Isolation of non-tuberculous mycobacteria from pastoral ecosystems of Uganda: Public Health significance

<p>Abstract</p> <p>Background</p> <p>The importance of non-tuberculous mycobacteria (NTM) infections in humans and animals in sub-Saharan Africa at the human-environment-livestock-wildlife interface has recently received increased attention. NTM are environmental opportunistic pathogens of humans and animals. Recent studies in pastoral ecosystems of Uganda detected NTM in humans with cervical lymphadenitis and cattle with lesions compatible with bovine tuberculosis. However, little is known about the source of these mycobacteria in Uganda. The aim of this study was to isolate and identify NTM in the environment of pastoral communities in Uganda, as well as assess the potential risk factors and the public health significance of NTM in these ecosystems.</p> <p>Method</p> <p>A total of 310 samples (soil, water and faecal from cattle and pigs) were examined for mycobacteria. Isolates were identified by the INNO-Lipa test and by 16S rDNA sequencing. Additionally, a questionnaire survey involving 231 pastoralists was conducted during sample collection. Data were analysed using descriptive statistics followed by a multivariable logistic regression analysis.</p> <p>Results</p> <p>Forty-eight isolates of NTM were detected; 25.3% of soil samples, 11.8% of water and 9.1% from animal faecal samples contained mycobacteria. Soils around water sources were the most contaminated with NTM (29.8%). Of these samples, <it>M. fortuitum-peregrinum </it>complex, <it>M. avium </it>complex, <it>M. gordonae</it>, and <it>M. nonchromogenicum </it>were the most frequently detected mycobacteria. Drinking untreated compared to treated water (OR = 33), use of valley dam versus stream water for drinking and other domestic use (OR = 20), sharing of water sources with wild primates compared to antelopes (OR = 4.6), sharing of water sources with domestic animals (OR = 5.3), and close contact with cattle or other domestic animals (OR = 13.8) were the most plausible risk factors for humans to come in contact with NTM in the environment.</p> <p>Conclusions</p> <p>The study detected a wide range of potentially pathogenic NTM from the environment around the pastoral communities in Uganda. Drinking untreated water and living in close contact with cattle or other domestic animals may be risk factors associated with the possibility of humans and animals acquiring NTM infections from these ecosystems.</p

DC Priming by M. vaccae Inhibits Th2 Responses in Contrast to Specific TLR2 Priming and Is Associated with Selective Activation of the CREB Pathway

The environmental mycobacterium, M. vaccae has been used in mouse models to support the contemporary hygiene hypothesis that non-pathogenic microorganisms reduce allergy associated T helper (Th)2 responses and inflammatory diseases by augmenting regulatory T cells. However, data for human models and possible mechanisms are limited. We tested the effect of innate immune interactions between human DC and M. vaccae on DC-dependent T cell responses. M. vaccae activation of DC via Toll like receptor (TLR)2 was compared to a specific TLR2 ligand (Pam(3)CSK4) and alternative stimulation with a TLR4 ligand (LPS). M. vaccae induced DC dependent inhibition of Th2 responses, in contrast to Pam(3)CSK4, which had the opposite effect and LPS, which had no polarizing effect. DC maturation, gene expression and cytokine production, in response to each stimulus did not correlate with the specific functional effects. Comparable DC transcriptional responses to M. vaccae and Pam(3)CSK4 suggested that TLR2 mediated transcriptional regulation was not sufficient for inhibition of Th2 responses. Transcription factor enrichment analysis and assessment of signaling events, implicated a role for selective early activation of the CREB pathway by M. vaccae. Further study of the CREB pathway may provide novel insight into the molecular mechanisms of DC-dependent T cell polarization

Whole genome sequencing reveals mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients

YesBackground In the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments. Methods From a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis. Results Of the 25 concordant pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16–101)/mm3 and ten (77 %) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution. Using a phylogenetic approach to identify the ancestral compartment, in two (15 %) patients the blood isolate was ancestral to the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs were identical. Conclusions Among HIV-infected patients with poor cellular immunity, infection with multiple strains of M. tuberculosis was found in half of the patients. In those patients with identical strains, whole genome sequencing indicated that M. tuberculosis intra-patient microevolution does occur in a few patients, yet did not reveal a consistent direction of spread between sputum and blood. This suggests that these compartments are highly connected and potentially seed each other repeatedly

Associations of prenatal exposure to Ramadan with small stature and thinness in adulthood: results from a large Indonesian population-based study

A growing body of evidence suggests that maternal diet during pregnancy can lead to permanent alterations to the physiology of the fetus. It is unknown whether intermittent maternal fasting during Ramadan has long-term associations with the offspring's body composition. By using data from the third wave of the Indonesian Family Life Survey (2000), we compared the body mass indices (weight (kg)/height (m)(2)) of Muslims who had been in utero during Ramadan with those of Muslims who had not been in utero during Ramadan. Adult Muslims who had been in utero during Ramadan were slightly thinner than Muslims who had not been in utero during Ramadan (adjusted adult body mass index: -0.32, 95% confidence interval: -0.57, -0.06). Those who were conceived during Ramadan also had smaller stature, being on average 0.80 cm shorter than those who were not exposed to Ramadan prenatally. Among non-Muslims, no such associations were found. This study suggests that exposure to Ramadan during pregnancy may have lasting consequences for adult body size of the offsprin

Ramadan exposure and birth outcomes:A population-based study from the Netherlands

Background:Ramadan, the Islamic month of daytime fasting, is observed by many pregnant Muslims. Although pregnant women are exempt, many prefer to fast. Previous research has shown long-term adverse effects on various health outcomes among the offspring, but evidence on effects on perinatal outcomes is mixed. This study investigates effects of Ramadan during pregnancy among Muslims in the Netherlands.Methods:Data from the Perinatal Registry of the Netherlands (Perined) on all births between 2000 and 2010 to mothers recorded as Mediterranean (i.e. of Turkish/Moroccan descent, a proxy for Muslim) (n = 139,322) or as ethnically Dutch (n = 1,481,435) were used. Ramadan exposure was defined using an intention-to-treat approach as the occurrence of a Ramadan during gestation. Muslims with versus without a Ramadan occurring during gestation were compared using difference-in-differences analyses. In these multiple linear/logistic regressions, non-Muslims were additionally included in order to take out potentially remaining confounding through seasonal effects.Results:The occurrence of a Ramadan during pregnancy among Muslims was not associated with altered birth weight, gestational length, newborn's sex, perinatal mortality, low Apgar, or mild congenital anomalies. Odds for severe congenital anomalies were higher among the exposed (odds ratio: 1.17; 95% confidence interval: 1.00, 1.37), but this association became non-significant when adjusting for multiple testing.Conclusions:Despite earlier research showing long-term adverse health effects of prenatal exposure to Ramadan, there seems to be little or no relation between exposure to Ramadan during pregnancy and birth outcomes

Ramadan exposure and birth outcomes: A population-based study from the Netherlands

Background:Ramadan, the Islamic month of daytime fasting, is observed by many pregnant Muslims. Although pregnant women are exempt, many prefer to fast. Previous research has shown long-term adverse effects on various health outcomes among the offspring, but evidence on effects on perinatal outcomes is mixed. This study investigates effects of Ramadan during pregnancy among Muslims in the Netherlands.Methods:Data from the Perinatal Registry of the Netherlands (Perined) on all births between 2000 and 2010 to mothers recorded as Mediterranean (i.e. of Turkish/Moroccan descent, a proxy for Muslim) (n = 139,322) or as ethnically Dutch (n = 1,481,435) were used. Ramadan exposure was defined using an intention-to-treat approach as the occurrence of a Ramadan during gestation. Muslims with versus without a Ramadan occurring during gestation were compared using difference-in-differences analyses. In these multiple linear/logistic regressions, non-Muslims were additionally included in order to take out potentially remaining confounding through seasonal effects.Results:The occurrence of a Ramadan during pregnancy among Muslims was not associated with altered birth weight, gestational length, newborn's sex, perinatal mortality, low Apgar, or mild congenital anomalies. Odds for severe congenital anomalies were higher among the exposed (odds ratio: 1.17; 95% confidence interval: 1.00, 1.37), but this association became non-significant when adjusting for multiple testing.Conclusions:Despite earlier research showing long-term adverse health effects of prenatal exposure to Ramadan, there seems to be little or no relation between exposure to Ramadan during pregnancy and birth outcomes

Ramadan fasting and newborn's birth weight in pregnant Muslim women in The Netherlands

Many Muslim women worldwide are pregnant during Ramadan and adhere to Ramadan fasting during pregnancy. In the present study, we determined whether maternal adherence to Ramadan fasting during pregnancy has an impact on the birth weight of the newborn, and whether the effects differed according to trimester in which Ramadan fasting took place. A prospective cohort study was conducted in 130 pregnant Muslim women who attended antenatal care in Amsterdam and Zaanstad, The Netherlands. Data on adherence to Ramadan fasting during pregnancy and demographics were self-reported by pregnant women, and the outcome of the newborn was retrieved from medical records after delivery. The results showed that half of all the women adhered to Ramadan fasting. With strict adherence to Ramadan fasting in pregnancy, the birth weight of newborns tended to be lower than that of newborns of non-fasting mothers, although this was not statistically significant ( - 198 g, 95 % CI - 447, 51, P= 0·12). Children of mothers who fasted in the first trimester of pregnancy were lighter at birth than those whose mothers had not fasted ( - 272 g, 95 % CI - 547, 3, P= 0·05). There were no differences in birth weight between children whose mothers had or had not fasted if Ramadan fasting had taken place later in pregnancy. Ramadan fasting during early pregnancy may lead to lower birth weight of newborns. These findings call for further confirmation in larger studies that should also investigate potential implications for perinatal and long-term morbidity and mortalit