Prevalence and risk factors of anemia in the mother-child population from a region of the Colombian Caribbean.

BACKGROUND: Despite Colombia's robust well-child visits program, Colombian children and mothers still suffer from anemia, especially in populations of lower socioeconomic status. In this study, we aimed to quantify the prevalence and risk factors among mothers and their children attending their well-child visits in Apartadó, a municipality in the Urabá region of the Colombian Caribbean. METHODS: There were 100 mother-child pairs enrolled in this secondary data-analysis study from a health facility in the municipality of Apartadó, Urabá, Colombia, during well-child visits. Self-reported data included child illnesses in the past two weeks (diarrheal, fever, or respiratory symptoms), child feeding practices (breastfeeding, complementary feeding), child vaccinations, and demographic characteristics (mother's and child's age, mother's education, marital status, race, and child sex) and socioeconomic status. Mother and child anthropometry data were collected via standardized weight and height measurements. Mother or child anemia status was collected via a blood test. Chi-squared tests and multivariable logistic regression were used to assess associations between risk factors and anemia. RESULT: The anemia prevalence in children (74%) and mothers (47%) was higher than the Colombian national prevalence. Reported child comorbidities in the preceding two weeks were not significantly associated with child anemia and included respiratory illnesses (60%), fever (46%), and diarrhea (30%). Stunting (8%) was not significantly associated with anemia. Wasting (0%) was not observed in this study. Reported child breastfeeding and complementary feeding were also not significantly associated with child anemia. In adjusted models, the child's significant risk factors for anemia included the mother's "Mestiza" race (OR: 4.681; 95% CI: 1.258, 17.421) versus the Afro-Colombian race. Older children (25-60 months) were less likely to develop anemia than younger (6-24 months) children (OR: 0.073; 95% CI: 0.015, 0.360). CONCLUSIONS: The finding of high anemia prevalence in this study advances our understanding of child and maternal anemia in populations of low socioeconomic status where health care is regularly accessed through well-child programs.

Transcription Factor HES-1: How Is the Expression of This Transcriptional Factor in Paucibacillary Leprosy Patients?

INTRODUCTION: Leprosy is an ancient and chronic infectious disease caused by 2 mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Recently, our research group observed that HES-1, an innate cellular component of the Notch signaling pathway, is related to the pathogenesis of leprosy. Therefore, it could be helpful in its detection. OBJECTIVE: To determine the expression of HES-1 in the skin of patients with paucibacillary (PB) leprosy. METHODS: A cross-sectional, descriptive, observational study was conducted. Forty-five skin samples from patients with leprosy were evaluated (30 samples from MB leprosy and 15 from PB leprosy) using immunohistochemistry of HES-1 and S-100. RESULTS: PB leprosy biopsies revealed a reduction of HES-1 in 66.7% of the epidermis, 80% of the eccrine glands, and 62.5% of the hair follicles of these patients, with statistical differences in the control group (P < 0.0001). Besides, HES-1 showed similar utility to S-100 immunostaining in detecting the MB and PB leprosy. CONCLUSIONS: HES-1 is a transcriptional factor also reduced in PB patients' epidermis and skin appendages. Finally, our data show that HES-1 could be a biomarker in diagnosing PB and MB leprosy.

Transcriptional changes during metacyclogenesis of a Colombian Trypanosoma cruzi strain.

During its life cycle, Trypanosoma cruzi undergoes physiological modifications in order to adapt to insect vector and mammalian host conditions. Metacyclogenesis is essential, as the parasite acquires the ability to infect a variety of mammalian species, including humans, in which pathology is caused. In this work, the transcriptomes of metacyclic trypomastigotes and epimastigotes were analyzed in order to identify differentially expressed genes that may be involved in metacyclogenesis. Toward this end, in vitro induction of metacyclogenesis was performed and metacyclic trypomastigotes obtained. RNA-Seq was performed on triplicate samples of epimastigotes and metacyclic trypomastigotes. Differential gene expression analysis showed 513 genes, of which 221 were upregulated and 292 downregulated in metacyclic trypomastigotes. The analysis showed that these genes are related to biological processes relevant in metacyclogenesis. Within these processes, we found that most of the genes associated with infectivity and gene expression regulation were upregulated in metacyclic trypomastigotes, while genes involved in cell division, DNA replication, differentiation, cytoskeleton, and metabolism were mainly downregulated. The participation of some of these genes in T. cruzi metacyclogenesis is of interest, as they may be used as potential therapeutic targets in the design of new drugs for Chagas disease.

Mycobacterium lepromatosis as Cause of Leprosy, Colombia.

Leprosy is a granulomatous infection caused by infection with Mycobacterium leprae or M. lepromatosis. We evaluated skin biopsy and slit skin smear samples from 92 leprosy patients in Colombia by quantitative PCR. Five (5.4%) patients tested positive for M. lepromatosis, providing evidence of the presence of this pathogen in Colombia.

Neuropathic ulcers in leprosy: clinical features, diagnosis and treatment.

Leprosy is a neglected disease caused by Mycobacterium leprae and Mycobacterium lepromatosis, and is related to significant disabilities resulting from the neural damage generated by this mycobacteria. Neuropathic ulcers-lesions that can appear at the plantar and extra-plantar levels-are one such disability, and diagnosis requires an adequate dermatological, neurological and microbiological evaluation. The treatment of these lesions is based on a multidisciplinary approach that includes debridement of the necrotic tissue, controlling infections, reducing pressure areas, optimising blood flow, and nerve decompression. This review aims to describe the clinical features, diagnostic methods and treatment of neuropathic ulcers in leprosy. The diagnostic methods and medical management used in leprosy ulcers are based on those used for diabetic foot. This requires radical change as these diseases are immunologically and physiologically very different.

Social and environmental conditions related to Mycobacterium leprae infection in children and adolescents from three leprosy endemic regions of Colombia.

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.

Protocol for a Randomised Controlled Trial Investigating Decompression for Leprous Neuropathy (The DELN Protocol).

Objectives: An expert group of peripheral nerve surgeons, reconstructive surgeons, and immunologists who have extensive experience with Hansen's Disease convened to discuss the status of nerve decompression as a treatment for leprous neuropathy. The expert group recommended an international, multi-center randomised controlled trial (RCT). Subsequently, a study protocol called Decompression for Leprous Neuropathy (DELN) was designed and further refined by multiple investigators worldwide. The DELN Protocol: The DELN RCT seeks to determine the long-term effect of nerve decompression on sensibility, motor function, neuropathic pain, disability, and quality of life. The RCT would enroll patients with clinically diagnosed leprous neuropathy and positive Tinel signs in the upper and lower extremities. Patients would then be randomized to receive nerve decompression or not. Outcomes of interest include sensory function, motor function, pain, disability, and quality of life. The development of ulcers or amputations after surgery and the influence of corticosteroid therapy are also important outcomes that DELN seeks to determine. Conclusions: The study Decompression for Leprous Neuropathy (DELN) is an international, multi-center RCT with the potential to produce high quality data to address whether nerve decompression for leprous neuropathy can conclusively improve patient outcomes. We invite discussion from all those involved in the peripheral nerve and leprosy communities.

Leprosy reactions: Unraveling immunological mechanisms underlying tissue damage in leprosy patients.

Leprosy is a chronic granulomatous infectious and disabling disease caused by two mycobacteria, Mycobacterium leprae and Mycobacterium lepromatosis. Acute inflammatory responses, known as leprosy reactions, are significant contributors to disabilities. Three types of leprosy reactions have been identified based on excessive cytokine release (e.g. type 1) or the accumulation of immune complexes in tissues inducing multiorgan damage (e.g. types 2 and 3). The type of leprosy reaction has implications on treatment and management strategies, yet are not well understood by health workers caring for leprosy patients. We attempt to describe the immunologic mechanisms behind the different leprosy reactions and the rationale for tailoring clinical treatment and management to the particular type of leprosy reaction based on the underlying immunologic situation.

Leprosy in Colombia: post elimination stage?

Leprosy in Colombia is not considering as a public health problem since a prevalence rate less than 1/10000 was achieved more than ten years ago. Nevertheless, reports of 2012 from 11 of 27 departments (48%) showed incidence rates from 0.12 to 4.73 cases per 100000 inhabitants. The Ministry of Health and the National Institute of Health direct and organize the National Leprosy Program (NLP), which plan the activities for prevention, surveillance, and control at national level. The operational activities are delegated to the regional levels (municipalities, districts, departments) however in many areas poor hospital infrastructure, high costs, lack of health personnel trained, difficult access to the health services are some of the barriers that impede the development and access to the activities that the NLP publishes in guides. The above mentioned facts have as consequence late case detection with 30% of disability rates (grade 1 and 2) at the time of diagnosis. Also, there is not awareness in general population neither in health professionals about the existence of leprosy cases in Colombia. This is a review of the situation of leprosy in Colombia, taking into account not only statistical data, but also some aspects that influence late diagnosis and disability found in patients at the time of diagnosis. In this review may appear author's personal perceptions that may differ from others.

Pure neuritic leprosy in patients from a high endemic region of Colombia.

Agua de Dios was a leprosarium for leprosy patients' obligatory isolation (1872-1961). Its leprosy incidence is the highest in Colombia (1.5-7/10000). Relapses are common. Government grant of US$ 200 per month subsidy is available to patients with disabilities. Spontaneous consultation with neural symptoms is frequent and simulation to get the subsidy has to be considered. We studied 36 subjects (2007-2009), with ages from 29-78, 19 of them men, with neural symptoms of 6 months to 20 years evolution. All had clinical examination, bacteriological examination, skin and nerve biopsies, electromyography (EMG), PCR for M. leprae, IgM anti-PGL1, and lepromin A. All but two are household contacts of leprosy patients. Symptoms were hypoesthesia of the hands and feet, and difficulty using hands with loss of muscular strength. None had skin lesions. Three had thickening of ulnar nerve. Lepromin was positive in all; bacteriology and biopsies were negative in all. The speed and amplitude of neural conduction were altered in 34 patients; two women had normal EMG and were considered to be feigning the disease; 21 were diagnosed as PNL by clinical, epidemiological and EMG findings; five of them had a positive PCR and one, high titers for IgM anti PGL1. Nine other subjects had diabetes and six carpal tunnel syndrome (CTS). Slow progression of disease, the lack of neural enlargement and the neural biopsies without inflammation suggest that most of these patients could have spontaneously cured PNL, as happens with other cases of paucibacillary leprosy. Diabetes and CTS are important differential diagnoses of PNL. Patients were treated with MDT and received the state subsidy.

High seropositivity against NDO-LID in a group of household contacts of leprosy patients. Are we close to leprosy elimination in Colombia?

INTRODUCTION: Leprosy is a chronic infectious disease caused by two mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). The household contacts (HHC) of leprosy index cases are at higher risk of being infected with these mycobacteria. Therefore, serological testing in HHC would be an effective strategy to eliminate leprosy in Colombia. OBJECTIVE: To determine the seroprevalence and factors associated with the infection by M. leprae in HHC. METHODS: An observational study was conducted in 428 HHC located in the Colombian Caribbean, Andean, Pacific, and Amazonian regions. We evaluated the seropositivity and titrations of IgM, IgG, and protein A against NDO-LID. RESULTS: The evaluated HHC showed high seropositivity, precisely 36.9% anti-NDO-LID IgM, 28.3% anti-NDO-LID IgG, and 47.7% protein A. Furthermore, Protein A showed a greater capacity to detect infected individuals than other anti-NDO-LID conjugates (p < 0.0001). This study did not show differences in the seropositivity according to sex or age of the HHC (p > 0.05). Higher seropositivity for IgM was evidenced mainly in HHC located in the Colombian Pacific region (p 0.001). This research did not show differences in the seropositivity for these serological tests between HHC of PB or MB leprosy patients (p > 0.05). CONCLUSION: Leprosy transmission is still active between Colombian HHC. Consequently, controlling leprosy transmission in this population is fundamental to eradicating this disease.

Pilot study of the productivity and Salmonella seroprevalence in pigs administered organic acids.

Control of Salmonella in pig/pork production is important to protect public health because pork is one of the main sources of human infection. Moreover, antimicrobial use in pig farms should be kept low to minimize development and transmission of antimicrobial resistance. This pilot study evaluated the productivity and Salmonella seroprevalence in pigs administered organic acids (OA) compared to pigs given growth promoters in one farm in Antioquia, Colombia. Two groups each consisting of 60 pigs of 6-weeks of age were studied for 4 months. One group was provided feed and water with OA (Selko pH® and Selacid®), whereas the other group (control) received antimicrobial growth promoters according to routine feeding practices (tylosin and zinc bacitracin). Blood samples were taken three times (T1-T3) and pigs were weighted five times to calculate daily weight gain (DWG) and feed conversion ratio (FCR). Initially when the pigs were 6 weeks old (T1), the Salmonella seroprevalence was 1.7% in both groups. When the pigs were 11 weeks old (T2), the seroprevalence was significantly lower in pigs provided OA compared to the control group (19 vs. 47%, P < 0.001), whereas when the pigs were 23 weeks old (T3), the seroprevalence did not differ between the groups (62 vs. 77%; P = 0.075). The cumulative DWG was significantly higher in the intervention group than in the control group (713 vs. 667 g/day; P < 0.001). The cumulative FCR did not differ between groups (2.80 vs. 2.77; P = 0.144). The pilot study indicates that cleaning the water pipes and administrating OA improve productivity in pigs and delay exposure to Salmonella spp. when compared with growth promoters. Thus, OA could replace antimicrobial growth promoters and reduce antimicrobial use and resistance. However, the study should be repeated before firmer conclusions can be drawn.

Cholangiocyte derived carcinomas and local microbiota.

Trillions of bacteria are present in the gastrointestinal tract as part of the local microbiota. Bacteria have been associated with a wide range of gastrointestinal diseases including malignant neoplasms. The association of bacteria in gastrointestinal and biliary tract carcinogenesis is supported in the paradigm of Helicobacter pylori and intestinal-type gastric cancer. However, the association of bacterial species to a specific carcinoma, different from intestinal-type gastric cancer is unresolved. The relationship of bacteria to a specific malignant neoplasm can drive clinical interventions. We review the classic bacteria risk factors identified using cultures and PCR (polymerase chain reaction) with new research regarding a microbiota approach through 16S rRNA (16S ribosomal ribonucleic acid gene) or metagenomic analysis for selected carcinomas in the biliary tract.

Detection of Mycobacterium leprae infection in family clusters from six leprosy-endemic regions in Colombia.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which continues to be endemic in tropical countries, making it necessary to implement strategies for its elimination. The objective of the current article was to detect M. leprae infection and associated factors through serological and epidemiological evaluation in family clusters of leprosy patients. METHODS: Mycobacterium leprae infection was determined in 50 family clusters of leprosy patients from the departments of Bolívar, Atlántico, Santander, Boyacá, Chocó and Antioquia through the detection of antibodies (protein A, IgM, IgG) against anti-natural octyl disacharide-leprosy IDRI diagnostic (NDO-LID). RESULTS: Higher seroconversion and elevated titers of these antibodies against NDO-LID were observed in the population of Chocó and Atlántico (p<0.05). Additionally, a higher frequency of infection was observed in large family groups that consumed armadillo meat and belonged to a low socioeconomic stratum (p<0.05). Multivariate analysis established that the main associated factors for a family cluster experiencing this infection were belonging to a vulnerable economic stratum and a large family group. CONCLUSIONS: This study found that the set of social and demographic variables (i.e. armadillo consumption, geographic area, low socioeconomic status and belonging to a large family cluster) are related to the promotion of seropositivity in family clusters.

Advances in the treatment of Chagas disease: Promising new drugs, plants and targets.

Chagas disease, caused by Trypanosoma cruzi, is treated with only two drugs; benznidazole and nifurtimox. These drugs have some disadvantages, including their efficacy only in the acute or early infection phases, adverse effects during their use, and the resistance that the parasite has developed to their activity. Therefore, it is necessary to identify new, safe and effective therapeutic alternatives to treat Chagas disease, though governments and the pharmaceutical industry have shown a lack of interest in contributing to this solution. Institutions and research groups on the other hand have worked on some strategies that can help to address the problem. Some of these include the modification of conventional drug dosages, drug repurposing, and combined therapy. Plants and derived compounds with antiparasitic effects have also been studied, taking advantage of traditional medicinal knowledge. Others have studied the parasite to identify essential genes that can be used as therapeutic targets to design new, targeted drugs. Some of these studies have generated promising results, but few reach clinical phase studies. Institutions and research groups should be encouraged to unify efforts and cover all aspects of drug development according to resources and knowledge availability. In the end, this exchange of knowledge would lead to the development of new therapeutic alternatives to treat Chagas disease and benefit the populations it affects.

Innate immune response: ally or enemy in cutaneous leishmaniasis?

Cutaneous leishmaniasis (CL) is an infectious and neglected disease caused by parasites of the genus Leishmania, which produces a wide spectrum of cutaneous manifestations. CL research has shown that the innate immune activity of cells such as neutrophils, natural killers, macrophages, dendritic cells and the complement system are capable of controlling this infection. However, Leishmania can also modulate the immune activity of these cells to promote its own survival and proliferation at the intracellular level. This review discusses the role of the innate immune response in the control and spread of this infection.

Oct-6 transcriptional factor a possible biomarker for leprosy diagnosis.

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. The nerve damage in leprosy may be related to alterations in transcriptional factors, such as Krox-20, Oct-6, Sox-10. Thirty skin biopsies in leprosy patients and 15 non-leprosy skin biopsies were evaluated using RT-qPCR to assess Krox-20, Oct-6, and Sox-10 and these data was related with S-100 immunohistochemistry. Changes in gene expression were observed in the skin and dermal nerves of leprosy patients in Oct-6 and Sox-10. When comparing Oct-6 with S-100 IHC as diagnostic tests for leprosy, Oct-6 showed a sensitivity of 73.3%, and specificity of 100%, while S-100 IHC showed a sensitivity of 96.6% and specificity of 100%. Our data suggest Oct-6 could be an auxiliary biomarker specific to detecting changes in dermal nerves in leprosy and thus useful to health workers and pathologists with no expertise to observe nerve injuries in leprosy.

Notch Signaling Pathway Expression in the Skin of Leprosy Patients: Association With Skin and Neural Damage.

Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. It is possible that tissue changes during infection with leprosy are related to alterations in the activity of the Notch signaling pathway, an innate signaling pathway in the physiology of the skin and peripheral nerves. Methods: This is a descriptive observational study. Thirty skin biopsies from leprosy patients and 15 from individuals with no history of this disease were evaluated. In these samples, gene expressions of cellular components associated with the Notch signaling pathway, Hes-1, Hey-1, Runx-1 Jagged-1, Notch-1, and Numb, were evaluated using q-PCR, and protein expression was evaluated using immunohistochemistry of Runx-1 and Hes-1. Results: Changes were observed in the transcription of Notch signaling pathway components; Hes-1 was downregulated and Runx-1 upregulated in the skin of infected patients. These results were confirmed by immunohistochemistry, where reduction of Hes-1 expression was found in the epidermis, eccrine glands, and hair follicles. Increased expression of Runx-1 was found in inflammatory cells in the dermis of infected patients; however, it is not related to tissue changes. With these results, a multivariate analysis was performed to determine the causes of transcription factor Hes-1 reduction. It was concluded that tissue inflammation was the main cause. Conclusions: The tissue changes found in the skin of infected patients could be associated with a reduction in the expression of Hes-1, a situation that would promote the survival and proliferation of M. leprae in this tissue.

Biliary Tract Carcinogenesis Model Based on Bile Metaproteomics.

Purpose: To analyze human and bacteria proteomic profiles in bile, exposed to a tumor vs. non-tumor microenvironment, in order to identify differences between these conditions, which may contribute to a better understanding of pancreatic carcinogenesis. Patients and Methods: Using liquid chromatography and mass spectrometry, human and bacterial proteomic profiles of a total of 20 bile samples (7 from gallstone (GS) patients, and 13 from pancreatic head ductal adenocarcinoma (PDAC) patients) that were collected during surgery and taken directly from the gallbladder, were compared. g:Profiler and KEGG (Kyoto Encyclopedia of Genes and Genomes) Mapper Reconstruct Pathway were used as the main comparative platform focusing on over-represented biological pathways among human proteins and interaction pathways among bacterial proteins. Results: Three bacterial infection pathways were over-represented in the human PDAC group of proteins. IL-8 is the only human protein that coincides in the three pathways and this protein is only present in the PDAC group. Quantitative and qualitative differences in bacterial proteins suggest a dysbiotic microenvironment in the PDAC group, supported by significant participation of antibiotic biosynthesis enzymes. Prokaryotes interaction signaling pathways highlight the presence of zeatin in the GS group and surfactin in the PDAC group, the former in the metabolism of terpenoids and polyketides, and the latter in both metabolisms of terpenoids, polyketides and quorum sensing. Based on our findings, we propose a bacterial-induced carcinogenesis model for the biliary tract. Conclusion: To the best of our knowledge this is the first study with the aim of comparing human and bacterial bile proteins in a tumor vs. non-tumor microenvironment. We proposed a new carcinogenesis model for the biliary tract based on bile metaproteomic findings. Our results suggest that bacteria may be key players in biliary tract carcinogenesis, in a long-lasting dysbiotic and epithelially harmful microenvironment, in which specific bacterial species' biofilm formation is of utmost importance. Our finding should be further explored in future using in vitro and in vivo investigations.

Identification and comparison of Mycobacterium leprae genotypes in two geographical regions of Colombia.

OBJECTIVE: To evaluate and establish genomic strain typing markers suitable for the identification of transmission patterns of leprosy in different regions of Colombia. DESIGN: Patients from Agua de Dios, Barranquilla and Cartagena cities and neighbouring towns were enrolled during 2006-2007. Slit skin smears or biopsies were obtained from newly detected untreated patients, and those undergoing multidrug therapy. DNA was extracted from the clinical samples and tested using 15 different short tandem repeat and three SNP polymorphic markers. RESULTS AND CONCLUSION: Differences or similarities between strain types from the northeast (n = 20) and central regions of Colombia (n = 18) were noted. The alleles at two loci, 27-5 and 12-5 were different in the M. leprae in the two regions. The other microsatellite loci may be useful for further intra-population differentiation. There was strong association of 27-5 and 12-5 alleles with the SNP types. The 4-5 combination of alleles was associated with SNP type 3, while the 5-4 combination was mostly associated with SNP type 1, 2 or 4. The SNP type 4 m. leprae isolates were seen in patients in the northeast, but not in the central part.