Publications
118 results found
Cucunuba Perez ZM, Nouvellet P, Conteh L, et al., 2017, Modelling historical changes in the force-of-infection of Chagas disease to inform control and elimination programmes: application in Colombia, BMJ Global Health, Vol: 2, ISSN: 2059-7908
Background WHO's 2020 milestones for Chagas disease include having all endemic Latin American countries certified with no intradomiciliary Trypanosoma cruzi transmission, and infected patients under care. Evaluating the variation in historical exposure to infection is crucial for assessing progress and for understanding the priorities to achieve these milestones.Methods Focusing on Colombia, all the available age-structured serological surveys (undertaken between 1995 and 2014) were searched and compiled. A total of 109 serosurveys were found, comprising 83 742 individuals from rural (indigenous and non-indigenous) and urban settings in 14 (out of 32) administrative units (departments). Estimates of the force-of-infection (FoI) were obtained by fitting and comparing three catalytic models using Bayesian methods to reconstruct temporal and spatial patterns over the course of three decades (between 1984 and 2014).Results Significant downward changes in the FoI were identified over the course of the three decades, and in some specific locations the predicted current seroprevalence in children aged 0–5 years is <1%. However, pronounced heterogeneity exists within departments, especially between indigenous, rural and urban settings, with the former exhibiting the highest FoI (up to 66 new infections/1000 people susceptible/year). The FoI in most of the indigenous settings remain unchanged during the three decades investigated. Current prevalence in adults in these 15 departments varies between 10% and 90% depending on the dynamics of historical exposure.Conclusions Assessing progress towards the control of Chagas disease requires quantifying the impact of historical exposure on current age-specific prevalence at subnational level. In Colombia, despite the evident progress, there is a marked heterogeneity indicating that in some areas the vector control interventions have not been effective, hindering the possibility of achieving interruption by 2020. A su
Cucunubá ZM, Manne-Goehler JM, Diaz D, et al., 2017, How universal is coverage and access to diagnosis and treatment for Chagas disease in Colombia? A health systems analysis, Social science & medicine, Vol: 175, Pages: 187-198, ISSN: 0037-7856
Limited access to Chagas disease diagnosis and treatment is a major obstacle to reaching the 2020 World Health Organization milestones of delivering care to all infected and illpatients. Colombia has been identified as a health system in transition, reporting one of the highest levels of health insurance coverage in Latin America. We explore if and how this high level of coverage extends to those with Chagas disease, a traditionally marginalised population. Using a mixed methods approach, we calculate coverage for screening, diagnosis and treatment of Chagas. We then identify supply-side constraints both quantitatively and qualitatively. A review of official registries of tests and treatments for Chagas disease delivered between 2008 and 2014 is compared to estimates of infected people. Using the Flagship Framework, we explore barriers limiting access to care. Screening coverage is estimated at 1.2% of the population at risk. Aetiological treatment with either benznidazol or nifurtimox covered 0.3–0.4% of the infected population. Barriers to accessing screening, diagnosis and treatment are identified for each of the Flagship Framework’s five dimensions of interest: financing, payment, regulation, organisation and persuasion. The main challenges identified were: a lack of clarity in terms of financial responsibilities in a segmented health system, claims of limited resources for undertaking activities particularly in primary care, non-inclusion of confirmatory test(s) in the basic package of diagnosis and care, poor logistics in the distribution and supply chain of medicines, and lack of awareness of medical personnel. Very low screening coverage emerges as a key obstacle hindering access to care for Chagas disease. Findings suggest serious shortcomings in this health system for Chagas disease, despite the success of universal health insurance scale-up in Colombia. Whether these shortcomings exist in relation to other neglected tropical diseases need
Routledge I, Chevez JER, Cucunuba Z, et al., 2017, UNDERSTANDING THE MALARIA TRANSMISSION PROCESS IN NEAR-ELIMINATION SETTINGS, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 332-332, ISSN: 0002-9637
Marchiol A, Forsyth C, Bernal O, et al., 2017, Increasing access to comprehensive care for Chagas disease: development of a patient-centered model in Colombia, REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH, Vol: 41, ISSN: 1020-4989
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- Citations: 14
Hernandez C, Javier Vera M, Cucunuba Z, et al., 2016, High-resolution molecular typing of trypanosoma cruzi in 2 large outbreaks of acute chagas disease in Colombia, Journal of Infectious Diseases, Vol: 214, Pages: 1252-1255, ISSN: 0022-1899
Oral transmission of Trypanosoma cruzi has gained relevance because of its association with high morbidity and lethality rates. This transmission route is responsible for maintaining the infection of the parasite in sylvatic cycles, and human cases have been associated mainly with the consumption of food contaminated with triatomine feces or didelphid secretions. Several ecological changes allow the intrusion of sylvatic reservoirs and triatomines to the domestic environments with subsequent food contamination. Here, high-resolution molecular tools were used to detect and genotype T. cruzi across humans, reservoirs, and insect vectors in 2 acute outbreaks of presumptive oral transmission in eastern Colombia.
Hernandez C, Cucunuba Z, Florez C, et al., 2016, Molecular diagnosis of Chagas disease in Colombia: parasitic loads and discrete typing units in patients from acute and chronic phases, PLoS Neglected Tropical Diseases, Vol: 10, Pages: 1-20, ISSN: 1935-2727
BackgroundThe diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases.Methodology/Principal FindingsSamples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml).Conclusions/SignificanceThe molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic patients high
Ferguson NM, Cucunubá ZM, Dorigatti I, et al., 2016, Countering the Zika epidemic in Latin America, Science, Vol: 353, Pages: 353-354, ISSN: 1095-9203
Cucunubá ZM, Okuwoga O, Basanez MG, et al., 2016, Increased mortality attributed to Chagas disease: a systematic review and meta-analysis., Parasites & Vectors, Vol: 9, ISSN: 1756-3305
BACKGROUND: The clinical outcomes associated with Chagas disease remain poorly understood. In addition to the burden of morbidity, the burden of mortality due to Trypanosoma cruzi infection can be substantial, yet its quantification has eluded rigorous scrutiny. This is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. There is a pressing need for accurate estimates of mortality due to Chagas disease that can be used to improve mathematical modelling, burden of disease evaluations, and cost-effectiveness studies. METHODS: A systematic literature review was conducted to select observational studies comparing mortality in populations with and without a diagnosis of Chagas disease using the PubMed, MEDLINE, EMBASE, Web of Science and LILACS databases, without restrictions on language or date of publication. The primary outcome of interest was mortality (as all-cause mortality, sudden cardiac death, heart transplant or cardiovascular deaths). Data were analysed using a random-effects model to obtain the relative risk (RR) of mortality, the attributable risk percent (ARP), and the annual mortality rates (AMR). The statistic I(2) (proportion of variance in the meta-analysis due to study heterogeneity) was calculated. Sensitivity analyses and publication bias test were also conducted. RESULTS: Twenty five studies were selected for quantitative analysis, providing data on 10,638 patients, 53,346 patient-years of follow-up, and 2739 events. Pooled estimates revealed that Chagas disease patients have significantly higher AMR compared with non-Chagas disease patients (0.18 versus 0.10; RR = 1.74, 95 % CI 1.49-2.03). Substantial heterogeneity was found among studies (I(2) = 67.3 %). The ARP above background mortality was 42.5 %. Through a sub-analysis patients were classified by clinical group (severe, moderate, asymptomatic). While RR did not differ significantly betw
Bianchi F, Cucunuba Z, Guhl F, et al., 2015, Follow-up of an asymptomatic chagas disease population of children after treatment with nifurtimox (lampit) in a sylvatic endemic transmission area of Colombia, PLoS Neglected Tropical Diseases, Vol: 9, ISSN: 1935-2727
BackgroundChagas disease is an anthropozoonosis caused by Trypanosoma cruzi. Two drugs are currently used for the etiological treatment of the disease: Nifurtimox (Lampit) and Benznidazole. This study presents a quasi-experimental trial (non-control group) of sixty-two patients who were treated for Chagas disease with Nifurtimox (Lampit), and were then followed for 30 months post-treatment. The safety of Nifurtimox (Lampit) for Chagas disease in this group of children primarily between 4 and 19 years old was also evaluated.Materials and methodsThe 62 patients included in the study were selected when resulted seropositive for two out of three fundamentally different serological tests. All children were treated during two months according to protocols established by WHO. Monitoring was performed every twenty days to evaluate treatment safety. In 43 patients, two different serological tests: ELISA and IFAT; and two parasitological tests: blood culture, and real time PCR, (qPCR) were performed to assess therapeutic response, defined as post-treatment serological negativization.Principal findingsAll patients completed the treatment successfully, and six patients abandoned the post-treatment follow-up. Adverse effects occurred in 74% of patients, but only 4.8% of cases required temporary suspension to achieve 100% adherence to the 60-day treatment, and all symptoms reverted after treatment completion. Both parasite load (measured through qPCR) and antibodies (ELISA absorbance) evidenced a significant median reduction 6 months after treatment from 6.2 to 0.2 parasite equivalents/mL, and from 0.6 to 0.2 absorbance units respectively (p<0.001). Serological negativization by ELISA was evident since 6 months post-treatment, whereas by IFAT only after 18 months. Serological negativization by the two tests (ELISA and IFAT) was 41.9% (95%CI: 26.5–57.3) after 30 months post-treatment. qPCR was positive in 88.3% of patients pre-treatment and only in 12.1% of patients after
Nouvellet P, Cucunuba ZM, Gourbiere S, 2015, Ecology, Evolution and Control of Chagas Disease: A Century of Neglected Modelling and a Promising Future, MATHEMATICAL MODELS FOR NEGLECTED TROPICAL DISEASES: ESSENTIAL TOOLS FOR CONTROL AND ELIMINATION, PT A, Vol: 87, Pages: 135-191, ISSN: 0065-308X
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- Citations: 48
Ripoll J, Giraldo N, Bolanos N, et al., 2014, The fraction of T. cruzi-antigen specific T cells in chronic chagasic patients detected by CD154 and membrane TNFα expression, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767
Echeverria LE, Suarez EU, Zambrano P, et al., 2014, Chagas disease and its oral transmission in Colombia: chronicles of an epidemia. Description of eight outbreaks (2008-2010), Publisher: WILEY-BLACKWELL, Pages: 36-37, ISSN: 1388-9842
Cucunubá ZM, Valencia-Hernández CA, Puerta CJ, et al., 2014, First Colombian consensus on congenital Chagas and clinical approach to women of fertile age diagnosed with Chagas, Infectio, Vol: 18, Pages: 50-65, ISSN: 0123-9392
Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. In order to generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: «Chagas disease/congenital», «prevention and control», «diagnosis», «therapeutics» and «pregnancy». Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-to-face discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia. © 2013 ACIN. Published by Elsevier España, S.L. All rights reserved.
Zulay Castellanos Y, Milena Cucunuba Z, Carolina Florez A, et al., 2013, Reproducibility of serological tests for the diagnosis of <i>Trypanosoma cruzi</i> infection in pregnant women in an endemic area of Santander, Colombia, BIOMEDICA, Vol: 34, Pages: 198-206, ISSN: 0120-4157
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- Citations: 3
Latz A, Llano M, Pavia P, et al., 2013, Performance evaluation of enzyme linked immunosorbent assay and lineblot for serological diagnosis of Chagas (<i>Trypanosoma cruzi</i>) disease, Publisher: WILEY-BLACKWELL, Pages: 131-131, ISSN: 1360-2276
Ramirez JD, Guhl F, Messenger LA, et al., 2013, Contemporary cryptic sexuality in <i>Trypanosoma cruzi</i> (vol 21, pg 4216, 2012), MOLECULAR ECOLOGY, Vol: 22, Pages: 1482-1482, ISSN: 0962-1083
David Ramirez J, Montilla M, Cucunuba ZM, et al., 2013, Molecular epidemiology of human oral Chagas disease outbreaks in Colombia, PLoS Neglected Tropical Diseases, Vol: 7, Pages: 1-7, ISSN: 1935-2727
BackgroundTrypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes.Methodology and Principal FindingsHigh-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission.ConclusionsThese findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.Author SummaryChagas disease represents a serious health problem affecting more than 10 million people in the Americas. The oral transmission route has emerged as a new epidemiological scenario that needs to be considered in prevention and control strategies. Herein was developed a high-resoluti
Milena Cucunuba Z, Patricia Guerra A, Alonso Rivera J, et al., 2013, Comparison of asymptomatic <i>Plasmodium</i> spp. infection in two malaria-endemic Colombian locations, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, Vol: 107, Pages: 129-136, ISSN: 0035-9203
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- Citations: 18
Cucunubá ZM, Flórez AC, Cárdenas A, et al., 2012, Prevalence and risk factors for Chagas disease in pregnant women in Casanare, Colombia., Am J Trop Med Hyg, Vol: 87, Pages: 837-842
Knowledge of the prevalence and risk factors associated with maternal infection is the first step to develop a surveillance system for congenital transmission of Chagas disease. We conducted a cross-sectional study in Casanare, a disease-endemic area in Colombia. A total of 982 patients were enrolled in the study. A global prevalence of Trypanosoma cruzi infection of 4.0% (95% confidence interval [CI] = 2.8-5.3%) was found. Multivariate analysis showed that the most important risk-associated factors were age > 29 years (adjusted odds ratio [aOR] = 3.4, 95% CI = 0.9-12.4), rural residency (aOR = 2.2, 95% CI = 1.0-4.6), low education level (aOR = 10.2, 95% CI = 1.6-82.7), and previous knowledge of the vector (aOR = 2.2, 95% CI = 1.0-4.9). Relatives and siblings of infected mothers showed a prevalence of 9.3%. These findings may help physicians to investigate congenital cases, screen Chagas disease in siblings and relatives, and provide early treatment to prevent the chronic complications of Chagas disease.
Cucunuba Z, Valencia C, Florez C, et al., 2012, Pilot program for surveillance of congenital Chagas disease in Colombia 2010-2011, Publisher: ELSEVIER SCI LTD, Pages: E343-E343, ISSN: 1201-9712
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- Citations: 2
Giraldo N, Bolanos N, Cuellar A, et al., 2012, Proliferative dysfunction in chronically activated T lymphocytes from chagasic patients, 99th Annual Meeting of the American-Association-of-Immunologists, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767
Lucia Ospina O, Jazmin Cortes L, Milena Cucunuba Z, et al., 2012, Characterization of the National Malaria Diagnostic Network, Colombia, 2006-2010, BIOMEDICA, Vol: 32, Pages: 46-57, ISSN: 0120-4157
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- Citations: 7
Ramirez JD, Montilla M, Cucunuba Z, et al., 2011, Molecular characterization of <i>Trypanosoma cruzi</i> stocks isolated from oral infection outbreaks in Colombia, Publisher: WILEY-BLACKWELL, Pages: 236-236, ISSN: 1360-2276
Andres Valencia C, Alfredo Fernandez J, Milena Cucunuba Z, et al., 2010, Correlation between malaria incidence and prevalence of soil-transmitted helminths in Colombia: An ecologic evaluation, BIOMEDICA, Vol: 30, Pages: 501-508, ISSN: 0120-4157
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- Citations: 4
Flechas ID, Cuellar A, Cucunuba ZM, et al., 2009, Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients, BMC INFECTIOUS DISEASES, Vol: 9, Pages: 1-11, ISSN: 1471-2334
BackgroundAntigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein192-433, and the entire Trypanosoma rangeli HSP-70 protein.MethodsSeventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests.ResultsThe T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass.ConclusionT. cruzi KMP-11 and the T. rangeli HSP-70 recombinant proteins may be explored together in the immunodiagnosis of Chagas' disease.
Cucunuba ZM, Guerra AP, Rahirant SJ, et al., 2008, Asymptomatic <i>Plasmodium</i> spp. infection in Tierralta, Colombia, MEMORIAS DO INSTITUTO OSWALDO CRUZ, Vol: 103, Pages: 668-673, ISSN: 0074-0276
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- Citations: 47
Fernández-Ñino JA, Idrovo AJ, Cucunubá ZM, et al., 2008, Validity of studies on the association between soil-transmitted helminths and the incidence of malaria: Should it impact health policies?, Revista Brasileira de Epidemiologia, Vol: 11, Pages: 365-378, ISSN: 1415-790X
Introduction: The global distribution of malaria and soil-transmitted helminths is widely overlapped. Some studies suggest a possible association between helminth infection and incidence of malaria. Objectives: To identify the available epidemiologic evidence and to assess the validity of these studies. Methods: A systematic review was carried out in specialized databases. The studies identified were critically analyzed and ranked according to the U.S. Preventive Services Task Force's classification. The major methodological limitations of each study were identified. Results: Six studies on the topic were found. Only two studies had a high evidence level (level I), three had level II-2, and one had level III-3. There are important methodological limitations for clarifying the association between soil-transmitted helminths and the incidence of malaria. Conclusion: It is too early to discuss the potential public health implications of these findings, given the lack of studies and limited validity of the evidence available. Further studies with new methodological considerations could improve the knowledge on the association. However, it is more important to carry out actions on structural determinants to control and prevent the occurrence of both diseases.
Nicholls RS, Cucunuba ZM, Knudson A, et al., 2007, Acute Chagas disease in Colombia:: a rarely suspected disease.: Report of 10 cases presented during the 2002-2005 period, BIOMEDICA, Vol: 27, Pages: 8-17, ISSN: 0120-4157
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- Citations: 14
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