Improved tools and strategies for the prevention and control of arboviral diseases: A research-to-policy forum

Background Research has been conducted on interventions to control dengue transmission and respond to outbreaks. A summary of the available evidence will help inform disease control policy decisions and research directions, both for dengue and, more broadly, for all Aedes-borne arboviral diseases. Method A research-to-policy forum was convened by TDR, the Special Programme for Research and Training in Tropical Diseases, with researchers and representatives from ministries of health, in order to review research findings and discuss their implications for policy and research. Results The participants reviewed findings of research supported by TDR and others. Surveillance and early outbreak warning. Systematic reviews and country studies identify the critical characteristics that an alert system should have to document trends reliably and trigger timely responses (i.e., early enough to prevent the epidemic spread of the virus) to dengue outbreaks. A range of variables that, according to the literature, either indicate risk of forthcoming dengue transmission or predict dengue outbreaks were tested and some of them could be successfully applied in an Early Warning and Response System (EWARS). Entomological surveillance and vector management. A summary of the published literature shows that controlling Aedes vectors requires complex interventions and points to the need for more rigorous, standardised study designs, with disease reduction as the primary outcome to be measured. House screening and targeted vector interventions are promising vector management approaches. Sampling vector populations, both for surveillance purposes and evaluation of control activities, is usually conducted in an unsystematic way, limiting the potentials of entomological surveillance for outbreak prediction. Combining outbreak alert and improved approaches of vector management will help to overcome the present uncertainties about major risk groups or areas where outbreak response should be initiated and where resources for vector management should be allocated during the interepidemic period. Conclusions The Forum concluded that the evidence collected can inform policy decisions, but also that important research gaps have yet to be filled

Analytical Performance of a Multiplex Real-Time PCR Assay Using TaqMan Probes for Quantification of Trypanosoma cruzi Satellite DNA in Blood Samples

Background: The analytical validation of sensitive, accurate and standardized Real-Time PCR methods for Trypanosoma cruzi quantification is crucial to provide a reliable laboratory tool for diagnosis of recent infections as well as for monitoring treatment efficacy. Methods/Principal Findings: We have standardized and validated a multiplex Real-Time quantitative PCR assay (qPCR) based on TaqMan technology, aiming to quantify T. cruzi satellite DNA as well as an internal amplification control (IAC) in a single-tube reaction. IAC amplification allows rule out false negative PCR results due to inhibitory substances or loss of DNA during sample processing. The assay has a limit of detection (LOD) of 0.70 parasite equivalents/mL and a limit of quantification (LOQ) of 1.53 parasite equivalents/mL starting from non-boiled Guanidine EDTA blood spiked with T. cruzi CLBrener stock. The method was evaluated with blood samples collected from Chagas disease patients experiencing different clinical stages and epidemiological scenarios: 1- Sixteen Venezuelan patients from an outbreak of oral transmission, 2- Sixty three Bolivian patients suffering chronic Chagas disease, 3- Thirty four Argentinean cases with chronic Chagas disease, 4- Twenty seven newborns to seropositive mothers, 5- A seronegative receptor who got infected after transplantation with a cadaveric kidney explanted from an infected subject. Conclusions/Significance: The performing parameters of this assay encourage its application to early assessment of T. cruzi infection in cases in which serological methods are not informative, such as recent infections by oral contamination or congenital transmission or after transplantation with organs from seropositive donors, as well as for monitoring Chagas disease patients under etiological treatment.Fil: Duffy, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; ArgentinaFil: Cura, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Ramírez, Juan C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Abate, Teresa. Universidad Central de Venezuela. Instituto de Medicina Tropical; VenezuelaFil: Cayo, Nelly M.. Universidad Nacional de Jujuy. Instituto de Biologia de la Altura; ArgentinaFil: Parrado, Rudy. Universidad San Simón; BoliviaFil: Diaz Bello, Zoraida. Universidad Central de Venezuela. Instituto de Medicina Tropical; VenezuelaFil: Velazquez, Elsa Beatriz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Muñoz Calderón, Arturo. Universidad Central de Venezuela. Instituto de Medicina Tropical; VenezuelaFil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Basile, Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Garcia, Lineth. Universidad San Simón; BoliviaFil: Riarte, Adelina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Ocampo, Susana B.. Universidad Nacional de Jujuy. Instituto de Biologia de la Altura; ArgentinaFil: Yadon, Zaida E.. Pan-American Health Organization; Estados UnidosFil: Torrico, Faustino. Universidad San Simón; BoliviaFil: Alarcón de Noya, Belkisyole. Universidad Central de Venezuela. Instituto de Medicina Tropical; VenezuelaFil: Ribeiro, Isabela. Drugs and Neglected Diseases Initiative; SuizaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentin

Un brote inusual de Hantavirus en el sur de Argentina: ¿transmisión persona a persona?

El síndrome pulmonar por Hantavirus es una zoonosis sostenida por roedores reconocida primero en los Estados Unidos en 1993. La transmisión persona a persona no ha sido informada; sin embargo, en un brote de 20 casos informados aquí, la evidencia epidemiológica sugiere fuertemente esta ruta de transmisión.Facultad de Ciencias Veterinaria

Un brote inusual de Hantavirus en el sur de Argentina: ¿transmisión persona a persona?

El síndrome pulmonar por Hantavirus es una zoonosis sostenida por roedores reconocida primero en los Estados Unidos en 1993. La transmisión persona a persona no ha sido informada; sin embargo, en un brote de 20 casos informados aquí, la evidencia epidemiológica sugiere fuertemente esta ruta de transmisión.Facultad de Ciencias Veterinaria

Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of Trypanosoma cruzi DTUs in Biological and Clinical Samples

Background: Trypanosoma cruzi has been classified into six Discrete Typing Units (DTUs), designated as TcI–TcVI. In order to effectively use this standardized nomenclature, a reproducible genotyping strategy is imperative. Several typing schemes have been developed with variable levels of complexity, selectivity and analytical sensitivity. Most of them can be only applied to cultured stocks. In this context, we aimed to develop a multiplex Real-Time PCR method to identify the six T. cruzi DTUs using TaqMan probes (MTq-PCR).Methods/Principal Findings: The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples from vectors, reservoirs and patients from different geographical regions and transmission cycles in comparison with a multi-locus conventional PCR algorithm. The MTq-PCR was inclusive for laboratory stocks and natural isolates and sensitive for direct typing of different biological samples from vectors, reservoirs and patients with acute, congenital infection or Chagas reactivation. The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq-PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir samples that had been typed by conventional PCR methods. Regarding clinical samples, 100% of those derived from acute infected patients, 62.5% from congenitally infected children and 50% from patients with clinical reactivation could be genotyped. Sensitivity for direct typing of blood samples from chronic Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic patients) and mixed infections was lower than that of the conventional PCR algorithm.Conclusions/Significance: Typing is resolved after a single or a second round of Real-Time PCR, depending on the DTU. This format reduces carryover contamination and is amenable to quantification, automation and kit production.This work received financial support from the Ministry of Science and Technology of Argentina [PICT 2011-0207 to AGS] and the National Scientific and Technical Research Council in Argentina (CONICET) [PIP 112 2011-010-0974 to AGS]. Work related to evaluation of biological samples was partially sponsored by the Pan-American Health Organization (PAHO) [Small Grants Program PAHO-TDR]; the Drugs and Neglected Diseases Initiative (DNDi, Geneva, Switzerland), Wellcome Trust (London, United Kingdom), SANOFI-AVENTIS (Buenos Aires, Argentina) and the National Council for Science and Technology in Mexico (CONACYT) [FONSEC 161405 to JMR]

Indoor and peridomestic transmission of American cutaneous leishmaniasis in northwestern Argentina: a retrospective case-control study.

A case-control study was carried out during 1990-1994 to identify risk factors associated with American cutaneous leishmaniasis (ACL) in Santiago del Estero, Argentina. The study subjects consisted of 171 cases and 308 controls matched by age, sex, and place of residence. The analysis was performed by conditional logistic regression. Risk factors found to be significantly associated with ACL were related to indoor transmission (few rooms in the house, dirt floor, and a permanent opening in lieu of a window); peridomestic transmission (presence of a pond or woodland within 150 m of the house and an agricultural area within 200 m of the house); and human behavior (sleeping in the backyard, collecting water, bathing, and performing agricultural activities). Most transmission appears to have occurred indoors and in the peridomicile. These environments should be included in further research and control policies

Implementation of the national tuberculosis guidelines on culture and drug sensitivity testing in Guatemala, 2013

ABSTRACT Objective To assess whether the National Tuberculosis Program (NTP) guidelines for culture and drug sensitivity testing (DST) in Guatemala were successfully implemented, particularly in cases of smear-negative pulmonary tuberculosis (TB) or previously treated TB, by documenting notification rates by department (geographic area), disease type and category, and culture and DST results. Methods This was a cross-sectional, operational research study that merged and linked all patients registered by the NTP and the National Reference Laboratory in 2013, eliminating duplicates. The proportions with culture (for new smear negative pulmonary cases) and culture combined with DST (for previously treated patients) were estimated and analyzed by department. Data were analyzed using EpiData Analysis version 2.2. Results There were 3 074 patients registered with TB (all forms), for a case notification rate of 20/100 000 population. Of these, 2 842 had new TB, of which 2 167 (76%) were smear-positive pulmonary TB (PTB), 385 (14%) were smear-negative PTB, and 290 (10%) were extrapulmonary TB. There were 232 (8%) previously treated cases. Case notification rates (all forms) varied by department from 2–68 per 100 000 population, with the highest rates seen in the southwest and northeast part of Guatemala. Of new TB patients, 136 had a culture performed and 55 had DST of which the results were 33 fully sensitive, 9 monoresistant, 3 polyresistant, and 10 multidrug resistant TB (MDR-TB). Only 21 (5%) of new smear-negative PTB patients had cultures. Of 232 previously treated patients, 54 (23%) had a culture and 47 (20%) had DST, of which 29 were fully sensitive, 7 monoresistant, 2 polyresistant, and 9 MDR-TB. Of 22 departments (including the capital), culture and DST was performed in new smear-negative PTB in 7 departments (32%) and in previously treated TB in 13 departments (59%). Conclusions Despite national guidelines, only 5% of smear-negative PTB cases had a culture and only 20% of previously treated TB had a culture and DST. Several departments did not perform culture or DST. These short comings must be improved if Guatemala is to curtail the spread of drug resistant forms of TB, while striving to eliminate all TB

Contrasting trends of tuberculosis in the cities of San Pedro Sula and Tegucigalpa, Honduras, 2005–2014

ABSTRACT Objective To 1) describe and compare the trends of tuberculosis (TB) case notification rates (CNRs) and treatment outcomes in the two largest cities in Honduras (San Pedro Sula and Tegucigalpa) for the period 2005–2014 and 2) identify possible related socioeconomic and health sector factors. Methods This retrospective ecological operational research study used aggregated data from the National TB Program (socioeconomic and health sector information and individual data from the 2014 TB case notification report). Results TB CNRs declined steadily over the study period in Tegucigalpa (from 46 to 28 per 100 000 inhabitants) but remained high in San Pedro Sula (decreasing from 89 to 78 per 100 000 inhabitants). Similar trends were observed for smear-positive TB. While presumptive TB cases examined were similar for both cities, in San Pedro Sula the proportions of presumptive cases with a positive smear; (7.7% versus 3.6%) relapses (8.9% versus 4.2%); and patients lost to follow-up (10.9% versus 2.7%) were significantly higher, and the treatment success lower (75.7% versus 87.0%). San Pedro Sula had lower annual income per capita, fewer public sector health workers and facilities, and a higher and increasing homicide index. The 2014 TB case data from San Pedro Sula showed a significantly lower median age and a higher proportion of assembly plant workers, prisoners, drug abusers, and diabetes. Conclusions The TB rate was higher and treatment success lower, and health care resources and socio-demographic indicators less favorable, in San Pedro Sula versus Tegucigalpa. City authorities, the NTP, and the health sector overall should strengthen early case detection, treatment, and infection control, involving both public and private health sectors

Quality of tuberculosis care at different levels of health care in Brazil in 2013

ABSTRACT Objective To assess 1) the burden and socio-demographic and clinical characteristics of tuberculosis (TB) cases, and 2) the quality of TB care provided to patients who entered and remained within each health care service level (primary, secondary, or tertiary) and those who moved from one level to another, using process and results indicators. Methods This cross-sectional operational research study assessed new smear-positive pulmonary TB cases diagnosed in Brazilian state capitals in 2013 using TB program records and the TB surveillance system. Quality of care was assessed based on process and results indicators including HIV screening, TB contact screening, Directly Observed Treatment (DOT), sputum smear microscopy monitoring, and treatment outcomes. Results There were 12 977 new smear-positive TB cases reported. Of these, 7 964 (61.4%) cases were diagnosed and treated at the primary care level, 1 195 (9.2%) at the secondary level, 1 521 (11.7%) at the tertiary level, and 2 296 (17.7%) at more than one level, with 65% of the latter group moved from the tertiary level to the primary level. The proportion of cases tested for HIV was significantly higher in patients receiving care at the primary level compared to those receiving care at the secondary level (prevalence ratio (PR): 1.17; 95% confidence interval (CI): 1.07–1.28) and those attending more than one service level. Patients attending the tertiary health care level had a 122% higher PR for not doing DOT (“DOT not done”) compared to patients at the primary level (PR: 2.22; CI: 2.12–2.32). When the two levels were compared, the prevalence for an unfavorable outcome (lost to follow-up, death from TB, death with TB, transferred out, or not evaluated) was higher at the tertiary health care level. Conclusions Primary health services are successfully incorporating the management of new smear-positive TB cases. Primary health care obtained better operational indicators than secondary or tertiary levels

Malaria epidemiology in Suriname from 2000 to 2016: trends, opportunities and challenges for elimination

Abstract Background Suriname has experienced a significant change in malaria transmission risk and incidence over the past years. The country is now moving toward malaria elimination. The first objective of this study is to describe malaria epidemiological trends in Suriname between 2000 and 2016. The second objective is to identify spatiotemporal malaria trends in notification points between 2007 and 2016. Methods National malaria surveillance data resulting from active and passive screening between 2000 and 2016 were used for the temporal trend analysis. A space–time cluster analysis using SaTScan™ was conducted on Malaria Programme-data from 2007 to 2016 comparing cases (people tested positive) with controls (people tested negative). Results Suriname experienced a period of high malaria incidence during 2000–2005, followed by a steep decline in number of malaria cases from 2005 onwards. Imported malaria cases, mostly of Brazilian nationality and travelling from French Guiana, were major contributors to the reported number of cases, exceeding the national malaria burden (94.2% of the total). Most clusters in notification points are found in the border area between Suriname and French Guiana. Clustering was also found in the migrant clinic in Paramaribo. Conclusions Suriname has successfully reduced malaria to near-elimination level in the last 17 years. However, the high malaria import rate resulting from cross-border moving migrants is a major challenge for reaching elimination. This requires continued investment in the national health system, with a focus on border screening and migrant health. A regional approach to malaria elimination within the Guianas and Brazil is urgently needed