Yaws Eradication

@article{10.1371/journal.pntd.0011319b,

title = {Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis},

author = {Abdullah Alshehri and Yashpal S. Chhonker and Veenu Bala and Constant Edi and Catherine M. Bjerum and Benjamin G. Koudou and Lucy N. John and Oriol Mitjà and Michael Marks and Christopher L. King and Daryl J. Murry},

doi = {10.1371/journal.pntd.0011319},

year  = {2023},

date = {2023-01-01},

journal = {PLOS Neglected Tropical Diseases},

volume = {17},

number = {6},

pages = {1-17},

publisher = {Public Library of Science},

abstract = {Background Ivermectin (IVM) is a broad–spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple–drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub–Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single–oral dose in LF–infected subjects and healthy individuals. Methodology / Principal findings In this analysis, 724 samples were collected from treatment–naïve Wuchereria bancrofti–infected (n = 32) and uninfected (n = 24) adults living in Côte d’Ivoire who had received one dose of IVM as a part of triple–drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two–compartment model with zero–order dose input into the absorption compartment with a lag time function followed by first–order absorption and linear elimination best described the IVM’s pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex. Conclusion/Significance We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF. Trial registration NCT02845713; NCT03664063},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lucy2022b,

title = {Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication},

author = {Lucy N. John and Camila G. Beiras and Wendy Houinei and Monica Medappa and Maria Sabok and Reman Kolmau and Eunice Jonathan and Edward Maika and James K. Wangi and Petra Pospíšilová and David Šmajs and Dan Ouchi and Iván Galván-Femenía and Mathew A. Beale and Lorenzo Giacani and Bonaventura Clotet and Eric Q. Mooring and Michael Marks and Martí Vall-Mayans and Oriol Mitjà},

doi = {https://doi.org/10.1056/NEJMoa2109449},

year  = {2022},

date = {2022-01-01},

journal = {New England Journal of Medicine},

volume = {386},

number = {1},

pages = {47-56},

abstract = {textitTreponema pallidum subspecies textitpertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lucy2021,

title = {Safety of mass drug coadministration with ivermectin, diethylcarbamazine, albendazole, and azithromycin for the integrated treatment of neglected tropical diseases: a cluster randomized community trial},

author = {Lucy N. John and Camila Gonzalez-Beiras and Marti Vall-Mayans and Reman Kolmau and Wendy Houinei and James Wangi and Michael Marks and Oriol Mitja},

doi = {https://doi.org/10.1016/j.lanwpc.2021.100293},

issn = {2666-6065},

year  = {2021},

date = {2021-01-01},

journal = {The Lancet Regional Health – Western Pacific},

publisher = {Elsevier},

abstract = {Neglected tropical diseases control programmes run separately. For settings with more than one endemic disease, combined mass drug administration (MDA) has potential practical advantages compared with separate programmes but needs confirmation of safety. We assessed the safety of combined MDA for multiple neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole (IDA) and azithromycin (AZI).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2018,

title = {Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study},

author = {Oriol Mitjà and Charmie Godornes and Wendy Houinei and August Kapa and Raymond Paru and Haina Abel and Camila González-Beiras and Sibauk V. Bieb and James Wangi and Alyssa E. Barry and Sergi Sanz and Quique Bassat and Sheila A. Lukehart},

doi = {10.1016/S0140-6736(18)30204-6},

issn = {0140-6736},

year  = {2018},

date = {2018-01-01},

journal = {The Lancet},

volume = {391},

number = {10130},

pages = {1599-1607},

publisher = {Elsevier},

abstract = {Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marks2018,

title = {Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea},

author = {Michael Marks and Oriol Mitjà and Christian Bottomley and Cynthia Kwakye and Wendy Houinei and Mathias Bauri and Paul Adwere and Abdul A. Abdulai and Fredrick Dua and Laud Boateng and James Wangi and Sally-Ann Ohene and Regina Wangnapi and Shirley V. Simpson and Helen Miag and Kennedy K. Addo and Laud A. Basing and Damien Danavall and Kai H. Chi and Allan Pillay and Ronald Ballard and Anthony W. Solomon and Cheng Y. Chen and Sibauk V. Bieb and Yaw Adu-Sarkodie and David C. W. Mabey and Kingsley Asiedu and Wendy Hounei and Sayy-Ann Ohene and Sivuak V. Bieb and David CW Mabey and Nsire Agana and Edwin Ampadu and Kwame Amponsah-Achiano and Asare Bediako and Michael Biredu and Kyei Faried and Ahmed Iddrisu and Nana K. Kotey and George NY Yeboah and Philip El-Duah and Richard Phillips and Fred Binka and Frank Nyonator and Anthony Zunuo and Mercy A. Ackumey and Ivy Amanor and Christian Bnosu and Sieghard Frischmann and Patrick Lammie and Diana Martin and Tun Ye and Eva Christophel and Alexandre Tiendrebeogo and Lasse Vestergard and Quique Bassat and Yazid Abdad and Henson Dima and Bethuel Kotty and Kaiok Mamore and Walerius Manup and Benson Olowau and Enoch O. Agyei and David Agyemang and Ebenezer P. Ako and Prince Antwi and Jane Darko and Ophelia O. Darko and Phylis Darko and Bertha Duodu and Daniel Jabasi and Fuseini L. Karim and Obed K. Koomson and Bernard A. Labri and John Nartey and Randsford Tamatey and Benjamin Yirenkyi and Mercy Arhin and Frank Biney and Juliana O. Danso and Martin A. Dei and Moses Djan and Samuel Sasu and Brefo A. Solomon and Victor Torvinya and Hagar Amankwaah and James Baffoe and Lydia Keteku and Kofi Kondobala and Rita D. Lomotey and Augustina A. Nartey and Paul Oppong and Millicent A. Quainoo and Theophilus Abotsi and Dzighordi Agebshie and Amos Ameamu and Paul Angwaawie and Rose Ayibor and Margaret Mwingmendeli and John Nakodia and Amatus Nambagyira and Dominic Nanga and Nichola Tetteh and Augustine Wanaom},

doi = {10.1016/S2214-109X(18)30023-8},

issn = {2214-109X},

year  = {2018},

date = {2018-01-01},

journal = {The Lancet Global Health},

volume = {6},

number = {4},

pages = {e401-e410},

publisher = {Elsevier},

abstract = {A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2017,

title = {Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study},

author = {Oriol Mitjà and Camila González-Beiras and Charmie Godornes and Reman Kolmau and Wendy Houinei and Haina Abel and August Kapa and Raymond Paru and Sibauk V. Bieb and James Wangi and Sergi Sanz and Kingsley Asiedu and Sheila A. Lukehart and Quique Bassat},

doi = {10.1016/S2214-109X(17)30388-1},

issn = {2214-109X},

year  = {2017},

date = {2017-01-01},

journal = {The Lancet Global Health},

volume = {5},

number = {12},

pages = {e1268-e1274},

publisher = {Elsevier},

abstract = {Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1371/journal.pntd.0004958,

title = {Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea},

author = {Wendy Houinei and Charmie Godornes and August Kapa and Sascha Knauf and Eric Q. Mooring and Camila González-Beiras and Ronald Watup and Raymond Paru and Paul Advent and Sivauk Bieb and Sergi Sanz and Quique Bassat and Stanley M. Spinola and Sheila A. Lukehart and Oriol Mitjà},

doi = {10.1371/journal.pntd.0004958},

year  = {2017},

date = {2017-01-01},

journal = {PLOS Neglected Tropical Diseases},

volume = {11},

number = {5},

pages = {1-10},

publisher = {Public Library of Science},

abstract = {Author summary Children in rural communities of tropical countries often suffer skin ulcers that are caused by the bacteria Haemophilus ducreyi–causative agent of chancroid- and Treponema pallidum subsp. pertenue -causative agent of yaws-. The currently recommended strategy for yaws eradication is one round of mass drug administration (MDA) with azithromycin. We attempted to find reasons for the limited impact of yaws MDA on the prevalence of H. ducreyi leg ulcers by examining potential sources of infection in healthy carriers, flies, and bed linen. H. ducreyi DNA was found in skin swabs from 20% of asymptomatic children, in 9/10 flies, and 3/6 bed sheets from the houses of children with ulcers. While H. ducreyi DNA has been detected in the genital tract of asymptomatic women without genital ulcers, this is the first report of such detection on the skin of asymptomatic individuals. Importantly, skin cultures obtained from two asymptomatic children yielded viable H. ducreyi, confirming colonization and a potential reservoir of infection. If confirmed to contain viable bacteria, flies and fomites may also contribute to the continued presence of this infection after mass treatment with azithromycin. Our findings provide evidence that persistence of H. ducreyi ulcers after antibiotic MDA is due to the ubiquity of the organism in the environment. Improved hygiene and additional strategies such as repeated rounds of MDA could be able to control such a reservoir.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gonzalez2016,

title = {Epidemiology of emphHaemophilus ducreyi Infections},

author = {Camila González-Beiras and Michael Marks and Cheng Chen Y. and Sally Roberts and Oriol Mitjà},

doi = {10.3201/eid2201.150425},

year  = {2016},

date = {2016-01-01},

journal = {Emerging Infectious Diseases},

volume = {22},

number = {1},

pages = {1-8},

publisher = {CDC},

abstract = {The global epidemiology of emphHaemophilus ducreyi infections is poorly documented because of difficulties in confirming microbiological diagnoses. We evaluated published data on the proportion of genital and nongenital skin ulcers caused by emphH. ducreyi before and after introduction of syndromic management for genital ulcer disease (GUD). Before 2000, the proportion of GUD caused by emphH. ducreyi ranged from 0.0% to 69.0% (35 studies in 25 countries). After 2000, the proportion ranged from 0.0% to 15.0% (14 studies in 13 countries). In contrast, emphH. ducreyi has been recently identified as a causative agent of skin ulcers in children in the tropical regions; proportions ranged from 9.0% to 60.0% (6 studies in 4 countries). We conclude that, although there has been a sustained reduction in the proportion of GUD caused by emphH. ducreyi, this bacterium is increasingly recognized as a major cause of nongenital cutaneous ulcers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oriol2015,

title = {Mass Treatment with Single-Dose Azithromycin for Yaws},

author = {Oriol Mitjà and Wendy Houinei and Penias Moses and August Kapa and Raymond Paru and Russell Hays and Sheila Lukehart and Charmie Godornes and Sibauk Vivaldo Bieb and Tim Grice and Peter Siba and David Mabey and Sergi Sanz and Pedro L. Alonso and Kingsley Asiedu and Quique Bassat},

doi = {10.1056/NEJMoa1408586},

year  = {2015},

date = {2015-01-01},

journal = {New England Journal of Medicine},

volume = {372},

number = {8},

pages = {703-710},

abstract = {Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marks2015,

title = {Challenges and key research questions for yaws eradication},

author = {Michael Marks and Oriol Mitjà and Lasse S. Vestergaard and Allan Pillay and Sascha Knauf and Cheng-Yen Chen and Quique Bassat and Diana L. Martin and David Fegan and Fasihah Taleo and Jacob Kool and Sheila Lukehart and Paul M. Emerson and Anthony W. Solomon and Tun Ye and Ronald C. Ballard and David C. W. Mabey and Kingsley B. Asiedu},

doi = {10.1016/S1473-3099(15)00136-X},

issn = {1473-3099},

year  = {2015},

date = {2015-01-01},

journal = {The Lancet Infectious Diseases},

volume = {15},

number = {10},

pages = {1220-1225},

publisher = {Elsevier},

abstract = {Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that emphHaemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2015,

title = {Global epidemiology of yaws: a systematic review},

author = {Oriol Mitjà and Michael Marks and Diby J. P. Konan and Gilbert Ayelo and Camila Gonzalez-Beiras and Bernard Boua and Wendy Houinei and Yiragnima Kobara and Earnest N. Tabah and Agana Nsiire and Damas Obvala and Fasiah Taleo and Rita Djupuri and Zhang Zaixing and Jürg Utzinger and Lasse S. Vestergaard and Quique Bassat and Kingsley Asiedu},

doi = {10.1016/S2214-109X(15)00011-X},

issn = {2214-109X},

year  = {2015},

date = {2015-01-01},

journal = {The Lancet Global Health},

volume = {3},

number = {6},

pages = {e324-e331},

publisher = {Elsevier},

abstract = {To achieve yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with yaws at national and subnational levels and to estimate at-risk populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2014,

title = {Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study},

author = {Oriol Mitjà and Sheila A. Lukehart and Gideon Pokowas and Penias Moses and August Kapa and Charmie Godornes and Jennifer Robson and Sarah Cherian and Wendy Houinei and Walter Kazadi and Peter Siba and Elisa Lazzari and Quique Bassat},

doi = {10.1016/S2214-109X(14)70019-1},

issn = {2214-109X},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {The Lancet Global Health},

volume = {2},

number = {4},

pages = {e235-e241},

publisher = {Elsevier},

abstract = {Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands emphHaemophilus ducreyi as causes of skin ulceration in a yaws-endemic region. Additionally, we identified specific signs and symptoms associated with these causative agents of cutaneous ulcers and compared these findings with laboratory-based diagnoses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2013,

title = {Yaws},

author = {Oriol Mitjà and Kingsley Asiedu and David Mabey},

doi = {10.1016/S0140-6736(12)62130-8},

issn = {0140-6736},

year  = {2013},

date = {2013-01-01},

journal = {The Lancet},

volume = {381},

number = {9868},

pages = {763-773},

publisher = {Elsevier},

abstract = {Yaws is an infectious disease caused by Treponema pallidum pertenue?a bacterium that closely resembles the causative agent of syphilis?and is spread by skin-to-skin contact in humid tropical regions. Yaws causes disfiguring, and sometimes painful lesions of the skin and bones. As with syphilis, clinical manifestations can be divided into three stages; however, unlike syphilis, mother-to-child transmission does not occur. A major campaign to eradicate yaws in the 1950s and 1960s, by mass treatment of affected communities with longacting, injectable penicillin, reduced the number of cases by 95% worldwide, but yaws has reappeared in recent years in Africa, Asia, and the western Pacific. In 2012, one oral dose of azithromycin was shown to be as effective as intramuscular penicillin in the treatment of the disease, and WHO launched a new initiative to eradicate yaws by 2020.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2012,

title = {Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial},

author = {Oriol Mitjà and Russell Hays and Anthony Ipai and Moses Penias and Raymond Paru and David Fagaho and Elisa Lazzari and Quique Bassat},

doi = {10.1016/S0140-6736(11)61624-3},

issn = {0140-6736},

year  = {2012},

date = {2012-01-01},

journal = {The Lancet},

volume = {379},

number = {9813},

pages = {342-347},

publisher = {Elsevier},

abstract = {Yaws is an endemic treponematosis and, as such, a neglected tropical disease?is re-emerging in children in rural, tropical areas. Oral azithromycin is effective for syphilis. We assessed the efficacy of azithromycin compared with intramuscular long-acting penicillin to treat patients with yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/cid/cix723,

title = {Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in Papua New Guinea},

author = {Camila González-Beiras and August Kapa and Marti Vall-Mayans and Raymond Paru and Sergi Gavilán and Wendy Houinei and Sibauk Bieb and Sergi Sanz and Rosario Martins and Oriol Mitjà},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/cid/ciy343,

title = {Multiple Class I and Class II Haemophilus ducreyi Strains Cause Cutaneous Ulcers in Children on an Endemic Island},

author = {Jacob C Grant and Camila González-Beiras and Kristen M Amick and Kate R Fortney and Dharanesh Gangaiah and Tricia L Humphreys and Oriol Mitjà and Ana Abecasis and Stanley M Spinola},

keywords = {},

pubstate = {published},

tppubtype = {article}

}