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Nymphaea tetragona Georgi (Nymphaceae) is traditionally used in Asia for the treatment of diarrhea, dysentery and fever. The plant contains various active compounds, including methyl gallate (MG) which are reported to inhibit bacterial virulence mechanisms. This study aimed to evaluate the alterations on viability, membrane potential and integrity of Salmonella enterica Serovar Typhimurium exposed to MG in combination with Tylosin (Ty), which is relatively inactive against Gram-negative bacteria, but it is commonly used as a feed additive in livestock. Besides, the effects of sub-inhibitory concentrations of the combination (MT) on the interaction between S. Typhimurium and the host cell, as well as on the indirect host responses, were characterized. Flow cytometry, confocal and electron microscopic examinations were undertaken to determine the effects of MT on S. Typhimurium. The impacts of sub-inhibitory concentrations of MT on biofilm formation, as well as on the adhesion, invasion and intracellular survival of S. Typhimurium were assessed. The result demonstrated significant damage to the bacterial membrane, leakage of cell contents and a reduction in the membrane potential when treated with MT. Sub-inhibitory concentrations of MT significantly reduced (P < 0.05) the biofilm-forming, adhesive and invasive abilities of S. Typhimurium. Exposure to MT drastically reduced the bacterial count in macrophages. Up-regulation of interleukin (IL)-6, IL-8 and IL-10 cytokine genes were detected in intestinal epithelial cells pre-treated with MT. This report is the first to describe the effects of MT against S. Typhimurium. The result indicates a synergistic interaction between MG and Ty against S. Typhimurium. Therefore, the combination may be a promising option to combat S. Typhimurium in swine and, indirectly, safeguard the health of the public. [ABSTRACT FROM AUTHOR]

Background: Severe falciparum malaria is a medical emergency characterised by potentially lethal vital organ dysfunction. Patient fatality rates even with parenteral artesunate treatment remain high. Despite considerable research into adjuvant therapies targeting organ and tissue dysfunction, none have shown efficacy apart from renal replacement therapy. Understanding the causal contributions of clinical and laboratory abnormalities to mortality is essential for the design and evaluation of novel therapeutic interventions.Methods and Findings: We used a structural model causal inference approach to investigate causal relationships between epidemiological, laboratory, and clinical variables in patients with severe falciparum malaria enrolled in clinical trials and their in-hospital mortality. Under this causal model, we analysed records from 9,040 hospitalised children (0-12 years, n = 5,635) and adults (n = 3,405, 12-87 years) with severe falciparum malaria from 15 countries in Africa and Asia who were studied prospectively over the past 35 years. On admission, patient covariates associated with increased in-hospital mortality were severity of acidosis (odds ratio [OR] 2.10 for a 7-mEq/L increase in base deficit [95% CI 1.93-2.28]), renal impairment (OR 1.71 for a 2-fold increase in blood urea nitrogen [95% CI 1.58, 1.86]), coma (OR 3.59 [95% CI 3.07-4.21]), seizures (OR 1.40 [95% CI 1.16-1.68]), shock (OR 1.51 [95% CI 1.14-1.99]), and presumed pulmonary oedema (OR 1.58 [95% CI 1.04-2.39]). Lower in-hospital mortality was associated with moderate anaemia (OR 0.87 for a decrease of 10 percentage points in haematocrit [95% CI 0.80-0.95]). Circulating parasite density was not associated with mortality (OR 1.02 for a 6-fold increase [95% CI 0.94-1.11]), so the pathological effects of parasitaemia appear to be mediated entirely by the downstream effects of sequestration. Treatment with an artemisinin derivative decreased mortality compared with quinine (OR 0.64 [95% CI 0.56-0.74]). These estimates were consistent across children and adults (mainly representing African and Asian patients, respectively). Using inverse probability weighting, transfusion was not estimated to be beneficial in children with admission haematocrit values between 15% and 25% (OR 0.99 [95% CI 0.97-1.02]). Except for the effects of artemisinin treatment and transfusion, causal interpretations of these estimates could be biased by unmeasured confounding from severe bacterial sepsis, immunity, and duration of illness.Conclusion: These data suggest that moderate anaemia is associated with a reduced risk of death in severe falciparum malaria. This is possibly a direct causal association. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered. [ABSTRACT FROM AUTHOR]

Structural and individual level factors in prisons create challenges towards detection and management of HIV/tuberculosis. WHO and India’s HIV/tuberculosis control programs recommend intensified case finding in prisons. Low HIV and tuberculosis detection rates suggest poor implementation of existing surveillance strategies within the prison healthcare system in Mizoram’s capital city of Aizawl. We explored the operational feasibility of implementing the intensified case finding strategy in Aizawl central prison. We implemented the intensified screening through entry screening of new inmates, mass screening of resident inmates and exit screening at release. We set up digital chest radiography, sputum smear microscopy and HIV testing facilities within the prison and referral to external facility for Cartridge Based Nucleic Acid Amplification Test (CBNAAT). We screened 738 inmates (Male: 626; Female: 112). Of 53% inmates having presumptive tuberculosis symptoms, 37% underwent sputum microscopy. We detected 14 new tuberculosis cases; overall tuberculosis positivity 1.9%. We tested 65% of 657 inmates for HIV, of which 41 new cases were detected; overall HIV positivity 16.5%. Three male inmates had HIV-tuberculosis co-infection. It is feasible to implement intensified case detection for tuberculosis/HIV in the prison with inter-departmental coordination, albeit with certain challenges. [ABSTRACT FROM AUTHOR]

Background: Strongyloides stercoralis is a neglected soil-transmitted helminth that occurs worldwide, though it is particularly endemic in tropical and subtropical areas. It can cause long-lasting and potentially fatal infections due to its ability to replicate within its host. S. stercoralis causes gastrointestinal and dermatological morbidity. The objective of this study was to assess the S. stercoralis infection risk and, using geostatistical models, to predict its geographical distribution in Cambodia. Methodology / Principal findings: A nation-wide, community-based parasitological survey was conducted among the Cambodian population, aged 6 years and older. S. stercoralis was diagnosed using a serological diagnostic test that detects IgG antibodies in urine. Data on demography, hygiene and knowledge about helminth infection were collected. S. stercoralis prevalence among 7,246 participants with a complete data record was 30.5%, ranging from 10.9% to 48.2% across provinces. The parasite was ubiquitous in Cambodia; only five south-eastern provinces had prevalence rates below 20%. Infection risk increased with age for both men and women, although girls under the age of 13 and women aged 50 years and over had lower odds of infection than their male counterparts. Open defecation was associated with higher odds of infection, while having some knowledge of the health problems caused by worms was a protective factor. Infection risk was positively associated with nighttime maximum temperature, minimum rainfall, and distance to water; it was negatively associated with land occupied by rice fields. Conclusions / Significance: S. stercoralis infection is rampant in Cambodia. Control programs delivering ivermectin are needed to manage the parasite. However, the high cost of this drug in Cambodia currently precludes the implementation of control initiatives. Donations, subsidies or affordable generics are needed so that S. stercoralis, which infects almost a third of the Cambodian population, can be addressed through an adequate control program. [ABSTRACT FROM AUTHOR]

Background: Population Services International (PSI) Myanmar’s social franchise network of general practitioners, known as Sun Quality Health Clinics (SQHC), provided tuberculosis (TB) diagnosis and treatment with Direct Observed Treatment Short course (DOTs) across Myanmar since 2004, with a total of 898 clinics across the country. People who sought TB treatment from these SQHC by themselves were regarded as walk-in patients. To augment TB case notification, PSI Myanmar developed two treatment seeking channels: Community Health Services Providers (CHSP) and Interpersonal Communicators (IPC). They actively sought people who were suspected to have TB and referred them to SQH clinics. In this study, we compared the loss to follow-up rates of TB patients across three treatment seeking channels; and investigated risk-factors for loss to follow-up. Methods and findings: A retrospective cohort design was applied using TB client records between 2012 and 2016. Outcome was defined as loss to follow-up in comparison to successful TB treatment (completed or cured). Multivariate Poisson regression was conducted to estimate incidence rate ratio of loss to follow-up. Of the 62,664 TB patients registered at the SQHC, around 10% each were actively screened by the CHSP and the IPC, and 78.9% were walk-in patients. Overall cumulative incidence for loss to follow-up rate was significantly higher in the IPC channel (14.2%, 95% CI 13.4–15.1%) than walk-in patients (8.9%, 95% CI 8.6–9.1%) and the CHSP channel (5.5%, 95% CI 5.0–6.1%) (p<0.001). The median time after which patients were lost to follow-up from treatment was 4.04 months. We found that patients with older age, male sex, patients residing in hilly region, unknown smear status, retreated cases, HIV co-infection, and unknown HIV status were risk-factors for loss to follow-up in the continuation phase of treatment; whereas patients with higher initial body weight, patients who received travel support and patients taking treatment in older providers were less likely to be lost to follow-up. Conclusions: Based on these findings, we recommend that implementation strategies for improving case notification and treatment seeking should carefully consider retention strategies in parallel, and the identified influencing factors for loss to follow-up should be taken account for such consideration. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID99) of HTNV by the intramuscular and ~1 ID99 of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID99 of PUUV by the intramuscular or ~1 ID99 of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. In marmosets a 1,000 PFU HTNV intramuscular challenge led to robust seroconversion and neutralizing antibody production. Similarly to the ferret model of HTNV infection, no renal impairment, serum viremia or viral dissemination to organs was detected in marmosets. This is the first report of hantavirus infection in ferrets and marmosets. [ABSTRACT FROM AUTHOR]

A new genus and species of non-hadrosaurid hadrosauroid, Gobihadros mongoliensis, is described from a virtually complete and undeformed skull and postcranial skeleton, as well as extensive referred material, collected from the Baynshire Formation (Cenomanian-Santonian) of the central and eastern Gobi Desert, Mongolia. Gobihadros mongoliensis is the first non-hadrosaurid hadrosauroid from the Late Cretaceous of central Asia known from a complete, articulated skull and skeleton. The material reveals the skeletal anatomy of a proximate sister taxon to Hadrosauridae in remarkable detail. Gobihadros is similar to Bactrosaurus johnsoni and Gilmoreosaurus mongoliensis, but can be distinguished from them in several autapomorphic traits, including the maximum number (three) of functional dentary teeth per tooth position, a premaxillary oral margin with a ‘double-layer morphology’, and a sigmoidal dorsal outline of the ilium with a well-developed, fan-shaped posterior process. All of these characters in Gobihadros are inferred to be convergent in Hadrosauridae. Phylogenetic analysis positions Gobihadros mongoliensis as a Bactrosaurus-grade hadrosauromorph hadrosauroid. Its relationship with Maastrichtian hadrosaurids from Asia (e.g., Saurolophus angustirostris, Kerberosaurus manakini, Wulagasaurus dongi, Kundurosaurus nagornyi) are sufficiently distant to indicate that these latter taxa owe their distribution to migration from North America across Beringia, rather than having a common Asian origin with Go. mongoliensis. [ABSTRACT FROM AUTHOR]

Objectives: Candida lusitaniae is an opportunistic yeast pathogen in certain high-risk patient populations/cohorts. The species exhibits an unusual antifungal susceptibility profile with tendency to acquire rapid resistance. Here, we describe prevalence of C. lusitaniae in clinical specimens in Kuwait, its antifungal susceptibility profile and role in neonatal fungemia. Methods: Clinical C. lusitaniae isolates recovered from diverse specimens during 2011 to 2017 were retrospectively analyzed. All isolates were identified by germ tube test, growth on CHROMagar Candida and by Vitek 2 yeast identification system. A simple species-specific PCR assay was developed and results were confirmed by PCR-sequencing of ITS region of rDNA. Antifungal susceptibility was determined by Etest. Minimum inhibitory concentrations (MICs) were recorded after 24 h incubation at 35°C. Results: Of 7068 yeast isolates, 134 (1.89%) were identified as C. lusitaniae including 25 (2.52%) among 990 bloodstream isolates. Species-specific PCR and PCR-sequencing of rDNA confirmed identification. Of 11 cases of neonatal candidemia, 9 occurred in NICU of Hospital A and are described here. Eight of 9 neonates received liposomal amphotericin B, which was followed by fluconazole in 7 and additionally by caspofungin in 2 cases as salvage therapy. Three of 8 (37.5%) patients died. No isolate exhibited reduced susceptibility to amphotericin B, fluconazole, voriconazole, caspopfungin, micafungin and anidulafungin. The MIC ± geometric mean values for amphotericin B, fluconazole, voriconazole, and caspofungin were as follows: 0.072 ± 0.037 μg/ml, 2.32 ± 0.49 μg/ml, 0.09 ± 0.01 μg/ml and 0.16 ± 0.08 μg/ml, respectively. Only two isolates exhibited reduced susceptibility to fluconazole. Conclusions: This study describes the prevalence and antifungal susceptibility profile of clinical C. lusitaniae isolates in Kuwait. No isolate showed reduced susceptibility to amphotericin B. The study highlights the emerging role of C. lusitaniae as a healthcare-associated pathogen capable of causing fungemia in preterm neonates and causing significant mortality. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is increasingly used for rapid bacterial identification. Studies of Burkholderia pseudomallei identification have involved small isolate numbers drawn from a restricted geographic region. There is a need to expand the reference database and evaluate B. pseudomallei from a wider geographic distribution that more fully captures the extensive genetic diversity of this species. Here, we describe the evaluation of over 650 isolates. Main spectral profiles (MSP) for 26 isolates of B. pseudomallei (N = 5) and other Burkholderia species (N = 21) were added to the Biotyper database. MALDI-TOF MS was then performed on 581 B. pseudomallei, 19 B. mallei, 6 B. thailandensis and 23 isolates representing a range of other bacterial species. B. pseudomallei originated from northeast and east Thailand (N = 524), Laos (N = 12), Cambodia (N = 14), Hong Kong (N = 4) and Australia (N = 27). All 581 B. pseudomallei were correctly identified, with 100% sensitivity and specificity. Accurate identification required a minimum inoculum of 5 x 107 CFU/ml, and identification could be performed on spiked blood cultures after 24 hours of incubation. Comparison between a dendrogram constructed from MALDI-TOF MS main spectrum profiles and a phylogenetic tree based on recA gene sequencing demonstrated that MALDI-TOF MS distinguished between B. pseudomallei and B. mallei, while the recA tree did not. MALDI-TOF MS is an accurate method for the identification of B. pseudomallei, and discriminates between this and other related Burkholderia species. [ABSTRACT FROM AUTHOR]