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At least 19 recordsLinked to original sources
PubMed2026

Effect of repeated mass drug administration on the transmission of yaws: a retrospective genomic epidemiology study.

BACKGROUND: Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue (T p pertenue), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of T p pertenue. METHODS: We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for T p pertenue underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on T p pertenue diversity and transmission. FINDINGS: Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality Tp pertenue genomes. We identified 20 sublineages of T p pertenue in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0&#xb7;0036) and longer ulcer duration (p=0&#xb7;015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7&#xb7;1, 95% CI 5&#xb7;7-8&#xb7;8; p<0&#xb7;0001) or neighbouring wards (4&#xb7;3, 3&#xb7;3-5&#xb7;4; p<0&#xb7;0001) more likely to share the same sublineages compared with pairs from different LLGs. Additionally, older individuals were more likely to share sublineages than were younger individuals (1&#xb7;5, 1&#xb7;2-1&#xb7;9; p<0&#xb7;0001). INTERPRETATION: Repeated MDA was successful in reducing and maintaining the genetic diversity of T p pertenue at a low level but was associated with the development of macrolide resistance. Yaws re-emergence after MDA was attributed to multiple sublineages, of which the majority were detected in the population before MDA. Participants within the same ward were more likely to share sublineages than those that were more widely geographically separated, suggesting that re-emergence was driven by local transmission. These findings could inform future yaws elimination strategies. FUNDING: European Research Council, EU, Provincial Deputation of Barcelona, Barber&#xe0; Solid&#xe0;ria Foundation, Wellcome, and Fundaci&#xf3; "la Caixa".

Adolescent↗
PubMed1977

Pinta, yaws, and venereal syphilis in Colombia.

Three treponemal infections of man have coexisted in Colombia, South America for centuries. In former years, Colombia and Mexico were the world's most highly endemic countries for pinta. Within Colombia, highest rates of infection with pinta occurred among the mestizo and Indian populations in the Andean and Caribbean departments of Huila, Tolima, Antiochia, Magdalena and Cesar. Yaws occurred primarily in rural areas along the Pacific coast among descendants of African slaves. Infectious syphilis is most often reported from the three largest urban areas, and from three other densely populated departments in the Andean region. During the 21-year period from 1954 to 1974, almost four times as many cases of pinta as yaws were reported. The incidence rates of yaws and pinta have declined almost in parallel in Colombia, even though there has been a national campaign against yaws, but not against pinta. The incidence of primary and secondary syphilis increased only slightly during the same period. The total burden of reported treponematoses (excluding tertiary and congenital syphilis) declinded by over 40 per cent, while the ratios of reported yaws, pinta and infectious syphilis rose from 1:3:4 in 1954 to 1:7:975 in 1974.

Colombia↗
PubMed1979

Comparison of cardiolipin and treponemal tests in the serodiagnosis of yaws.

Results of the Veneral Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), Treponema pallidum haemagglutination (TPHA), T. pallidum immobilisation (TPI), and fluorescent treponemal antibody absorption (FTA-ABS) tests on sera of 661 children from a region where yaws is hypoendemic are compared. For 107 (16.2%) out of 661 sera the FTA-ABS test was the only one showing reactivity; in these instances the test was weakly reactive (intensity of fluorescence scored as +) and the children had no history and no signs or symptoms of treponemal disease. A solitary, weakly reactive FTA-ABS test result seems to have no clinical significance in these cases. The FTA-ABS test can be used as a confirmatory test for yaws instead of the TPI test, if only the results of sera showing an intensity of fluorescence scored as ++ or more are considered to be positive. There appeared to be no significant differences in the results of the VDRL, RPR, and TPHA tests as screening tests for yaws when the TPI or FTA-ABS tests were used as reference tests.

Adolescent↗
PubMed1977

Comparison of RPR 'teardrop' card test, VDRL and FTA-ABS tests results on sera from persons with suspected yaws in Columbia.

A small study comparing results of the rapid plasma reagin (RPR) teardrop card test performed in the field, with results of Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) tests performed in the laboratory on venous blood specimens from the same suspected yaws patients was undertaken in Columbia in July 1975. The results suggest that the RPR teardrop card test may be used to screen for infectious, or potentially infectious, yaws patients under field conditions, but that it will not reliably detect patients with VDRL titres of 1:2 or less, or all patients in whom sera are reactive in the FTA-ABS test.

Colombia↗
PubMed1979

Attenuated yaws in Surinam.

Results of a pilot survey in the central, northern region of Surinam indicate that yaws is prevalent (hypoendemic) in this part of the country. No classical symptoms of yaws were seen. The observed lesions were scanty or solitary, dry papillomatous, or macular and scaly, which fits into the clinical picture of attenuated endemic treponematosis.

Adolescent↗
PubMed1977

Psychophysical determination of the phase characteristic of the vestibular system of man for sinusoidal oscillation in yaw.

UNLABELLED: The phase characteristic of the vestibular system of man was determined for sinusoidal oscillation in yaw in the frequency range from 0.0025 to 0.4 Hz. Three different sets of experimental conditions were used: (1) a dark room with a fixation light; stimulus: sinusoidal rotation; (2) a dark room without a fixation light; stimulus: sinusoidal rotation + noise, and (3) a dark room without a fixation light; stimulus; sinusoidal rotation. RESULTS: the sensation leads the velocity by about 90 degrees at 0.005 Hz. The phase lead decreased for higher frequencies becoming nearly zero at 0.05 Hz and remaining constant in the frequency range 0.05 to 0.4 Hz. A phase lag was not found. At very low frequencies (less than 0.005 Hz), the phase lead was more than 90 degrees. The results can be described in terms of a second-order model with time constants Tau1 = 20 sec and Tau2 = 0.013 sec and an adaptation term with a time constant of Taau = 0.40 sec.

Humans↗
PubMed1978

Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons.

1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the beta type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 degrees at 0.025 Hz to 126 degrees at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 degrees and 130 degrees at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 degrees. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 degrees (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the response of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.

Animals↗
PubMed1978

Visual-vestibular interaction in the control of eye movement.

Three experimental conditions have been used to investigate the extent to which inappropriate reflex eye movements of vestibular origin can be suppressed by visual feedback. First, the ability to read digits in a display which moved with the head was assessed during angular oscillation about the yaw and pitch axes of the body. Performance decrement was observed at frequencies above 0.2 Hz in pitch and 1.0 Hz in yaw, being greater at higher stimulus velocity levels. A second experiment revealed that the performance decrement was associated with eye movements relative to the head, which increased with the frequency of stimulation. Finally, the response of the pursuit reflex was investigated under similar experimental conditions. The results indicated that the breakdown in the pursuit reflex and in the suppression of the vestibulo-ocular reflex occurred over the same frequency band, implying the similarity of the mechanisms responsible for suppression and pursuit.

Aerospace Medicine↗
PubMed1979

[Contribution of Achille Breda to the understanding of American mucocutaneous leishmaniasis].

The majority of Parasitology textbooks and reference lists on Leishmaniasis do not quote the name of Achille Breda. This Italian dermatologist (1850-1934) however must be considered the first who clinically identified and carefully described the American muco-cutaneous Leishmaniasis, a disease for which some scientists proposed the name of "Breda's disease" (Jeanselme, 1910). Breda studied at the University of Padua, attending as postgraduate the famous Hebra's school of Wien. He became professor of "Syphilodermatopathology" in 1878 and during 47 years taught in Padua. He never was in South or Central America, but studied the illness in Padua itself, in 18 Italian emigrants who had come back ill from the São Paulo region, Brazil. At that time the agents of yaws, cutaneous and muco-cutaneous leishmaniasis and syphilis had not yet discovered and there was great confusion about the granulomatous lesions of the skin and mucosae seen in tropical areas. In this situation he exactly differentiated the condition from syphilis, yaws and lupus and could affirm, with the security of a highly skilled observer that it was an autonomous, different illness, peculiar to some rural areas of Brazil, non contagious directly, appearing in determinate season of the year but lasting for years and often conducting the subjects to the cachexia. His description of the symptomatology, post-morten anatomy, histology and his epidemiological observations, even nowadays represent one of the most accurate and complete pictures of this illesss. Breda's life and works are here reviewed and some passages of his papers on mucocutaneous leishmaniasis reported.

Diagnosis, Differential↗
PubMed2026

[Syphilis and human treponemes: a long evolutionary history revealed by paleogenomics].

Recent discoveries in paleogenomics have revolutionized our understanding of syphilis and other human treponematoses. Far from being a pathogen that suddenly appeared in Europe in the late Middle Ages, we now know that Treponema pallidum has been circulated among human populations for millennia. Ancient genomes recovered from pre-Columbian contexts in the Americas show that major treponemal lineages had already diversified well before the modern era, often in the absence of recognizable skeletal lesions. Genomic analyses further indicate that treponemal diversity is not the result of extensive genetic acquisition, but rather of small-scale modulation of a highly conserved genome, notably via antigenic variation involving the tpr gene family. Combined with data on endemic treponematoses, congenital syphilis, and historical pathology collections, these findings support a model in which syphilis, yaws, and bejel represent context-dependent expressions of an ancient treponemal continuum, with implications for diagnosis, epidemiology, and vaccine design.

Humans↗
PubMed1977

Response characteristics and vestibular receptor convergence of frog cerebellar purkinje cells. A natural stimulation study.

1. The horizontal sinusoidal frequency response and the problem of vestibular receptor convergence in Purkinje cells (P-cells) of the auriculum, dorsal rim and corpus cerebelli were studied in curarized frogs with natural stimulation. 2. Primarily "simple" but also "complex" spikes were evoked by sinusoidal stimulation of the horizontal canals. P-cell "simple" spike activity could be grouped into types I-IV. Type I and II responses were directionally sensitive and thus were evoked at the stimulus frequency. Type III (and IV) cells, on the other hand, had response waveforms double that of the input frequency, with peak increases (or decreases) in discharge inphase with head velocity in the mid-frequency range. Except in the cerebellar midline regions where type III response waveforms were symmetrical, ipsilateral sinusoidal responses were larger in magnitude than those evoked during contralateral rotation. Despite the differences in magnitudes, ipsi- and contralateral response phase angles for one cell were approximately equal. "Complex" spikes were evoked with ipsi (type I) or contralateral (type II) horizontal rotation. Generally only 1-2 spikes were evoked per cycle with short (0-60 degrees) or long (120-150 degrees) phase-lags following acceleration. 3. A Bode analysis of type I "simple" spike activity in yaw indicates a slightly greater phase-lag and a 10-15 fold smaller P-cell gain in the range 0.05-0.5 Hz when compared to peripheral horizontal canal neurons. 4. Stimulation of the vertical canals and otolith organs also evoked "simple" and, to a lesser extent, "complex" P-cell spikes. "Simple" spikes were in most cases (85%) evoked by stimulation of several canal and/or otolithic receptors thus demonstrating a high degree of receptor convergence. "Complex" spikes, however, were only evoked by stimulation of one canal or otolith receptor. 5. Otolithic input to P-cells, examined statically and with low level constant velocity rolls, was mainly phasic or phasic-tonic in nature.

Animals↗
PubMed1978

Response characteristics of semicircular canal and otolith systems in cat. I. Dynamic responses of primary vestibular fibers.

1. The activity of cat semicircular canal and otolith afferents was studied during yaw and roll rotations, respectively, to examine their dynamic behavior. 2. A sinusoidal analysis of the canal afferent activities showed that their dynamic characteristics are similar to those of second order vestibular neurons, except for a two to three-fold lower absolute gain. This agrees with earlier studies using angular acceleration steps. 3. Both divisions of the eighth nerve were sampled so as to examine afferents from both the utriculus and sacculus. Within the range of inputs used (+/- 25 degrees lateral tilt), the presumed sacular afferents (inferior division) showed either a gamma- or beta-response. However, the gain of their response was generally much less than for the afferents of the superior division (mostly utricular). This behavior is to be expected on the basis of receptor orientations and the components of gravity acting upon the macular receptors. 4. In response to ramp changes in angular position, some otolith units showed a phasic-tonic response pattern, i.e., an overshoot followed by an adaptation to a new steady state level of activity. The majority of units showed predominantly tonic responses proportional to displacement. 5. During sinusoidal rotations the predominantly tonic units showed small phase leads of 0 to 15 degrees at 0.025 Hz which remained constant or decreased to 0 to -15 degrees at 1.0 Hz. The gains were flat or increased by up to 2 fold. The phasic-tonic units showed greater phase leads, 10 to 50 degrees, and gains which increased from 2 to 8 fold. 6. This behavior of otolith afferents suggests that they can provide information about both the magnitude and the rate of change of linear acceleration stimuli.

Acoustic Maculae↗
PubMed1979

The contribution of medical missionaries to tropical medicine. Service-training-research.

Medical missionaries, historically the pioneers in introducing Western medicine into many tropical countries, are today responsible for a significant proportion of health care in several of those countries. Illustrating his theme with references to personal experiences in the former Belgian Congo, the author enlarges on the organization of a church-related comprehensive health care programme based on a chain of rural health centres and satellite dispensaries that brought curative and preventive medicine to the whole population within the area covered. Trypanosomiasis was eradicated, yaws and tuberculosis controlled, cerebral malaria eliminated, worm-loads reduced and nutrition improved. Leprosy was treated within the integrated service as soon as the sulphones became available. Medical auxiliaries and nurse-midwives were trained practically to tackle the local problems. Students from many missions over a wide area went into government, mission and company employ after training. Research concentrated mainly on the solution of pressing local problems, such as onchocerciasis and leprosy, but incidentally investigated interesting clinical phenomena.

Community Health Services↗