Online First

2021 : Volume 1, Issue 1

Ecology, Transmission and Seasonal Patterns of Mycobacterium ulcerans Disease, Buruli Ulcer

Glob J Microbiol Infect Dis

Article Type : Review Article

Hubert Senanu Ahor^1,2*, Solomon Gyabaah^1,3, and Rejoice Agyeiwaa Arthur^1,4

¹Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
²School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
³Komfo Anokye Teaching Hospital, Kumasi, Ghana⁴Department of theoretical and applied biology, Faculty of Biosciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Abstract

Infectious diseases are observed to have their own seasonal window of occurrence and variations which differ with geographical location. Climate is well acknowledged to influence infectious disease outbreaks via changes in the pathogen, reservoir, and vector dynamics as well as influencing human behavior. This review looks into the ecology, transmission, and seasonal patterns of Buruli ulcer disease and its causative organism Mycobacterium ulcerans. The transmission of Buruli ulcer/M. ulcerans is via an environmental reservoir found in either the abiotic or biotic component of aquatic and or terrestrial ecosystems. However, there exist multiple transmission pathways dependent on the epidemiological settings and geographical areas. Rainfall patterns especially rainy seasons and periods right after the major raining seasons are known to influence the occurrence of Mycobacterium ulcerans in the environment and its infection among the human and animal populace. As such community case search activities ought to be done during the period between the rainy season and dry season. In addition, individuals in endemic communities must ensure maximum protective measures during the rainy seasons.

Keywords: Ecology; Transmission; Buruli ulcer; Mycobacterium ulcerans; Climate; Rainfall

Introduction

Buruli ulcer (BU) is a debilitating skin infection caused by Mycobacterium ulcerans [1]. It is the third most common mycobacterial infection after tuberculosis (TB) [2,3]. It is the third most common mycobacterial infection after tuberculosis (TB) and leprosy globally, but in endemic countries such as Cote d'Ivoire and Ghana, its prevalence rate is second to TB [2,3]. This disease is reported in over 33 countries in Africa, the Americas, Asia, and Western Pacific with most cases reported from poor rural communities in West Africa [4]. Within the last decade, there has been a 64% reduction in BU cases globally with only Australia and Nigeria reporting a high number of BU cases recently [1]. The clinical and epidemiological perspectives of BU differ across various settings. In Africa, children below the age of 15 years are mostly affected whereas in Australia cases are frequently reported in older populations [1].

BU initially presents clinically as painless pre-ulcerative lesion forms; nodule, plaque, or edema which usually ulcerate within weeks to the ulcerative form with undermined edges. Due to the painless nature of BU lesions, affected individuals present large ulcers at treatment centers which can lead to deformities or even amputation of the affected limb [1,5]. The pathogenesis of the disease is hinged on the production of an exotoxin called mycolactone which has anti-inflammatory, cytotoxicity, and analgesic effects rendering the typical lesions painless [5]. The lack of insight into the ecology and the exact mode of transmission of M. ulcerans hinders the prevention and control of BU worldwide [1]. The current control strategy outlined by the WHO is early detection of cases followed by prompt treatment with rifampicin and clarithromycin/streptomycin [1,6,7].

Infectious diseases are observed to have their own seasonal window of occurrence and variations which differ with geographical location [8]. Climate is well acknowledged to influence infectious disease outbreaks through changes in the pathogen, reservoir, and vector dynamics as well as influencing human behavior [8]. Seasonality patterns of infectious diseases such as tuberculosis (TB), malaria, diarrheal diseases, and many more have been reported in the incidences of these diseases, necessitating the need for specific control measures at particular periods [9-12]. With respect to TB, studies have reported the end of winter and the start of summer as periods for high TB incidences [9,13]. Various social, environmental, and host-related risk factors such as temperature, rainfall, humidity, sunlight, indoor activity, pollution, crowding, immune suppression, and delays in TB diagnosis are known to be involved in TB seasonality during the winter period [14]. Epidemiological and socio-demographic data have also been used to explain the trend and seasonality of TB [12,15]. In Buruli ulcer disease, studies have tried to elucidate the ecology of M. ulcerans and the possible transmission route. Few studies have noticed and reported the seasonal pattern of the occurrence of the BU and it causative organism, M. ulcerans in endemic countries [16-19]. As such this article reviewed works done with regard to the ecology, transmission, and seasonal variation in the detection of M. ulcerans in the environment or M. ulcerans infection among human and animal population.

Search Strategy and Selection strategy

We searched PubMed and Google Scholar with the search terms: “Buruli ulcer”, “Mycobacterium ulcerans” in association with the term “ecology”, “transmission”, “seasonality”, and “rainfall”. In some instances, key references within some articles were included. A systematic review of our search result was done and articles relevant to the aims of this review were selected (Figure 1).

Figure 1: Illustrates how the review articles were searched and selected.

Results and Discussion

Ecology, reservoir, vectors, and transmission of Mycobacterium ulcerans

The successful growth of M. ulcerans from Gerris sp. (Water Strider), an aquatic Hemiptera, provided a factual evidence of the presence of M. ulcerans in the environment [20]. The use of PCR based techniques has implicated environmental agents such soil, water plants, detritus, plant/biofilms, frogs, snails, turtles, fish, water filtrates, mosquitoes (Anopheles sp., Aedes sp., Coquillettidia sp. and Culex sp.) and aquatic insects (Naucoridae, Hydrophilidae, Belastomatidae) in many BU endemic areas as potential reservoir or vectors of M. ulcerans [16,21,22-30]. This suggests that the aquatic ecosystem/habitat could be the source of M. ulcerans from which it is transmitted to humans and possibly the vehicle for disseminating M. ulcerans strains in endemic communities. However, the transmission routes of M. ulcerans from the environment to humans/animals are still unclear but remain very speculative.

A conceptual hypothesis described by Portaels et al. and Marion et al. has been used to explain the possible M. ulcerans transmission mode. According to this hypothesis, M. ulcerans found in water, mud, water filtrates, detritus, and plant biofilms are picked and accumulated by filtering or grazing aquatic insects (such as mosquito larvae, midges, and water bugs) or other invertebrates (crustaceans, snails, plankton) during feeding. The invertebrate is then fed on by predatory aquatic invertebrates (beetles, dragonfly larvae, and true bugs) and vertebrates (fish, frogs), which are also fed on by aquatic insects capable of flight and Birds which disperse M. ulcerans to another aquatic environment. Humans are infected with M. ulcerans through direct contact with these potential reservoirs/vectors via skin abrasions or through insect bites [21,25,31]. BU patients living under poor hygienic conditions or those with large ulcerative lesions (category III) can help disseminate M. ulcerans in the environment through their activities such as bathing, washing of clothes, and swimming in water bodies albeit human to human transmission is rare [29,32,33]. The occurrence of BU lesions in domestic mammal species (dogs, cats, horses) and native wildlife (koalas (Phascolarctos cinereus), Alpacas, ringtail (Pseudocheirus peregrinus) and brushtail possums (Trichosurus cunninghami)) have been widely observed in Australia, suggesting that these animals could also be a major link between the environment and human in the transmissions of M. ulcerans [16]. However, in endemic countries such as Ghana, Cameroon, and Côte d’Ivoire where the endemicity of BU is high, few cases have been found or reported in domestic mammal species such as a dog, a goat, and few Mice (Mastomys sp.) [28,33,34].

Fyfe and his colleagues postulated that domestic animals get infected with M. ulcerans via contact with infected soils, environmental samples, or fecal matter of wild/ other domestic animals. Humans are then infected through direct contact with infected animal excreta or Animal bites. Ectoparasites of domestic animals that feed on humans can also transmit M. ulcerans from animals to humans. An insect vector particularly mosquitoes could transfer M. ulcerans from possum to humans during feeding. In addition, mosquitoes breeding sites (gutters, ponds, or drains) heavily contaminated with possum excreta harboring M. ulcerans can facilitate mosquitoes (either as adults or larvae or) to be infected with M. ulcerans [16]. However, this hypothesis cannot be extended to Africa, as studies are yet to found evidence of adult mosquitoes harboring and possibly transmitting M. ulcerans to humans. Also, animal excreta being the vehicle for dispersing M. ulcerans in the environment is yet to be proven in Africa [35,36]. The prevailing dogma with regard to the transmission of BU is that the environmental reservoir of M. ulcerans is either an abiotic or biotic component of aquatic and/terrestrial ecosystems and that there exist multiple transmission pathways dependent on the epidemiological setting and geographical areas [16,33,37]

Seasonality of Buruli Ulcer Disease

Outbreaks of Buruli ulcer in humans have been linked to close proximity to aquatic systems such slow-flowing or stagnant water bodies created by human activities [38]. Flooding of lakes during heavy rainfall, creation of dams/agriculture irrigation system on stream/rivers, modifying wetlands, deforestation, and agriculture activities resulting in increased flooding and alluvial, pit, and sand mining operations have been associated with high BU incidence in endemic communities [25,38,39]. These environmental disturbances are known to redistribute M. ulcerans in the environment increases the possibility of human contact with the pathogens.

There exist an interplay between ecosystem (habitat) changes and climatic patterns which result in both functional and abiotic environmental changes in biodiversity [3]. Studies have reported climatic/rainfall patterns to result in a cyclical incidence of MU/BU in many endemic communities (Table 1). During heavy rainfall/flooding, M. ulcerans in aquatic habitat are washed into and surface runoff water thereby contaminate them. In the dry season, these waterbodies move back leading to the formation of stagnant/small water bodies near urban and agricultural areas [3]. These events lead to a cyclic transformation of the ecosystem resulting in the creation of new ecological niches characterized by stagnation of water, increased amount of light in surface water, high water temperatures, and increase the acidity of water. These changes are accompanied by sedimentation (turbidity), growth of the aquatic plant and algal biofilm formation, decrease ultraviolet light, and dissolve oxygen which favors the growth, persistence, and transmission of M. ulcerans in the environment [3]. These changes also affect the composition of the aquatic ecosystem leading to a turnover of biotic communities favoring the species adapted to lentic habitats. Such aquatic systems are prone to M. ulcerans as well as human activities such as building, fishing, washing of clothes and hunting which increases the likelihood of human contact with M. ulcerans in the environment [40,41].

M. ulcerans exhibits major seasonal and intra-seasonal variations in large water bodies and temporarily flooded areas with its presence less variable between seasons in permanent swamps and streams [42]. Peak incidence of M. ulcerans DNA in crayfish has been observed to be in the summer season which comes right after the rainy season in Japan [43]. These findings correlate with studies conducted in Northern Malawi and Cameroon [31,44]. In Louisiana, USA, M. ulcerans DNA was abundant in the wet seasons than in fall and winter [45]. The link between M. ulcerans presence in the environment and Buruli ulcer seasonal pattern in the human population has been explored [17-19]. In Australia, Fyfe and his colleagues observed a positive correlation between human BU cases and the presence of M. ulcerans DNA in possum feces [16]. Williamson and colleagues also reported a positive correlation between M. ulcerans DNA presence in the environment and BU occurrence among humans [18]. In Ghana, the months with a high amount of rainfall are known to record the highest amount of M. ulcerans DNA in the environment which corresponds to the high incidence of BU in the human population compared to the dry season [17]. Genomic profiling of both M. ulcerans DNA detected in BU patients and environmental samples show a very close genetic relationship of M. ulcerans in the same niche [16,28,30]. In addition, BU lesions in patients were source tracked to water bodies present in endemic communities in Ghana [28]. These provide evidence that BU patients are infected by M. ulcerans present in the environment individuals are constantly exposed to.

Place of Study	Year	Sample used	Season with peak incidence of BU or MU	Reference
Uganda	1969-1970	Clinical samples	Rainy season	[46]
Uganda	1966-1970	Clinical samples	Rainy season	[47]
Ghana	1993	Clinical samples	Rainy season	[48]
Northern Malawi	2006	Environment samples	Dry Season	[44]
Australia	1981-2008	Clinical samples	Wet season	[49]
USA	2010	Environmental samples	Wet season	[45]
Cameroon	2010	Environmental samples	Dry season	[31]
Cameroon	2002-2012	Clinical samples	Rainy season	[50]
French Guiana	1969-2012	Clinical samples	Dry season	[19]
Japan	2015	Environment samples	Rainy season	[43]
Ghana	2016	Environment samples	Rainy season	[17]
Australia	2004-2016	Clinical samples	Rainy season	[51]

Table1: Summary of studies indicating season with peaked Buruli ulcer cases or M. ulcerans DNA in respective countries.

In Australia and French Guiana, it was observed that warmer and wet conditions before case emergence followed by a dry period to case emergence is a precursor to the occurrence of BU [19,49]. It was hypothesized that flooding during the rainy season influences the distribution of M. ulcerans in the environment leading to the infection of humans with clinical signs showing at the onset of the dry season similar to an earlier observation made in Uganda by Radford [49,52]. This phenomenon of high BU cases in the subsequent dry season and this lag phase can be attributed to the long incubation period of BU (estimated between 3-4.5 months) resulting in the delays between infection and diagnosis [49,53,54]. However, in a recent study conducted in Australia, high BU-incidents were observed in Bellarine and Mornington Peninsulas, in months with high rainfalls as compared to months with less rainfall [51]. These findings confirm observations earlier studies conducted in Cameroon and Uganda where a high number of cases were also reported during months with high rainfall compared to others with low rainfall [46,47,50]. In Ghana, it has been revealed that BU cases peaked from September to October which is a minor rainy season in the country [48]. A potential issue that may be a hindrance to understanding the seasonal patterns of BU in humans is the difference in time between the appearance of symptoms, reporting to health facilities as reflected in the size of lesion presented [19]. However, the variation of Buruli ulcer incidence by season can be associated with fluctuations of Mycobacterium ulcerans occurrences in the environment which are probably influenced by the dynamics of freshwater ecosystems [50]. There is the trend of BU/ M. ulcerans peak incidence to be associated with rainfall and period just after the wet season. This requiring that during these periods, BU control programs such as community case search activities in endemic communities should be intensified so as to enable early detection of cases to allow prompt treatment. This would prevent the various forms of deformities, disability, or even amputation of the affected Limb which commonly occur when BU lesions are not treated early. In addition, there ought to be intensive public education on BU protective measures such as Wearing long protective cloths, washing, and immediate application of alcohol at wounds [17,55].

Globally, there is a downward trend (64% reduction) in the incidence of Buruli ulcers in most endemic countries with the main reason for the reduction unknown [1]. However, we can speculate that this reduction in BU cases can be a result of the global warming effect which is known to affect rainfall patterns (reduction in rainfall). This speculation is based on this review, showing a high incidence of Buruli ulcer/M. ulcerans during the period of high precipitation. However, we suggest that the seasonal patterns of BU/ M. ulcerans may be dependent on the epidemiological settings and geographical areas similar to its transmission’s mode due to the differences in climatic conditions.

Conclusion

The mode of transmission of M. ulcerans from the environment to humans is not known and not well established. As a result, individuals living around or visiting BU endemic areas must take precautions, especially during the wet seasons or period prior to dry season as these periods are known to be associated with a high incidence of BU. However, it is very important to consider any seasonal variation associated with Buruli ulcer disease in a particular endemic area in order to predict seasons for implementation of BU control programs.

Author Contributions

Ahor Hubert Senanu, Solomon Gyabaah, Rejoice Agyeiwaa Arthur: drafting and revising the article, concept, and design. Ahor Hubert Senanu: Final revision of the article; concept and design.

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Correspondence & Copyright

Corresponding author: Dr. Hubert Senanu Ahor, Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Copyright: © 2021 All copyrights are reserved by Ahor Hubert Senanu, published by Coalesce Research Group. This work is licensed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.