Prevalence surveys for podoconiosis and other neglected skin diseases: time for an integrated approach

Understanding of the geographical distribution of diseases is needed to inform health service design and delivery. It is also a necessary step in targeting priority areas and serves as a baseline to measure the impact of future interventions. In The Lancet Global Health, Kebede Deribe and colleagues1 present a large-scale nationwide prevalence survey for podoconiosis in all 30 districts across Rwanda. Podoconiosis is a neglected tropical disease and data on its prevalence and geographical distribution worldwide is scarce.2 Podoconiosis is a type of elephantiasis (lymphoedema) found in farming communities in the tropics and is triggered by an abnormal reaction to irritant mineral particles in volcanic soils amongst people who cannot afford shoes. The disease can be avoided by appropriate use of footwear and is treated through simple lymphoedema management measures, such as proper foot hygiene, bandaging, and exercises.3 As such, detection of affected and at-risk populations is vital to ensure prevention and treatment measures are available for everyone in need

Epidemiology of Haemophilus ducreyi Infections

The global epidemiology of Haemophilus 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 H. ducreyi before and after introduction of syndromic management for genital ulcer disease (GUD). Before 2000, the proportion of GUD caused by H. 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, H. 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 here has been a sustained reduction in the proportion of GUD caused by H. ducreyi, this bacterium is increasingly recognized as a major cause of nongenital cutaneous ulcer

Prioritizing surveillance activities for certification of yaws eradication based on a review and model of historical case reporting

BACKGROUNDt: The World Health Organization (WHO) has targeted yaws for global eradication. Eradication requires certification that all countries are yaws-free. While only 14 Member States currently report cases to WHO, many more are known to have a history of yaws and some of them may have ongoing transmission. We reviewed the literature and developed a model of case reports to identify countries in which passive surveillance is likely to find and report cases if transmission is still occurring, with the goal of reducing the number of countries in which more costly active surveillance will be required. METHODSt: We reviewed published and unpublished documents to extract data on the number of yaws cases reported to WHO or appearing in other literature in any year between 1945 and 2015. We classified countries as: a) having interrupted transmission; b) being currently endemic; c) being previously endemic (current status unknown); or d) having no history of yaws. We constructed a panel dataset for the years 1945-2015 and ran a regression model to identify factors associated with some countries not reporting cases during periods when there was ongoing (and documented) transmission. For previously endemic countries whose current status is unknown, we then estimated the probability that countries would have reported cases if there had in fact been transmission in the last three years (2013-2015)." - Label: RESULTS content: Yaws has been reported in 103 of the 237 countries and areas considered. 14 Member States and 1 territory (Wallis and Futuna Islands) are currently endemic. 2 countries are believed to have interrupted transmission. 86 countries and areas are previously endemic (current status unknown). Reported cases peaked in the 1950s, with 55 countries reporting at least one case in 1950 and a total of 2.35 million cases reported in 1954. Our regression model suggests that case reporting during periods of ongoing transmission is positively associated with socioeconomic development and, in the short-term, negatively associated with independence. We estimated that for 66 out of the 86 previously endemic countries whose current status is unknown, the probability of reporting cases in the absence of active surveillance is less than 50%. DISCUSSION: Countries with a history of yaws need to be prioritized so that international resources for global yaws eradication may be deployed efficiently. Heretofore, the focus has been on mass treatment in countries currently reporting cases. It is also important to undertake surveillance in the 86 previously endemic countries for which the current status is unknown. Within this large and diverse group, we have identified a group of 20 countries with more than a 50% probability of reporting cases in the absence of active surveillance. For the other 66 countries, international support for active surveillance will likely be required

Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study

Background: 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. Methods: Between April 15, 2013, and Oct 24, 2016, we did a longitudinal study on a Papua New Guinea island (Lihir; 16 092 population) in which yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued every 6 months for 42 months. We used genotyping and travel history to identify importation events. Active yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator. The study is registered with ClinicalTrials.gov, number NCT01955252. Findings: Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programmes reduced the prevalence of active yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline −1·7%, 95% CI, −1·9 to −1·4; p<0·0001), but the infection began to re-emerge after 24 months with a significant increase to 0·4% at 42 months (difference from 18 months 0·3%, 95% CI 0·1 to 0·4; p<0·0001). At each timepoint after baseline, more than 70% of the total community burden of yaws was found in individuals who had not had the mass treatment or as new infections in non-travelling residents. At months 36 and 42, five cases of active yaws, all from the same village, showed clinical failure following azithromycin treatment, with PCR-detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin. A sustained decrease in the prevalence of high-titre latent yaws from 13·7% to <1·5% in asymptomatic children aged 1–5 years old and of genetic diversity of yaws strains from 0·139 to less than 0·046 between months 24 and 42 indicated a reduction in transmission of infection. Interpretation: The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to the individuals who were absent at the time of mass treatment in whom yaws reactivated; repeated mass treatment might be necessary to eliminate yaws. To our knowledge, this is the first report of the emergence of azithromycin-resistant T p pertenue and spread within one village. Communities' surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance

Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study

BACKGROUND: 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. METHODS: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre >/=1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2.0%, 95% CI -8.3 to 4.3), meeting the prespecified criteria for non-inferiority. INTERPRETATION: On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. FUNDING: Newcrest Mining Limited and ISDIN laboratories

Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws

BACKGROUND: The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. METHODS: We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. RESULTS: Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (>/=1:16) for both the T1 (98.2% vs 90.1%, P < .0001) and the T2 component (98.2% vs 80.6%, P < .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%-86.1%). Agreement was highest for high-titer active infection and lowest for past infection. CONCLUSIONS: The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

Strategies to control Yaws and other Neglected Tropical Diseases in the South Pacific Islands / Estrategias para el control del Pián y otras Enfermedades Tropicales Desatendidas en Islas del Pacífico Sur

Every year, through mass drug administration (MDA), hundreds of millions of the world’s poorest people receive a single annual dose of one or more drugs to eliminate certain parasitic worm or bacterial infections. Some of these infections, mostly prevalent in tropical areas, have traditionally been neglected from the public health and research point of view. These conditions, collectively known as the neglected tropical diseases (NTDs), still cause, at the cusp of the second decade of the 21st century, a significant amount of morbidity and mortality. The existing control measures for NTD have an enormous potential, although there are still some challenges that require further investigation. For some diseases, alternative strategies may be needed, including longer duration of MDA programmes or modified drug regimens. For other diseases, such as yaws, the work must start almost from scratch, since little has been achieved in terms of control of this disease in the past 50 years. Although eight NTDs affect the region, two diseases pose a major public health problem in the South Pacific Islands, namely yaws and lymphatic filariasis and are the basis for his thesis. These two infections were selected for a number of reasons. First, they affect the South Pacific region disproportionately. Secondly, little research has been conducted in the past years. And third, but more importantly, several epidemiological, technological and historical factors make these two diseases amenable to elimination. Safe and effective tools and interventions to achieve these targets are available and concerted efforts to scale them up are likely to lead to success. Yaws is one of the most neglected of the NTDs. Yaws was one of the first diseases to be targeted for eradication on a global scale, efforts which almost led to the disease disappearance as a result of a massive treatment program started in the 1950s. After the successful eradication campaigns the primary health care systems were supposed to give the last push towards eradication of yaws. However a combination of various factors including poor political commitment and limited funding resulted in a progressive abandonment of efforts and the resurgence of the disease. Every new case of yaws was the disappointing confirmation that the public health world had missed a great opportunity. Today yaws has resurged in many tropical areas and presents new challenges including its unknown epidemiological situation, the attenuated clinical forms of the disease, a poor awareness and knowledge among health care workers, the lack of knowledge about the effectiveness of classic treatment with penicillin and, an obvious need for research into simplified administration schemes or new antibiotic treatments, particularly oral ones. There is an enormous knowledge gap regarding current reliable epidemiological information about the disease. Certainly we know little about the burden in the three Melanesian countries where the disease is highly endemic, Papua New Guinea, Solomon Islands and, Vanuatu. In Solomon Islands and Vanuatu there are indications that Yaws is widespread and prevalent, but we know that the diagnosis is unreliable. This takes us to the next point, what does a diagnosis of yaws mean? Overall the natural history of the disease in this era, where it is often subject to inadequate antibiotic pressure, is very unclear. Some authors have suggested that yaws appears to be attenuated in both Solomon Islands and Vanuatu. They state that bone involvement in yaws is now rare and implies that yaws is a mild disease not requiring efforts for elimination. However, the first paper of this thesis describes the epidemiology of yaws in Lihir Island (Papua New Guinea, PNG) and shows a high rate of classical primary ulcers (almost 60%) and significant bone and periosteal involvement (more than 15%), suggesting that “attenuation” is not an important issue. When we look at the diagnostic criteria for yaws, signs and symptoms alone are still used often in many areas to diagnose the disease. This reliance on clinical findings was the result of the difficulty of performing serological tests in remote areas. Today, available rapid serological tests are simple, rapid, inexpensive and useful for guiding confirmation of cases, making them adequate tools for the diagnosis and monitoring of the disease. The clinical diagnosis of yaws is complicated because its clinical manifestations may be unspecific. Thus, it is possible that a significant proportion of yaws cases may in fact have been falsely diagnosed. We show, in the first article, that in our experience only 60% of the cases with a clinical suspicion of yaws were finally confirmed by serologic tests. Therefore, a proper diagnosis of yaws requires the interpretation of clinical findings with reference to laboratory results and the epidemiologic history of the patient. Serological testing in yaws is not only important for diagnostic accuracy, but also is very helpful in defining the disease’s evolution and eventual cure after treatment. Rapid plasma regain (RPR) titres should decline within 6-12 months, becoming negative in less than 2 years. The second article of this thesis combines a clinical and serological approach to assess the response after treatment with benzathine benzylpenicillin, and it identifies an overall 20% treatment failure. This could be related to resistance to the antimicrobial drug used or to re-infection caused. The distinction between re-infection and true resistance to antibiotic treatment is difficult to make but these failures are worrisome. This article also proposes a multivariate model performed to identify independent determinants of failure that affected the outcome after treatment. The risk for reinfection caused by repeated contact with infected children seems to be a pivotal predictor of failure. Low baseline titters (<1:32) of RPR are also an important and independent predictor of failure, possibly as a result of the greater difficulty in resolving chronic infections which are usually accompanied by low titters. With yaws re-emerging, the development of new strategies against this infection aimed at simplifying its treatment and potentially re-focussing strategies towards its eradication seems essential. Injectable penicillin is still effective but management with an oral drug that can be easily administered on a large scale should be the preferred method for treatment. To date, there had been no studies that directly compared the efficacy of penicillin with any of the potentially alternative agents shown to work in the treatment of the non-venereal treponematoses. The fourth paper in this thesis has shown that a single-dose of oral azithromycin is non-inferior to benzathine benzylpenicillin for the treatment of yaws in children in PNG. In an open-label randomised trial, at 6-month follow-up, 96% of patients treated with azithromycin were cured, as were 93% in the benzathine benzylpenicillin group. The prospects of eliminating and eventually eradicating yaws may now be enhanced by the use of a single-dose of oral azithromycin in mass drug administration campaigns. Community based mass administration of azithromycin has been widely used in many locations for the control of trachoma, which, like yaws, is a disease of poor rural communities in developing countries, and has been used in a more limited way to control granuloma inguinale and outbreaks of venereal syphilis. Elimination of yaws and lymphatic filariasis in the South-Pacific Islands is now considered biologically feasible and programmatically attainable. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) has expanded quickly to reach the target of elimination by 2020. On the other hand the strategy to eliminate yaws is again at the centre of discussions and given that infected humans are the only source of disease, its eradication could be achieved within a very relatively short time. The fifth article of the thesis comprehensively reviews antimicrobial treatments and elimination strategies against yaws. In order to control yaws and push it towards elimination, we propose to move away from penicillin to azithromycin and use mass treatment campaigns of the entire population in endemic communities irrespective of the prevalence. Also, to make sure all cases are tracked down and treated, strict follow-up measures and selective mass treatment will be required until zero case prevalence is reached. Importantly, we suggest testing the principle of interrupting transmission in pilot implementation studies, including prevalence surveys to assess the impact of the intervention and macrolide resistance monitoring which in our opinion will be essential evaluation tools to guide us towards a sustainable elimination. Lymphatic filariasis (LF), caused by the mosquito-borne nematode Wuchereria Bancrofti, is a major public-health problem in the Melanesian countries. Annual MDA over five years is currently the WHO’s recommended strategy to eliminate lymphatic filariasis. This approach aims to suppress microfilaraemia in infected individuals and bring the infection below a threshold that leads to interruption of transmission. However theoretical work and clinical field experience has highlighted how the ecological diversity between different endemic regions can result in elimination thresholds that vary between local communities. This means that the duration required might be different for different areas. Other variables have also been previously identified as potentially having an influence on the outcome of the program, including baseline prevalence of infection, vector density or the treatment coverage. The last article of this thesis provides data about the impact of a five-year filariasis control program in Papua New Guinea. The findings reported support this strategy for areas with low-to-moderate rates of transmission in regions where anopheline mosquitoes transmit this infectious disease. Additional measures or longer periods of treatment may be necessary in areas with a high rate of transmission. The experience acquired on Lihir Island in MDA programs during the campaigns for the elimination of filariasis, will be very valuable when implementing a pilot strategy for yaws control. Also, in the near future it might be important to link yaws mass treatment with other mass programmes to increase efficiency. The plan for elimination of lymphatic filariasis in PNG was approved as a pilot project in 2005 but the program still needs to be extended to the total of 20 provinces in the country where filariasis is endemic. In this context, an integrated approach to NTD control could represent an important global public health solution in PNG and other South Pacific Islands. Little has been achieved in the past decade in NTDs. We are now in a good position to translate into policies the results of our research projects. A new elimination policy for yaws around the azithromycin pillar has been sketched a WHO consultation meeting held in Morges, Switzerland last March. In the intentions of the organization, a last global mass campaign to tackle yaws should permit to reach zero cases in 2017, and the subsequent certification of worldwide interruption of transmission by 2020.Cada año, a través de la administración masiva de medicamentos (MDA), cientos de millones de personas, las más pobres del mundo, reciben una dosis única de uno o más medicamentos para eliminar ciertas infecciones, parasitarias o bacterianas. Algunas de estas infecciones, frecuentes sobre todo en las zonas tropicales, han sido tradicionalmente desatendidas desde el punto de vista de salud pública e investigación. Estas enfermedades, conocidas comúnmente como las enfermedades tropicales desatendidas (ETD), aún causan, en el inicio de la segunda década del siglo 21, una cantidad significativa de morbilidad y mortalidad. Las medidas de control actuales para ETDs tienen un enorme potencial, pero todavía existen algunas cuestiones que requieren investigación. Para algunas de estas infecciones, son necesarias estrategias alternativas, incluyendo una mayor duración de los programas de MDA o regímenes modificados de medicamentos. Para otras enfermedades, como la enfermedad de pián, el trabajo debe comenzar casi desde cero, ya que poco se ha logrado, en términos de control de esta enfermedad, en los últimos 50 años. Aunque ocho ETDs afectan a la región, dos enfermedades constituyen un problema importante de salud pública en las Islas del Pacífico Sur, a saber: el pián y la filariasis linfática y son la base de esta tesis. Estas dos infecciones fueron elegidas por muchas razones. En primer lugar, afectan a la región del Pacífico Sur de forma desproporcionada. En segundo lugar, pocas investigaciones se han llevado a cabo en los últimos años. Y en tercer lugar, pero lo más importante, varios factores epidemiológicos, tecnológicos e históricos hacen que estas dos enfermedades sean susceptibles de eliminación. Existen armas terapéuticas seguras y eficaces para lograr este objetivo, y esfuerzos coordinados para ejecutar los programas de control pueden conducir al éxito. El pián es una de las más olvidadas de las ETDs. Ésta fue una de las primeras enfermedades en ser objetivo de erradicación a escala global. Los esfuerzos de un programa de tratamiento masivo, que se inició en la década de 1950, casi llevaron a la desaparición de la enfermedad. Después de las exitosas campañas de erradicación, los sistemas de salud de atención primaria debían dar el último empujón hacia la erradicación del pián. Sin embargo, una combinación de varios factores, incluyendo un pobre compromiso político y una financiación limitada, dieron como resultado el abandono progresivo de los esfuerzos y el resurgimiento de la enfermedad. Cada nuevo caso de pián era la decepcionante confirmación de que el mundo de la salud pública había perdido una gran oportunidad. Hoy la enfermedad de pián ha resurgido en muchas áreas tropicales con nuevos desafíos: una situación epidemiológica desconocida, formas clínicas atípicas o atenuadas, poco conocimiento de la enfermedad entre el personal sanitario, la falta de datos acerca de la eficacia del tratamiento clásico con penicilina inyectable y la necesidad de desarrollar esquemas terapéuticos simplificados o investigar en nuevos tratamientos antibióticos, en especial de administración oral. Actualmente hay una enorme brecha de conocimiento entorno a la información epidemiológica fiable sobre la enfermedad. Ciertamente, sabemos poco acerca de la incidencia en los tres países melanesios, donde la enfermedad es altamente endémica, Papúa Nueva Guinea (PNG), Islas Salomón y Vanuatu. En las Islas Salomón y Vanuatu, las cifras de incidencia son muy altas lo que demuestra que el pián es una enfermedad frecuente y ampliamente extendida, pero sabemos que el diagnóstico no es muy fiable. Esto nos lleva al siguiente punto: ¿Cuáles son los criterios diagnósticos del pián? En general, la historia natural de la enfermedad en la época actual, donde la bacteria es objeto de presión antibiótica inadecuada, no es muy clara. Algunos autores han escrito que el pián parece presentar manifestaciones “atenuadas” en las Islas Salomón y Vanuatu. Afirman que la afectación ósea en el pián es poco frecuente, lo que implica que el pián es una enfermedad leve que no requeriría esfuerzos para su eliminación. Sin embargo, el primer trabajo de esta tesis describe la epidemiología del pián en la Isla de Lihir (Papúa Nueva Guinea) y muestra una alta tasa de úlceras primarias clásicas (casi el 60% de casos) y una afectación significativa del hueso y periostio (más del 15%) que sugiere que la "atenuación" no es un tema importante. Cuando nos fijamos en los criterios diagnósticos, únicamente signos y síntomas todavía se utilizan en muchas áreas para el diagnóstico de la enfermedad. Esta confianza en los hallazgos clínicos fue el resultado de la dificultad de realizar pruebas serológicas en las zonas remotas. Hoy en día, las pruebas serológicas rápidas son simples, rápidas, económicas y útiles para orientar la confirmación de los casos. El diagnóstico clínico del pián es complicado debido a que sus manifestaciones pueden ser inespecíficas. Así, es posible, que una proporción significativa de los casos de pián puedan haber sido falsamente diagnosticados. En el primer artículo, presentamos que, en nuestra experiencia, sólo el 60% de los casos con sospecha clínica de pián fueron finalmente confirmados por pruebas serológicas. Por lo tanto, un diagnóstico adecuado del pián requiere la interpretación de los hallazgos clínicos con referencia a los resultados de laboratorio y la historia epidemiológica de los pacientes. Las pruebas serológicas en el pián no sólo son importantes para el diagnóstico de la enfermedad, también son muy útiles en la definición de curación después del tratamiento. En la prueba de la Reagina plasmática rápida (RPR) los títulos deben descender a los 6-12 meses, llegando a ser negativa en menos de 2 años. El segundo artículo de esta tesis combina un enfoque clínico / serológico para evaluar la respuesta a bencilpenicilina benzatina, e identifica una tasa de fracaso terapéutico del 20% a los 12 meses del tratamiento. Esto podría estar relacionado con resistencia al fármaco antimicrobiano, o bien indicar una re-infección por re-exposición. La distinción entre la re-infección y la resistencia verdadera al tratamiento es difícil, pero estos fracasos terapéuticos son preocupantes. En este artículo se describe un modelo multivariante realizado para identificar los factores determinantes del fracaso terapéutico. El riesgo de re-infección causado por el contacto repetido con otros niños infectados parece ser un predictor fundamental de fracaso. También es un factor de riesgo, los títulos basales bajos (< 1:32) de RPR. Este último factor podría estar relacionado con la mayor dificultad para resolver infecciones crónicas (en estadio secundario), habitualmente acompañadas de títulos bajos. Con la enfermedad de pián re-emergiendo, el desarrollo de nuevas estrategias contra la infección para hacer más fácil los esfuerzos de erradicación es esencial. La penicilina inyectable sigue siendo eficaz, pero el tratamiento con un fármaco por vía oral que pueda ser fácilmente administrado a gran escala es el método preferido para el tratamiento, prevención y finalmente eliminación en todas las regiones endémicas del mundo. Hasta la fecha, no ha habido estudios que comparen directamente la eficacia de la penicilina con cualquiera de los agentes alternativos en el tratamiento de las treponematosis no venéreas. El cuarto artículo de esta tesis ha demostrado que una dosis única de azitromicina por vía oral no es inferior a la bencilpenicilina benzatina intramuscular, para el tratamiento del pián en niños en Papúa Nueva Guinea. En un ensayo abierto, aleatorio, el 96% de los pacientes tratados con azitromicina estaban curados a los 6 meses de seguimiento, al igual que el 93% en el grupo de bencilpenicilina benzatina. Las perspectivas de finalmente erradicar el pián son ahora mayores, mediante el uso de una dosis única de azitromicina oral en campañas masivas de tratamiento. El tratamiento masivo con azitromicina ha sido ampliamente utilizado para el control del tracoma, que, al igual que el pián es una enfermedad de comunidades rurales pobres de países en desarrollo. También se ha utilizado de una manera más limitada para controlar el granuloma inguinal y brotes de sífilis venérea. En general, el uso de azitromicina ha demostrado ser seguro, y de hecho ha habido beneficios inesperados de salud en algunos programas. La eliminación del pián y la filariasis linfática en las Islas del Pacífico Sur se considera ahora biológicamente factible y operacionalmente alcanzable. El Programa Global para Eliminar la Filariasis Linfática (GPELF) se ha expandido rápidamente para alcanzar la meta de eliminación en el año 2020. Por otro lado la estrategia para eliminar el pián es nuevamente centro de atención. Además, dado que los seres humanos infectados son la única fuente de la enfermedad, su eliminación podría lograrse en un plazo relativamente corto. El quinto artículo de la tesis revisa de forma integral el tratamiento con antimicrobianos y las estrategias de eliminación contra el pián. Con el fin de controlar el pián hasta la erradicación, se propone pasar de la penicilina a la azitromicina, y el uso de campañas de tratamiento masivo de toda la población en todas las comunidades endémicas. Además, para asegurar que todos los casos son encontrados y tratados, serán necesarias medidas estrictas de seguimiento y tratamiento masivo selectivo hasta llegar al objetivo de cero casos clínicos. Es importante destacar que el principio de interrupción de la transmisión se debe probar en estudios piloto, incluyendo estudios de prevalencia, para monitorizar el impacto de la intervención, y también la valoración de resistencia a macrolidos, que en nuestra opinión, serán herramientas fundamentales que nos guíen en el camino hacia una eliminación sostenible La filariasis linfática (FL), causada por el nematodo Wuchereria bancrofti, es otro de los grandes problemas de salud pública en los países de la Melanesia. Un curso de MDA anual, durante cinco años, es la estrategia que la OMS recomienda para eliminar la FL. Este enfoque tiene como objetivo suprimir la microfilaremia en los individuos infectados y disminuir los niveles de infección por debajo de un umbral que conduzca a la interrupción de la transmisión. Sin embargo, trabajo teórico y experiencia práctica clínica han puesto de relieve cómo la diversidad ecológica, entre diferentes

Epidemiology of Haemophilus ducreyi Infections

The global epidemiology of Haemophilus 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 H. ducreyi before and after introduction of syndromic management for genital ulcer disease (GUD). Before 2000, the proportion of GUD caused by H. 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, H. 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 here has been a sustained reduction in the proportion of GUD caused by H. ducreyi, this bacterium is increasingly recognized as a major cause of nongenital cutaneous ulcer

Chilblain and Acral Purpuric Lesions in Spain during Covid Confinement: Retrospective Analysis of 12 Cases

Desde la aparición de la infección por COVID-19 en Espa na, a principios de febrero de 2020, las regiones más pobladas como Madrid y Catalu na han concentrado la mayor incidencia de casos. La sospecha de COVID-19 se basa en signos clínicos que comprenden fiebre, tos, fatiga, ageusia, anosmia, mialgia y disnea. Las alteraciones de laboratorio incluyen linfopenia, aumento de LDH, dímero-D, ferritina y PCR. El diagnóstico se basa en la detección de virus en frotis orofaríngeos. Algunas pruebas rápidas están disponibles para la determinación de IgM e IgG específicas, pero su uso es aún limitado debido a la baja disponibilidad y la validación incompleta. Se han realizado medidas restrictivas en la población espa nola. El estado de alarma y el encierro general en Espa na comenzaron el 14 de marzo y aún no han finalizado a fecha de hoy. Ya se han descrito varias dermatosis asociadas con la infección por COVID-191, que incluyen una erupción eritematosa o purpúrica en el tronco, lesiones urticariales y lesiones similares a la varicela. Se han notificado lesiones acroisquémicas en pacientes ingresados en unidades de cuidados intensivos2, debido a la coagulación intravascular diseminada (CID) y comportándose clínicamente como una gangrena seca. Recientemente se ha notificado un caso de lesiones acroisquémicas agudas en un ni no en Italia3