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Abstract Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC–MS/MS in 30 study participants—20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA Cmax was 0.4 mg/L—and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.

Abstract Introduction Skin diseases such as impetigo pose a significant public health challenge in low resource settings. Despite this, there is a dearth of epidemiological data on the prevalence of this condition in Ghana. Methods We conducted a cross sectional study in three settings in Ghana: community members in East Mamprusi district in the North East region, a secondary school in Sekyere East district, and inmates of the Kumasi central prisons both in the Ashanti region. Following a period of training, we performed a standardised skin examination on each participant to assess for scabies and impetigo. We calculated the prevalence of each skin condition and investigated determinants of impetigo. Results/ findings Of the 1327 participants [males 64.1% and median age 22 (16–29) years], 746 (56.2%) had scabies and 186 (14%) had impetigo which was usually very mild or mild in severity. Most participants with impetigo also had scabies (161/186, 86.6%). Having an itch [RR 6.05 (95% CI 2.53–14.47)], presence of scabies burrows [RR 1.99 (95% CI 1.54–2.59)], clinical scabies [RR 3.15 (2.11–4.72)] or being in preschool [RR 4.56 (1.78–11.67)] increased the risk for impetigo. A combination of the presence of clinical scabies, age, sex and itch most accurately predicted the odds of having impetigo. Conclusions There is substantial burden of impetigo and scabies in Ghana. There is a need to institute measures to improve detection and control of these common dermatoses as part of Universal Health Coverage package to reduce the scourge of the diseases in this setting.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Introduction Antivenom is a lifesaving medicine for treating snakebite envenoming, yet there has been a crisis in antivenom supply for many decades. Despite this, substantial quantities of antivenom stocks expire before use. This study has investigated whether expired antivenoms retain preclinical quality and efficacy, with the rationale that they could be used in emergency situations when in-date antivenom is unavailable.Methods Using WHO guidelines and industry test requirements, we examined the in vitro stability and murine in vivo efficacy of eight batches of the sub-Saharan African antivenom, South African Institute for Medical Research polyvalent, that had expired at various times over a period of 30 years.Results We demonstrate modest declines in immunochemical stability, with antivenoms older than 25 years having high levels of turbidity. In vitro preclinical analysis demonstrated all expired antivenoms retained immunological recognition of venom antigens and the ability to inhibit key toxin families. All expired antivenoms retained comparable in vivo preclinical efficacy in preventing the lethal effects of envenoming in mice versus three regionally and medically important venoms.Conclusions This study provides strong rationale for stakeholders, including manufacturers, regulators and health authorities, to explore the use of expired antivenom more broadly, to aid in alleviating critical shortages in antivenom supply in the short term and the extension of antivenom shelf life in the longer term.

Snakebite envenoming is a debilitating neglected tropical disease disproportionately affecting the rural poor in low and middle-income countries in the tropics and sub-tropics. Critical questions and gaps in public health and policy need to be addressed if major progress is to be made towards reducing the negative impact of snakebite, particularly in the World Health Organisation (WHO) Africa region. We engaged key stakeholders to identify barriers to evidence-based snakebite decision making and to explore how development of research and policy hubs could help to overcome these barriers. We conducted an electronic survey among 73 stakeholders from ministries of health, health facilities, academia and non-governmental organizations from 15 countries in the WHO Africa region. The primary barriers to snakebite research and subsequent policy translation were limited funds, lack of relevant data, and lack of interest from policy makers. Adequate funding commitment, strong political will, building expert networks and a demand for scientific evidence were all considered potential factors that could facilitate snakebite research. Participants rated availability of antivenoms, research skills training and disease surveillance as key research priorities. All participants indicated interest in the development of research and policy hubs and 78% indicated their organization would be willing to actively participate. In conclusion, our survey affirms that relevant stakeholders in the field of snakebite perceive research and policy hubs as a promising development, which could help overcome the barriers to pursuing the WHO goals and targets for reducing the burden of snakebite.

IntroductionResearch on snakebite has mostly been conducted on settled populations and current risk factors and potential interventions are therefore most suited for these populations. There is limited epidemiological data on mobile and nomadic populations, who may have a higher risk of snakebite.Methods and resultsWe conducted a scoping review to gather evidence on survey methods used in nomadic populations and compared them with contemporary survey methods used for snakebite research. Only 16 (10.5%) of 154 articles reportedly conducted on pastoralist nomadic populations actually involved mobile pastoralists. All articles describing snakebite surveys (n = 18) used multistage cluster designs on population census sampling frames, which would not be appropriate for nomadic populations. We used geospatial techniques and open-source high-resolution satellite images to create a digital sampling frame of 50,707 households and used a multistage sampling strategy to survey nomadic and semi-nomadic populations in Samburu County, Kenya. From a sample of 900 geo-located households, we correctly identified and collected data from 573 (65.4%) households, of which 409 were in their original locations and 164 had moved within 5km of their original locations. We randomly sampled 302 (34.6%) households to replace completely abandoned and untraceable households.ConclusionHighly mobile populations require specific considerations in selecting or creating sampling frames and sampling units for epidemiological research. Snakebite risk has a strong spatial component and using census-based sampling frames would be inappropriate in nomadic populations. We propose using open-source satellite imaging and geographic information systems to improve the conduct of epidemiological research in these populations.

BackgroundHalving snakebite morbidity and mortality by 2030 requires countries to develop both prevention and treatment strategies. The paucity of data on the global incidence and severity of snakebite envenoming causes challenges in prioritizing and mobilising resources for snakebite prevention and treatment. In line with the World Health Organisation's 2019 Snakebite Strategy, this study sought to investigate Eswatini's snakebite epidemiology and outcomes, and identify the socio-geographical factors associated with snakebite risk.MethodologyProgrammatic data from the Ministry of Health, Government of Eswatini 2019-2021, was used to assess the epidemiology and outcomes of snakebite in Eswatini. We developed a snake species richness map from the occurrence data of all venomous snakes of medical importance in Eswatini that was subjected to niche modelling. We formulated four risk indices using snake species richness, various geospatial datasets and reported snakebites. A multivariate cluster modelling approach using these indices was developed to estimate risk of snakebite and the outcomes of snakebite in Eswatini.Principal findingsAn average of 466 snakebites was recorded annually in Eswatini. Bites were recorded across the entire country and peaked in the evening during summer months. Two cluster risk maps indicated areas of the country with a high probability of snakebite and a high probability of poor snakebite outcomes. The areas with the highest rate of snakebite risk were primarily in the rural and agricultural regions of the country.SignificanceThese models can be used to inform better snakebite prevention and treatment measures to enable Eswatini to meet the global goal of reducing snakebite morbidity and mortality by 50% by 2030. The supply chain challenges of antivenom affecting southern Africa and the high rates of snakebite identified in our study highlight the need for improved snakebite prevention and treatment tools that can be employed by health care workers stationed at rural, community clinics.

IntroductionSnakebite is one of the most neglected tropical diseases. In Ghana, there has been a limited interest in snakebite envenoming research despite evidence of high human-snake conflicts. In an effort to meet the World Health Organisation's (WHO) 2030 snakebite targets, the need for research evidence to guide policy interventions is evident. However, in setting the research agenda, community and healthcare workers' priorities are rarely considered.MethodsThree categories of focus groups were formed in the Ashanti and Upper West regions of Ghana, comprising of community members with and without a history of snakebite and healthcare workers who manage snakebite patients. Two separate focus group discussions were conducted with each group in each region. Using the thematic content analysis approach, the framework method was adopted for the data analysis. A predefined 15-item list of potential snakebite-associated difficulties and the WHO's 2030 snakebite strategic key activities were ranked in order of priority based on the participants' individual assessment.ResultsBoth acute and chronic effects of snakebite such as bite site management, rehabilitation and mental health were prioritised by the community members. Health system challenges including training, local standard treatment protocols and clinical investigations on the efficacy of available antivenoms were identified as priorities by the healthcare workers. Notably, all the participant groups highlighted the need for research into the efficacy of traditional medicines and how to promote collaborative strategies between traditional and allopathic treatment practices.ConclusionThe prioritisation of chronic snakebite envenoming challenges by community members and how to live and cope with such conditions accentuate the lack of post-hospital treatment follow-ups for both mental and physical rehabilitation. To improve the quality of life of patients, it is essential to involve grassroots stakeholders in the process of developing and prioritising future research agenda.

BackgroundScabies commonly affects poor populations in low-middle-income countries. The WHO has advocated for country-driven and country-owned control strategies. Knowledge of context specific issues will be important for design and implementation of scabies control interventions. We aimed to assess beliefs, attitudes and practices towards scabies in central Ghana.Methodology/principal findingsData was collected via semi-structured questionnaires for people who had active scabies or scabies in the past year and people who never had scabies in the past. The questionnaire covered several domains: knowledge about the causes and risk factors; perceptions towards stigmatisation and consequences of scabies in daily life; and treatment practices. Out of 128 participants, 67 were in the (former) scabies group and had a mean age of 32.3 ± 15.6 years. Overall scabies group participants less often indicated a factor to predispose to scabies than community controls; only 'family/friends contacts' was more often mentioned in the scabies group. Scabies causation was attributed to poor hygiene, traditional beliefs, heredity and drinking water. Individuals with scabies delay care seeking (median time from symptom onset to visiting the health centre was 21 [14 - 30] days) and this delay is enhanced by their beliefs (like witchcraft and curses) and a perception of limited disease severity. Compared to past scabies participants in the dermatology clinic, participants with past scabies in the community tended to have a longer delay (median [IQR] 30 [14-48.8] vs 14 [9.5-30] days, p = 0.002). Scabies was associated with health consequences, stigma, and loss of productivity.Conclusion/significanceEarly diagnosis and effective treatment of scabies can lead to persons less frequently associating scabies with witchcraft and/ or curses. There is the need to enhance health education to promote early care seeking, enhance knowledge of communities on impact and dispel negative perceptions about scabies in Ghana.

Snakebite envenoming is an acute medical emergency which affects hundreds of thousands of people worldwide, primarily in remote rural areas of low-and middle income countries in the Global South. A considerable proportion of snakebite patients turn to traditional healers (THs) for help, driven by a number of push and pull factors. These include socio-cultural factors, geographical proximity, and the absence or inaccessibility of overstretched and often costly allopathic healthcare services. Although traditional healers and allopathic healthcare staff share a common focus -the recovery and well-being of their patients- both systems operate largely in parallel to each other with collaborations being an exception rather than the rule. This is to the detriment of snakebite patients, who frequently find themselves being caught-up in the dualism between the two separate systems. Given the right circumstances, snakebite patients could benefit from elements of care from both modalities. Here, we have reviewed the role of THs in snakebite care and explored how their integration into the formal healthcare system could improve the implementation and outcome of care. The effective recruitment of THs to aid in disease control and treatment efforts in diseases other than snakebite underscores the potential benefits of this strategy. Carefully devised proof of concept studies are needed to test our hypothesis that collaborations between the formal healthcare sector and THs are feasible and improve outcomes in snakebite care.

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

BackgroundScabies is a global health concern disproportionately affecting vulnerable populations such as refugees and asylum seekers. Greece is a main point of entry in Europe for refugees, but epidemiological data on scabies in this population are scarce. We aimed to describe the epidemiology of scabies, including trends over the study period.Methodology/principal findingsData were collected from June, 2016 to July, 2020, using the surveillance system of the Greek National Public Health Organization. Daily reports on scabies and other infectious diseases were submitted by staff at health centers for refugees/asylum seekers. Observed proportional morbidity for scabies was calculated using consultations for scabies as a proportion of total consultations. There were a total of 13118 scabies cases over the study period. Scabies was the third most frequently observed infectious disease in refugees/asylum seekers population after respiratory infections and gastroenteritis without blood in the stool. The scabies monthly observed proportional morbidity varied between 0.3% (August 2017) to 5.7% (January 2020). Several outbreaks were documented during the study period. The number of cases increased from October 2019 until the end of the study period, with a peak of 1663 cases in January 2020, related to an outbreak at one center. Spearman correlation test between the number of reported scabies cases and time confirmed an increasing trend (ρ = 0.67).Conclusions/significanceScabies is one of the most frequently reported infectious diseases by health care workers in refugee/asylum seekers centers in Greece. Observed proportional morbidity for scabies increased over time and there were several outbreaks. The current surveillance system with daily reports of the new cases effectively detects new cases in an early stage. Public health interventions, including mass drug administration, should be considered to reduce the burden of scabies in refugee/migrant populations.

Abstract Background Previous studies have reported that presence and severity of Buruli ulcer (BU) may reflect the underlying immunosuppression in HIV infected individuals by causing increased incidence of multiple, larger and ulcerated lesions. We report cases of BU-HIV coinfection and the accompanying programmatic challenges encountered in central Ghana. Methods Patients with PCR confirmed BU in central Ghana who were HIV positive were identified and their BU01 forms were retrieved and reviewed in further detail. A combined 16S rRNA reverse transcriptase / IS2404 qPCR assay was used to assess the Mycobacterium ulcerans load. The characteristics of coinfected patients (BU+HIV+) were compared with a group of matched controls. Results The prevalence of HIV in this BU cohort was 2.4% (compared to national HIV prevalence of 1.7%). Eight of 9 BU+HIV+ patients had a single lesion and ulcers were the most common lesion type. The lesions presented were predominantly category II (5/9) followed by category I lesions. The median (IQR) time to healing was 14 (8–28) weeks in the BU+HIV+ compared to 28 (12–33) weeks in the control BU+HIV− group (p = 0.360). Only one BU+HIV+ developed a paradoxical reaction at week 16 but the lesion healed completely at week 20. The median bacterial load (16SrRNA) of BU+HIV+ patients was 750 copies /ml (95% CI 0–398,000) versus 500 copies/ml (95% CI 0–126,855,500) in BU+HIV− group. Similarly, the median count using the IS2404 assay was 500 copies/ml (95% CI 0–500) for BU+HIV+ patients versus 500 copies/ml (95% CI 500–31,000) for BU+HIV− patients. BU+HIV− patients mounted a significantly higher interferon-γ response compared to the BU+HIV+ co-infected patients with respective median (range) responses of [1687(81.11–4399) pg/ml] versus [137.5(4.436–1406) pg/ml, p = 0.03]. There were challenges with the integration of HIV and BU care in this cohort. Conclusion The prevalence of HIV in the BU+ infected population was not significantly increased when compared to the prevalence of HIV in the general population. There was no clear relationship between BU lesion severity and HIV viral load or CD4 counts. Efforts should be made to encourage the integration of care of patients with BU-HIV coinfection.

BackgroundThe estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records.MethodsThis community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite.FindingsThe median (IQR) time since the snakebite was 8.0 (3.5-16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17-2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities.ConclusionThe burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations.

Objectives: Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). Methods: Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0–90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. Results: Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. Conclusions: VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.

Abstract Background Establishing a correct diagnosis is challenging. We aimed to investigate the sensitivity and specificity of routine tuberculosis (TB) diagnostic work-up in lung clinics in Indonesia, a country with the third highest TB burden and the second highest gap between notifications of TB cases and the best estimate of incident cases in the world. Methods In the lung clinics of the Province of Yogyakarta, Indonesia, we recruited all consecutive patients with symptoms suggesting TB, aged ≥18 years. Routine TB examination consisted of clinical evaluation, sputum smear microscopy, and chest radiography. For research purposes, we added sputum culture, Human Immunodeficiency Virus (HIV) testing, and follow-up for 1.5 years or 2.5 years if culture results disagreed with the initial clinical diagnosis. The initial diagnosis was considered incorrect if patients did not respond to treatment. We calculated sensitivity and specificity of the TB routine examination using culture and a composite reference standard (CRS – a combination of routine examination, culture, and follow-up) as the reference standards. All analyses were conducted with IBM SPSS Statistics 25 (IBM Corp., Armonk, NY, USA). Results Between 2013 and 2015, we included 360 participants, and 21 were excluded due to incomplete data. Among those analyzed, 115 were initially diagnosed with smear-positive TB, 12 with smear-negative TB, and 212 non-TB. In 15 study participants, the diagnosis was changed after median 45 (range: 14–870) days; 14 participants initially not diagnosed with TB were later diagnosed with TB, while one subject initially diagnosed with TB actually did not have TB. Compared with culture and CRS, TB routine examination had sensitivity of 85% (95%CI: 77–91) and 90% (95%CI: 84–94), and specificity of 86.3% (95%CI: 81–91) and 99.5% (95%CI: 97–100), respectively. Conclusions A combination of clinical evaluation with sputum microscopy and chest radiography provided high sensitivity and specificity in diagnosing TB in lung clinics; in only 4.4% the diagnosis was incorrect. There is a need to improve routine TB diagnostic work by using clinical evaluation, sputum smear microscopy, and chest radiography all together in other settings, such as in primary health centers. Trial registration NCT02219945, clinicaltrials.gov. Registered 19 August 2014 (retrospectively registered).

Abstract Background Several studies have shown a high prevalence of multi-drug resistant organisms (MDRO) amongst asylum seekers when compared to the general population. The aim of this study is to assess the duration of MDRO carriage in this population. Methods Data were retrospectively collected between January 1st 2014 through December 31st 2016. Study material included screening samples for MDRO carriage and clinical samples from asylum seekers in need of medical care. The study focused on methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Enterobacteriaceae (MDRE). The rates of MRSA and MDRE detected were calculated every four weeks after arrival in the Netherlands. Results Samples from 2091 asylum seekers were included. 1270 (60.7%) were female, median age was 26 years (IQR 20–34) and median number of days in the Netherlands until first sample was 67 (IQR 4–235). In the patients’ first obtained samples, the rate of MRSA varied between 4.5 and 13.0% per time interval after arrival. The rate of MDRE fluctuated between 7.4% and 25.0%. No particular decline in positivity rates in first obtained samples was observed after arrival in the Netherlands. In the group of asylum seekers who arrived more than one year ago, MRSA was isolated in a percentage of 5.1% (n = 273, median months after arrival 34.1 (IQR 16.5–63.1)) and MDRE in 9.4% (n = 276, median months after arrival 35.4 (IQR 17–65)). Conclusion To our knowledge, this is the first study demonstrating that carriage rate of MDRO in asylum seekers remains high even after prolonged stay in the Netherlands. Longitudinal data on MDRO carriage after arrival in countries with a low MDRO prevalence are needed to determine optimal screening strategies, infection control measures and empirical antibiotic therapy.

BackgroundSnakebite envenoming is a medical emergency which is common in many tropical lower- and middle-income countries. Traditional healers are frequently consulted as primary care-givers for snakebite victims in distress. Traditional healers therefore present a valuable source of information about how snakebite is perceived and handled at the community level, an understanding of which is critical to improve and extend snakebite-related healthcare.MethodThe study was approached from the interpretive paradigm with phenomenology as a methodology. Semi-structured interviews were conducted with 19 traditional healers who treat snakebite patients in two rural settings in Ghana. From the Ashanti and Upper West regions respectively, 11 and 8 healers were purposively sampled. Interview data was coded, collated and analysed thematically using ATLAS.ti 8 software. Demographic statistics were analysed using IBM SPSS Statistics version 26.FindingsSnakebite was reportedly a frequent occurrence, perceived as dangerous and often deadly by healers. Healers felt optimistic in establishing a diagnosis of snakebite using a multitude of methods, ranging from herbal applications to spiritual consultations. They were equally confident about their therapies; encompassing the administration of plant and animal-based concoctions and manipulations of bite wounds. Traditional healers were consulted for both physical and spiritual manifestations of snakebite or after insufficient pain control and lack of antivenom at hospitals; referrals by healers to hospitals were primarily done to receive antivenom and care for wound complications. Most healers welcomed opportunities to engage more productively with hospitals and clinical staff.ConclusionsThe fact that traditional healers did sometimes refer victims to hospitals indicates that improvement of antivenom stocks, pain management and wound care can potentially improve health seeking at hospitals. Our results emphasize the need to explore future avenues for communication and collaboration with traditional healers to improve health seeking behaviour and the delivery of much-needed healthcare to snakebite victims.

BackgroundThere is a dearth of data on scabies from Ghana. In September 2019, local health authorities in the East Mamprusi district of northern Ghana received reports of scabies from many parts of the district. Due to on-going reports of more cases, an assessment team visited the communities to assess the effect of the earlier individual treatment on the outbreak. The assessment team furthermore aimed to contribute to the data on scabies burden in Ghana and to demonstrate the use of the International Alliance for the Control of Scabies (IACS) diagnostic tool in a field survey in a resource limited setting.Methodology/principal findingsThis was a cross sectional study. Demographic information and medical history was collected on all participants using a REDCap questionnaire. A standardised skin examination of exposed regions of the body was performed on all participants. Scabies was diagnosed based on the criteria of the International Alliance for the Control of Scabies (IACS). Participants were mostly female (61.5%) and had a median age of 18.8 years (IQR 13-25). Two hundred out of 283 (71%) of participants had scabies with most (47%) presenting with moderate disease. Impetigo was found in 22% of participants with scabies and 10.8% of those without scabies [RR 2.27 (95% CI 1.21-4.27)]. 119 participants who received scabies treatment in the past months still had clinical evidence of the disease. 97% of participants reported a recent scabies contact. Scabies was commoner in participants ≤16 years compared to those >16 years [RR 3.06 (95% CI 1.73-5.45)].Conclusion/significanceThe prevalence of scabies was extremely high. The lack of a systematic approach to scabies treatment led to recurrence and ongoing community spread. The IACS criteria was useful in this outbreak assessment in Ghana. Alternative strategies such as Mass drug administration may be required to contain outbreaks early in such settings.

Abstract Background With a large number of forcibly displaced people seeking safety, the EU is facing a challenge in maintaining solidarity. Europe has seen millions of asylum seekers crossing European borders, the largest number of asylum seekers since the second world war. Endemic diseases and often failing health systems in their countries of origin, and arduous conditions during transit, raise questions around how to meet the health needs of this vulnerable population on arrival in terms of screening, vaccination, and access to timely and appropriate statutory health services. This paper explores the potential role of the principle of reciprocity, defined as the disposition ‘to return good in proportion to the good we receive, and to make reparations for the harm we have done’, as a mid-level principle in infectious disease screening policies. Main text More than half of the European countries implemented screening programmes for newly arrived asylum seekers. Screening may serve to avoid potential infectious disease risks in the receiving countries as well as help identify health needs of asylum seekers. But screening may infringe upon basic rights of those screened, thus creating an ethical dilemma. The use of the principle of reciprocity can contribute to the identification of potential improvements for current screening programmes and emphasizes the importance of certain rights into guidelines for screening. It may create a two way moral obligation, upon asylum seekers to actively participate in the programme, and upon authorities to reciprocate the asylum seekers’ participation and the benefits for the control of public health. Conclusion The authors argue that the reciprocity principle leads to a stronger ethical justification of screening programmes and help achieve a balance between justifiable rights claims of the host population and the asylum seekers. The principle deserves a further and more thorough exploration of its potential use in the field of screening, migration and infectious diseases.

BACKGROUND:Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic. METHODS:A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders. RESULTS:A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. CONCLUSION:The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU.

BackgroundBuruli Ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Former BU patients may experience participation restrictions due to physical limitations, stigmatization and other social factors. A scale that measures participation restrictions among children, who represent almost half of the affected population, has not been developed yet. Here, we present the development of a scale that measures participation restrictions in former BU paediatric patients, the psychometric properties of this scale and the scales' results.MethodsItems were selected and a scale was developed based on interviews with health care workers and former BU patients in and around the BU treatment centre in Lalo, Benin. Construct validity was tested using six a priori formulated hypotheses. Former BU patients under 15 years of age who received treatment in one of the BU treatment centres in Ghana and Benin between 2007-2012 were interviewed.ResultsA feasible 16-item scale that measures the concept of participation among children under 15 years of age was developed. In total, 109 (Ghana) and 90 (Benin) former BU patients were interviewed between 2012-2017. Five construct validity hypotheses were confirmed of which 2 hypotheses related to associations with existing questionnaires were statistically significant (pConclusionThe preliminary results of the PP-scale validation are promising but further validation is needed. The developed PP-scale may be valid for use in patients with more severe BU lesions. This is the first research to confirm that former BU patients under 15-year face participation restrictions in important aspects of their lives.

INTRODUCTION:Europe has been dealing with an increasing number of refugees during the past 5 years. The timing of screening and vaccination of refugees is debated by many professionals, however refugees' perspectives on health issues are infrequently taken into account. In this study, we aimed to investigate asylum seekers' perspectives on infectious diseases screening and vaccination policies. MATERIALS AND METHODS:Interviews were conducted in Greece and the Netherlands. Asylum seekers and recently arrived refugees were approached and informed with the help of interpreters; consent forms were acquired. The survey focused on demographic data, vaccination status, screening policies and prevention of infectious diseases. RESULTS:A total of 61 (43 male, 70.5%) refugees (30 Afghanis, 16 Syrian, 7 Erithrean) were interviewed. Mean age was 35.2 years (SD 13.5) and 50% had received primary or secondary education, while 24.6% received none. Median time after arrival in Greece and the Netherlands was 24 months (IQR 8.5-28). 44 out of 61 (72.1) participants were willing to be vaccinated after arrival in Europe, 26 preferred vaccination and screening to be performed at the point of entry. The need for screening and vaccination was perceived higher amongst participants in Greece (100% vs 43.3%) due to living conditions leading to increased risk of outbreaks. CONCLUSION:Participants were willing to communicate their perspectives and concerns. Screening and vaccination programs could be more effective when implemented shortly after arrival and by involving asylum seekers and refugees when developing screening and vaccination interventions.

ObjectiveTo investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB.MethodsSetting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5-2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum's Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum's ROC-curve. Differences between Area-under-the-Curve between strata (pResultsOf 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75-92%) and 78% (95%CI: 70-85%), specificity was 55% (95%CI: 44-65%) and 42% (95%CI: 34-50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men.ConclusionThe electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings.

Objective/Background: Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. Methods: A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. Results: GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. Conclusion: These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting.

Scabies is a skin infestation with the mite Sarcoptes scabiei causing itch and rash and is a major risk factor for bacterial skin infections and severe complications. Here, we evaluated the treatment outcome of 2866 asylum seekers who received (preventive) scabies treatment before and during a scabies intervention programme (SIP) in the main reception centre in the Netherlands between January 2014 and March 2016. A SIP was introduced in the main national reception centre based on frequent observations of scabies and its complications amongst Eritrean and Ethiopian asylum seekers in the Netherlands. On arrival, all asylum seekers from Eritrea or Ethiopia were checked for clinical scabies signs and received ivermectin/permethrin either as prevention or treatment. A retrospective cohort study was conducted to compare the reinfestations and complications of scabies in asylum seekers who entered the Netherlands before and during the intervention and who received ivermectin/permethrin. In total, 2866 asylum seekers received treatment during the study period (January 2014 -March 2016) of which 1359 (47.4%) had clinical signs of scabies. During the programme, most of the asylum seekers with scabies were already diagnosed on arrival as part of the SIP screening (580 (64.7%) of the 897). Asylum seekers with more than one scabies episode reduced from 42.0% (194/462) before the programme to 27.2% (243/897) during the programme (RR = 0.64, 95% CI = 0.55-0.75). Development of scabies complications later in the asylum procedure reduced from 12.3% (57/462) to 4.6% (41/897). A scabies prevention and treatment programme at start of the asylum procedure was feasible and effective in the Netherlands; patients were diagnosed early and risk of reinfestations and complications reduced. To achieve a further decrease of scabies, implementation of the programme in multiple asylum centres may be needed.

Objectives:Staphylococcus aureus infections in burn patients can lead to serious complications and death. The frequency of S. aureus infection is high in low- and middle-income countries presumably due to limited resources, misuse of antibiotics and poor infection control. The objective of the present study was to apply population genomics to precisely define, for the first time, the transmission of antibiotic resistant S. aureus in a resource-limited setting in sub-Saharan Africa.Methods:Staphylococcus aureus surveillance was performed amongst burn patients and healthcare workers during a 7-months survey within the burn unit of the Korle Bu Teaching Hospital in Ghana.Results: Sixty-six S. aureus isolates (59 colonizing and 7 clinical) were obtained from 31 patients and 10 healthcare workers. Twenty-one of these isolates were ST250-IV methicillin-resistant S. aureus (MRSA). Notably, 25 (81%) of the 31 patients carried or were infected with S. aureus within 24 h of admission. Genome comparisons revealed six distinct S. aureus clones circulating in the burn unit, and demonstrated multiple transmission events between patients and healthcare workers. Further, the collected S. aureus isolates exhibited a wide range of genotypic resistances to antibiotics, including trimethoprim (21%), aminoglycosides (33%), oxacillin (33%), chloramphenicol (50%), tetracycline (59%) and fluoroquinolones (100%).Conclusion: Population genomics uncovered multiple transmission events of S. aureus, especially MRSA, within the investigated burn unit. Our findings highlight lapses in infection control and prevention, and underscore the great importance of active surveillance to protect burn victims against multi-drug resistant pathogens in resource-limited settings.

In developing countries, hospitalized burn victims are at high risk of nosocomial infections caused by Staphylococcus aureus. Risk factors include poor infection control practices, prolonged hospitalisation and limited capacity for laboratory microbiological analyses. These problems are compounded by widespread use of antibiotics that drives the spread of multi-drug resistant bacteria.During the study period (November 2014-June 2015), nasal and invasive S. aureus isolates were collected consecutively from patients and healthcare workers (HCWs) within the burn unit of the Reconstructive Plastic Surgery and Burn Center of Korle Bu Teaching Hospital in Ghana. Antibiotic prescription, antibiotic susceptibility and bacterial typing were used to assess antibiotic pressure, antibiotic resistance, and possible transmission events among patients and HCWs.Eighty S. aureus isolates were obtained from 37 of the 62 included burn patients and 13 of the 29 HCWs. At admission, 50% of patients carried or were infected with S. aureus including methicillin resistant S. aureus (MRSA). Antibiotic use per 100 days of hospitalization was high (91.2 days), indicating high selective pressure for resistant pathogens. MRSA isolates obtained from 11 patients and one HCW belonged to the same spa-type t928 and multi-locus sequence type 250, implying possible transmission events. A mortality rate of 24% was recorded over the time of admission in the burn unit.This study revealed a high potential for MRSA outbreaks and emergence of resistant pathogens amongst burn patients due to lack of patient screening and extended empirical use of antibiotics. Our observations underscore the need to implement a system of antibiotic stewardship and infection prevention where microbiological diagnostics results are made available to physicians for timely and appropriate patient treatment.

Routine physical examinations might be of value in HIV-infected patients, but the yield is unknown. We determined the diagnoses that would have been missed without performing annual routine physical examinations in HIV-infected patients with stable disease.Data were collected from the medical records of 299 HIV-1-infected patients with CD4 count >350 cells/mm3 if not using combination antiretroviral therapy (cART), or CD4 count >100 cells/mm3 and undetectable viral load if using cART. We defined the diagnoses that would have been missed without performing routine physical examinations on annual check-ups in 2010. Exclusion criteria were hepatitis B/C co-infection, start/ switch of cART < 24 weeks, pregnancy, and transgenderism.215 patients (72%) had positive findings: lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.4%) were the most common. Two-thirds of all findings were not new or were based on complaints indicating a physical examination even if not routinely scheduled. For 24 patients (8.0%) the routine physical examination led to the finding of a new diagnosis: six-all men who have sex with men (MSM)-had a concurrent sexually transmitted infection, eight had hypertension, and ten others had a large variety of diagnoses. A total atrioventricular block with bradycardia was the most clinically relevant finding.Annual physical examinations of HIV-infected patients with stable disease brought few new diagnoses that would have been missed without performing a routine examination. Our results suggest that standard assessments could be restricted to six-monthly measuring blood pressure in all patients and annually performing anogenital and digital rectal examination on MSM.

Migration is one of the risk factors for the spread of multidrug-resistant organisms (MDRO). The increasing influx of migrants challenges local health care systems. To provide evidence for both hospital hygiene measure and empirical antibiotic therapy, we analysed all cultures performed in asylum seekers between January 1st 2014 and December 31st 2015 for methicillin resistant Staphylococcus aureus (MRSA) and for multidrug-resistant Enterobacteriaceae (MDRE). We compared these with cultures from the Dutch patient population with risk factors for carriage of MDRO. A total of 7181 patients were screened for MRSA. 7357 S. aureus were isolated in clinical cultures. Of 898 screened asylum seekers, almost 10% were MRSA positive. Of 118 asylum seekers with S. aureus in clinical cultures almost 19% were MRSA positive. The general patient population had a 1.3% rate of MRSA in S. aureus isolates. A higher rate of Panton-Valentine leukocidin (PVL) positive strains (RR: 2.4; 95% CI: 1.6-3.4) was found in asylum seekers compared to the general patient population. In 33475 patients one or more Enterobacteriaceae were obtained. More than 21% of the asylum seekers were carrier of MDRE, most of them producing extended spectrum beta-lactamases (20.3%). 5.1% of the general patient population was MDRE carrier. It can be concluded that asylum seekers present with higher rate of MDRO compared to the general patient population. These results justify continued screening of asylum seekers to anticipate multidrug-resistant organisms during hospital care of patients.

BACKGROUND:Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical disease frequently leading to permanent disabilities. The ulcers are treated with rifampicin and streptomycin, wound care and, if necessary surgical intervention. Professionals have exclusively shaped the research agenda concerning management and control, while patients' perspective on priorities and preferences have not explicitly been explored or addressed. METHODOLOGY/PRINCIPAL FINDINGS:To get insight into patient perception of the management and control of Buruli ulcer a mixed methods research design was applied with a questionnaire and focus group discussions among former BU patients. Data collection was obtained in collaboration with a local team of native speakers in Ghana. A questionnaire was completed by 60 former patients and four focus group discussions were conducted with eight participants per group. Former patients positively evaluated both the effectiveness of the treatment and the financial contribution received for the travel costs to the hospitals. Pain experienced during treatment procedures, in particular wound care and the streptomycin injections, and the side-effects of the treatment were negatively evaluated. Former patients considered the development of preventive measures and knowledge on the transmission as priorities. Additionally, former patients asked for improved accessibility of health services, counselling and economic support. CONCLUSIONS:These findings can be used to improve clinical management and to guide the international research agenda.

Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU.The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable.Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ(2)), larger lesions (p = .021 by Χ(2)) and genetic factors. The polymorphisms 3'UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms.Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene.

INTRODUCTION:The current refugee crisis emphasizes the need for information on infectious diseases and resistant microorganisms in asylum seekers with possible consequences for public health and infection control. METHODS:We collected data from asylum seekers admitted to our university hospital or who presented at the Emergency Department (n = 273). We collected general and demographic characteristics including country of origin, the reason of presentation, and the screening results of multi-drug resistant organisms. RESULTS:67% of the patients were male with a median age of the study group of 24 years (IQR 15-33); 48% of the patients had an infectious disease-predominantly malaria with P. vivax or tuberculosis. Patients also reported with diseases which are less common-e.g. leishmaniasis, or even conditions rarely diagnosed in Europe-e.g. louse borne relapsing fever. A carriage rate of 31% for multi-drug resistant microorganisms (MDRO) was observed, with ESBL-expressing E.coli (n = 20) being the most common MDRO. No carriage of Carbapenemase Producing Enterobacteriaceae was found. CONCLUSION:The current refugee crisis in Europe challenges hospitals to quickly identify and respond to communicable diseases and the carriage of MDRO. A rapid response is necessary to optimize the treatment of infectious diseases amongst asylum seekers to maximize infection control.

Mycobacterium ulcerans causes Buruli ulcer (BU), a debilitating infection of subcutaneous tissue. There is a WHO-recommended antibiotic treatment requiring an 8-week course of streptomycin and rifampicin. This regime has revolutionized the treatment of BU but there are problems that include reliance on daily streptomycin injections and side effects such as ototoxicity. Trials of all-oral treatments for BU show promise but additional drug combinations that make BU treatment safer and shorter would be welcome. Following on from reports that avermectins have activity against Mycobacterium tuberculosis, we tested the in-vitro efficacy of ivermectin and moxidectin on M. ulcerans. We observed minimum inhibitory concentrations of 4-8 μg/ml and time-kill assays using wild type and bioluminescent M. ulcerans showed a significant dose-dependent reduction in M. ulcerans viability over 8-weeks. A synergistic killing-effect with rifampicin was also observed. Avermectins are well tolerated, widely available and inexpensive. Based on our in vitro findings we suggest that avermectins should be further evaluated for the treatment of BU.

BACKGROUND:Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. METHODOLOGY:We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. PRINCIPAL FINDINGS:Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). CONCLUSION/SIGNIFICANCE:The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene.

BACKGROUND:Buruli ulcer (BU) is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment. Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU. METHODOLOGY:A mixed methods approach was used, consisting of information retrieved from medical records on prescribed pain medication from Ghana and Benin, and semi-structured interviews with health care personnel (HCP) from Ghana on pain perceptions, assessment and treatment. Medical records (n = 149) of patients treated between 2008 and 2012 were collected between November 2012 and August 2013. Interviews (n = 11) were audio-taped, transcribed verbatim and qualitatively analyzed. PRINCIPAL FINDINGS:In 113 (84%) of the 135 included records, pain medication, mostly simple analgesics, was prescribed. In 48% of the prescriptions, an indication was not documented. HCP reported that advanced BU could be painful, especially after wound care and after a skin graft. They reported not be trained in the assessment of mild pain. Pain recognition was perceived as difficult, as patients were said to suppress or to exaggerate pain, and to have different expectations regarding acceptable pain levels. HCP reported a fear of side effects of pain medication, shortage and irregularities in the supply of pain medication, and time constraints among medical doctors for pain management. CONCLUSIONS:Professionals perceived BU disease as potentially painful, and predominantly focused on severe pain. Our study suggests that pain in BU deserves attention and should be integrated in current treatment.

Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. People living in remote areas in tropical Sub Saharan Africa are mostly affected. Wound care is an important component of BU management; this often needs to be extended for months after the initial antibiotic treatment. BU is reported in the literature as being painless, however clinical observations revealed that some patients experienced pain during wound care. This was the first study on pain intensity during and after wound care in BU patients and factors associated with pain. In Ghana and Benin, 52 BU patients above 5 years of age and their relatives were included between December 2012 and May 2014. Information on pain intensity during and after wound care was obtained during two consecutive weeks using the Wong-Baker Pain Scale. Median pain intensity during wound care was in the lower range (Mdn = 2, CV = 1), but severe pain (score > 6) was reported in nearly 30% of the patients. Nevertheless, only one patient received pain medication. Pain declined over time to low scores 2 hours after treatment. Factors associated with higher self-reported pain scores were; male gender, fear prior to treatment, pain during the night prior to treatment, and pain caused by cleaning the wound. The general idea that BU is painless is incorrect for the wound care procedure. This procedural pain deserves attention and appropriate intervention.

BACKGROUND:Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. METHODOLOGY:This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere(+) software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. PRINCIPAL FINDINGS:SeqSphere(+) analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus.

Because of the emergence of Buruli ulcer disease, the World Health Organization launched a Global Buruli Ulcer Initiative in 1998. This indolent skin infection is caused by Mycobacterium ulcerans. During a study of risk factors for the disease in Ghana, adequate excisional skin-biopsy specimens were obtained from 124 clinically suspicious lesions. Buruli ulcer disease was diagnosed in 78 lesions since acid-fast bacilli (AFB) were found by histopathologic examination. Lesions with other diagnoses included filariasis (3 cases), zygomycosis (2 cases), ulcerative squamous cell carcinomas (2 cases), keratin cyst (1 case), and lymph node (1 case). Thirty-seven specimens that did not show AFB were considered suspected Buruli ulcer disease cases. Necrosis of subcutaneous tissues and dermal collagen were found more frequently in AFB-positive specimens compared with specimens from suspected case-patients (p

Buruli ulcer may induce severe disabilities impacting on a person's well-being and quality of life. Information about long-term disabilities and participation restrictions is scanty. The objective of this study was to gain insight into participation restrictions among former Buruli ulcer patients in Ghana and Benin.In this cross-sectional study, former Buruli ulcer patients were interviewed using the Participation Scale, the Buruli Ulcer Functional Limitation Score to measure functional limitations, and the Explanatory Model Interview Catalogue to measure perceived stigma. Healthy community controls were also interviewed using the Participation Scale. Trained native interviewers conducted the interviews. Former Buruli ulcer patients were eligible for inclusion if they had been treated between 2005 and 2011, had ended treatment at least 3 months before the interview, and were at least 15 years of age.In total, 143 former Buruli ulcer patients and 106 community controls from Ghana and Benin were included in the study. Participation restrictions were experienced by 67 former patients (median score, 30, IQR; 23;43) while 76 participated in social life without problems (median score 5, IQR; 2;9). Most restrictions encountered related to employment. Linear regression showed being female, perceived stigma, functional limitations, and larger lesions (category II) as predictors of more participation restrictions.Persisting participation restrictions were experienced by former BU patients in Ghana and Benin. Most important predictors of participation restrictions were being female, perceived stigma, functional limitations and larger lesions.

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually BU begins as a painless nodule, plaque or edema, ultimately developing into an ulcer. The high number of patients presenting with ulcers in an advanced stage is striking. Such late presentation will complicate treatment and have long-term disabilities as a consequence. The disease is mainly endemic in West Africa. The primary strategy for control of this disease is early detection using community village volunteers.In this retrospective, observational study, information regarding Buruli ulcer patients that reported to one of the four BU centers in Bénin between January 2008 and December 2010 was collected using the WHO/BU01 forms. Information used from these forms included general characteristics of the patient, the results of diagnostic tests, the presence of functional limitations at start of treatment, lesion size, patient delay and the referral system. The role of the different referral systems on the stage of disease at presentation in the hospital was analyzed by a logistic regression analysis. About a quarter of the patients (26.5%) were referred to the hospital by the community health volunteers. In our data set, patients referred to the hospital by community health volunteers appeared to be in an earlier stage of disease than patients referred by other methods, but after adjustment by the regression analysis for the health center, this effect could no longer be seen. The Polymerase Chain Reaction (PCR) for IS2404 positivity rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems.This study clarifies the role played by community health volunteers in Bénin, and shows that they play an important role in the control of BU.

Buruli Ulcer is a tropical skin disease caused by Mycobacterium ulcerans, which, due to scarring and contractures can lead to stigma and functional limitations. However, recent advances in treatment, combined with increased public health efforts have the potential to significantly improve disease outcome.To study the Quality of Life (QoL) of former Buruli Ulcer patients who, in the context of a randomized controlled trial, reported early with small lesions (cross-sectional diameter

Buruli Ulcer (BU) is a tropical infectious skin disease that is currently treated with 8 weeks of intramuscular streptomycin and oral rifampicin. As prolonged streptomycin administration can cause both oto- and nephrotoxicity, we evaluated its long term toxicity by following-up former BU patients that had received either 4 or 8 weeks of streptomycin in addition to other drugs between 2006 and 2008, in the context of a randomized controlled trial.Former patients were retrieved in 2012, and oto- and nephrotoxicity were determined by audiometry and serum creatinine levels. Data were compared with baseline and week 8 measurements during the drug trial.Of the total of 151 former patients, 127 (84%) were retrieved. Ototoxicity was present in 29% of adults and 25% of children. Adults in the 8 week streptomycin group had significantly higher hearing thresholds in all frequencies at long term follow-up, and these differences were most prominent in the high frequencies. In children, no differences between the two treatment arms were found. Nephrotoxicity that had been detected in 14% of adults and in 13% of children during treatment, was present in only 2.4% of patients at long term follow-up.Prolonged streptomycin administration in the adult study subjects caused significant persistent hearing loss, especially in the high frequency range. Nephrotoxicity was also present in both adults and children but appeared to be transient. Streptomycin should be given with caution especially in patients aged 16 or older, and in individuals with concurrent risks for renal dysfunction or hearing loss.

BackgroundBuruli ulcer is a stigmatising disease treated with antibiotics and wound care, and sometimes surgical intervention is necessary. Permanent limitations in daily activities are a common long term consequence. It is unknown to what extent patients perceive problems in participation in social activities. The psychometric properties of the Participation Scale used in other disabling diseases, such as leprosy, was assessed for use in former Buruli ulcer patients.MethodsFormer Buruli ulcer patients in Ghana and Benin, their relatives, and healthy community controls were interviewed using the Participation Scale, Buruli Ulcer Functional Limitation Score, and the Explanatory Model Interview Catalogue to measure stigma. The Participation Scale was tested for the following psychometric properties: discrimination, floor and ceiling effects, internal consistency, inter-item correlation, item-total correlation and construct validity.ResultsIn total 386 participants (143 former Buruli ulcer patients with their relatives (137) and 106 community controls) were included in the study. The Participation Scale displayed good discrimination between former Buruli ulcer patients and healthy community controls. No floor and ceiling effects were found. Internal consistency (Cronbach's alpha) was 0.88. In Ghana, mean inter-item correlation of 0.29 and item-total correlations ranging from 0.10 to 0.69 were found while in Benin, a mean inter-item correlation of 0.28 was reported with item-total correlations ranging from -0.08 to 0.79. With respect to construct validity, 4 out of 6 hypotheses were not rejected, though correlations between various constructs differed between countries.ConclusionThe results indicate the Participation Scale has acceptable psychometric properties and can be used for Buruli ulcer patients in Ghana and Benin. Future studies can use this Participation Scale to evaluate the long term restrictions in participation in daily social activities of former BU patients.

BACKGROUND: The emerging disease Buruli ulcer is treated with streptomycin and rifampicin and surgery if necessary. Frequently other antibiotics are used during treatment. METHODS/PRINCIPAL FINDINGS: Information on prescribing behavior of antibiotics for suspected secondary infections and for prophylactic use was collected retrospectively. Of 185 patients that started treatment for Buruli ulcer in different centers in Ghana and Bénin 51 were admitted. Forty of these 51 admitted patients (78%) received at least one course of antibiotics other than streptomycin and rifampicin during their hospital stay. The median number (IQR) of antibiotic courses for admitted patients was 2 (1, 5). Only twelve patients received antibiotics for a suspected secondary infection, all other courses were prescribed as prophylaxis of secondary infections extended till 10 days on average after excision, debridement or skin grafting. Antibiotic regimens varied considerably per indication. In another group of BU patients in two centers in Bénin, superficial wound cultures were performed. These cultures from superficial swabs represented bacteria to be expected from a chronic wound, but 13 of the 34 (38%) S. aureus were MRSA. CONCLUSIONS/SIGNIFICANCE: A guide for rational antibiotic treatment for suspected secondary infections or prophylaxis is needed. Adherence to the guideline proposed in this article may reduce and tailor antibiotic use other than streptomycin and rifampicin in Buruli ulcer patients. It may save costs, reduce toxicity and limit development of further antimicrobial resistance. This topic should be included in general protocols on the management of Buruli ulcer.

BACKGROUND: Delay in seeking treatment at the hospital is a major challenge in current Buruli ulcer control; it is associated with severe sequelae and functional limitations. Choosing alternative treatment and psychological, social and practical factors appear to influence delay. Objectives were to determine potential predictors for pre-hospital delay with Leventhal's commonsense model of illness representations, and to explore whether the type of available dominant treatment modality influenced individuals' perceptions about BU, and therefore, influenced pre-hospital delay. METHODOLOGY: 130 healthy individuals aged >18 years, living in BU-endemic areas in Benin without any history of BU were included in this cross-sectional study. Sixty four participants from areas where surgery was the dominant treatment and sixty six participants from areas where antibiotic treatment was the dominant treatment modality were recruited. Using a semi-structured interview we measured illness perceptions (IPQ-R), knowledge about BU, background variables and estimated pre-hospital delay. PRINCIPAL FINDINGS: The individual characteristics 'effectiveness of treatment' and 'timeline acute-chronic' showed the strongest association with pre-hospital delay. No differences were found between regions where surgery was the dominant treatment and regions where antibiotics were the dominant treatment modality. CONCLUSIONS: Individual characteristics, not anticipated treatment modality appeared predictors of pre-hospital delay.

Parasite loads were quantified in repeated skin biopsies from lesions of 2 patients with Old-World cutaneous leishmaniasis (CL) caused by Leishmania major and L. infantum during and after treatment with miltefosine. Miltefosine induced a rapid therapeutic effect on both infections with an initial decline of parasites of ∼1 log/week for the L. major infection. These observations illustrate the usability of quantifying parasite loads in skin lesions as a pharmacodynamic measure and quantitative descriptor of drug effect for CL supporting clinical assessment.

Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in several west African countries. It is prevalent in scattered foci around the world, predominantly in riverine areas with a humid, hot climate. We review the epidemiology, bacteriology, transmission, immunology, pathology, diagnosis and treatment of infections. M. ulcerans is an ubiquitous micro-organism and is harboured by fish, snails, and water insects. The mode of transmission is unknown. Lesions are most common on exposed parts of the body, particularly on the limbs. Spontaneous healing may occur. Many patients in endemic areas present late with advanced, severe lesions. BCG vaccination yields a limited, relatively short-lived, immune protection. Recommended treatment consists of surgical debridement, followed by skin grafting if necessary. Many patients have functional limitations after healing. Better understanding of disease transmission and pathogenesis is needed for improved control and prevention of Buruli ulcer.