Mario Javier Olivera

Paradoxical associations between soil-transmitted helminths and Plasmodium falciparum infection

Evidence on the comorbidity between soil-transmitted helminth infections and malaria is scarce and divergent. This study explored the interactions between soil-transmitted helminth infections and uncomplicated falciparum malaria in an endemic area of Colombia. A paired case-control study matched by sex, age and location in Tierralta, Cordoba, was done between January and September 2010. The incident cases were 68 patients with falciparum malaria and 178 asymptomatic controls. A questionnaire was used to gather information on sociodemographic variables. Additionally physical examinations were carried out, stool samples were analysed for intestinal parasites and blood samples for Ig E concentrations. We found associations between infection with hookworm (OR: 4.21; 95% CI: 1.68-11.31) and Ascaris lumbricoides (OR 0.43; 95% CI: 0.18-1.04) and the occurrence of falciparum malaria. The effects of soil-transmitted helminths on the occurrence of malaria were found to be paradoxical. While hookworm is a risk factor, A. lumbricoides has a protective effect. The findings suggest that, in addition to the comorbidity, the presence of common determinants of soil-transmitted helminth infections and malaria could also exist. While the biological mechanisms involved are not clear, public health policies aimed at the control of their common social and environmental determinants are suggested.

Blastocystis subtyping and its association with intestinal parasites in children from different geographical regions of Colombia

Blastocystis is a common enteric protist colonizing probably more than 1 billion people with a large variety of non-human hosts. Remarkable genetic diversity has been observed, leading to the subdivision of the genus into multiple subtypes (ST), some of which are exclusively found in non-human hosts. The aim of this study was to determine the distribution of Blastocystis STs/18S alleles in symptomatic (abdominal pain, anal pruritus, diarrhea, headache, nauseas and/or vomit) and asymptomatic children from nine geographical regions of Colombia. A total of 2026 fecal samples were collected as part of a national survey to estimate the frequency of intestinal parasites in children. A set of 256 samples that were Blastocystis positive was finally selected. The samples were submitted to DNA extraction, Real Time PCR and sequencing using Blastocystis-specific primers targeting the small subunit rRNA gene for ST identification. DNA of Ascaris lumbricoides (16.4%), Trichuris trichiura (8.2%), hookworms (Necator americanus/Ancylostoma duodenale) (7.3%), Giardia duodenalis (23.1%), Entamoeba complex (82%), Entamoeba coli (55%), Hymenolepis nana (0.8%), Endolimax nana (33.2%) and Neobalantidium coli (2.7%) was detected in the Blastocystis-positive samples. We detected ST1 (21.4%), ST2 (19.5%), ST3 (55.5%), ST4 (0.8%), ST6 (2%) and ST7 (0.8%); alleles 1, 2, 4, 81, 82 and 83 for ST1; alleles 9, 11, 12, 15, 67, 71 and 73 for ST2; alleles 34, 36, 38, 45, 49, 55, 134 and 128 for ST3; allele 42 for ST4; allele 122 for ST6, and allele 142 for ST7. Further studies implementing high-resolution molecular markers are necessary to understand the dynamics of Blastocystis transmission and the role of this Stramenopila in health and disease.

Safety Profile of Nifurtimox and Treatment Interruption for Chronic Chagas Disease in Colombian Adults

Nifurtimox (NFX) is one of the approved drugs used to treat Chagas disease. Safety profile studies and models on risk factors for treatment interruption in adults are scarce in Latin America. This study evaluated retrospectively the medical records of adult Chagas disease patients treated with NFX between 2007 and 2012 in Bogotá, Colombia. An accelerated failure time model was used, and associations were expressed as time ratio (TR). In total, 76 adult patients with NFX were included: 60 (79.0%) completed 60 days of treatment, 61 (80.3%) presented adverse drug reactions (ADRs), and 16 (21.0%) required treatment interruption. The predominant symptoms were epigastric pain (23.7%), nauseas (18.4%), sleep disturbances (18.4%), loss of appetite (17.1%), and temporary loss of memory (15.2%). ADRs were classified as mild (64.5%), moderate (30.4%), and severe (5.1%). Time of treatment was significantly longer when presenting ≤ 3 ADRs (TR: 1.78; 95% CI: 1.04–3.03), presence of non-severe ADRs (TR: 6.52; 95% CI: 3.24–13.1), doses of NFX ≤ 8 mg/kg/day (TR: 1.78; 95% CI: 0.90–3.49), and age < 48 years (TR: 1.57; 95% CI: 0.90–2.74). Treatment with NFX in adults caused a high frequency of ADRs, but most of the cases were mild and did not require treatment interruption. Severity and number of ADRs were the main predictors for treatment interruption.

Quality assessment of clinical practice guidelinesfor Chagas disease

INTRODUCTION The development of clinical practice guidelines (CPGs) has increased; this study aimed to assess the quality of CPGs for the management of Chagas disease. METHODS Following a systematic search of the scientific literature, two reviewers assessed the eligible guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. RESULTS Five CPGs were included. The AGREE domains of scope/purpose, stakeholder involvement, and clarity of presentation were rated well, and the domains of applicability and editorial independence received poor ratings. CONCLUSIONS The quality of CPGs for Chagas disease is poor, and significant work is required to develop high-quality guidelines.

Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease

Background Etiological treatment of Chagas disease in chronic asymptomatic patients is still in debate and the adverse effects of traditional drugs are one of the main concerns in clinical practice. This study evaluated retrospectively the safety profile of benznidazole (BZN) and identified predictive factors for definite treatment interruption and development of severe reactions in adult patients treated with BZN in Colombia. Methods Retrospective follow-up study conducted by review of medical records of adults with chronic Chagas disease treated with BZN in Colombia. A parametric survival analysis based on a generalized gamma distribution was used for assessing risk factors for treatment interruption. A multinomial logistic regression model was used to estimate the probability of severe adverse drug reactions (ADRs). Statistical associations were expressed as time ratios (TR) and adjusted odds ratios (aOR) respectively. Results In total 224 adults patients treated with BZN were included; 172 (76.8%) completed the standard therapy (60 days of treatment), 205 (91.5%) presented ADRs and 52 cases (23.2%) required treatment interruption. The predominant symptoms were: rash (37.9%), itching (33.7%), epigastric pain (26.4%), abdominal bloating (24.2%) and nausea (22.1%). ADRs were mild (57.4%), moderate (35.5%) and severe (7.3%). Time to treatment interruption was significantly shorter when using doses of BZN ≥ 6 mg/kg/day (TR 0.55; 95% CI 0.39–0.76), presenting severe ADRs (TR 0.12; 95% CI: 0.07–0.19) and eosinophilia (TR 0.68; 95% CI: 0.49–0.94). Female sex (aOR 3.98; 95% CI 1.56–10.16), dose of BZN ≥ 6 mg/kg/day (aOR 1.41; 95% CI 1.17–1.70) and presence of > 3 ADRs (aOR 6.47; 95% CI 1.24–34.34) were considered as risk factors for developing severe ADRs. Conclusions Dose, severity of ADRs, eosinophilia and female sex were the main predictors for treatment interruption or severe ADRs. The potential implications of these findings are discussed.

Molecular Epidemiology of Entamoeba: First Description of Entamoeba moshkovskii in a Rural Area from Central Colombia

Background Entamoeba histolytica, E. dispar and E. moshkovskii are the most frequent species described in human infection where E. histolytica is the only true pathogen. The epidemiology of this infection is complex due to the absence of a routine exam that allows a correct discrimination of the Entamoeba species complex. Therefore, molecular methods appear as the unique epidemiological tool to accomplish the species discrimination. Herein, we conducted a cross-sectional study to determine the frequency of Entamoeba species infections in a group of asymptomatic individuals from a rural area in central Colombia. Methodology/Principal Findings A total of 181 fecal samples from asymptomatic children under 16 years old from the hamlet La Vírgen, Cundinamarca (Colombia) that voluntarily accepted to participate in the study were collected. The fecal samples were examined by light microscopy and DNA-extracted, subsequently submitted to molecular discrimination of E. dispar/E. histolytica/E. moshkovskii infection based on a multiplex PCR assay targeting the 18S rRNA fragment. To confirm the species description, twenty samples were randomly submitted to DNA sequencing of the aforementioned fragment. By direct microscopic examination, frequency of the complex E. histolytica/E. dispar/E. moshkovskii was 18.8% (34/181). PCR showed a frequency of 49.1% (89/181), discriminated as 23.2% (42/181) that were positive for E. dispar, 25.4% (46/181) for E. moshkovskii and 0.55% (1/ 181) for E. histolytica. Also, mixed infections were detected between E. dispar and E. moshkovskii at 4.42% (8/181) of the samples. Molecular barcoding confirmed the diagnosis depicted by the multiplex PCR assay. Conclusions/Significance This is the first description of E. moshkovskii in Colombia and the second report in South-America to our knowledge. Our results suggest the need to unravel the true epidemiology of Entamoeba infections around the world, including the real pathogenic role that E. moshkovskii may have.

Therapeutic drug monitoring of benznidazole and nifurtimox: a systematic review and quality assessment of published clinical practice guidelines

The pharmacological management of adults with chronic-phase Chagas disease is challenging despite it being the recent focus of extensive research. One of the challenges in the current clinical practice guidelines (CPGs) landscape is the existence of non-evidence-based recommendations for the use of laboratory tests in treatment monitoring. This study aimed to systematically assess the quality and consistency of recommendations of CPGs on the pharmacological management of adults with chronic-phase Chagas disease. Systematic literature searches were conducted in MEDLINE, EMBASE, SciELO and Google to identify all published CPGs relevant to the pharmacological management of Chagas disease, between January 2010 and March 2016. Three independent reviewers assessed the quality of each CPG using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. A total of five CPGs were included and the overall quality of the guidelines for therapeutic drug monitoring of Chagas disease was moderate-to-low. There was considerable variation in the quality of the CPGs across the AGREE II domains. The domains of scope/purpose, stakeholder involvement, and clarity of presentation were rated well, and the domains of applicability and editorial independence received poor ratings. This review showed that the methodological quality of CPGs for Chagas disease was generally inappropriate, and there was no explicit link between the best available evidence and current recommendations.

Anisakiasis gastro-alérgica, primera descripción de un caso en Colombia y revisión de literatura

La anisakiasis es una enfermedad parasitaria zoonótica causada por el consumo de pescados o mariscos crudos o poco cocidos infectados con nematodos de los géneros Anisakis, Pseudoterranova y Contracaecum. Se describe el primer caso de anisakiasis en Colombia y se resume la literatura médica disponible. Una mujer de 52 años de edad consultó por dolor epigástrico agudo de inicio abrupto, náuseas, vómitos, diarrea y urticaria después de consumir pescado. El examen físico reveló sensibilidad moderada en el epigastrio. El examen de laboratorio evidenció leucocitosis, en tanto que la radiografía simple y el electrocardiograma no reflejaron ninguna anormalidad. El diagnóstico se hizo mediante una endoscopia de vías digestivas altas, la cual reveló engrosamiento de la pared gástrica y un parásito en movimiento. Se encontró una larva de Anisakis y se la extrajo por endoscopia, lo que alivió el dolor de la paciente. Clínicamente, la anisakiasis puede presentarse como una enfermedad gástrica, intestinal, en otros sistemas o alérgica. El diagnóstico se hace con base en la elaboración del historial alimentario del paciente y la visualización directa de las larvas; el único tratamiento efectivo consiste en su extracción endoscópica.

Barriers to Diagnosis Access for Chagas Disease in Colombia

Chagas disease is the leading cause of nonischemic cardiomyopathy in Latin America. Timely access to diagnosis and trypanocidal treatment and preventive tools for millions of infected people continues to be a challenge. The purpose of this study was to identify potential barriers for the diagnosis of Chagas disease in Colombia from the perspective of healthcare providers. Using a simultaneous mixed-methods study design, we analyzed trends in access to screening and diagnosis for Chagas disease in Colombia and assessed the national barriers to access. The main barriers to access at the national level included a limited governmental public health infrastructure for the diagnosis of Chagas disease and limited physician awareness and knowledge of the disease. Data indicate that 1.5% of total expected cases based on national prevalence estimates were reported. Few public health laboratories have the capacity to perform complementary tests for the diagnosis of Chagas disease and almost 6 months elapse between the requests of the tests and the confirmation of the disease. This study shows that infected people must overcome a number of barriers to achieve diagnosis. Reducing barriers to early diagnosis of Chagas disease is an important goal in the fight against the disease.