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1.
Parasit Vectors ; 14(1): 111, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597000

RESUMO

BACKGROUND: Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC. METHODS: Quantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and the direct agglutination test (DAT) were carried out on blood samples, and the Leishmania antigen ELISA was carried out on urine samples collected from 720 household and neighbouring contacts of 276 VL and post-kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL or PKDL, in endemic regions of Bangladesh between September 2016 and March 2018. RESULTS: Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only one (0.1%) participant was detected positive by all four diagnostic tests. Poor agreement between tests was calculated using Cohen's kappa (κ) statistics; however, the Leishmania antigen ELISA and DAT in combination captured all participants as positive by more than one test. We find evidence for a moderately strong association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004), and being positive for at least one of the four tests. CONCLUSIONS: Leishmania antigen ELISA on urine detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in a rapid diagnostic test (RDT) format would be of benefit to the elimination campaign.

2.
BMJ Open ; 11(1): e045826, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495264

RESUMO

INTRODUCTION: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care. METHODS AND ANALYSIS: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies. ETHICS AND DISSEMINATION: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings. TRIAL REGISTRATION NUMBER: NCT04285021.

3.
Parasitol Int ; 80: 102230, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33147502

RESUMO

Evidence-based diagnostic algorithm is highly recommended for the visceral leishmaniasis (VL). This cross-sectional study was performed in Bangladesh to evaluate VL diagnostic tools including serology, buffy coat smear microscopy for LD body and various DNA-based techniques using buffy coat in 100 confirmed VL cases and 100 controls. The performance of tools against spleen smear (gold standard) was evaluated using kappa coefficient. Diagnostic precision and other inherent indicators were considered for index scoring (IS) of performance of tools using factor analysis. A diagnostic algorithm was formulated based on the IS and availability of the tools at different health care facilities of Bangladesh. A high level of agreement (kappa ≥  0.80) was observed for all the diagnostic tools. The highest kappa coefficients were found for rK39 RDT and rK39 ELISA (0.95), followed by ssuRNA-PCR (0.94), Buffy coat smear (0.93), rK28 ELISA (0.92), rK28 RDT (0.89), LAMP (0.89), Mini-exon PCR (0.86), ITS1 (0.85), and ITS2 PCR (0.80). rK39 RDT was found to be the best diagnostic test (IS: 1.7) followed by rK28 RDT (IS: 1.5), buffy coat smear microscopy (IS: 0.5), rK39 & rK28 ELISA (IS: 0.3), ssuRNA-PCR (IS: -0.7) and LAMP, Mini-exon, ITS1, & ITS2 PCR (IS: -0.9). rK39 RDT has been proposed as the best option for primary health care facilities, while buffy coat smear microscopy was found to be a good adjunct for confirmation of serology-positive cases and proposed for secondary and tertiary facilities. ssuRNA-PCR or LAMP can be an alternate confirmation tool only applicable to the tertiary facilities.

4.
Vaccine ; 39(1): 59-67, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33121844

RESUMO

BACKGROUND: Vaccine-preventable infectious diseases are often responsible for childhood morbidity and high rates of mortality. Immune response to the vaccine is associated with multiple factors in early childhood and measured by antibody titers. Among them, micronutrient deficiencies such as vitamin D and zinc deficiencies are the most important in resource-limited settings like Bangladesh. OBJECTIVE: We aimed to evaluate the association of vaccine response to low serum zinc and vitamin D levels in children. METHODS: We evaluated vaccine response for measles and poliovirus, tetanus and pertussis toxoid, and Ig A antibody levels to rotavirus by ELISA and serum vitamin D and zinc at 7 and 15 months in the MAL-ED birth cohort of the Bangladesh site. By using population-specific generalized estimating equations (GEE), the association between each explanatory variable and the binary outcome variable was examined longitudinally where the dependent variable was vaccine titers and the independent variables were low serum vitamin D and zinc levels. RESULTS: The GEE multivariable model identified a positive association between serum zinc level and tetanus vaccine titer (OR: 1.84; 95% CI: 1.07-3.17 and p value = 0.028) after adjusting for age, gender, birth weight, WAMI score, diarrhea, ALRI, exclusive breastfeeding, serum ferritin, serum retinol and undernutrition (stunting, wasting, underweight). No association was found between the rest of the vaccine titers with serum vitamin D and zinc level (p > 0.05). CONCLUSION: In the MAL-ED birth cohort, where children were followed for five years, serum zinc level had a positive impact on tetanus vaccine titers.

5.
Microbiol Resour Announc ; 9(42)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060272

RESUMO

Chromobacterium violaceum is an emerging environmental opportunistic pathogen that causes life-threatening infections in humans. Here, we describe the draft genome sequence of Chromobacterium violaceum RDN09, isolated from the infected wound of an adult male patient in Bangladesh. The genome assembly consists of 4,736,739 bp spread across 84 contigs.

6.
Proc Natl Acad Sci U S A ; 117(41): 25742-25750, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32973088

RESUMO

Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which additional estimation methods are required. Here, we develop such methods to analyze longitudinal incidence data on visceral leishmaniasis (VL) and its sequela, post-kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on VL and PKDL infectiousness, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: 85% of mean distances from inferred infectors to their secondary VL cases were <300 m, and estimated average times from infector onset to secondary case infection were <4 mo for 88% of VL infectors, but up to 2.9 y for PKDL infectors. Estimated numbers of secondary cases per VL and PKDL case varied from 0 to 6 and were strongly correlated with the infector's duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced overall VL incidence by up to 25%. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally targeted interventions against VL.

7.
Trop Med Infect Dis ; 5(2)2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32517156

RESUMO

To detect Post-kala-azar leishmaniasis (PKDL) cases, several molecular methods with promising diagnostic efficacy have been developed that involve complicated and expensive DNA extraction methods, thus limiting their application in resource-poor settings. As an alternative, we evaluated two rapid DNA extraction methods and determined their impact on the detection of the parasite DNA using our newly developed recombinase polymerase amplification (RPA) assay. Skin samples were collected from suspected PKDL cases following their diagnosis through national guidelines. The extracted DNA from three skin biopsy samples using three different extraction methods was subjected to RPA and qPCR. The qPCR and RPA assays exhibited highest sensitivities when reference DNA extraction method using Qiagen (Q) kit was followed. In contrast, the sensitivity of the RPA assay dropped to 76.7% and 63.3%, respectively, when the boil & spin (B&S) and SpeedXtract (SE) rapid extraction methods were performed. Despite this compromised sensitivity, the B&S-RPA technique yielded an excellent agreement with both Q-qPCR (k = 0.828) and Q-RPA (k = 0.831) techniques. As expected, the reference DNA extraction method was found to be superior in terms of diagnostic efficacy. Finally, to apply the rapid DNA extraction methods in resource-constrained settings, further methodological refinement is warranted to improve DNA yield and purity through rigorous experiments.

8.
Genes Cells ; 25(9): 615-625, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562326

RESUMO

Chikungunya fever is a mosquito-borne disease cause of persistent arthralgia. The current diagnosis of Chikungunya virus (CHIKV) relies on a conventional reverse transcription polymerase chain reaction assay. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a rapid and simple tool used for DNA-based diagnosis of a variety of infectious diseases. In this study, we established an RT-LAMP system to recognize CHIKV by targeting the envelope protein 1 (E1) gene that could also detect CHIKV at a concentration of 8 PFU without incorrectly detecting other mosquito-borne viruses. The system also amplified the E1 genome in the serum of CHIKV-infected mice with high sensitivity and specificity. Moreover, we established a dry RT-LAMP system that can be transported without a cold chain, which detected the virus genome in CHIKV-infected patient samples with high accuracy. Thus, the dry RT-LAMP system has great potential to be applied as a novel CHIKV screening kit in endemic areas.

9.
Parasit Vectors ; 13(1): 159, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228668

RESUMO

The 5th Post-Kala-Azar Dermal Leishmaniasis (PKDL) Consortium meeting brought together PKDL experts from all endemic areas to review and discuss existing and new data on PKDL. This report summarizes the presentations and discussions and provides the overall conclusions and recommendations.


Assuntos
Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Animais , Humanos , Cinética , Vacinas contra Leishmaniose , Leishmaniose Cutânea , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/terapia , Sri Lanka/epidemiologia , Xenodiagnóstico
10.
Parasit Vectors ; 13(1): 196, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295617

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of the human disease propagating form of Leishmania donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. METHODS: By using an immunoinformatic approach, CD4+ and CD8+ T cell-specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a Toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization. RESULTS: Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum, covering theoretically more than 98% of the global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response. CONCLUSIONS: The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.


Assuntos
Antígenos de Protozoários/imunologia , Epitopos de Linfócito T/imunologia , Leishmania donovani/imunologia , Vacinas contra Leishmaniose/imunologia , Adjuvantes Imunológicos/química , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Biologia Computacional , Leishmania infantum/imunologia , Leishmaniose Visceral/parasitologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteômica , Proteínas de Protozoários/imunologia , Vacinas de Subunidades/imunologia
11.
Cell Host Microbe ; 27(2): 199-212.e5, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32053789

RESUMO

Stunting, a severe and multigenerational growth impairment, globally affects 22% of children under the age of 5 years. Stunted children have altered gut bacterial communities with higher proportions of Proteobacteria, a phylum with several known human pathogens. Despite the links between an altered gut microbiota and stunting, the role of bacteriophages, highly abundant bacterial viruses, is unknown. Here, we describe the gut bacterial and bacteriophage communities of Bangladeshi stunted children younger than 38 months. We show that these children harbor distinct gut bacteriophages relative to their non-stunted counterparts. In vitro, these gut bacteriophages are infectious and can regulate bacterial abundance and composition in an age-specific manner, highlighting their possible role in the pathophysiology of child stunting. Specifically, Proteobacteria from non-stunted children increased in the presence of phages from younger stunted children, suggesting that phages could contribute to the bacterial community changes observed in child stunting.


Assuntos
Bacteriófagos/isolamento & purificação , Microbioma Gastrointestinal , Transtornos do Crescimento/microbiologia , Transtornos do Crescimento/virologia , Fatores Etários , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , Pré-Escolar , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Genes Bacterianos , Genes Virais , Interações entre Hospedeiro e Microrganismos , Humanos , Lactente , Masculino , Metagenômica , Proteobactérias/classificação , Proteobactérias/genética , Proteobactérias/isolamento & purificação , Proteobactérias/virologia , RNA Ribossômico 16S
12.
Parasit Vectors ; 12(1): 527, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699125

RESUMO

BACKGROUND: The main clinical forms of leishmaniasis in Bangladesh are visceral leishmaniasis and post-kala-azar dermal leishmaniasis, which are caused by Leishmania donovani. Imported cutaneous leishmaniasis (CL) is emerging globally due mainly to increased human mobility. In recent years, several imported CL cases have also been reported in Bangladesh. Sporadic atypical cases of CL can be challenging for diagnosis and clinical management, while occurrence of infection on a frequent basis can be alarming. We report of a case of a Bangladeshi temporary-migrant worker who, upon return, presented development of skin lesions that are characteristic of CL. METHODS: A serum sample was collected and tested with an rK39 immunochromatographic test. Nucleic acid from skin biopsy derived culture sample was extracted and screened with a real-time PCR assay which targets the conserved REPL repeat region of L. donovani complex. The internal transcribed spacer 2 region of the ribosomal RNA gene cluster was amplified and sequenced. RESULTS: The suspect had a history of travel in both CL and VL endemic areas and had a positive rK39 test result. Based on clinical presentation, travel history and demonstration of the parasite in the skin biopsy, CL was diagnosed and the patient underwent a combination therapy with Miltefosine and liposomal amphotericin B. While typical endemic species were not detected, we identified Leishmania major, a species that, to our knowledge, has never been reported in Bangladesh. CONCLUSIONS: Proper monitoring and reporting of imported cases should be given careful consideration for both clinical and epidemiological reasons. Molecular tests should be performed in diagnosis to avoid dilemma, and identification of causative species should be prioritized.


Assuntos
Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/patologia , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/patologia , Adulto , Anticorpos Antiprotozoários/sangue , Bangladesh , Biópsia , Doenças Transmissíveis Importadas/parasitologia , Humanos , Imunoensaio , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Pele/parasitologia , Pele/patologia , Viagem
13.
Front Microbiol ; 10: 2268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649631

RESUMO

Introduction: To sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value. Materials and Methods: Serum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA. Results: The mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF. Conclusion: Our data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

14.
Pathog Dis ; 77(6)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589291

RESUMO

Visceral leishmaniasis (VL) in the Old World is caused by infection with Leishmania donovani. Although the numbers of new reported cases of VL in Africa have been relatively stable for several years, the low numbers currently reported on the Indian subcontinent suggest a positive impact of new treatments and intervention strategies. In both regions, however, VL relapse and post-kala-azar dermal leishmaniasis (PKDL) maintain infectious reservoirs and therefore present a threat to control programs. In this review, we outline the evolving appreciation of PKDL as an impactful disease in its own right and discuss the various diagnostic methods that can be applied for the detection and characterization of PKDL cases. We also highlight the data that indicate the potential, and likely contribution, of PKDL cases to ongoing transmission of L. donovani.


Assuntos
Transmissão de Doença Infecciosa , Leishmania donovani/crescimento & desenvolvimento , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/transmissão , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologia , Reservatórios de Doenças , Saúde Global , Humanos , Recidiva
15.
PLoS One ; 14(9): e0221805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557172

RESUMO

The association of vitamin D with neuro-behavioral outcomes of young children is unclear, particularly of those who reside in tropical countries and are otherwise exposed to adequate sun light. To investigate this association, we analysed the existing data of poor infants, who participated in an observational, prospective-cohort (MalED) study, conducted in a slum of Dhaka-city. We assessed 265 infants aged 6-8 months for cognitive, motor, language and behavior development using Bayley-III. Information about infants' temperament and communicative skills were provided by the mothers through a culturally modified "temperament-scale" and a "communicative-developmental inventory". Serum concentration of vitamin D [25(OH)D] was measured in 205 infants. Around 28.3% of infants in this community had low level vitamin D, with the cut-off at <50 nmol/L. After controlling for all possible covariates, a multivariable-adjusted linear regression showed that children with vitamin D levels <50 nmol/L had significantly lower scores in two dimensions of temperament: activity (B±SE 1.64±0.78; 95%CI 0.10, 3.18; p = 0.037; effect size 0.37 SDs) and soothabilty (2.02±0.70; 0.64, 3.41; p = 0.004; 0.53 SDs), compared to children with vitamin D levels of ≥50nmol/L. These infants also scored low in word comprehensions (1.28±0.62; 0.05, 2.51; p = 0.042; 0.23 SDs) and were less active during test-procedures (0.33±0.16; 0.02, 0.64; p = 0.035; 0.27 SDs). Both the groups tested similarly in cognitive and motor scores. This study found, despite adequate sunlight-exposure, one in four infants of this slum-community are suffering from a subclinical vitamin D deficiency. Higher levels of vitamin D in these infants showed a positive association with temperament, language and behavior but not with cognitive and motor development. Our findings highlight the early-detected extra-skeletal neuro-behavioral role of vitamin D. Future studies in this area will give more insight.


Assuntos
Desenvolvimento Infantil , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/psicologia , Vitamina D/sangue , Bangladesh/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Comportamento do Lactente , Masculino , Transtornos do Neurodesenvolvimento/sangue , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/psicologia , Áreas de Pobreza , Estudos Prospectivos , Fatores Socioeconômicos , Temperamento , Deficiência de Vitamina D/epidemiologia
16.
Nutrients ; 11(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394828

RESUMO

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.


Assuntos
Transtornos do Crescimento/sangue , Substâncias de Crescimento/sangue , Adipocinas/sangue , Bangladesh , Biomarcadores/análise , Biomarcadores/sangue , Índice de Massa Corporal , Citocinas/sangue , Suplementos Nutricionais , Fezes/química , Feminino , Flumazenil/análogos & derivados , Flumazenil/análise , Flumazenil/sangue , Transtornos do Crescimento/terapia , Humanos , Lactente , Masculino , Áreas de Pobreza , Psicologia
17.
PLoS One ; 14(8): e0220397, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393913

RESUMO

Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Usually this test involves a time consuming procedure of about 5 hour's urine collection, which makes the test incompatible to some extent. As the results are expressed as the ratio of lactulose and mannitol recovered in urine within certain time, it may be possible to get similar result despite the reduced urine collection time of 2 hours. Moreover, different laboratories do the test by different methods, which make the results incomparable between laboratories. Here, we are also trying to find the correlation between results from most commonly used methods: HPAE-PAD and LC-MSMS. The lactulose: mannitol (LM) test was performed in a cohort of Bangladeshi infants considered at-risk for environmental enteropathy. 208 urine specimens from 104 (52 male and 52 female) infants were collected at 2 and 5 hours after LM solution administration and were tested for lactulose and mannitol by two different methods, one HPAE-PAD platform and another LC-MSMS platform. Median age of the children was 15.0 months (range 6.9 to 25.8 months) and their mean weight-for-age z-score was -0.92. A higher percentage of lactulose and mannitol recovery was found in 5 hours urine collection than in the corresponding 2 hours by both HPAE-PAD and LC-MSMS method, but when results were expressed as lactulose to mannitol ratio (LMR) there was no significant difference between 2 and 5 hours urine collection in both HPAE-PAD (P = 0.138) and LC-MSMS (P = 0.099) method. LMR based on 2 hours urine collection correlated well with LMR based on traditional 5 hours urine collection (Spearman's correlation coefficient 0.578 and 0.604 respectively for HPAE-PAD and LC-MSMS). In future, LM test to assess intestinal permeability in children can be simplified by shortening the urine collection time from 5 hours to 2 hours.


Assuntos
Absorção Intestinal/efeitos dos fármacos , Enteropatias , Mucosa Intestinal/metabolismo , Lactulose , Manitol , Coleta de Urina , Pré-Escolar , Feminino , Humanos , Lactente , Enteropatias/diagnóstico , Enteropatias/urina , Mucosa Intestinal/patologia , Lactulose/administração & dosagem , Lactulose/farmacocinética , Masculino , Manitol/administração & dosagem , Manitol/farmacocinética , Permeabilidade , Fatores de Tempo
18.
PLoS Negl Trop Dis ; 13(8): e0007653, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415565

RESUMO

BACKGROUND: We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development. METHODS: Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate (SSG), miltefosine (MF), paromomycin intramuscular injection (PMIM), liposomal amphotericin B [AmBisome (AMB)] in a single dose (SDAMB) and in multidose (MDAMB), and combination therapies by AMB+PMIM, AMB+MF, and PMIM+MF. Follow up period was 4 years after treatment. Cohorts were prospective except SSG (retrospective) and MF (partially retrospective). We compared incidence proportion and rate in 100-person-4year of PKDL and VLR by treatment regimens using univariate and multivariate analysis. FINDINGS: 974 of 984 enrolled participants completed the study. Overall incidence proportion for PKDL and VLR was 12.3% (95% CI, 10.4%-14.5%) and 7.0% (95% CI, 5.6%-8.8%) respectively. The incidence rate (95% CI) of PKDL and VLR was 14.0 (8.6-22.7) and 7.6 (4.1-14.7) accordingly. SSG cohort had the lowest incidence rate of PKDL at 3.0 (1.3-7.3) and VLR at 1.8 (0.6-5.6), followed by MDAMB at 8.2 (4.3-15.7) for PKDL and at 2.7 (0.9-8.4) for VLR. INTERPRETATION: Development of PKDL and VLR is related with treatment regimens for VL. SSG and MDAMB resulted in less incidence of PKDL and VLR compared to other treatment regimens. MDAMB should be considered for VL as a first step for prevention of PKDL and VLR since SSG is highly toxic and not recommended for VL.


Assuntos
Antiprotozoários/uso terapêutico , Tratamento Farmacológico/métodos , Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh/epidemiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Incidência , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Food Nutr Bull ; 40(3): 357-368, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31272212

RESUMO

BACKGROUND: In order to improve calcium status, fortified rice should have acceptable organoleptic properties of that food. OBJECTIVE: We aimed to assess whether home fortification of rice with slaked lime can increase calcium content of rice and whether this fortified rice is well tolerated in a nutritionally at-risk population. METHODS: This experimental study measured the calcium content of rice cooked with different concentration of lime and assessed the acceptability of fortified rice among 400 women and children. Each participant received fortified rice with one of five concentrations of lime (0, 2.5, 5, 7.5 or 10 gm per 500 gm of rice), with or without additional foods (lentil soup or fried green papaya). All participants were asked to score the organoleptic qualities on a hedonic scale. RESULTS: Analysis showed that rice calcium content increased in a dose- response manner with increased lime during cooking (76.03, 205.58, 427.55, 614.29 and 811.23 mg/kg for given lime concentrations). Acceptability of the meal was greater when additional foods were served with rice at all lime concentrations. In both groups, the 7.5M arm reported highest overall acceptability (children, 6.25; women 6.10). This study found significant association between overall acceptability (different concentrations of lime mixed rice; with/without additional foods) and between groups (women vs. children) (p value = < 0.001) where-as no association was found within groups. CONCLUSIONS: Lime-fortified rice can be feasible considering the calcium uptake of rice and organoleptic character. Further research on bioavailability can establish a solid foundation that will support design of an effective intervention to reduce calcium deficiency in this population.


Assuntos
Compostos de Cálcio/administração & dosagem , Cálcio/deficiência , Oryza , Óxidos/administração & dosagem , Bangladesh , Disponibilidade Biológica , Cálcio/análise , Cálcio/farmacocinética , Criança , Comportamento do Consumidor , Feminino , Alimentos Fortificados/análise , Humanos , Oryza/química , Sensação
20.
Ther Drug Monit ; 41(6): 714-718, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31169760

RESUMO

BACKGROUND: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. METHODS: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. RESULTS: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. CONCLUSIONS: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient.


Assuntos
Antituberculosos/sangue , Teste em Amostras de Sangue Seco/normas , Monitoramento de Medicamentos/métodos , Manejo de Espécimes/normas , Tuberculose/sangue , Bangladesh , Teste em Amostras de Sangue Seco/métodos , Humanos , Umidade , Indonésia , Paraguai , Reprodutibilidade dos Testes , República de Belarus , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Tuberculose/diagnóstico , Tuberculose Pulmonar
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