A Longitudinal, Population-Level, Big-Data Study of Helicobacter pylori-Related Disease across Western Australia.

Helicobacter pylori, responsible for chronic ulcers and most stomach cancers, infects half of the world's population. The Urea Breath Test (UBT) is one of the most accurate and reliable non-invasive methods for diagnosing active H. pylori infection. The objective was to use longitudinal, population-wide UBT data for Western Australia to look for H. pylori-related disease patterns. We collected 95,713 UBT results from 77,552 individuals for the years 2010-2015, likely representing all of the UBT samples analysed in Western Australia. Data collected also included sex, age and residential postcode. Other data reported here were inferred via a comparison with the 2011 Australian Census using a specially written Python program. While women appear to have more H. pylori-related disease than men, there is no difference in the disease rates once women's higher rates of presentation for testing are taken into account. On the other hand, while the treatment strategy for H. pylori infection is generally very effective in Western Australia, failure of the first-line treatment is significantly more common in women than men. Migrants and Aboriginal Australians have elevated rates of H. pylori-related disease, while the rate for non-Aboriginal Australian-born West Australians is very low. However, no significant associations were found with other socio-economic indicators. We conclude that, for some people, H. pylori-related disease is not a solved problem.

Noninvasive Diagnosis of Irritable Bowel Syndrome via Bowel Sound Features: Proof of Concept.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common and debilitating disorder estimated to affect approximately 11% of the world's population. Typically, IBS is a diagnosis of exclusion after patients undergo a costly and invasive colonoscopy to exclude organic disease. Clinician's and researchers have identified a need for a new cost-effective, accurate, and noninvasive diagnostic test for IBS. METHODS: Using a diagnostic case-control study, we explored the use of bowel sounds to characterize IBS with a view to diagnostic use. We recruited participants with an existing clinical diagnosis of IBS or healthy (asymptomatic) digestive systems. We recorded bowel sounds for 2 hours after fasting and then for 40 minutes after a standard meal. RESULTS: We here report our results including our accuracy in characterizing IBS-related bowel sounds and differentiation between participants with IBS and healthy participants. Leave-one-out cross-validation of our model developed using the first 31 IBS and 37 healthy participants gave 90% sensitivity and 92% specificity for IBS diagnosis. Independent testing using the next 15 IBS and 15 healthy participants demonstrated 87% sensitivity and 87% specificity for IBS diagnosis. CONCLUSIONS: These preliminary results provide proof of concept for the use of bowel sound analysis to identify IBS. A prospective study is needed to confirm these findings. TRANSLATIONAL IMPACT: Our belt and model offer hope of a new approach for IBS diagnosis in primary practice. Combined with screening tests for organic disease, it would offer greater confidence to patients and could reduce the burden of unnecessary colonoscopies for health care systems and patients.

Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori.

BACKGROUND: Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug. METHODS: We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori. RESULTS: Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl-AMP synthase (HP0918). CONCLUSIONS: Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.

Gastric Helicobacter pylori infection perturbs human oral microbiota.

BACKGROUND: We investigated the effects of gastric Helicobacter pylori infection on the daytime and overnight human oral microbiota. METHODS: Twenty four volunteers were recruited. Ten tested positive for H. pylori infection by the Carbon-14 Urea Breath Test, and the rest were negative. Two oral swabs were collected: one immediately after waking up in the morning and before brushing teeth, and another in the evening before teeth-brushing. DNA extract acquired from each swab was subjected to Illumina sequencing of 16S rRNA gene amplicons. The microbial abundance and composition were analysed in relation to H. pylori infection status. RESULTS: Helicobacter pylori-positive individuals had significant changes in the alpha and beta diversities in the daytime samples in comparison to those who were H. pylori negative. To identify which taxa could be significantly affected within the cohorts in the daytime, we employed the LEfSe method. When compared against UBT-negative samples, significantly higher abundances were detected in both Pseudomonas and Roseomonas, while Fusobacterium, Solobacterium, Haemophilus and Streptococcus were significantly decreased in the UBT-positive samples. DISCUSSION: Our data demonstrated that H. pylori infection affects the human daytime oral microbiota. The hitherto undocumented changes of several bacterial genera due to H. pylori infection require more studies to examine their potential health effects on affected individuals.

Advances in Acoustic Signal Processing Techniques for Enhanced Bowel Sound Analysis.

With the invention of the electronic stethoscope and other similar recording and data logging devices, acoustic signal processing concepts and methods can now be applied to bowel sounds. In this paper, the literature pertaining to acoustic signal processing for bowel sound analysis is reviewed and discussed. The paper outlines some of the fundamental approaches and machine learning principles that may be used in bowel sound analysis. The advances in signal processing techniques that have allowed useful information to be obtained from bowel sounds from a historical perspective are provided. The document specifically address the progress in bowel sound analysis, such as improved noise reduction, segmentation, signal enhancement, feature extraction, localization of sounds, and machine learning techniques. We have found that advanced acoustic signal processing incorporating novel machine learning methods and artificial intelligence can lead to better interpretation of acoustic information emanating from the bowel.

The potential of computerised analysis of bowel sounds for diagnosis of gastrointestinal conditions: a systematic review.

BACKGROUND: Gastrointestinal (GI) conditions are highly prevalent, and their standard diagnostic tests are costly and carry risks. There is a need for new, cost-effective, non-invasive tests. Our main objective was to assess the potential for use of bowel sounds computerised analysis in the diagnosis of GI conditions. METHODS: The systematic review followed the PRISMA requirements. Searches were made of four databases (PubMed, MEDLINE, Embase, and IEEE Xplore) and the references of included papers. Studies of all types were included. The titles and abstracts were screened by one author. Full articles were reviewed and data collected by two authors independently. A third reviewer decided on inclusion in the event of disagreement. Bias and applicability were assessed via a QUADAS tool adapted to accommodate studies of multiple types. RESULTS: Two thousand eight hundred eighty-four studies were retrieved; however, only 14 studies were included. Most of these simply assessed associations between a bowel sound feature and a condition. Four studies also included assessments of diagnostic accuracy. We found many significant associations between a bowel sound feature and a GI condition. Receiver operating characteristic curve analyses revealed high sensitivity and specificity for an irritable bowel syndrome test, and a high negative predictive value for a test for post-operative ileus. Assessment of methodological quality identified weaknesses in all studies. We particularly noted a high risk of bias in patient selection. Because of the limited number of trials included and the variety in conditions, technology, and statistics, we were unable to conduct pooled analyses. CONCLUSIONS: Due to concerns over quality and small sample sizes, we cannot yet recommend an existing BSCA diagnostic test without additional studies. However, the preliminary results found in the included studies and the technological advances described in excluded studies indicate excellent future potential. Research combining sophistical clinical and engineering skills is likely to be fruitful. SYSTEMATIC REVIEW REGISTRATION: The review protocol (review ID number 42016054028) was developed by three authors (AI, KMW, and JM) and was published in the PROSPERO International prospective register of systematic reviews. It can be accessed from https://www.crd.york.ac.uk/PROSPERO/ .

A mathematical model of bowel sound generation.

Humans have been interested in bowel sounds and wondered about their origins for millennia. To better understand the phenomenon, a mathematical model of bowel sound generation was developed based on a spring-mass-damping system. This is similar to vocal folds models for speech. The bowel sound model has four parameters that link to bowel activities: the individual wave component, pressure index, component quantity, and component interval time. All types of bowel sound documented previously can be modelled by combining different values for these parameters. Further, a 2500 ms bowel sound incorporating all the common types was simulated to present the model's accuracy.

Helicobacter pylori overcomes natural immunity in repeated infections.

Repeated experimental reinfection of two subjects indicates that Helicobacter pylori infection does not promote an immune response protective against future reinfection. Our results highlight the importance of preventing reinfection after eradication, through public health initiatives, and possibly treatment of family members. They indicate difficulties for vaccine development, especially therapeutic vaccines.

Sexually transmitted disease epidemics in a natural insect population.

1. The epidemiology of sexually transmitted diseases (STDs) in human and domesticated populations is well documented. However, there has been less study of STDs in natural populations. 2. We investigated STD dynamics in the model system involving a host from the most speciose group of animals: the insects. We investigated temporal variation in the prevalence of the sexually transmitted mite Coccipolipus hippodamiae on its ladybird host, Adalia bipunctata. 3. Field surveys over two seasons showed a repeated pattern of a profound epidemic in the overwintered cohort and a later prevalence decline. 4. In order to understand the key factors in the dynamics of this system we studied the phenology of the host and simulated parasite dynamics in the overwintered cohort using a model with within-sex homogeneity in mating rate and field-measured parameter values. The similarity of natural and simulation prevalence levels allowed us to carry out sensitivity analysis and hence to identify the key determinants of the dynamics. 5. The observed pattern of periodic extreme prevalence combined with system persistence probably results from time lags in host recruitment and widespread promiscuity. 6. Our findings improve our understanding of STDs in natural populations and illustrate the importance of examining seasonality and time delays in population dynamics in order to fully understand the characteristics of natural populations and their parasites.

Measuring the transmission dynamics of a sexually transmitted disease.

Sexually transmitted diseases (STDs) occur throughout the animal kingdom and are generally thought to affect host population dynamics and evolution very differently from other directly transmitted infectious diseases. In particular, STDs are not thought to have threshold densities for persistence or to be able to regulate host population density independently; they may also have the potential to cause host extinction. However, these expectations follow from a theory that assumes that the rate of STD spread depends on the proportion (rather than the density) of individuals infected in a population. We show here that this key assumption ("frequency dependence"), which has not previously been tested in an animal STD system, is invalid in a simple and general experimental model. Transmission of an STD in the two-spot ladybird depended more on the density of infected individuals in the study population than on their frequency. We argue that, in this system, and in many other animal STDs in which population density affects sexual contact rate, population dynamics may exhibit some characteristics that are normally reserved for diseases with density-dependent transmission.

Sexually transmitted diseases of insects: distribution, evolution, ecology and host behaviour.

Sexually transmitted diseases (STDs) of insects are known from the mites, nematodes, fungi, protists and viruses. In total 73 species of parasite and pathogen from approximately 182 species of host have been reported. Whereas nearly all vertebrate STDs are viruses or bacteria, the majority of insect STDs are multicellular ectoparasites, protistans or fungi. Insect STDs display a range of transmission modes, with 'pure' sexual transmission only described from ectoparasites, all of which are mites, fungi or nematodes, whereas the microparasitic endo-parasites tend to show vertical as well as sexual transmission. The distribution of STDs within taxa of insect hosts appears to be related to the life histories of the hosts. In particular, STDs will not be able to persist if host adult generations do not overlap unless they are also transmitted by some alternative route. This explains the observation that the Coleoptera seem to suffer from more STDs than other insect orders, since they tend to diapause as adults and are therefore more likely to have overlapping generations of adults in temperate regions. STDs of insects are often highly pathogenic, and are frequently responsible for sterilizing their hosts, a feature which is also found in mammalian STDs. This, combined with high prevalences indicates that STDs can be important in the evolution and ecology of their hosts. Although attempts to demonstrate mate choice for uninfected partners have so far failed it is likely that STDs have other effects on host mating behaviour, and there is evidence from a few systems that they might manipulate their hosts to cause them to mate more frequently. STDs may also play a part in sexual conflict, with males in some systems possibly gaining a selective advantage from transmitting certain STDs to females. STDs may well be important factors in host population dynamics, and some have the potential to be useful biological control agents, but empirical studies on these subjects are lacking.

The effect of aggregative overwintering on an insect sexually transmitted parasite system.

In contrast to the extensively studied sexually transmitted diseases (STDs) of humans, little is known of the ecology or evolutionary biology of sexually transmitted parasites in natural systems. This study of a sexually transmitted parasite on an insect host augments our understanding of both the parasite's population dynamics and virulence effects. The impact of overwintering was assessed on the prevalence of the parasitic mite Coccipolipus hippodamiae on the two-spot ladybird, Adalia bipunctata. First, the effect of infection on host survival was examined during the stressful overwintering period. Box experiments in the field revealed that the infected ladybirds, especially males, are less likely to survive overwintering. The study provides the first evidence that the parasite harms males and suggests revisions of theories on the adaptive virulence of sexually transmitted parasites. It also indicates the importance of using a range of experimental conditions because virulence can be dependent on host condition and sex. Box experiments were also used to examine whether transmission of the parasite occurs within overwintering aggregations. These revealed that substantial transmission does not occur in aggregations and that transmission is predominantly sexual. Overall, the virulence effects and the lack of transmission mean that the overwintering period acts to diminish parasite prevalence and will retard the spring epidemic associated with host reproductive activity.