According to the current World Health Organization guidelines, the drug prevention of malaria during pregnancy does not adequately cover the first trimester of gestation in high-transmission areas. ...Although the pathophysiological mechanisms of early infections are not completely understood yet, a review of the most recent studies on the topic suggests that their consequences are serious in terms of maternal anemia and low birth weight. Consequently, there is a need to focus on the awareness of women in a period hard to access, to develop safe drugs to be used in the first trimester, and to consider preconceptional interventions in teenage girls, such as a new malaria vaccine to be used in pregnancy.
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The spread of extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-PE) in low-income countries, where the burden of neonatal sepsis is high, may have a serious impact on neonatal ...mortality rates. Given the potential for mother-to-child transmission of multiresistant bacteria, this study investigated the ESBL-PE rectal colonization among pregnant women at delivery in the community in Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to 22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo-β-lactamase-1 (NDM-1) producer.
Long-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a ...high proportion of silent (non-symptomatic) infections and limited testing resources.
We used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing.
In the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6-224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34-66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19-36% probability of detecting outbreaks prior to any nosocomial transmission, and 26-46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16-27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6-9 additional tests and 11-28 additional swabs to detect outbreaks 1-6 days earlier, prior to an additional 11-22 infections.
COVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we ...assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. Methods. A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. Results. Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. Discussions. We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy.
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Data of next-generation sequencing (NGS) and their analysis have been facilitating advances in our understanding of microbial ecosystems such as human gut microbiota. However, inference of microbial ...interactions occurring within an ecosystem is still a challenge mainly due to sequencing data (e.g., 16S rDNA sequences) providing relative abundance of microbes instead of absolute cell count. In order to describe growtth dynamics of microbial communities and estimate the involved microbial interactions, we introduce a procedure by integrating generalized Lotka-Volterra equations, forward stepwise regression and bootstrap aggregation. First, we successfully identify experimentally confirmed microbial interactions based on relative abundance data of a cheese microbial community. Then, we apply the procedure to time-series of 16S rDNA sequences of gut microbiomes of children who were progressing to Type 1 diabetes (T1D progressors), and compare their gut microbial interactions to a healthy control group. Our results suggest that the number of inferred microbial interactions increased over time during the first 3 years of life. More microbial interactions are found in the gut flora of healthy children than that of T1D progressors. The inhibitory effects from
and
to
, from
to
, and the beneficial effect from
to
are shared between healthy children and T1D progressors. An inhibition of
by
is found in healthy children that maintains through their first 3 years of life. This suppression appears in T1D progressors during the first year of life, which transforms to a commensalism relationship at the age of 3 years old.
is found exerting an inhibition on
in the T1D progressors, which is not identified in the healthy controls.
Antibiotic resistance is a global public health issue, particularly in low- and middle-income countries (LMICs), where antibiotics required to treat resistant infections are not affordable. LMICs ...also bear a disproportionately high burden of bacterial diseases, particularly among children, and resistance jeopardizes progress made in these areas. Although outpatient antibiotic use is a major driver of antibiotic resistance, data on inappropriate antibiotic prescribing in LMICs are scarce at the community level, where the majority of prescribing occurs. Here, we aimed to characterize inappropriate antibiotic prescribing among young outpatient children and to identify its determinants in 3 LMICs.
We used data from a prospective, community-based mother-and-child cohort (BIRDY, 2012 to 2018) conducted across urban and rural sites in Madagascar, Senegal, and Cambodia. Children were included at birth and followed-up for 3 to 24 months. Data from all outpatient consultations and antibiotics prescriptions were recorded. We defined inappropriate prescriptions as antibiotics prescribed for a health event determined not to require antibiotic therapy (antibiotic duration, dosage, and formulation were not considered). Antibiotic appropriateness was determined a posteriori using a classification algorithm developed according to international clinical guidelines. We used mixed logistic analyses to investigate risk factors for antibiotic prescription during consultations in which children were determined not to require antibiotics. Among the 2,719 children included in this analysis, there were 11,762 outpatient consultations over the follow-up period, of which 3,448 resulted in antibiotic prescription. Overall, 76.5% of consultations resulting in antibiotic prescription were determined not to require antibiotics, ranging from 71.5% in Madagascar to 83.3% in Cambodia. Among the 10,416 consultations (88.6%) determined not to require antibiotic therapy, 25.3% (n = 2,639) nonetheless resulted in antibiotic prescription. This proportion was much lower in Madagascar (15.6%) than in Cambodia (57.0%) or Senegal (57.2%) (p < 0.001). Among the consultations determined not to require antibiotics, in both Cambodia and Madagascar the diagnoses accounting for the greatest absolute share of inappropriate prescribing were rhinopharyngitis (59.0% of associated consultations in Cambodia, 7.9% in Madagascar) and gastroenteritis without evidence of blood in the stool (61.6% and 24.6%, respectively). In Senegal, uncomplicated bronchiolitis accounted for the greatest number of inappropriate prescriptions (84.4% of associated consultations). Across all inappropriate prescriptions, the most frequently prescribed antibiotic was amoxicillin in Cambodia and Madagascar (42.1% and 29.2%, respectively) and cefixime in Senegal (31.2%). Covariates associated with an increased risk of inappropriate prescription include patient age greater than 3 months (adjusted odds ratios (aOR) with 95% confidence interval (95% CI) ranged across countries from 1.91 1.63, 2.25 to 5.25 3.85, 7.15, p < 0.001) and living in rural as opposed to urban settings (aOR ranged across countries from 1.83 1.57, 2.14 to 4.40 2.34, 8.28, p < 0.001). Diagnosis with a higher severity score was also associated with an increased risk of inappropriate prescription (aOR = 2.00 1.75, 2.30 for moderately severe, 3.10 2.47, 3.91 for most severe, p < 0.001), as was consultation during the rainy season (aOR = 1.32 1.19, 1.47, p < 0.001). The main limitation of our study is the lack of bacteriological documentation, which may have resulted in some diagnosis misclassification and possible overestimation of inappropriate antibiotic prescription.
In this study, we observed extensive inappropriate antibiotic prescribing among pediatric outpatients in Madagascar, Senegal, and Cambodia. Despite great intercountry heterogeneity in prescribing practices, we identified common risk factors for inappropriate prescription. This underscores the importance of implementing local programs to optimize antibiotic prescribing at the community level in LMICs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although consequences of malaria in pregnancy are well known, the period of pregnancy in which infection has the highest impact is still unclear. In Benin, we followed up a cohort of 1,037 women ...through pregnancy until delivery. The objective was to evaluate the relationship between the timing of infection and birth weight, and maternal anemia at delivery. At the beginning of pregnancy, peripheral infections were associated with a decrease in mean birth weight (-98.5 g; P = 0.03) and an increase in the risk of anemia at delivery (adjusted odds ratio aOR = 1.6; P = 0.03). Infections in late pregnancy were related to a higher risk of maternal anemia at delivery (aOR = 1.7; P = 0.001). To fully protect the women during the whole pregnancy, already implemented measures (insecticide-treated nets and intermittent preventive treatment) should be reinforced. In the future, a vaccine against pregnancy-associated malaria parasites could protect the women in early pregnancy, which seems to be a high-risk period.
Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to ...estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal. From October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram's coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATAR through univariate and multivariate analysis. A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) 95% CI 15.4-22.6) and was similar in suburban and rural areas (18.9% versus 18.1%, p = 0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR 0.35 95% CI 0.17-0.72). Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.
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ABSTRACT
The protein O-mannosyltransferase catalyzes O-mannosylation in the endoplasmic reticulum by transferring mannose to the seryl or threonyl residues of substrate proteins. We previously ...reported a deletion mutant of O-mannosyltransferase C (ΔpmtC) in Aspergillus nidulans with impaired vegetative growth and sterigmatocystin (ST) production. In this study, we investigated whether osmotic conditions contribute to the developmental processes and ST biosynthesis of the ΔpmtC deletion mutant. We found that hyphal growth and ST production partially improved in the presence of NaCl, KCl or sorbitol as osmotic stabilizers. Conidiation of the ΔpmtC deletion mutant was not restored under osmotic stress conditions when the hogA gene was deleted. The hogA gene encodes a protein required for the cellular response to osmotic pressure. However, the yield of ST and the vegetative growth of the ΔhogA ΔpmtC double deletant was restored by high osmolarity in a HogA-independent manner.
Osmotic stress plays an essential role in developmental morphogenesis and stergimatocystin production in Aspergillus nidulans ΔpmtC deletion mutants.
Aspergillus nidulans
produces sterigmatocystin (ST), a precursor of a carcinogenic secondary metabolite aflatoxin (AF), during its developmental process. ST biosynthesis has been shown to be affected ...by various regulatory factors. In this study, we investigated the involvement of
O-
mannosyltransferases (PmtA, PmtB, PmtC), in ST production and morphological development. Deletion of
pmtA
(Δ
pmtA
),
pmtB
(Δ
pmtB
) or
pmtC
(Δ
pmtC
) caused no spore production and a significant decline of vegetative growth. A tremendous decline of ST level was observed in all Δ
pmt
mutants at the third day after inoculation. By extending the growth period, ST production of Δ
pmtA
and Δ
pmtB
increased to the wild-type level 7 days after inoculation. On the other hand, ST was not detected from 7- or 14-day cultures in Δ
pmtC
. Expression levels of
aflR
gene, an essential regulator of the ST biosynthesis pathway, were also down-regulated in the Δ
pmt
strains. By introducing the
aflR
overexpression cassette, ST production in the Δ
pmtA
and Δ
pmtB
significantly increased to levels comparable to the wild type. However, the presence of the
aflR
overexpression cassette could not improve ST production in the Δ
pmtC
mutant. These data suggest that the PMT family is a new endogenous factor that is required for ST biosynthesis in
A. nidulans
. These findings provide better understanding of the regulatory mechanisms of AF/ST biosynthesis, which can ultimately contribute to our ability to control aflatoxin contamination.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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