Emerging human infectious diseases of aquatic origin: a comparative biogeographic approach using Bayesian spatial modelling.

BACKGROUND: With the increase in unprecedented and unpredictable disease outbreaks due to human-driven environmental changes in recent years, we need new analytical tools to map and predict the spatial distribution of emerging infectious diseases and identify the biogeographic drivers underpinning their emergence. The aim of the study was to identify and compare the local and global biogeographic predictors such as landscape and climate that determine the spatial structure of leptospirosis and Buruli Ulcer (BU). METHODS: We obtained 232 hospital-confirmed leptospirosis (2007-2017) cases and 236 BU cases (1969-2017) in French Guiana. We performed non-spatial and spatial Bayesian regression modeling with landscape and climate predictor variables to characterize the spatial structure and the environmental drivers influencing the distribution of the two diseases. RESULTS: Our results show that the distribution of both diseases is spatially dependent on environmental predictors such as elevation, topological wetness index, proximity to cropland and increasing minimum temperature at the month of potential infection. However, the spatial structure of the two diseases caused by bacterial pathogens occupying similar aquatic niche was different. Leptospirosis was widely distributed across the territory while BU was restricted to the coastal riverbeds. CONCLUSIONS: Our study shows that a biogeographic approach is an effective tool to identify, compare and predict the geographic distribution of emerging diseases at an ecological scale which are spatially dependent to environmental factors such as topography, land cover and climate.

Comparison of Mycobacterium ulcerans (Buruli ulcer) and Leptospira sp. (Leptospirosis) dynamics in urban and rural settings.

BACKGROUND: Zoonotic pathogens respond to changes in host range and/or pathogen, vector and host ecology. Environmental changes (biodiversity, habitat changes, variability in climate), even at a local level, lead to variability in environmental pathogen dynamics and can facilitate their transmission from natural reservoirs to new susceptible hosts. Whilst the environmental dynamics of aquatic bacteria are directly linked to seasonal changes of their habitat they also rely on the ecological processes underpining their transmission. However data allowing the comparison of these ecological processes are lacking. Here we compared the environmental dynamics of generalist and vector-borne aquatic bacterial pathogens in the same unit of time and space, and across rural and urban habitats in French Guiana (South America). PRINCIPAL FINDINGS: Using Leptospira sp. and Mycobacterium ulcerans we performed an environmental survey that allowed the detection of both pathogens in urban vs. rural areas, and during rainy vs. dry weather conditions. All samples were subjected to qPCR amplifications of LipL32 (Leptospira sp.) and IS2404 and KR (M. ulcerans) genetic markers. We found (i) a greater presence of M. ulcerans in rural areas compared with Leptospira sp., (ii) that modified urban environments were more favourable to the establishment of both pathogens, (iii) that Leptospira sp. presence was enhanced during the rainy season and M. ulcerans during the dry period, and (iv) differences in the spatial distribution of both bacteria across urban sites, probably due to the mode of dissemination of each pathogen in the environment. CONCLUSIONS: We propose that in French Guiana simplified and modified urban ecosystems might favour leptospirosis and Buruli ulcer emergence and transmission. Moreover, disease risk was also constrained by seasonality. We suggest that the prevention of aquatic bacterial disease emergence in impoverished urban areas of developing countries would benefit from seasonal diseases targeted surveys, which would maximise limited budgets from cash-strapped health agencies.

Deforestation-driven food-web collapse linked to emerging tropical infectious disease, Mycobacterium ulcerans.

Generalist microorganisms are the agents of many emerging infectious diseases (EIDs), but their natural life cycles are difficult to predict due to the multiplicity of potential hosts and environmental reservoirs. Among 250 known human EIDs, many have been traced to tropical rain forests and specifically freshwater aquatic systems, which act as an interface between microbe-rich sediments or substrates and terrestrial habitats. Along with the rapid urbanization of developing countries, population encroachment, deforestation, and land-use modifications are expected to increase the risk of EID outbreaks. We show that the freshwater food-web collapse driven by land-use change has a nonlinear effect on the abundance of preferential hosts of a generalist bacterial pathogen, Mycobacterium ulcerans. This leads to an increase of the pathogen within systems at certain levels of environmental disturbance. The complex link between aquatic, terrestrial, and EID processes highlights the potential importance of species community composition and structure and species life history traits in disease risk estimation and mapping. Mechanisms such as the one shown here are also central in predicting how human-induced environmental change, for example, deforestation and changes in land use, may drive emergence.

Buruli ulcer in traveler from Suriname, South America, to the Netherlands.

We report Buruli ulcer in a man in the Netherlands. Phenotyping of samples indicate the Buruli pathogen was acquired in Suriname and activated by trauma on return to the Netherlands. Awareness of this disease by clinicians in non-Buruli ulcer-endemic areas is critical for identification.

First detection of Mycobacterium ulcerans DNA in environmental samples from South America.

The occurrences of many environmentally-persistent and zoonotic infections are driven by ecosystem changes, which in turn are underpinned by land-use modifications that alter the governance of pathogen, biodiversity and human interactions. Our current understanding of these ecological changes on disease emergence however remains limited. Buruli ulcer is an emerging human skin disease caused by the mycobacterium, Mycobacterium ulcerans, for which the exact route of infection remains unclear. It can have a devastating impact on its human host, causing extensive necrosis of the skin and underlying tissue, often leading to permanent disability. The mycobacterium is associated with tropical aquatic environments and incidences of the disease are significantly higher on floodplains and where there is an increase of human aquatic activities. Although the disease has been previously diagnosed in South America, until now the presence of M. ulcerans DNA in the wild has only been identified in Australia where there have been significant outbreaks and in western and central regions of Africa where the disease is persistent. Here for the first time, we have identified the presence of the aetiological agent's DNA in environmental samples from South America. The DNA was positively identified using Real-time Polymerase Chain Reaction (PCR) on 163 environmental samples, taken from 23 freshwater bodies in French Guiana (Southern America), using primers for both IS2404 and for the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes (KR). Five samples out of 163 were positive for both primers from three different water bodies. A further nine sites had low levels of IS2404 close to a standard CT of 35 and could potentially harbour M. ulcerans. The majority of our positive samples (8/14) came from filtered water. These results also reveal the Sinnamary River as a potential source of infection to humans.

A cutaneous ulcer resulting from Mycobacterium ulcerans--Leishmania braziliensis coinfection in South America.

Buruli ulcer is a tropical skin disease caused by Mycobacterium ulcerans. Its mode of transmission is not yet clearly understood. We report here a cutaneous ulcer in a European traveler in South America resulting from a coinfection detected specifically for Mycobacterium ulcerans and Leishmania braziliensis DNA with real-time polymerase chain reaction. This observation of a unique cutaneous ulcer raises the issue about possible modes of transmission of those two pathogens by the same vector.

Buruli ulcer in United Kingdom tourist returning from Latin America.

We report a case of Buruli ulcer in a tourist from the United Kingdom. The disease was almost certainly acquired in Brazil, where only 1 case had previously been reported. The delay in diagnosis highlights the need for physicians to be aware of the disease and its epidemiology.

Mycobacterium ulcerans disease, Peru.

Eight adult patients (ages 18-58, 5 women) with Buruli ulcer (BU) confirmed by at least 2 diagnostic methods were seen in a 10-year period. Attempts to culture Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from the swampy northern coast of Peru. The patients had 1-5 lesions, most of which were on the lower extremities. One patient had 5 clustered gluteal lesions; another patient had 2 lesions on a finger. Three patients were lost to follow-up. All 5 remaining patients had moderate disease. Diverse treatments (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial drug treatment for BU, and for 3 patients, excision surgery) were successful. Only 1 patient (patient 7) received the specific drug treatment recommended by WHO. BU is endemic in Peru, although apparently infrequent. Education of populations and training of health workers are first needed to evaluate and understand the full extent of BU in Peru.

Ulcerative cutaneous mycobacteriosis due to Mycobacterium ulcerans: report of two Mexican cases.

We report two patients from Central Mexico, with ulcerated cutaneous lesions containing acid-fast bacilli (AFB) and ultimately diagnosed as Mycobacterium ulcerans disease. The first patient had a long history (11 years) of disease involving multiple lesions of both upper and lower extremities. Histopathological changes included necrosis of the subcutaneous tissue with large numbers of extracellular AFB. Cultures at 32 degrees C were "positive for mycobacteria," but were not further identified. The polymerase chain reaction for M. ulcerans performed on skin bopsies was positive. The lesions improved after treatment with rifampin and isoniazid (INH) for one month, followed by ethambutol and streptomycin. The second case followed trauma to the right hand, which spread over 2 years to the right upper extremity, the back, and both legs, with a loss of digits and metacarpal bones of the right hand. The histopathological findings were similar to the first case, including presence of AFB. PCR for M. ulcerans on extracts of skin biopsies was positive. Rifampin, INH, pyrazinamide, and levofloxacin resulted in marked improvement of the ulcer; ethambutol and streptomycin were later used, also. We report these cases because they are rare (approximately 6 previous cases were reported from Mexico), and both are unusually disseminated. They are significant in alerting the medical community to M. ulcerans infection, which is still active in Mexico, and the treatment used has not been reported previously.

[Diagnosis of Mycobacterium ulcerans infections in French Guiana]. / Diagnostic de l'infection à Mycobacterium ulcerans en Guyane française.

THE SITUATION: Buruli's ulcer is a severe necrotic cutaneous infection due to Mycobacterium ulcerans. It is a major public health problem in developing countries. FROM A CLINICAL POINT OF VIEW: The early stage of the infection corresponds to a painless cutaneous nodule, whereas the late stage corresponds to ulceration with detachment of the edges. There is currently no other treatment than surgical excision combined with heat therapy. FROM A DIAGNOSTIC POINT OF VIEW: Three methods can be used: direct examination of swabs stained according to Ziehl-Neelsen's method, culture in specific medium at 32 degrees C and the polymerization chain reaction assay (PCR). The latter is the technique of choice.

Isolation of three Mycobacterium ulcerans strains resistant to rifampin after experimental chemotherapy of mice

By use of a murine model for Buruli ulcer, Mycobacterium ulcerans was found to be susceptible to rifampin, with the MIC being 0.5 to 1 micro g/ml. Three mutants were isolated after rifampin monotherapy. Two were resistant to rifampin at 8 micro g/ml, and one was resistant to rifampin at 32 micro g/ml. The mutants harbored Ser416Phe mutations and His420Tyr mutations in the rpoB gene, and these mutations have also been found to be responsible for rifampin resistance in the leprosy and tubercle bacilli. The results indicate that while rifampin may be active against M. ulcerans, it should never be used as monotherapy in humans.