in Lima, Peru to examine this issue. Cases were out-of-care for ≥12 months (n = 66) and controls were recruited from patients in active care presenting for a clinic visit (n = 110). A previously validated HIV stigma scale with four domains was used. Associations between being out-of-care and each stigma domain were assessed using multivariable logistic regression. Stigma scores were highest for disclosure concerns. Modest associations were found for greater disclosure concerns (OR 1.16; 95 % CI 0.99, 1.36) and concerns with public attitudes (OR 1.20; 95 % CI 1.03, 1.40). Enacted stigma and negative self-image showed non-linear associations with being out-of-care that plateaued or declined, respectively, at higher levels of stigma. The threshold effect for enacted stigma warrants further exploration, while disclosure concerns may be especially amenable to intervention in this population.

Pre-travel preparation for Cusco, Peru: a comparison between European and North American travelers.

BACKGROUND: Demographics, preferences on health care, and regional differences in pre-travel advice guidelines may influence the preparation of travelers to developing countries. METHODS: A secondary data analysis of the database of a travelers' health survey conducted in Cusco in 2002 was performed. Data from those whose place of residence was North America or Western Europe were selected. Illness rates, vaccinations, prophylactic medication use, and general recommendations on disease prevention were compared between the two groups. RESULTS: Data from 1,612 North Americans (NAM) and 3,590 Western Europeans (EUR) were analyzed. NAM were older, stayed longer in Cusco, and had less experience traveling to developing countries (p < 0.01). They reported being ill more often than EUR (58% vs 42%, p < 0.01). Diarrhea was more frequent among EUR (55.6% vs 46.7%, p < 0.01), and acute mountain sickness (AMS) was more frequent among NAM (52.8% vs 35.2%, p < 0.01). EUR sought advice from health care professionals (67.1% vs 52.0%, p < 0.01) and travel medicine practitioners (45.8% vs 37%, p < 0.01) more often. NAM used prophylactic medications more often (53% vs 48.6%, p = 0.00) and received a lower mean number of vaccines (1.97 ± 1.68 vs 2.63 ± 1.49; t-test 14.02, p < 0.01). Advice on safe sex and alcohol consumption was low in both groups, especially among NAM. CONCLUSIONS: Pre-travel preparation and travel-related illnesses varied between NAM and EUR. Improving consistency of pre-travel preparation based on the best evidence should become a priority among different national bodies providing travel medicine recommendations.

Formación de investigadores en el contexto de proyectos colaborativos: experiencias en el Instituto de Medicina Tropical “Alexander von Humboldt”, Universidad Peruana Cayetano Heredia / Researchers training in the context of the collaborative projects: experiences of Instituto de Medicina Tropical “Alexander von Humbolt”, Universidad Peruana Cayetano Heredia

La investigación constituye un elemento fundamental de desarrollo humano y social. Bajo esta perspectiva, supone desafíos y oportunidades particulares para los llamados países “en vías de desarrollo”. Una aproximación a tales desafíos y oportunidades se desprende del análisis de dos actividades interrelacionadas: la formación de nuevos investigadores y el desarrollo de investigación con instituciones o investigadores externos a la propia institución (“investigación colaborativa”). Ambas actividades son esenciales en la consolidación, ampliación y actualización de las capacidades institucionales de producción científica. Presentamos aquí las experiencias del Instituto de Medicina Tropical “Alexander von Humboldt” de la Universidad Peruana Cayetano Heredia con relación a la formación de investigadores, discutimos los cuatro elementos que consideramos clave en dicho proceso: promoción de entornos estimulantes para investigación, identificación proactiva de becarios, asesorías complementarias y consolidación de redes; y analizamos tres modelos de colaboración internacional exitosos en la formación de nuevos investigaciones bajo distintas aproximaciones institucionales.

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.

Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing.

BACKGROUND: Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking. METHODS: Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time. RESULTS: Decreased initial regimen durability was observed with weight <60 kg [hazards ratio (HR) = 1.77; 95% confidence interval (CI) = 1.25-2.51], CD4 <200 (HR = 1.73; 95% CI = 1.03-2.91), and zidovudine (AZT) use at <120 days (HR = 2.09; 95% CI = 1.22-3.57). In contrast, after 120 days, AZT use decreased risk of discontinuation (HR = 0.52; 95% CI = 0.28-0.95). Early (<120 days) toxicity-related discontinuation of AZT containing regimens was observed in 44% of patients <50 kg at baseline vs. 14% of those >70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight <60 kg (HR = 2.52; 95% CI = 1.46-4.35). CONCLUSIONS: Lower baseline weight and lower CD4 values at ART initiation were associated with decreased regimen durability. Compared with didanosine/stavudine, AZT use initially increased, then subsequently (>120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.

Self-reported health problems among travelers visiting Cuzco: a Peruvian Airport survey.

Travel related illnesses are a concern among travelers visiting developing countries. These illnesses affect the travelers' plans and the local tourism industry. Few data on travel related illnesses are available from tourist destinations. Foreign travelers answered a self-administered questionnaire on health issues at the departures area of Cuzcos' International Airport between August and November 2002. Self-reported travel related illnesses that occurred during the travelers stay in Cuzco were compared with demographic and risk factors. The total number of participants was 5988. Their mean age was 35.4 years (SD 11.4), and slightly over half were female. The most common countries of residence were the United States (23.5%) and the United Kingdom (20%). The median length of stay in Cuzco was 5 days (IQR: 4-7 days). Pre-travel advice was received by 93.6% of the participants. Half (47.6%) of the participants became ill while in Cuzco. The most common illnesses reported were diarrhea (49.8%), altitude sickness (43.2%), and upper respiratory infections (21.7%). Most participants who reported an illness treated themselves (75.5%), and only 22.1% sought medical attention. It is concluded that a significant burden of disease is observed in travelers to Cuzco. Self-medication is very common and apparently preferred over formal medical attention.

Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries.

BACKGROUND: Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission. METHODS: A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Löwenstein-Jensen medium. These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium. RESULTS: All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively). CONCLUSION: Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries.

Rapid dissemination and diversity of CTX-M extended-spectrum beta-lactamase genes in commensal Escherichia coli isolates from healthy children from low-resource settings in Latin America.

A survey carried out in 2005 among members of a healthy population of children living in Bolivia and Peru revealed that fecal carriage of Escherichia coli strains resistant to expanded-spectrum cephalosporins was remarkably increased compared to that observed in the same settings in 2002 (1.7% in 2005 versus 0.1% in 2002). In this work, we demonstrated that this phenomenon was mainly related to the dissemination of CTX-M-type extended-spectrum beta-lactamase (ESBL) determinants among commensal E. coli strains. Of 50 ESBL-producing isolates collected in the 2005 survey, 44 harbored a CTX-M-type and 6 an SHV-type (SHV-2 or SHV-12) ESBL. Compared to 2002 results, an increased diversity of CTX-M-type ESBLs was also observed: members of the CTX-M-1 group (CTX-M-15) emerged in Bolivia (where only CTX-M-2 was observed in 2002), while members of the CTX-M-9 group (CTX-M-14 and CTX-M-24) emerged in Peru (where only CTX-M-15 and CTX-M-2 were observed in 2002). A new CTX-M-2 variant named CTX-M-56 was also detected. Molecular characterization of the CTX-M-producing isolates and gene transfer experiments suggested that different mechanisms could be involved in the spreading of different CTX-M group determinants and revealed that additional resistance determinants for non-beta-lactam antibiotics were preferentially carried by plasmids encoding certain CTX-M variants (CTX-M-15 and variants of the CTX-M-2 group). Three CTX-M-15-encoding conjugative plasmids from Peruvian isolates carried the new fluoroquinolone resistance gene aac(6')-Ib-cr. To our best knowledge, this is the first report of the detection of aac(6')-Ib-cr in Latin America.

Síndrome respiratorio agudo. Manual de manejo sindrómico / Acute respiratory syndrome. Syndromic Management Manual

La publicación describe las presentaciones clínicas que comprometen el sistema respiratorio de diferentes niveles, que causan sobreposición en los cuadros clínicos, pudiendo tener enfermedades con la aparición aguda de disfunción respiratoria como síndrome respiratorio agudo

Deteccion de portadores de Salmonella Typhi mediante la prueba de hemaglutinacion indirecta con antigeno Vi muy purificado / Screening of Salmonella Typhi carriers by indirect hemagglutination using highly purified Vi antigen

A study was carrried out to determine the predictive value and the cost-effectiveness of the indirect hemagglutination test using highly purified Vi antigen as a means of screening Salmonella Typhi carrriers in a high-risk group living in an área where typhoid fever is emdemic. The group consisted of women over age 30 who were participating in a municipal sanitary control program for food handlers in Lima, Perú. Test yielding an anti-Vi antibody titer= 1:40 were considered positive (79 percent sensitivity, and 99 percent and 100 percent specificity for the local population). On this basis, 29 women (1.5 percent) tested positive out of a total of 1 931. A follow-up bacteriological study demonstrated that 26 of these 29 women were carriers of S. typhi; thus, the test had a predictive value of 15 percent. The prevalence of carriers in this group was estimated at 292 per 100 000 population. The test cost $US 0.30 per person. In comparison, the method that requires a series of three fecal cultures to isolate the causative agent would have cost $US 1.72. It can be concluded that the test studied is suficiently sensitive, that it is highly specific, and that it is cost-effective when used to detect S. typhi carriers in áreas where typhoid fever is endemic