Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 35 Records) |
Query Trace: Contreras M [original query] |
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Farmworker mobility and COVID-19 vaccination strategies: Yuma County, Arizona, 2021
Franc KA , Phippard AE , Ruedas P , Pinto SJ , Mehta K , Montiel S , Contreras S , Katz H , McIntyre E , Lopez B , Kreutzberg-Martinez M , Steiner D , Gomez D , Merrill R . Am J Trop Med Hyg 2024 Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population. |
Pyrethroid susceptibility reversal in Aedes aegypti: A longitudinal study in Tapachula, Mexico
Penilla-Navarro P , Solis-Santoyo F , Lopez-Solis A , Rodriguez AD , Vera-Maloof F , Lozano S , Contreras-Mejía E , Vázquez-Samayoa G , Torreblanca-Lopez R , Perera R , Black Iv WC , Saavedra-Rodriguez K . PLoS Negl Trop Dis 2024 18 (1) e0011369 Pyrethroid resistance in Aedes aegypti has become widespread after almost two decades of frequent applications to reduce the transmission of mosquito-borne diseases. Because few insecticide classes are available for public health use, insecticide resistance management (IRM) is proposed as a strategy to retain their use. A key hypothesis of IRM assumes that negative fitness is associated with resistance, and when insecticides are removed from use, susceptibility is restored. In Tapachula, Mexico, pyrethroids (PYRs) were used exclusively by dengue control programs for 15 years, thereby contributing to selection for high PYR resistance in mosquitoes and failure in dengue control. In 2013, PYRs were replaced by organophosphates-insecticides from a class with a different mode of action. To test the hypothesis that PYR resistance is reversed in the absence of PYRs, we monitored Ae. aegypti's PYR resistance from 2016 to 2021 in Tapachula. We observed significant declining rates in the lethal concentration 50 (LC50), for permethrin and deltamethrin. For each month following the discontinuation of PYR use by vector control programs, we observed increases in the odds of mosquitoes dying by 1.5% and 8.4% for permethrin and deltamethrin, respectively. Also, knockdown-resistance mutations (kdr) in the voltage-gated sodium channel explained the variation in the permethrin LC50s, whereas variation in the deltamethrin LC50s was only explained by time. This trend was rapidly offset by application of a mixture of neonicotinoid and PYRs by vector control programs. Our results suggest that IRM strategies can be used to reverse PYR resistance in Ae. aegypti; however, long-term commitment by operational and community programs will be required for success. |
Outcomes up to age 36 months after congenital Zika virus infection-U.S. states
Neelam V , Woodworth KR , Chang DJ , Roth NM , Reynolds MR , Akosa A , Carr CP , Anderson KN , Mulkey SB , DeBiasi RL , Biddle C , Lee EH , Elmore AL , Scotland SJ , Sowunmi S , Longcore ND , Ahmed M , Langlois PH , Khuwaja S , Browne SE , Lind L , Shim K , Gosciminski M , Blumenfeld R , Khuntia S , Halai UA , Locklear A , Chan M , Willabus T , Tonzel J , Marzec NS , Barreto NA , Sanchez C , Fornoff J , Hale S , Nance A , Iguchi L , Adibhatla SN , Potts E , Schiffman E , Raman D , McDonald MF , Stricklin B , Ludwig E , Denson L , Contreras D , Romitti PA , Ferrell E , Marx M , Signs K , Cook A , Leedom VO , Beauregard S , Orantes LC , Cronquist L , Roush L , Godfred-Cato S , Gilboa SM , Meaney-Delman D , Honein MA , Moore CA , Tong VT . Pediatr Res 2023 BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models. |
Fleaborne typhus-associated deaths - Los Angeles County, California, 2022
Alarcón J , Sanosyan A , Contreras ZA , Ngo VP , Carpenter A , Hacker JK , Probert WS , Terashita D , Balter S , Halai UA . MMWR Morb Mortal Wkly Rep 2023 72 (31) 838-843 Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts. |
Seasonal influenza vaccination in the Americas: Progress and challenges during the COVID-19 pandemic
Nogareda F , Gharpure R , Contreras M , Velandia M , Lucia Pacis C , Elena Chevez A , Azziz-Baumgartner E , Salas D . Vaccine 2023 BACKGROUND: Vaccination is one of the most effective measures to prevent influenza illness and its complications; influenza vaccination remained important during the COVID-19 pandemic to prevent additional burden on health systems strained by COVID-19 demand. OBJECTIVES: We describe policies, coverage, and progress of seasonal influenza vaccination programs in the Americas during 2019-2021 and discuss challenges in monitoring and maintaining influenza vaccination coverage among target groups during the COVID-19 pandemic. METHODS: We used data on influenza vaccination policies and vaccination coverage reported by countries/territories via the electronic Joint Reporting Form on Immunization (eJRF) for 2019-2021. We also summarized country vaccination strategies shared with PAHO. RESULTS: As of 2021, 39 (89 %) out of 44 reporting countries/territories in the Americas had policies for seasonal influenza vaccination. Countries/territories adapted health services and immunization delivery strategies using innovative approaches, such as new vaccination sites and expanded schedules, to ensure continuation of influenza vaccination during the COVID-19 pandemic. However, among countries/territories that reported data to eJRF in both 2019 and 2021, median coverage decreased; the percentage point decrease was 21 % (IQR = 0-38 %; n = 13) for healthcare workers, 10 % (IQR = -1.5-38 %; n = 12) for older adults, 21 % (IQR = 5-31 %; n = 13) for pregnant women, 13 % (IQR = 4.8-20.8 %; n = 8) for persons with chronic diseases, and 9 % (IQR = 3-27 %; n = 15) for children. CONCLUSIONS: Countries/territories in the Americas successfully adapted influenza vaccination delivery to continue vaccination services during the COVID-19 pandemic; however, reported influenza vaccination coverage decreased from 2019 to 2021. Reversing declines in vaccination will necessitate strategic approaches that prioritize sustainable vaccination programs across the life course. Efforts should be made to improve the completeness and quality of administrative coverage data. Lessons learned from COVID-19 vaccination, such as the rapid development of electronic vaccination registries and digital certificates, might facilitate advances in coverage estimation. |
Improving water, sanitation, and hygiene (WASH), with a focus on hand hygiene, globally for community mitigation of COVID-19
Berendes D , Martinsen A , Lozier M , Rajasingham A , Medley A , Osborne T , Trinies V , Schweitzer R , Prentice-Mott G , Pratt C , Murphy J , Craig C , Lamorde M , Kesande M , Tusabe F , Mwaki A , Eleveld A , Odhiambo A , Ngere I , Kariuki Njenga M , Cordon-Rosales C , Contreras APG , Call D , Ramay BM , Ramm RES , Paulino CJT , Schnorr CD , Aubin M , Dumas D , Murray KO , Bivens N , Ly A , Hawes E , Maliga A , Morazan GH , Manzanero R , Morey F , Maes P , Diallo Y , Ilboudo M , Richemond D , Hattab OE , Oger PY , Matsuhashi A , Nsambi G , Antoine J , Ayebare R , Nakubulwa T , Vosburgh W , Boore A , Herman-Roloff A , Zielinski-Gutierrez E , Handzel T . PLOS Water 2022 1 (6) Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors. |
The use of readily available laboratory tests for the identification of the emerging yeast Candida auris in Mexico
González-Durán E , Contreras-Pérez CU , Caceres DH , Ríos-Rosas C , Piñón-Ortega JJ , Téllez-Saucedo MD , Marín-Suro ES , Wong-Arámbula CE , Moreno-Escobar EA , Ramírez-González JE , Ramírez-Barrios JG , Montes-Colima NA , Lockhart SR , Martínez-Montiel N , Martínez-Contreras RD , García-Ruíz P , Salazar-Sánchez MI , Hernández-Rivas L , López-Martínez I . Arch Microbiol 2022 204 (9) 592 Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America). |
Fitness cost of sequential selection with deltamethrin in Aedes aegypti (Diptera: Culicidae)
Gonzalez-Santillan FJ , Contreras-Perera Y , Davila-Barboza JA , Juache-Villagrana AE , Gutierrez-Rodriguez SM , Ponce-Garcia G , Lopez-Monroy B , Rodriguez-Sanchez IP , Lenhart AE , Mackenzie-Impoinvil L , Flores AE . J Med Entomol 2022 59 (3) 930-939 In Mexico, Aedes aegypti (L.) is the primary dengue vector, chikungunya, and Zika viruses. The continued use of synthetic pyrethroids has led to the development of resistance in target populations, which has diminished the effectiveness of vector control programs. Resistance has been associated with disadvantages that affect the biological parameters of resistant mosquitoes compared to susceptible ones. In the present study, the disadvantages were evaluated by parameters related to survival and reproduction ('fitness cost') after selection with deltamethrin for five generations. The parameters analyzed were the length of the development cycle, sex ratio, survival, longevity, fecundity, egg viability, preoviposition, oviposition and postoviposition periods, and growth parameters. In the deltamethrin-selected strain, there was a decrease in the development cycle duration, the percentage of pupae, the oviposition period, and eggs viability. Although mean daily fecundity was not affected after the selection process, this, together with the decrease in the survival and fecundity levels by specific age, significantly affected the gross reproductive rate (GRR), net reproductive rate (Ro), and intrinsic growth rate (rm) of the group selected for five generations with deltamethrin compared to the group without selection. Identifying the 'cost' of resistance in biological fitness represents an advantage if it is desired to limit the spread of resistant populations since the fitness cost is the less likely that resistant individuals will spread in the population. This represents an important factor to consider in designing integrated vector management programs. |
Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection - U.S. Zika Pregnancy and Infant Registry, December 1, 2015-March 31, 2018
Roth NM , Reynolds MR , Lewis EL , Woodworth KR , Godfred-Cato S , Delaney A , Akosa A , Valencia-Prado M , Lash M , Elmore A , Langlois P , Khuwaja S , Tufa A , Ellis EM , Nestoridi E , Lyu C , Longcore ND , Piccardi M , Lind L , Starr S , Johnson L , Browne SE , Gosciminski M , Velasco PE , Johnson-Clarke F , Locklear A , Chan M , Fornoff J , Toews KE , Tonzel J , Marzec NS , Hale S , Nance AE , Willabus T , Contreras D , Adibhatla SN , Iguchi L , Potts E , Schiffman E , Lolley K , Stricklin B , Ludwig E , Garstang H , Marx M , Ferrell E , Moreno-Gorrin C , Signs K , Romitti P , Leedom V , Martin B , Castrodale L , Cook A , Fredette C , Denson L , Cronquist L , Nahabedian JF3rd , Shinde N , Polen K , Gilboa SM , Martin SW , Cragan JD , Meaney-Delman D , Honein MA , Tong VT , Moore CA . MMWR Morb Mortal Wkly Rep 2022 71 (3) 73-79 Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance. |
Descriptive exploration of overdose codes in hospital and emergency department discharge data to inform development of drug overdose morbidity surveillance indicator definitions in ICD-10-CM
Tyndall Snow LM , Hall KE , Custis C , Rosenthal AL , Pasalic E , Nechuta S , Davis JW , Jacquemin BJ , Jagroep SR , Rock P , Contreras E , Gabella BA , James KA . Inj Prev 2021 27 i27-i34 BACKGROUND: In October 2015, discharge data coding in the USA shifted to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), necessitating new indicator definitions for drug overdose morbidity. Amid the drug overdose crisis, characterising discharge records that have ICD-10-CM drug overdose codes can inform the development of standardised drug overdose morbidity indicator definitions for epidemiological surveillance. METHODS: Eight states submitted aggregated data involving hospital and emergency department (ED) discharge records with ICD-10-CM codes starting with T36-T50, for visits occurring from October 2015 to December 2016. Frequencies were calculated for (1) the position within the diagnosis billing fields where the drug overdose code occurred; (2) primary diagnosis code grouped by ICD-10-CM chapter; (3) encounter types; and (4) intents, underdosing and adverse effects. RESULTS: Among all records with a drug overdose code, the primary diagnosis field captured 70.6% of hospitalisations (median=69.5%, range=66.2%-76.8%) and 79.9% of ED visits (median=80.7%; range=69.8%-88.0%) on average across participating states. The most frequent primary diagnosis chapters included injury and mental disorder chapters. Among visits with codes for drug overdose initial encounters, subsequent encounters and sequelae, on average 94.6% of hospitalisation records (median=98.3%; range=68.8%-98.8%) and 95.5% of ED records (median=99.5%; range=79.2%-99.8%), represented initial encounters. Among records with drug overdose of any intent, adverse effect and underdosing codes, adverse effects comprised an average of 74.9% of hospitalisation records (median=76.3%; range=57.6%-81.1%) and 50.8% of ED records (median=48.9%; range=42.3%-66.8%), while unintentional intent comprised an average of 11.1% of hospitalisation records (median=11.0%; range=8.3%-14.5%) and 28.2% of ED records (median=25.6%; range=20.8%-40.7%). CONCLUSION: Results highlight considerations for adapting and standardising drug overdose indicator definitions in ICD-10-CM. |
Impact of deltamethrin selection on kdr mutations and insecticide detoxifying enzymes in Aedes aegypti from Mexico.
Contreras-Perera Y , Ponce-Garcia G , Villanueva-Segura K , Lopez-Monroy B , Rodriguez-Sanchez IP , Lenhart A , Manrique-Saide P , Flores AE . Parasit Vectors 2020 13 (1) 224 BACKGROUND: Insecticide resistance is a serious problem for vector control programmes worldwide. Resistance is commonly attributed to mutations at the insecticide's target site or increased activity of detoxification enzymes. METHODS: We determined the knockdown concentration (KC50) and lethal concentration (LC50) of deltamethrin in six natural populations of adult Aedes aegypti from southeastern Mexico. These populations were then selected over five generations using the LC50 from the preceding generation that underwent selection, and the heritability of deltamethrin resistance was quantified. For each generation, we also determined the frequency of the kdr alleles L410, I1016 and C1534, and the levels of activity of three enzyme families (alpha- and beta-esterases, mixed-function oxidases and glutathione S-transferases (GST)) associated with insecticide detoxification. RESULTS: There was an increase in KC50 and LC50 values in the subsequent generations of selection with deltamethrin (FS5vs FS0). According to the resistance ratios (RRs), we detected increases in LC50 ranging from 1.5 to 5.6 times the values of the parental generation and in KC50 ranging from 1.3-3.8 times the values of the parental generation. Triple homozygous mutant individuals (tri-locus, LL/II/CC) were present in the parental generations and increased in frequency after selection. The frequency of L410 increased from 1.18-fold to 2.63-fold after selection with deltamethrin (FS5vs FS0) in the populations analyzed; for I1016 an increase between 1.19-fold to 2.79-fold was observed, and C1534 was fixed in all populations after deltamethrin selection. Enzymatic activity varied significantly over the generations of selection. However, only alpha- esterase activity remained elevated in multiple populations after five generations of deltamethrin selection. We observed an increase in the mean activity levels of GSTs in two of the six populations analyzed. CONCLUSIONS: The high levels of resistance and their association with high frequencies of kdr mutations (V410L, V1016I and F1534C) obtained through artificial selection, suggest an important role of these mutations in conferring resistance to deltamethrin. We highlight the need to implement strategies that involve the monitoring of kdr frequencies in insecticide resistance monitoring and management programmes. |
Factors associated with fatal cases of acute respiratory infection (ARI) among hospitalized patients in Guatemala
Tomczyk S , McCracken JP , Contreras CL , Lopez MR , Bernart C , Moir JC , Escobar K , Reyes L , Arvelo W , Lindblade K , Peruski L , Bryan JP , Verani JR . BMC Public Health 2019 19 (1) 499 BACKGROUND: Acute respiratory infection (ARI) is an important cause of mortality in children and adults. However, studies assessing risk factors for ARI-related deaths in low- and middle-income settings are limited. We describe ARI-related death and associated factors among children aged < 2 years and adults aged >/=18 years hospitalized with ARI in Guatemala. METHODS: We used respiratory illness surveillance data in Guatemala from 2007 to 2013. ARI was defined as evidence of acute infection and >/= 1 sign/symptom of respiratory disease in hospitalized patients. Clinical, sociodemographic, and follow-up data were gathered. Nasopharyngeal/oropharyngeal swabs were collected from patients with ARI and tested for 6 respiratory viruses; urine was collected only from adults with ARI and tested for pneumococcal antigen. Blood cultures and chest radiographs were performed at the physician's discretion. Radiographs were interpreted per World Health Organization guidelines to classify endpoint pneumonia (i.e. suggestive of bacterial pneumonia). Multivariable logistic regression was used to compare characteristics of patients with fatal cases, including those who died in-hospital or were discharged in a moribund state, with those of patients with non-fatal cases. RESULTS: Among 4109 ARI cases identified in hospitalized children < 2 years old, 174 (4%) were fatal. Median age at admission was 4 and 6 months for children with fatal and non-fatal cases, respectively. Factors associated with fatality included low weight-for-age, low family income, heart disease, and endpoint pneumonia; breastfeeding and respiratory syncytial virus (RSV) detection were negatively associated with fatality. Among 1517 ARI cases identified in hospitalized adults >/=18 years, 181 (12%) episodes were fatal. Median age at admission was 57 years for adults with fatal and non-fatal cases. Low body mass index, male sex, kidney disease, and endpoint pneumonia were significantly more common among patients with fatal versus non-fatal cases. CONCLUSIONS: Our findings highlight some of the factors that must be addressed in order to reduce ARI-related mortality, including promotion of good nutrition, breastfeeding, management and prevention of chronic comorbidities, and poverty reduction. Although no specific pathogen increased risk for death, endpoint pneumonia was significantly associated with fatality, suggesting that the pneumococcal conjugate vaccine could contribute to future reductions in ARI-related mortality. |
Testing for Coccidioidomycosis among community-acquired pneumonia patients, southern California, USA
Tartof SY , Benedict K , Xie F , Rieg GK , Yu KC , Contreras R , Truong J , Fong K , Tseng HF , Jacobsen SJ , Mody RK . Emerg Infect Dis 2018 24 (4) 779-781 We conducted a cohort study to identify characteristics associated with testing for, and testing positive for, coccidioidomycosis among patients with community-acquired pneumonia in southern California, USA. Limited and delayed testing probably leads to underdiagnosis among non-Hispanic black, Filipino, or Hispanic patients and among high-risk groups, including persons in whom antimicrobial drug therapy has failed. |
House screening with insecticide-treated netting provides sustained reductions in domestic populations of Aedes aegypti in Merida, Mexico
Che-Mendoza A , Medina-Barreiro A , Koyoc-Cardena E , Uc-Puc V , Contreras-Perera Y , Herrera-Bojorquez J , Dzul-Manzanilla F , Correa-Morales F , Ranson H , Lenhart A , McCall PJ , Kroeger A , Vazquez-Prokopec G , Manrique-Saide P . PLoS Negl Trop Dis 2018 12 (3) e0006283 BACKGROUND: There is a need for effective methods to control Aedes aegypti and prevent the transmission of dengue, chikungunya, yellow fever and Zika viruses. Insecticide treated screening (ITS) is a promising approach, particularly as it targets adult mosquitoes to reduce human-mosquito contact. METHODOLOGY/PRINCIPAL FINDINGS: A cluster-randomised controlled trial evaluated the entomological efficacy of ITS based intervention, which consisted of the installation of pyrethroid-impregnated long-lasting insecticide-treated netting material fixed as framed screens on external doors and windows. A total of 10 treatment and 10 control clusters (100 houses/cluster) were distributed throughout the city of Merida, Mexico. Cross-sectional entomological surveys quantified indoor adult mosquito infestation at baseline (pre-intervention) and throughout four post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over two years (2012-2014). A total of 844 households from intervention clusters (86% coverage) were protected with ITS at the start of the trial. Significant reductions in the indoor presence and abundance of Ae. aegypti adults (OR = 0.48 and IRR = 0.45, P<0.05 respectively) and the indoor presence and abundance of Ae. aegypti female mosquitoes (OR = 0.47 and IRR = 0.44, P<0.05 respectively) were detected in intervention clusters compared to controls. This high level of protective effect was sustained for up to 24 months PI. Insecticidal activity of the ITS material declined with time, with ~70% mortality being demonstrated in susceptible mosquito cohorts up to 24 months after installation. CONCLUSIONS/SIGNIFICANCE: The strong and sustained entomological impact observed in this study demonstrates the potential of house screening as a feasible, alternative approach to a sustained long-term impact on household infestations of Ae. aegypti. Larger trials quantifying the effectiveness of ITS on epidemiological endpoints are warranted and therefore recommended. |
Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study
Sharma A , Hill A , Kurbatova E , van der Walt M , Kvasnovsky C , Tupasi TE , Caoili JC , Gler MT , Volchenkov GV , Kazennyy BY , Demikhova OV , Bayona J , Contreras C , Yagui M , Leimane V , Cho SN , Kim HJ , Kliiman K , Akksilp S , Jou R , Ershova J , Dalton T , Cegielski P . Lancet Infect Dis 2017 17 (7) 707-715 BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5% (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. |
MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors.
Firacative C , Roe CC , Malik R , Ferreira-Paim K , Escandon P , Sykes JE , Castanon-Olivares LR , Contreras-Peres C , Samayoa B , Sorrell TC , Castaneda E , Lockhart SR , Engelthaler DM , Meyer W . PLoS Negl Trop Dis 2016 10 (8) e0004861 The emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate its population genetic structure to understand if there are potential genotype-dependent characteristics in its epidemiology, environmental niche(s), host range and clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical, environmental and veterinary C. gattii VGIII isolates from Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome sequencing (WGS) of 60 isolates representing all established MLST types identified four divergent sub-populations. The majority of the isolates belong to two main clades, corresponding either to serotype B or C, indicating an ongoing species evolution. Both major clades included clinical, environmental and veterinary isolates. The C. gattii VGIII population was genetically highly diverse, with minor differences between countries, isolation source, serotype and mating type. Little to no recombination was found between the two major groups, serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a likely origin of the serotype B VGIII population and Colombia as a possible origin of the serotype C VGIII population. Serotype B isolates are more virulent than serotype C isolates in a murine model of infection, causing predominantly pulmonary cryptococcosis. No specific link between genotype and virulence was observed. Antifungal susceptibility testing against six antifungal drugs revealed that serotype B isolates are more susceptible to azoles than serotype C isolates, highlighting the importance of strain typing to guide effective treatment to improve the disease outcome. |
Effectiveness of monovalent and pentavalent rotavirus vaccines in Guatemala
Gastanaduy PA , Contreras-Roldan I , Bernart C , Lopez B , Benoit SR , Xuya M , Munoz F , Desai R , Quaye O , Tam KI , Evans-Bowen DK , Parashar UD , Manish Patel , McCracken JP . Clin Infect Dis 2016 62 S121-S126 Background. Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. Methods. A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] x 100%) was computed using logistic regression models. Results. We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children >=12 months of age (71% [95% CI, 44%-85%]) (P=.85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P=.96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. Conclusions. RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur. |
Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study
Velasquez GE , Cegielski JP , Murray MB , Yagui MJ , Asencios LL , Bayona JN , Bonilla CA , Jave HO , Yale G , Suarez CZ , Sanchez E , Rojas C , Atwood SS , Contreras CC , Cruz JS , Shin SS . BMC Infect Dis 2016 16 (1) 45 BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. METHODS: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. RESULTS: Of 1701 participants treated for tuberculosis, 136 (8.0 %) died during tuberculosis treatment. HIV-positive patients constituted 11.0 % of the cohort and contributed to 34.6 % of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9 %, P < 0.001) and less likely to be cured (28.3 vs. 39.4 %, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95 % confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95 % CI, 1.55-3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95 % CI, 1.10-3.31) were significantly associated with a higher hazard of death. CONCLUSIONS: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality. |
Association between regimen composition and treatment response in patients with multidrug-resistant tuberculosis: A prospective cohort study
Yuen CM , Kurbatova EV , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Ershova J , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Vasilyeva IA , Dalton T , Cegielski JP . PLoS Med 2015 12 (12) e1001932 BACKGROUND: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. METHODS AND FINDINGS: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. CONCLUSIONS: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens. |
Multidrug-resistant tuberculosis treatment outcomes in relation to treatment, initial and acquired second-line drug resistance
Cegielski JP , Kurbatova E , van der Walt M , Brand J , Ershova J , Tupasi T , Campos Caoili J , Dalton T , Contreras C , Yagui M , Bayona J , Kvasnovsky C , Leimane V , Kuksa L , Chen MP , Via LE , Hwang SH , Wolfgang M , Volchenkov GV , Somova T , Smith SE , Akksilp S , Wattanaamornkiet W , Kim HJ , Kim CK , Kazennyy BY , Khorosheva T , Kliiman K , Viiklepp P , Jou R , Huang AS , Vasilyeva IA , Demikhova OV . Clin Infect Dis 2015 62 (4) 418-430 BACKGROUND: Resistance to second-line drugs (SLD) develops during treatment of multidrug-resistant (MDR) tuberculosis (TB), but the impact on treatment outcome has not been determined. OBJECTIVES: To determine the relationship with treatment outcomes of (1) initial versus acquired drug resistance and (2) treatment regimens. METHODS: MDR-TB patients starting SLD treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectables (SLI), and (2) treatment regimens. RESULTS: Of 1,244 MDR-TB patients, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR-TB, 69.7% with initial resistance to either a fluoroquinolone or SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial XDR-TB, and 13.0% with acquired XDR-TB (P<0.0001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of proven effective drugs increased from ≤1 to ≥5 (P<0.0001 for trend); while acquired drug resistance decreased from 12%-16% range, depending on the drug, down to 0%-2% (P<0.0001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (CL 0.56,0.69) for each increment in drug resistance and increased 2.1-fold (1.40,3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient and program variables were also associated with treatment outcome. CONCLUSION: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance. |
Incidence of hospitalized pneumococcal pneumonia among adults in Guatemala, 2008-2012
Contreras CL , Verani JR , Lopez MR , Paredes A , Bernart C , Moscoso F , Roldan A , Arvelo W , Lindblade KA , McCracken JP . PLoS One 2015 10 (10) e0140939 BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. METHODS: Data from 2008-2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). RESULTS: Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18-24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. CONCLUSIONS: An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala. |
Using standardized interpretation of chest radiographs to identify adults with bacterial pneumonia - Guatemala, 2007-2012
Wortham JM , Gray J , Verani J , Contreras CL , Bernart C , Moscoso F , Moir JC , Reyes Marroquin EL , Castellan R , Arvelo W , Lindblade K , McCracken JP . PLoS One 2015 10 (7) e0133257 BACKGROUND: Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. METHODS: Patients (age ≥15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. FINDINGS: Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. INTERPRETATION: 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia. |
Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries
Kurbatova EV , Dalton T , Ershova J , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Cegielski JP . Emerg Infect Dis 2015 21 (6) 977-83 Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens. |
Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies
Kurbatova EV , Cegielski JP , Lienhardt C , Akksilp R , Bayona J , Becerra MC , Caoili J , Contreras C , Dalton T , Danilovits M , Demikhova OV , Ershova J , Gammino VM , Gelmanova I , Heilig CM , Jou R , Kazennyy B , Keshavjee S , Kim HJ , Kliiman K , Kvasnovsky C , Leimane V , Mitnick CD , Quelapio I , Riekstina V , Smith SE , Tupasi T , van der Walt M , Vasilyeva IA , Via LE , Viiklepp P , Volchenkov G , Walker AT , Wolfgang M , Yagui M , Zignol M . Lancet Respir Med 2015 3 (3) 201-9 BACKGROUND: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis. METHODS: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling. FINDINGS: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0.0001). Furthermore, conversion status at 6 months (adjusted OR 14.07 [95% CI 10.05-19.71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4.12 [95% CI 2.25-7.54]) or who had unknown HIV infection (3.59 [1.96-6.58]), but not in those who were HIV positive (0.38 [0.12-1.18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27.3% [95% confidence limit 16.6-41.4]) and high specificity (89.8% [82.3-94.4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91.8% [85.9-95.4]), but moderate specificity (57.8% [42.5-71.6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment. INTERPRETATION: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis. FUNDING: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention. |
Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis
Cegielski JP , Dalton T , Yagui M , Wattanaamornkiet W , Volchenkov GV , Via LE , Van Der Walt M , Tupasi T , Smith SE , Odendaal R , Leimane V , Kvasnovsky C , Kuznetsova T , Kurbatova E , Kummik T , Kuksa L , Kliiman K , Kiryanova EV , Kim H , Kim CK , Kazennyy BY , Jou R , Huang WL , Ershova J , Erokhin VV , Diem L , Contreras C , Cho SN , Chernousova LN , Chen MP , Caoili JC , Bayona J , Akksilp S . Clin Infect Dis 2014 59 (8) 1049-63 INTRODUCTION: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis (TB) is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. SUBJECTS AND METHODS: To assess the GLC's impact, we followed adults with pulmonary MDRTB from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLD) in nine countries that volunteered to participate, five countries that met GLC criteria and four countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) TB, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLI). The relative risk (95% confidence interval) of acquired resistance was lower at GLC-approved sites: 0.27 (0.16,0.47) for XDRTB, 0.28 (0.17,0.45) for FQ, and 0.15 (0.06,0.39) to 0.60 (0.34,1.05) for three different SLI. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios were 0.21 (0.07,0.62) for acquired XDRTB and 0.23 (0.09,0.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDRTB involves substantial risk of acquired resistance to SLD, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. |
Reducing communication delays and improving quality of care with a tuberculosis laboratory information system in resource poor environments: a cluster randomized controlled trial
Blaya JA , Shin SS , Yagui M , Contreras C , Cegielski P , Yale G , Suarez C , Asencios L , Bayona J , Kim J , Fraser HS . PLoS One 2014 9 (4) e90110 BACKGROUND: Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting). METHODS: Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert. RESULTS: 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65-0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047). CONCLUSIONS: The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system. TRIAL REGISTRATION: ClinicalTrials.gov NCT01201941. |
DNA barcoding for the identification of sand fly species (Diptera, Psychodidae, Phlebotominae) in Colombia.
Contreras Gutierrez MA , Vivero RJ , Velez ID , Porter CH , Uribe S . PLoS One 2014 9 (1) e85496 Sand flies include a group of insects that are of medical importance and that vary in geographic distribution, ecology, and pathogen transmission. Approximately 163 species of sand flies have been reported in Colombia. Surveillance of the presence of sand fly species and the actualization of species distribution are important for predicting risks for and monitoring the expansion of diseases which sand flies can transmit. Currently, the identification of phlebotomine sand flies is based on morphological characters. However, morphological identification requires considerable skills and taxonomic expertise. In addition, significant morphological similarity between some species, especially among females, may cause difficulties during the identification process. DNA-based approaches have become increasingly useful and promising tools for estimating sand fly diversity and for ensuring the rapid and accurate identification of species. A partial sequence of the mitochondrial cytochrome oxidase gene subunit I (COI) is currently being used to differentiate species in different animal taxa, including insects, and it is referred as a barcoding sequence. The present study explored the utility of the DNA barcode approach for the identification of phlebotomine sand flies in Colombia. We sequenced 700 bp of the COI gene from 36 species collected from different geographic localities. The COI barcode sequence divergence within a single species was <2% in most cases, whereas this divergence ranged from 9% to 26.6% among different species. These results indicated that the barcoding gene correctly discriminated among the previously morphologically identified species with an efficacy of nearly 100%. Analyses of the generated sequences indicated that the observed species groupings were consistent with the morphological identifications. In conclusion, the barcoding gene was useful for species discrimination in sand flies from Colombia. |
Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru
Magee MJ , Bloss E , Shin SS , Contreras C , Huaman HA , Ticona JC , Bayona J , Bonilla C , Yagui M , Jave O , Cegielski JP . Int J Infect Dis 2013 17 (6) e404-12 OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome. |
Impact of rapid drug susceptibility testing for tuberculosis: program experience in Lima, Peru
Shin SS , Asencios L , Yagui M , Yale G , Suarez C , Bayona J , Bonilla C , Jave O , Contreras CC , Atwood S , Blaya JA , Ershova J , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (11) 1538-43 SETTING: Programmatic implementation of decentralized rapid drug susceptibility testing (DST) in Lima, Peru. OBJECTIVE: Pre-post analysis compared time to diagnosis, treatment outcome and survival among patients tested with direct nitrate reductase assay (NRA) vs. indirect conventional methods. DESIGN: From 2005 to 2009, we prospectively followed all patients referred for DST before (control) and after (intervention) NRA implementation. Among those referred for DST, NRA was used for smear-positive samples of patients with no prior history of multidrug resistance or treatment for multidrug-resistant tuberculosis (TB). Data were abstracted from patient charts and laboratory registers. Endpoints were favorable outcomes, time to result and time to death. RESULTS: Of those patients who met the criteria for NRA, 740 underwent NRA and 621 underwent conventional DST. NRA yielded test results for 78.4% of cases vs. 68.8% for conventional DST (P < 0.0001); the median time to result was 44 vs. 133 days, respectively (adjusted HR 0.64, 95%CI 0.56-0.73). Among individuals without previous anti-tuberculosis treatment, NRA was associated with a favorable treatment outcome (adjusted OR 1.39, 95%CI 1.01-1.90) and prolonged survival (adjusted HR 0.53, 95%CI 0.31-0.90). CONCLUSION: Direct NRA significantly shortened time to test result and improved treatment outcomes and survival in certain groups. |
Secular trends in BMI and blood pressure among children and adolescents: the Bogalusa Heart Study
Freedman DS , Goodman A , Contreras OA , Dasmahapatra P , Srinivasan SR , Berenson GS . Pediatrics 2012 130 (1) e159-66 OBJECTIVE: The prevalence of obesity among children and adolescents increased by almost threefold from the 1970s to 2000. We examined whether these secular changes in BMI were accompanied by increases in blood pressure levels. METHODS: A total of 24,092 examinations were conducted among 11,478 children and adolescents (aged 5-17 years) from 1974 to 1993 in the Bogalusa Heart Study (Louisiana). RESULTS: The prevalence of obesity increased from 6% to 17% during this period. In contrast, only small changes were observed in levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and neither mean nor high (based on the 90th percentile from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents) levels increased over the 20-year period. Within each race-gender group, mean levels of SBP did not change, whereas mean levels of DBP decreased by 2 mm Hg (P < .001 for trend). Levels of BMI were positively associated with levels of SBP and DBP within each of the 7 examinations, and controlling for BMI (along with other covariates) indicated that only approximately 60% as many children as expected had high levels of blood pressure in 1993. CONCLUSIONS: Our finding that levels of DBP and SBP among children in this large sample did not increase despite the increases that were seen in obesity indicates that changes in blood pressure levels in a population do not necessarily parallel changes in obesity. Additional study of the potential characteristics that have ameliorated the expected increase in high blood pressure could lead to further reductions in risk. |
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