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Importantly, we found little evidence of resistance to first line anti-tuberculous agents in Kiribati MTBC strains. Interestingly, the Beijing strains are divided into two distinct branches, namely, branch-A and -B. Beijing-B strains, exhibiting the deletions RD, RD, RD and RD accounted for the majority of the Kiribati Beijing strains observed and were associated with clustering likely recent transmission.

When we compared the IS profile of the Beijing branches, all Beijing-B strains have a high band number profile as usually found for W-Beijing strains from Eastern Europe and Asia [19] while Beijing-A strains have a more unusual IS pattern with a low band number Figure 3. The subdivision of Beijing strains in different branches is an interesting finding that is in accordance with previous studies [18] , [20] , [21].

Our data further support the hypothesis that more recently evolved branches of the Beijing lineage are more adapted to spread and cause disease than more ancestral branches [20] , [22]. However, further studies investing larges sets of Beijing strains with valid phylogenetic markers are needed to further proof this and define pathobiological differences between different branches of the Beijing lineage e. Several other groups have also found region specific sub-lineages among Euro-American strains [23] — [25].

The very wide global distribution of Euro-American strains was not fully recognized until recently, largely because their valid identification is not possible by spoligotyping and IS typing alone, but requires loci MIRU-VNTR typing, ideally in combination with SNP typing as performed here [10]. More comprehensive investigations of the global and regional population structure of the Euro-American super-linage are needed for valid descriptions of the different sub-lineages and associations with clinical characteristics such as transmissibility or drug resistance, as already found for strains of the Beijing lineage in various settings [24].

This finding confirms previous observations by us and others that the discriminatory power of loci-MIRU-VNTR typing is less than that of IS typing for strains of particular groups of the Beijing lineage such as or [20] , [24].

However, it should be noted that the same phenomenon can be seen vice versa, meaning that clusters with strains having low IS band numbers less than four bands e. Beijing strains appear to be endemic in Kiribati; the high cluster rate and the overall close relationship strongly suggest ongoing endemic spread. The majority of clusters are formed by strains of the Beijing lineage 27 out of 43 clustered isolates , followed by one larger cluster formed by 6 S-type strains.

Accordingly, infection with a Beijing strain especially Beijing-B was found to be the strongest risk factor for being in a transmission chain. As patients infected with Beijing strains did not differ from patients with non-Beijing strain infection with regard to other patient characteristics, our data indicate a higher capability of Beijing-B strains to spread in this population and identifies them as one clear driver of the local TB epidemic.

Furthermore, when cluster data were compared to patient geographic origin, there was no clear association data not shown. We observed very little evidence of resistance to first line anti-tuberculous agents in Kiribati, with only three strains demonstrating reduced susceptibility to STR. In all cases, patients had never previously been treated for tuberculosis, suggesting primary drug resistance. No strain was resistant to any other first line agent.

This suggests an epidemic that has the potential to be controlled with active case finding and treatment with standard regimens. In the future, such efforts would ideally be aided by affordable rapid diagnostic tests, including systems e. While this study provides an important snapshot of the molecular epidemiology of pulmonary tuberculosis in Kiribati, it has a number of limitations. A factor that may have influenced culture results in this study was transit time between specimen collection and its arrival at the diagnostic facility in Noumea.

Flights out of Tarawa atoll only occur once per week, making transporting samples logistically challenging. Whilst prolonged transit times were associated with negative culture results, these were random events, not expected to influence the overall pattern of MTBC strains obtained and thus the MTBC strains cultured in this study are likely to be representative of those causing pulmonary TB in Kiribati.

The study findings are also limited by the paucity of patients who were tested for HIV. In conclusion, we report evidence of high rates of ongoing transmission of pulmonary TB in Kiribati, particularly among those infected with Beijing-B MTBC strains and in those living in crowded conditions. This provides the grounds for enhanced case finding amongst close contacts and continued supervised treatment of all identified cases using standard first-line drugs to reduce TB burden in Kiribati.

The importance of the sub classification of the Beijing lineage in different branches needs to be further investigated. We gratefully acknowledge the Ministry of Health and Medical Services, Kiribati, the participants of this study and all the TB nurses who supported recruitment in Kiribati. We thank T. We would like to thank the Secretariat of the Pacific Community for supporting this work including Ms. Kerrie Viney. Browse Subject Areas?

Click through the PLOS taxonomy to find articles in your field. Abstract Tuberculosis incidence rates in Kiribati are among the highest in the Western Pacific Region, however the genetic diversity of circulating Mycobacterium tuberculosis complex strains MTBC and transmission dynamics are unknown.

Introduction Tuberculosis is a major global health challenge with an estimated 9 million new active cases and 1. Materials and Methods Study population and sputum handling All patients with clinically suspected pulmonary TB who presented to the main TB centre in Kiribati at Tungaru Central Hospital, South Tarawa between November and October were eligible for this study, regardless of sputum smear SS result. Analysis of Beijing specific regions of difference RD, RD, RD and RD To further differentiate strains belonging to the Beijing lineage identified by the characteristic spoligotype, showing absence of spacer 1—34 we analysed all Beijing strains by PCR to determine the presence or absence of specific regions of difference RD.

Download: PPT. Table 2. Factors associated with sputum sample being culture positive. Figure 1. Figure 3. Discussion This is the first molecular epidemiologic study of MTBC strains from Kiribati, a Western Pacific island nation experiencing very high rates of pulmonary tuberculosis.

Supporting Information. Table S1. Acknowledgments We gratefully acknowledge the Ministry of Health and Medical Services, Kiribati, the participants of this study and all the TB nurses who supported recruitment in Kiribati. References 1. In: Region WP, editor. In: Development MoFE, editor. Asia Pac J Public Health 86— View Article Google Scholar 6. Pac Health Dialog — View Article Google Scholar 7. Tawara: Secretariat of the Pacific Community. Journal of Rural and Tropical Public Health 44— View Article Google Scholar 9.

Van Soolingen D Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. J Intern Med 1— View Article Google Scholar Randrianasolo, Madhi Naser-Moghadasi. Beta-Measure for Probabilistic Segmentation. Scheme-Based Synthesis of Inductive Theories. A Possibilistic Intuitionistic Logic. Oscar A. Massive Particles for Brain Tractography. Back Matter. Other volumes Advances in Artificial Intelligence.

Advances in Soft Computing. About these proceedings Introduction Artificial intelligence AI is a branch of computer science that models the human ability of reasoning, usage of human language and organization of knowledge, solving problems and practically all other human intellectual abilities.

Usually it is charact- ized by the application of heuristic methods because in the majority of cases there is no exact solution to this kind of problem. MICAI conferences traditionally publish high-quality papers in all areas of arti- cial intelligence and its applications. Since its foun- tion in , the conference has been growing in popularity and improving in quality. Emotion artificial intelligence automatic image annotation constrained optimization distributed systems error correction coding evolutionary systems fuzzy logic image processing image segmentation knowledge-based systems learning medical diagnosis modeling natural language.

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Competing interests: The authors have declared that no competing interests exist. Tuberculosis is a major global health challenge with an estimated 9 million new active cases and 1. Detailed data on factors contributing to the relatively high incidence of TB in Kiribati and other smaller Pacific Island countries and territories are lacking, hampering the development of improved public health measures for TB control in the area. The Secretariat of the Pacific Community, New Caledonia, and World Health Organization play an essential role in collating basic regional surveillance data, supporting the local National TB program NTP [5] — [7] , and strengthening the limited infrastructure in Kiribati.

The Kiribati NTP is based in the capital, South Tarawa, and works with 21 surrounding island councils to provide TB services [8] , with patients referred to one of two sites for diagnosis and treatment South Tarawa atoll or Kiritimati island. Little is known about the success of treatment or of drug susceptibility of Mycobacterium tuberculosis complex MTBC strains in Kiribati.

There has already been at least one case of multi-drug resistant pulmonary TB in Kiribati in the patient died within a year of diagnosis and no family members were subsequently diagnosed with TB; O'Connor J, personal communication. Molecular epidemiology is a useful tool for analysing MTBC strain diversity and transmission patterns in both low and high incidence settings [9] , [10].

The specific aims of this study were to identify and evaluate the diversity of circulating MTBC strains, investigate parameters associated with TB transmission and to evaluate the level of drug resistance in Kiribati. Diagnosis of SS positive TB was confirmed by microscopic examination of three consecutive Ziehl-Neelsen stained sputum smears.

Patients answered a brief medical and demographic questionnaire. The IS patterns were digitised and analysed for similarity using the Dice coefficient and a band-matching tolerance of 1. For both methods, similarity trees were calculated using the UPGMA unweighted pair group method with arithmetic averages method as instructed by the manufacturer.

The priority rule was to link types first that had highest number of single-locus variants. To further differentiate strains belonging to the Beijing lineage identified by the characteristic spoligotype, showing absence of spacer 1—34 we analysed all Beijing strains by PCR to determine the presence or absence of specific regions of difference RD. Genomic regions were identified as previously described [18].

Descriptive statistics are presented as number percentage or median range. Univariate comparisons were performed using Chi square tests, Wilcoxon rank-sum test or Fisher's exact test, as appropriate. The demographic characteristics of the study participants are shown in Table 1. Results of HIV testing were recorded for only nine patients 5. No patient was found to be HIV infected.

The majority Factors associated with culture positivity were the number of AFB seen on microscopy samples with more AFB seen were more likely to be culture positive and the time taken for the sample to reach the culture facility in Noumea longer delays were associated with negative culture; Table 2. No multi-drug resistant strains were identified. The three patients from whom strains with reduced STR susceptibility were isolated all had negative HIV serology recorded, did not report previous TB treatment and lived on South Tarawa.

A further nine strains were found and appear to form a previously undefined branch that was denominated Kiribati-H37Rv-like. The phylogenetic tree Figure 1 describes the diverse lineages observed in Kiribati. These were confirmed using an MST Figure 2 that identified all lineages as clonal complexes.

Neighbour joining tree left panel based on the copy numbers of 24 loci MIRU-VNTR right panel, spoligotyping results whereby a repeat region's presence or absence is indicated by a black box or white box respectively of the 73 strains investigated. Classification of the strains into the different phylogenetic lineages is visualized by color coding, key on Figure 2. Classification of the strains into the different phylogenetic lineages is visualized by color coding. The successive deletion of RD and RD subdivide the Beijing family and was shown to be a robust marker reflecting the phylogeny of Beijing family strains [18].

Isolates were defined as non-clustered if they had unique, non-shared genotyping results. We therefore looked for associations between patient demographics and cluster classification. There was a tendency for patients infected with a clustered MTBC strain to live in a more crowded home median: 5 people living per room, interquartile range IQR : 1.

However, the factor most strongly associated with clustering was having TB caused by modern and more ancestral Beijing strains. Twenty-seven On logistic regression modelling, having a Beijing strain was the only factor independently associated with being in a cluster of TB cases Odds Ratio 3. This is the first molecular epidemiologic study of MTBC strains from Kiribati, a Western Pacific island nation experiencing very high rates of pulmonary tuberculosis.

Data regarding patterns of MTBC transmission are urgently needed to guide effective local control measures. We show that strains from multiple MTBC lineages are circulating in Kiribati, with the most prevalent being strains of Beijing lineage and that one novel phylogenetic lineage has emerged denoted Kiribati-H37RV-like.

Strains from the Beijing lineage are widespread geographically and occur more frequently in clusters, suggesting enhanced transmission. Importantly, we found little evidence of resistance to first line anti-tuberculous agents in Kiribati MTBC strains. Interestingly, the Beijing strains are divided into two distinct branches, namely, branch-A and -B. Beijing-B strains, exhibiting the deletions RD, RD, RD and RD accounted for the majority of the Kiribati Beijing strains observed and were associated with clustering likely recent transmission.

When we compared the IS profile of the Beijing branches, all Beijing-B strains have a high band number profile as usually found for W-Beijing strains from Eastern Europe and Asia [19] while Beijing-A strains have a more unusual IS pattern with a low band number Figure 3. The subdivision of Beijing strains in different branches is an interesting finding that is in accordance with previous studies [18] , [20] , [21].

Our data further support the hypothesis that more recently evolved branches of the Beijing lineage are more adapted to spread and cause disease than more ancestral branches [20] , [22]. However, further studies investing larges sets of Beijing strains with valid phylogenetic markers are needed to further proof this and define pathobiological differences between different branches of the Beijing lineage e.

Several other groups have also found region specific sub-lineages among Euro-American strains [23] — [25]. The very wide global distribution of Euro-American strains was not fully recognized until recently, largely because their valid identification is not possible by spoligotyping and IS typing alone, but requires loci MIRU-VNTR typing, ideally in combination with SNP typing as performed here [10]. More comprehensive investigations of the global and regional population structure of the Euro-American super-linage are needed for valid descriptions of the different sub-lineages and associations with clinical characteristics such as transmissibility or drug resistance, as already found for strains of the Beijing lineage in various settings [24].

This finding confirms previous observations by us and others that the discriminatory power of loci-MIRU-VNTR typing is less than that of IS typing for strains of particular groups of the Beijing lineage such as or [20] , [24]. However, it should be noted that the same phenomenon can be seen vice versa, meaning that clusters with strains having low IS band numbers less than four bands e.

Beijing strains appear to be endemic in Kiribati; the high cluster rate and the overall close relationship strongly suggest ongoing endemic spread. The majority of clusters are formed by strains of the Beijing lineage 27 out of 43 clustered isolates , followed by one larger cluster formed by 6 S-type strains. Accordingly, infection with a Beijing strain especially Beijing-B was found to be the strongest risk factor for being in a transmission chain.

As patients infected with Beijing strains did not differ from patients with non-Beijing strain infection with regard to other patient characteristics, our data indicate a higher capability of Beijing-B strains to spread in this population and identifies them as one clear driver of the local TB epidemic.

Furthermore, when cluster data were compared to patient geographic origin, there was no clear association data not shown. We observed very little evidence of resistance to first line anti-tuberculous agents in Kiribati, with only three strains demonstrating reduced susceptibility to STR.

In all cases, patients had never previously been treated for tuberculosis, suggesting primary drug resistance. No strain was resistant to any other first line agent. This service is more advanced with JavaScript available. Front Matter. Pages Afraz Z. Dialog Structure Automatic Modeling.

Ana C. Tenorio-Gonzalez, Eduardo F. Music Composition Based on Linguistic Approach. Line Maps in Cluttered Environments. Optimizing Alternatives in Precedence Networks. Eddy C. Borera, Larry D. Pyeatt, Arisoa S. Randrianasolo, Madhi Naser-Moghadasi. Beta-Measure for Probabilistic Segmentation.

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