Nigeria is one of the countries endemic for Buruli ulcer (BU) in West Africa but did not have a control programme until recently. As a result, BU patients often access treatment services in neighbouring Benin where dedicated health facilities have been established to provide treatment free of charge for BU patients. This study aimed to describe the epidemiological, clinical, biological and therapeutic characteristics of cases from Nigeria treated in three of the four treatment centers in Benin. A series of 82 BU cases from Nigeria were treated in three centres in Benin during 2006–2016 and are retrospectively described. The majority of these patients came from Ogun and Lagos States which border Benin. Most of the cases were diagnosed with ulcerative lesions (80. 5%) and WHO category III lesions (82. 9%); 97. 5% were healed after a median hospital stay of 46 days (interquartile range [IQR]: 32–176 days). This report adds to the epidemiological understanding of BU in Nigeria in the hope that the programme will intensify efforts aimed at early case detection and treatment.
Buruli ulcer (BU) is a neglected tropical disease that mainly affects the skin. The disease results from infection with Mycobacterium ulcerans, an environmental bacterium. BU is found in often swampy and humid areas. The mode of transmission remains obscure to this day, although several hypotheses have been proposed. Many authors have discussed potential reservoirs as well as vectors and transmission mechanisms that vary from region to region depending on the epidemiological, social and local environmental context. Direct human to human transmission of M. ulcerans is a rare possibility [1]. The main hypothesis is that the surface of the patient’s skin was contaminated by bacteria from an environmental source (e. g. swamps) and introduced into the skin by trauma. It is assumed that insects (aquatic bugs and mosquitoes) are the host and vector of M. ulcerans. Several experimental and environmental studies have demonstrated the implication of aquatic bugs in transmission of the disease [2–4]. DNA of M. ulcerans was detected in mosquitoes collected in Australia but a field study conducted in Benin suggested that mosquitoes do not play a central role in the ecology and transmission of M. ulcerans [5]. Fish has also been identified as a passive reservoir of M. ulcerans but generally not responsible for direct transmission of the disease [6]. Acanthamoeba species have also been identified as natural hosts of M. ulcerans and have been suggested as responsible for transmission of the disease [7]. No definitive conclusion has yet been drawn about how the disease is transmitted. The World Health Organization (WHO) has classified BU as a neglected tropical disease [8–11]. BU is the third most common mycobacterial infection in the world among immunocompetent individuals after tuberculosis and leprosy [12]. BU is characterized by a chronic necrosis of subcutaneous tissues, ranging from a simple nodule to a large cutaneous ulceration. Sometimes the bone is affected and the resulting damage can impair the functional mobility of the affected limb. Without early and effective treatment, the disease can progress and cause cosmetic complications and sequelae or functional limitations [13] with attendant stigma and social problems [14,15]. It can even lead to limb amputation. WHO classifies BU lesions into three categories according to severity [16,17]. Category I lesions are single small lesions (e. g. nodules, papules, plaques and ulcers < 5 cm in diameter). Category II lesions consist of non-ulcerative or ulcerative plaques, oedematous forms and single large ulcerative lesions of 5–15 cm in cross-sectional diameter, while lesions in the head and neck regions and the face, disseminated and mixed forms including osteomyelitis, and extensive lesions of more than 15 cm are considered as Category III. BU mostly affects poor people in rural areas with limited access to health care [11,18–20]. Children aged < 15 years are most commonly affected by the disease [21]. Worldwide, BU has been reported in > 33 countries, mostly within the tropical areas [22]. The majority of BU cases occur in Africa; however, cases have been reported in Australia, French Guiana, Peru and Papua New Guinea [23]. Recognizing that BU constitutes an emerging public health threat, in 1998 WHO established the Global Buruli Ulcer Initiative (GBUI) to coordinate control and research activities worldwide [9,18,22–24]. Up until 2004, the only curative treatment for BU was surgery, which consisted of wide excision to remove all infected tissues including some of the adjacent healthy tissues. Large lesions require skin grafting [18,21,23]. Scientific studies have shown the effectiveness of using different combinations of antibiotics to treat BU [25–27]. The standard treatment since 2004 has been the combination of rifampicin and streptomycin [16]. WHO has issued a provisional recommendation to use the new combination full oral therapy [28]. The introduction of antibiotic therapy has reduced the number of surgical procedures and recurrence rates. Almost all Category I and some Category II lesions can be cured without surgery [29]. In Benin, the BU control programme is known as the Programme National de Lutte contre la Lèpre et l’UB (PNLLUB). It coordinates BU control activities through four care facilities known as Centres de Dépistage et de Traitement de l’Ulcère de Buruli (CDTUB), located in the southern departments where BU is endemic [30]. During the course of their activities, the CDTUBs also receive patients from Nigeria. BU cases were officially reported in Nigeria in 1967 [31] and in 1976 [32] in different Nigerian states. Between 1998 and 2000, BU cases at the Leprosy and Tuberculosis Hospital in Moniaya-Ogoja were confirmed by the Institute of Tropical Medicine, Antwerp, Belgium. In 2006, the Nigerian authorities, in collaboration with a team from Benin and WHO, conducted an assessment of the BU situation in order to identify the endemic areas in Nigeria. The assessment covered only 5 states and therefore could not identify all the endemic regions as originally planned [33]. That was the first time in 2006 when Nigeria notified 9 BU cases to WHO. During 2009–2016, Nigeria reported 511 cases to WHO with increasing numbers of cases each year [34]. BU is known to be endemic in the south of Nigeria mainly in states such as Akwa Ibom, Anambra, Benue, Cross River, Ebonyi, Enugu, Ogun and Oyo [33,35]. Ogun State is divided by two drainage basins, the Yewa and the Ogun rivers, which discharge in separate lagoons. South-west Nigeria is characterized by tropical rainforest, similar to the environments where BU occurs in endemic areas of West Africa [35,36]. In order to establish an effective BU control system in Nigeria, it is imperative that all endemic areas are identified; hence the necessity of providing data on the states where Nigerian BU patients treated in Benin have come from. In 2014, a study from CDTUB in Pobè, Benin reported 127 PCR-confirmed cases of Nigerian BU patients treated in the facility [35]. Pobè is a town on the border with south-western Nigeria, making it the first facility of contact by patients from Nigeria. The objective of our study therefore is to describe the epidemiological, clinical, biological and therapeutic characteristics of BU cases from Nigeria treated in the other three CDTUBs and contribute data to the health authorities in that country.
This is a retrospective descriptive study of a series of 82 BU cases from Nigeria who were treated in three of the four CDTUBs, namely the CDTUB of Allada, the CDTUB of Lalo and the Centre Nutritionel et Sanitaire Gbemonten (CNSG) of Zagnanado from 1 January 2006 to 31 December 2016. This was a comprehensive sampling. All the cases from Nigeria, who were clinically suspect for BU and treated in the CDTUBs of Allada, Lalo and Zagnanado during the study period and for whom data were available, were included in this study. For each patient the following information was collected from their medical records and analysed: The data on the BU cases from Nigeria treated in the three CDTUBs were taken from the PNLLUB’s Register BU 01, which is used to collect standard information for each BU patient. The data were supplemented with additional information from the patients’ medical records kept in each CDTUB. The complete data were recorded with the software Microsoft Excel 2010 and then analysed with the statistical software IBM SPSS Statistics version 20. We only performed a descriptive analysis of the epidemiological, clinical, biological and therapeutic variables of the cases. The maps were drawn from free-access shapefiles obtained from DIVA-GIS (http: //www. diva-gis. org/) with QGIS 1. 8. 0 and ArcView 3. 2 software. This retrospective study was conducted after the approval and with the authorization of the Ministry of Health of Benin. The case data in the PNLLUB database used by the authors for this study were anonymized.
A total of 82 new patients from Nigeria suspected of having BU were treated in the three Beninese CDTUB from 1 January 2006 to 31 December 2016, with an annual average of 7 patients. Table 1 shows details of the socio-demographic, epidemiological characteristics and states of origin of the patients. Of the 82 patients, 45 (54. 9%) were male. The median age of the patients was 20 years (IQR: 13. 5–42. 5 years). The State of residence in Nigeria was available for 66 patients, of whom 39 (59. 1%) were from Ogun State; 25 (37. 9%) from Lagos State and 2 (3. 0%) from Oyo State. Some 55 patients (67. 1%) were treated in the CDTUB of Zagnanado; 15 (18. 3%) in the CDTUB of Lalo and 12 (14. 6%) in the CDTUB of Allada. Patients from Lagos State were mostly treated in the CDTUB of Zagnanado while those from Ogun State were equally treated in the three centres (Fig 1). The person who referred the patient to the CDTUB was specified for 79 patients; 62 (78. 5%) were referred by former BU patients from Nigeria who had been treated in Benin. The other patients were either referred by health agents or by family members. The median delay before seeking medical assistance was 203 days (IQR: 87. 5–1638). Clinically, 66 (80. 5%) patients had ulcerative lesions; 11 (13. 4%) had nonulcerative lesions (plaque, nodule, oedema) and 5 (6. 1%) had osteomyelitis. Of the 82 patients, 53 (64. 6%) had lesions on their lower limbs; 22 (26. 8%) had lesions on their upper limbs; 3 (3. 6%) had lesions on other parts of their body (abdomen, back, head/neck); and 4 (4. 9%) had lesions on multiple parts of their body. Some 68 patients (82. 9%) had Category III lesions (multiple lesions or lesions > 15 cm in diameter) (Fig 2), 13 (15. 9%) had Category II lesions (lesions 5–15 cm in diameter or on their faces/breast/genitalia); only one patient (1. 2%) had a Category I lesion (lesion < 5 cm in diameter). For 78 patients, the medical records of 78 patients mentioned whether or not the movements of the affected part were limited at the time of diagnosis; 24 (30. 8%) had restricted joint movements. Samples were taken from 12 patients (100. 0%) in Allada, 12 patients (80. 0%) in Lalo and 23 patients (41. 8%) in Zagnanado giving a total of 47 out of the 82 patients (57. 3%) for PCR confirmation; 36 out of 47 tested positive. All the 82 patients received treatment free of charge including specific antibiotic therapy of combined rifampicin with streptomycin for 8 weeks as recommended by WHO as well as surgery and physiotherapy as required. However, 80 patients (97. 6%) received surgery. The median length of hospital stay was 46 days (IQR: 32–176 days). The length of hospital stay was relatively longer for the patients treated in the CDTUB of Allada with a median of 197 days (IQR: 184-318) and the CDTUB Lalo with a median of 256 days (IQR: 170–340), while the median length of hospital stay was 35 days (IQR: 27–48) in Zagnanado. Some 78 patients (97. 5%) were healed among whom two patients (2. 4%) healed without surgery; one patient (1. 2%) died during his hospital stay and one patient (1. 2%) was lost to follow up. Treatment outcome data were missed for two patients. The epidemiological, clinical, biological and therapeutic characteristics of the patients are summarized in Table 1.
In addition to local BU cases, the CDTUB of Benin receive BU cases from Nigeria, most of whom are advanced Category III lesions whose care requires more time as well as more material and financial resources and have a socioeconomic impact on both the patients and their caregivers. However, all the treatment was provided for free. These patients mainly come from Nigerian states that border Benin and are referred by former patients who received care from one of the CDTUBs. It is therefore important that BU control activities be intensified in these different states in order to detect cases early and reduce the severity of the disease.
Buruli ulcer (BU) is a neglected tropical disease that mainly affects the skin. The disease results from infection with Mycobacterium ulcerans, an environmental bacterium. In Benin, the BU treatment centres usually receive patients from Nigeria. In 2014, a study from one of the treatment centres (CDTUB, Pobe) which borders south-western Nigeria reported on a cohort of 127 PCR-confirmed cases between 2005 and 2013. We describe the epidemiological, clinical, biological and therapeutic characteristics of BU cases from Nigeria treated in the three other CDTUBs.
medicine and health sciences
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Report of a series of 82 cases of Buruli ulcer from Nigeria treated in Benin, from 2006 to 2016