<i>Haemophilus ducreyi</i>Associated with Skin Ulcers among Children, Solomon Islands

Marks, Michael; Chi, Kai-Hua; Vahi, Ventis; Pillay, Allan; Sokana, Oliver; Pavluck, Alex; Mabey, David; Chen, Cheng Y.; Solomon, Anthony W.

doi:10.3201/eid2010.140573

Cited by 73 publications

(84 citation statements)

References 13 publications

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“…Lesions not associated with positive serology may reflect early yaws before conversion, recent treatment of yaws with declining RPR titers, misclassification of the lesion by survey personnel, or alternative aetiologies of ulcerative skin lesions. Haemophilus ducreyi has recently been identified as a possible causative agent of yaws-like lesions in the Pacific region 18–20…”

Section: Discussionmentioning

confidence: 99%

Mapping the Epidemiology of Yaws in the Solomon Islands: A Cluster Randomized Survey

Marks¹,

Vahi²,

Sokana³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Yaws, a non-venereal treponemal disease, is targeted for eradication by 2020 but accurate epidemiological data to guide control programs remain sparse. The Solomon Islands reports the second highest number of cases of yaws worldwide. We conducted a cluster randomized survey of yaws in two provinces of the Solomon Islands. One thousand four hundred and ninety-seven (1,497) children 5–14 years of age were examined. Clinical signs of active yaws were found in 79 children (5.5%), whereas 140 children (9.4%) had evidence of healed yaws lesions. Four hundred and seventy (470) (31.4%) children had a positive Treponema pallidum particle agglutination assay (TPPA). Two hundred and eighty-five (285) children (19%) had a positive TPPA and rapid plasma regain assay. Risk of yaws increased with age and was more common in males. The prevalence of yaws at village level was the major risk factor for infection. Our findings suggest the village, not the household, should be the unit of treatment in the World Health Organization (WHO) yaws eradication strategy.

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Section: Discussionmentioning

confidence: 99%

Mapping the Epidemiology of Yaws in the Solomon Islands: A Cluster Randomized Survey

Marks¹,

Vahi²,

Sokana³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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“…pertenue, recent studies performed as part of a World Health Organization-directed yaws eradication campaign suggest that H. ducreyi is a major cause of this syndrome. In three large cross-sectional community surveys, the proportion of ulcers in which H. ducreyi DNA was detected greatly exceeded that of T. pallidum DNA (9)(10)(11). Considering the global prevalence of yaws, infections due to H. ducreyi may be much more common than was previously recognized.…”

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confidence: 94%

DksA and (p)ppGpp Have Unique and Overlapping Contributions to Haemophilus ducreyi Pathogenesis in Humans

et al. 2015

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jThe (p)ppGpp-mediated stringent response is important for bacterial survival in nutrient limiting conditions. For maximal effect, (p)ppGpp interacts with the cofactor DksA, which stabilizes (p)ppGpp's interaction with RNA polymerase. We previously demonstrated that (p)ppGpp was required for the virulence of Haemophilus ducreyi in humans. Here, we constructed an H. ducreyi dksA mutant and showed it was also partially attenuated for pustule formation in human volunteers. To understand the roles of (p)ppGpp and DksA in gene regulation in H. ducreyi, we defined genes potentially altered by (p)ppGpp and DksA deficiency using transcriptome sequencing (RNA-seq). In bacteria collected at stationary phase, lack of (p)ppGpp and DksA altered expression of 28% and 17% of H. ducreyi open reading frames, respectively, including genes involved in transcription, translation, and metabolism. There was significant overlap in genes differentially expressed in the (p)ppGpp mutant relative to the dksA mutant. Loss of (p)ppGpp or DksA resulted in the dysregulation of several known virulence determinants. Deletion of dksA downregulated lspB and rendered the organism less resistant to phagocytosis and increased its sensitivity to oxidative stress. Both mutants had reduced ability to attach to human foreskin fibroblasts; the defect correlated with reduced expression of the Flp adhesin proteins in the (p)ppGpp mutant but not in the dksA mutant, suggesting that DksA regulates the expression of an unknown cofactor(s) required for Flp-mediated adherence. We conclude that both (p)ppGpp and DksA serve as major regulators of H. ducreyi gene expression in stationary phase and have both overlapping and unique contributions to pathogenesis. Haemophilus ducreyi is the causative agent of chancroid, a sexually transmitted genital ulcer disease that facilitates both the transmission and acquisition of HIV-1 (1). Chancroid has a short duration of infectivity and is maintained only in populations with high sex partner change rates, such as commercial sex workers (2). Due to widespread implementation of syndromic management of genital ulcers, the epidemiology of chancroid is poorly defined, but its prevalence has declined in many areas where chancroid formerly was endemic (2). However, reports of chancroid persist from several countries in Africa and Asia, implying that these regions have clinical reservoirs of infected sex workers (3-8).Although non-sexually-transmitted cutaneous ulcers in children in the South Pacific islands and equatorial Africa are usually attributed to Treponema pallidum subsp. pertenue, recent studies performed as part of a World Health Organization-directed yaws eradication campaign suggest that H. ducreyi is a major cause of this syndrome. In three large cross-sectional community surveys, the proportion of ulcers in which H. ducreyi DNA was detected greatly exceeded that of T. pallidum DNA (9-11). Considering the global prevalence of yaws, infections due to H. ducreyi may be much more common than was previously recognized. Thu...

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“…In Ghana and the Solomon Islands, H . ducreyi DNA was detected in 9% to 32% of CU, and no other pathogen DNA was detected [1, 9, 12]. The reasons for the variation in the sensitivities of the PCR-based tests in these studies are unclear; but the data suggest that a substantial proportion of cases of CU may be caused by organism(s) that are yet to be identified.…”

Section: Introductionmentioning

confidence: 99%

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies

Gangaiah

Spinola

2016

PLoS Negl Trop Dis

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BackgroundHaemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown.Methodology/Principal FindingsWe performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree.Conclusions/SignificanceCU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

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Haemophilus ducreyiAssociated with Skin Ulcers among Children, Solomon Islands

Cited by 73 publications

References 13 publications

Mapping the Epidemiology of Yaws in the Solomon Islands: A Cluster Randomized Survey

Mapping the Epidemiology of Yaws in the Solomon Islands: A Cluster Randomized Survey

DksA and (p)ppGpp Have Unique and Overlapping Contributions to Haemophilus ducreyi Pathogenesis in Humans

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies

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