Epidemiological and Clinical Characteristics of Children and Adolescents with Leprosy Admitted Over 16 Years at a Rural Hospital in Ethiopia: A Retrospective Analysis

Epidemiological and Clinical Characteristics of Children and Adolescents with Leprosy Admitted... Abstract Aim To analyse differences in children and adolescents aged ≤18 years admitted to the leprosy ward in a rural Ethiopian hospital >16 years. Methods We retrospectively collected data from leprosy admission registry books on patients with leprosy who were admitted to a referral hospital from September 2000 to September 2016. Results There were 2129 admissions for leprosy during the study period: 180 (8.4%) patients were s ≤ 18 years old. Of these, 98 (54.4%) were male and 82 (45.6%) were female. The proportion of new diagnoses in children and adolescents was 31.7%, significantly higher than in adults (11.7%; p < 0.001). There were also significant differences in the prevalence of lepromatous ulcers (46.9 vs. 61.7%), leprosy reaction (29.4 vs. 13.0%) and neuritis (16.9 vs.5.3%) between these age groups. Conclusions There were more new diagnoses, leprosy reactions and neuritis, and fewer lepromatous ulcers, in children and adolescents compared with adults, with younger patients being referred more frequently to reference centres. leprosy, child, adolescents, Ethiopia, hospitals, rural, leprosy, multibacillary INTRODUCTION Leprosy is a chronic disease caused by Mycobacterium leprae, mainly affecting the skin and peripheral nervous system. Early detection and proper treatment are the most effective ways to prevent neural damage before it causes permanent physical disability [1]. Three decades after the introduction of multidrug therapy (MDT) for leprosy, its prevalence has dropped dramatically, from 5 351 408 cases in 1985 to 210 758 in 2015. Of these, there were 3970 new cases in Ethiopia in 2015, including 563 (14.2%) children [2]. The large proportion of diagnoses in children reflects the high level of community transmission and the persistent presence of undiagnosed cases. One of the objectives of the World Health Organization (WHO) in their Global Leprosy Strategy 2016–2020 is to eliminate Grade 2 disabilities in paediatric patients [3]. People with leprosy are treated with MDT as outpatients; although if they present with complications at diagnosis or during or after treatment, they may be admitted to improve the clinical case management. These patients may be admitted for other medical problems or because of issues arising from the sequelae of leprosy [4]. Children are considered the most vulnerable group for leprosy, and childhood leprosy reflects disease transmission in the community as well as the effectiveness of ongoing disease control programmes [5–7]. Indeed, it is often suggested that incidence in children is the best indicator for community transmission of the disease [5]. There are several reports on new childhood leprosy from tertiary care centres, mainly in India [5–9], but also in South American countries such as Brazil [9–12] and African countries like Nigeria and Ethiopia [13, 14]. The primary aim of the present article is to describe the epidemiological and clinical characteristics of children and adolescents (aged ≤18 years) admitted to a hospital with a diagnosis of leprosy and to compare them with adults (aged ≥19 years) admitted with the same disease. METHODS Setting The Gambo Rural Hospital is one of five reference centres for leprosy in Ethiopia, according to the manuals of the Tuberculosis and Leprosy Prevention and Control Programme (TLPCP), produced by the Federal Ministry of Health of Ethiopia [4, 15]. The hospital is located 250 km south-east of Addis Ababa; since being founded in 1961 as a leprosarium, it has gradually increased its offering of health services and became a rural hospital in 1985. Today, it has 49 beds for patients with leprosy, and hospitalization is free of charge. The Armauer Hansen Research Institute/All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Hospital in the capital city is the main tertiary centre to which patients are referred if necessary. The hospital is a reference centre for leprosy treatment and care; however, only the patients near the hospital are followed up there, while outpatients living elsewhere attend controls in their local health centres. Diagnosis of leprosy was made based on the TLPCP manual [15]. Leprosy cases were defined as people with one or more of the cardinal signs: (i) definite loss of sensation in a pale (hypo-pigmented) or reddish skin lesion; (ii) thickened or enlarged peripheral nerve, with or without tenderness; and (iii) presence of acid-fast bacilli in a slit skin smear. The Gambo Rural Hospital uses the following hospital admission criteria: severe leprosy reaction [Type 1 or Type 2 reaction such as erythema nodosum leprosum (ENL)], complicated lepromatous ulcer, red eye or eye pain, pregnancy, tuberculosis or other serious comorbid infection, age ≤12 years, recent history of peptic or duodenal ulcer, history of diabetes mellitus, general illness with fever, lack of improvement with prior treatment or recurrent (≥3) reactions [15]. Also, admitted were patients requiring surgical intervention and previously treated patients with new reactions who had an additional medical problem [4]. Study design and data collection The study period spanned 16 years, beginning at the Ethiopian New Year on 11 September 2000 and ending on 10 September 2016. We collected retrospective data on patients admitted to the leprosy unit from the admission registry books. We did not use the Ridley and Jopling classification. For the choice of the treatment regimen, patients were assessed according to the WHO classification based on the number of leprosy skin lesions and nerve involvement. Cases were classified as multibacillary (MB) leprosy if patients had more than five skin lesions or fewer than six skin lesions plus a positive smear test, and they were considered paucibacillary (PB) leprosy if patients had one to five leprosy skin lesions or only one enlarged nerve trunk. We also collected data for variables, including age, sex, place of residence, origin of admission, length of hospital stay, diagnosis, performance of test for HIV and the cause and result of hospitalization. Our case definitions were (i) new case: a patient with PB or MB leprosy who has never received treatment for the microbacteria and (ii) old case: a patient who has been previously diagnosed and treated for leprosy with MDT. Diagnoses were carried out using standard definitions. The reasons for hospital discharge were (i) improvement; (ii) exitus (death because of any cause); (iii) transfer (patients who commenced treatment in one centre and continued in another); (iv) no improvement despite treatment; and (v) voluntary discharge. Reasons for transferring care outside the Gambo Rural Hospital were to continue treatment in a health centre nearer to the patient’s residence or because a new case needed a specific surgery in the ALERT Hospital in Addis Ababa. Statistical analysis We entered data into a spreadsheet using Microsoft Excel 2011 and analysed the data using IBM SPSS statistical software, version 22.0 (SPSS Inc. Chicago, IL, USA). To analyse continuous variables (days of hospitalization), we used the Mann–Whitney U-test, as data did not follow a normal distribution. For categorical variables, we used either the χ2 test with Yates’ correction or Fisher’s exact test where appropriate. We used the χ2 test for trend to identify patterns in the admissions. We considered p values of <0.05 to be statistically significant. RESULTS During the 16-year study period, there were 2129 admissions to the leprosy ward of the Gambo Rural General Hospital. Of these, 180 (8.4%) were patients aged ≤18 years. Although the number of total admissions per 4-year period increased over the study period, paediatric admissions declined both in absolute terms and as a proportion of the total, from 68 of 421 (16.2%) in 2000–04 to 32 of 708 (4.5%) in 2012–16 (χ2 test for trend: 44.0; p < 0.001) (Table 1). Table 1 Admissions to the leprosy ward, by age group Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Table 1 Admissions to the leprosy ward, by age group Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Of the 180 children and adolescents admitted, 55 (30.6%) were aged ≤14 years and 125 (69.4%) were 15–18 years old. In total, 98 (54.4%) were males and 82 (45.6%) were females (ratio 1.2:1); however, of the 1947 patients aged ≥19 years for whom data were available, 66% were men and 34% were women (ratio 1.9:1) (p = 0.002). There were no cases of HIV among the younger group. Among the paediatric patients, 57 of 180 (31.7%) were new cases, compared with 229 of 1949 (11.7%) new cases in adults (p = 0.001). Of the 57 new cases in children and adolescents, 53 (93.0%) were MB and 4 (7.0%) were PB. Of the 123 old leprosy cases, most (n = 113; 91.9%) were also MB. The main reason for admission of young patients was lepromatous ulcer (n = 83), followed by leprosy reaction (n = 52) and neuritis (n = 30). Compared with adults, admittance because of lepromatous ulcer was lower in children and adolescents (46.9 vs. 61.7%, p < 0.001). On the other hand, admittance because of leprosy reaction and neuritis was higher in the younger group (leprosy reaction: 29.4 vs. 13.0%, p < 0.001; neuritis: 16.9 vs. 5.3%, p < 0.001). There were negligible admissions for other systemic diseases such as respiratory tract infection (RTI), gastroenteritis, cardiovascular diseases, diabetes mellitus or tuberculosis (Table 2). Table 2 Main epidemiological and clinical characteristics, diagnosis and outcome in leprosy patients aged ≤18 years and >18 years Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Note: A: adults. C: Children and adolescents. Table 2 Main epidemiological and clinical characteristics, diagnosis and outcome in leprosy patients aged ≤18 years and >18 years Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Note: A: adults. C: Children and adolescents. The median length of hospital stay in all patients was 58 days [interquartile range (IQR) 31, 96]; however, in the younger group, it was 73 days (IQR 44, 113), significantly higher than in adults (57 days, IQR 30, 94) (p < 0.001). Most children and adolescents (88.7%) were discharged to their home after their condition improved, while the rest (11.3%) were transferred to other centres; none of the patients died, saw their condition worsen or were voluntarily discharged. The rate of referral to other centres was lower in adults at 3.4% (p < 0.001), but the mortality among adult patients was higher at 2% (p = 0.07). DISCUSSION It is notable that in our series, 1 of every 10 patients admitted to hospital with leprosy was aged ≤18 years. The ratio of males to females is 1.2:1 in the younger age group, compared with 1.9:1 in adults. The ratio that we found in our study is higher than that reported by other studies on childhood leprosy [5, 6, 14]. This difference may be attributable to a higher admission rate for complications or morbidity among girls [4, 16–19]. One of every three patients aged ≤18 years had a new case of leprosy, usually MB leprosy. Proportionally, admission of new cases is higher in children and adolescents than in adults. This can be explained by the fact that all children (<12 years of age) newly diagnosed with leprosy must be admitted, and clinicians prefer to also admit adolescent patients to monitor the evolution of the treatment [4, 15]. In contrast, adults who are newly diagnosed with leprosy are only admitted in case of a severe leprosy reaction or complicated lepromatous ulcer [4]. Of all the reasons for admission, leprosy reaction and neuritis were the most common in the younger age group, which is logical given the associated risks and the need to admit these patients to avoid central nervous system sequalae. Leprosy reactions are a major cause of nerve damage and morbidity in these patients. Reactions are immunologically mediated and can occur even after successful completion of MDT. There are two types of leprosy reaction: Type 1 reaction (or reverse reaction) and Type 2 reaction (or ENL). Moreover, neuritis leads to nerve function impairment, which in turn can lead to permanent loss of nerve function. Thus, nerve function impairment is considered a risk factor for the development of deformities [20]. In our study, the percentage of admissions corresponding to leprosy reaction in young people was 29.4%. This is higher than the proportions reported in some studies, which range from 1.36 to 8.33% [7, 21–24] but more consistent with the findings in others, where estimates range from 18.0 to 29.7% [9, 6, 11, 12, 14, 25–27]. The high rate of admissions because of leprosy reaction in our study is attributable to the fact that the hospital is a reference centre, and many patients presumably come from other areas to be admitted for case management and follow-up. The appearance of neuropathy is considered to be a risk factor for the development of deformities [20, 26]. In our study, this occurs more frequently among those aged ≤18 years, necessitating a more rigorous follow-up to avoid disabilities. Other studies report proportions of neuritis of 6.4% [6] or estimates that range from 13.63 to 40.62% (affecting a single nerve) or from 4.54 to 59.38% (affecting several nerves) [28]. Clinical variability may be one reason for such wide ranges in the estimated prevalence. Variability may also exist in the data given the different cut-off ages used to define childhood, so it is preferable to perform a stratified study that is more in line with natural age groups in children. In any case, we know that there is a peak in new cases among young people aged 10–14 years and that the disease is rare in those aged ≤5 years. Ulcers are a serious problem in people with long-term leprosy [16, 19, 29]. Admissions for lepromatous ulcers that were secondary to neuropathic damage from leprosy were less frequent in young people, perhaps because the disease in these patients has had less time to evolve and to produce neuropathic damage or because of the better care now available for young people, which enables the prevention of lepromatous ulcers [16, 19]. Also, young patients are logically admitted less frequently for other medical problems than adults. Length of hospital stay was also longer in young people, which could mean that these patients require closer follow-up that translates to a longer stay. No young patients died from leprosy, and a higher proportion was referred to other centres for disease control compared with adults, who are transferred for management of complications. Patients were referred to the ALERT reference centre in Addis Ababa for surgery and for several complications that are not dealt with in our centre [30, 31]. Our study has the limitations inherent to retrospective data collection. The data from the registers in the admission books for leprosy were incomplete, at times lacking information on neurological assessment or type of leprosy reaction. Moreover, the register does not necessarily include all patients with leprosy, as clinical record-keeping has been heterogeneous. Another limitation is that the patient register is for episodes of hospital admissions and does not contemplate the possibility of a re-admission; this is because of the difficulties in normalizing the clinical records during the study period. Despite the study limitations, we see clear differences in the patient characteristics of children and adolescents admitted to the leprosy unit of the Gambo Rural Hospital. Compared with adults, this group presents with a lower ratio of males to females and a higher proportion of neuritis and leprosy reaction. Young people are more frequently referred to other reference centres. Additional prospective studies are necessary to enable interpretation of these and other differences in other groups of patients with leprosy and in other culturally diverse countries in Latin American or Asia. ACKNOWLEDGMENTS The authors wish to thank the leprosy officers at Gambo Rural Hospital for data collection, the laboratory staff for assistance with microbiological diagnosis and the nursing staff for patient care. The authors also thank Meggan Harris at Rosetta Manuscripts for her edition of this article. REFERENCES 1 World Health Organization . Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015), operational guidelines. Regional Office for South-East Asia. India: WHO, 2009 , 1–70. 2 World Health Organization . Global leprosy update, 2015: time for action, accountability and inclusion . Wkly Epidemiol Rec 2016 ; 35 : 405 – 20 . 3 World Health Organization, Regional Office for South-East Asia . 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Google Scholar CrossRef Search ADS PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

Epidemiological and Clinical Characteristics of Children and Adolescents with Leprosy Admitted Over 16 Years at a Rural Hospital in Ethiopia: A Retrospective Analysis

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Oxford University Press
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© The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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0142-6338
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1465-3664
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10.1093/tropej/fmx048
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Abstract

Abstract Aim To analyse differences in children and adolescents aged ≤18 years admitted to the leprosy ward in a rural Ethiopian hospital >16 years. Methods We retrospectively collected data from leprosy admission registry books on patients with leprosy who were admitted to a referral hospital from September 2000 to September 2016. Results There were 2129 admissions for leprosy during the study period: 180 (8.4%) patients were s ≤ 18 years old. Of these, 98 (54.4%) were male and 82 (45.6%) were female. The proportion of new diagnoses in children and adolescents was 31.7%, significantly higher than in adults (11.7%; p < 0.001). There were also significant differences in the prevalence of lepromatous ulcers (46.9 vs. 61.7%), leprosy reaction (29.4 vs. 13.0%) and neuritis (16.9 vs.5.3%) between these age groups. Conclusions There were more new diagnoses, leprosy reactions and neuritis, and fewer lepromatous ulcers, in children and adolescents compared with adults, with younger patients being referred more frequently to reference centres. leprosy, child, adolescents, Ethiopia, hospitals, rural, leprosy, multibacillary INTRODUCTION Leprosy is a chronic disease caused by Mycobacterium leprae, mainly affecting the skin and peripheral nervous system. Early detection and proper treatment are the most effective ways to prevent neural damage before it causes permanent physical disability [1]. Three decades after the introduction of multidrug therapy (MDT) for leprosy, its prevalence has dropped dramatically, from 5 351 408 cases in 1985 to 210 758 in 2015. Of these, there were 3970 new cases in Ethiopia in 2015, including 563 (14.2%) children [2]. The large proportion of diagnoses in children reflects the high level of community transmission and the persistent presence of undiagnosed cases. One of the objectives of the World Health Organization (WHO) in their Global Leprosy Strategy 2016–2020 is to eliminate Grade 2 disabilities in paediatric patients [3]. People with leprosy are treated with MDT as outpatients; although if they present with complications at diagnosis or during or after treatment, they may be admitted to improve the clinical case management. These patients may be admitted for other medical problems or because of issues arising from the sequelae of leprosy [4]. Children are considered the most vulnerable group for leprosy, and childhood leprosy reflects disease transmission in the community as well as the effectiveness of ongoing disease control programmes [5–7]. Indeed, it is often suggested that incidence in children is the best indicator for community transmission of the disease [5]. There are several reports on new childhood leprosy from tertiary care centres, mainly in India [5–9], but also in South American countries such as Brazil [9–12] and African countries like Nigeria and Ethiopia [13, 14]. The primary aim of the present article is to describe the epidemiological and clinical characteristics of children and adolescents (aged ≤18 years) admitted to a hospital with a diagnosis of leprosy and to compare them with adults (aged ≥19 years) admitted with the same disease. METHODS Setting The Gambo Rural Hospital is one of five reference centres for leprosy in Ethiopia, according to the manuals of the Tuberculosis and Leprosy Prevention and Control Programme (TLPCP), produced by the Federal Ministry of Health of Ethiopia [4, 15]. The hospital is located 250 km south-east of Addis Ababa; since being founded in 1961 as a leprosarium, it has gradually increased its offering of health services and became a rural hospital in 1985. Today, it has 49 beds for patients with leprosy, and hospitalization is free of charge. The Armauer Hansen Research Institute/All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Hospital in the capital city is the main tertiary centre to which patients are referred if necessary. The hospital is a reference centre for leprosy treatment and care; however, only the patients near the hospital are followed up there, while outpatients living elsewhere attend controls in their local health centres. Diagnosis of leprosy was made based on the TLPCP manual [15]. Leprosy cases were defined as people with one or more of the cardinal signs: (i) definite loss of sensation in a pale (hypo-pigmented) or reddish skin lesion; (ii) thickened or enlarged peripheral nerve, with or without tenderness; and (iii) presence of acid-fast bacilli in a slit skin smear. The Gambo Rural Hospital uses the following hospital admission criteria: severe leprosy reaction [Type 1 or Type 2 reaction such as erythema nodosum leprosum (ENL)], complicated lepromatous ulcer, red eye or eye pain, pregnancy, tuberculosis or other serious comorbid infection, age ≤12 years, recent history of peptic or duodenal ulcer, history of diabetes mellitus, general illness with fever, lack of improvement with prior treatment or recurrent (≥3) reactions [15]. Also, admitted were patients requiring surgical intervention and previously treated patients with new reactions who had an additional medical problem [4]. Study design and data collection The study period spanned 16 years, beginning at the Ethiopian New Year on 11 September 2000 and ending on 10 September 2016. We collected retrospective data on patients admitted to the leprosy unit from the admission registry books. We did not use the Ridley and Jopling classification. For the choice of the treatment regimen, patients were assessed according to the WHO classification based on the number of leprosy skin lesions and nerve involvement. Cases were classified as multibacillary (MB) leprosy if patients had more than five skin lesions or fewer than six skin lesions plus a positive smear test, and they were considered paucibacillary (PB) leprosy if patients had one to five leprosy skin lesions or only one enlarged nerve trunk. We also collected data for variables, including age, sex, place of residence, origin of admission, length of hospital stay, diagnosis, performance of test for HIV and the cause and result of hospitalization. Our case definitions were (i) new case: a patient with PB or MB leprosy who has never received treatment for the microbacteria and (ii) old case: a patient who has been previously diagnosed and treated for leprosy with MDT. Diagnoses were carried out using standard definitions. The reasons for hospital discharge were (i) improvement; (ii) exitus (death because of any cause); (iii) transfer (patients who commenced treatment in one centre and continued in another); (iv) no improvement despite treatment; and (v) voluntary discharge. Reasons for transferring care outside the Gambo Rural Hospital were to continue treatment in a health centre nearer to the patient’s residence or because a new case needed a specific surgery in the ALERT Hospital in Addis Ababa. Statistical analysis We entered data into a spreadsheet using Microsoft Excel 2011 and analysed the data using IBM SPSS statistical software, version 22.0 (SPSS Inc. Chicago, IL, USA). To analyse continuous variables (days of hospitalization), we used the Mann–Whitney U-test, as data did not follow a normal distribution. For categorical variables, we used either the χ2 test with Yates’ correction or Fisher’s exact test where appropriate. We used the χ2 test for trend to identify patterns in the admissions. We considered p values of <0.05 to be statistically significant. RESULTS During the 16-year study period, there were 2129 admissions to the leprosy ward of the Gambo Rural General Hospital. Of these, 180 (8.4%) were patients aged ≤18 years. Although the number of total admissions per 4-year period increased over the study period, paediatric admissions declined both in absolute terms and as a proportion of the total, from 68 of 421 (16.2%) in 2000–04 to 32 of 708 (4.5%) in 2012–16 (χ2 test for trend: 44.0; p < 0.001) (Table 1). Table 1 Admissions to the leprosy ward, by age group Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Table 1 Admissions to the leprosy ward, by age group Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Total N ≤18 years n (%) >18 years n (%) September 2000–August 2004 421 68 (16.8) 353 (83.8) September 2004–August 2008 472 43 (9.1) 429 (90.9) September 2008–August 2012 528 37 (7) 491 (93.0) September 2012–August 2016 708 32 (4.5) 676 (95.5) Of the 180 children and adolescents admitted, 55 (30.6%) were aged ≤14 years and 125 (69.4%) were 15–18 years old. In total, 98 (54.4%) were males and 82 (45.6%) were females (ratio 1.2:1); however, of the 1947 patients aged ≥19 years for whom data were available, 66% were men and 34% were women (ratio 1.9:1) (p = 0.002). There were no cases of HIV among the younger group. Among the paediatric patients, 57 of 180 (31.7%) were new cases, compared with 229 of 1949 (11.7%) new cases in adults (p = 0.001). Of the 57 new cases in children and adolescents, 53 (93.0%) were MB and 4 (7.0%) were PB. Of the 123 old leprosy cases, most (n = 113; 91.9%) were also MB. The main reason for admission of young patients was lepromatous ulcer (n = 83), followed by leprosy reaction (n = 52) and neuritis (n = 30). Compared with adults, admittance because of lepromatous ulcer was lower in children and adolescents (46.9 vs. 61.7%, p < 0.001). On the other hand, admittance because of leprosy reaction and neuritis was higher in the younger group (leprosy reaction: 29.4 vs. 13.0%, p < 0.001; neuritis: 16.9 vs. 5.3%, p < 0.001). There were negligible admissions for other systemic diseases such as respiratory tract infection (RTI), gastroenteritis, cardiovascular diseases, diabetes mellitus or tuberculosis (Table 2). Table 2 Main epidemiological and clinical characteristics, diagnosis and outcome in leprosy patients aged ≤18 years and >18 years Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Note: A: adults. C: Children and adolescents. Table 2 Main epidemiological and clinical characteristics, diagnosis and outcome in leprosy patients aged ≤18 years and >18 years Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Variables Missing values Total analysed ≤18 years >18 years p-value N % N % N % Sex C:0; A:2 0.002  Male 1383 65.0 98 54.4 1285 66.0  Female 744 35.0 82 45.6 662 34.0 HIV C:145; A 1239 4 0.8  Yes 4 0.5 0 0 4 0.5  No 706 95.5 35 100 796 995 Case history C:0; A:0 <0.001  New 286 13.4 57 31.7 229 11.7  Old 1843 86.6 123 68.3 1720 88.3 WHO classification C:0; A:0  New MB 275 12.9 53 29.4 222 0.1 <0.001  New PB 11 0.5 4 2,2 7 0.0 0.9  Old MB 1712 80.4 113 62.8 1599 0.8 <0.001  Old PB 131 6.2 10 5.6 121 0.1 0.8 Diagnosis C:3; A:11  Ulcer 1279 60.4 83 46.9 1196 61.7 <0.001  Leprosy reaction 305 14.4 52 29.4 253 13 <0.001  Neuritis 132 6.2 30 16.9 102 5.3 <0.001  Osteomyelitis 115 5.4 6 3.4 109 94.8 0.2  Cellulitis 19 0.9 4 2.3 15 0.8 0.07  RTI 80 3.8 0 0 80 4.1 0.001  Diabetes mellitus 21 1.0 0 0 21 1.1 0.2  Epigastric pain 36 1.6 1 0.6 35 1.8 0.9  Gastroenteritis 25 1.2 0 0 25 1.3 0.9  Tuberculosis 14 0.7 1 0.6 13 0.7 0.9  Cardiovascular disease 25 1.2 0 0 25 1.3 0.9  Chronic liver disease 10 0.5 0 0 10 0.5 0.9 Outcome C:2; A:166  Improved 1807 92.6 149 88.7 1658 93.0 0.04  Referred 79 4.0 19 11.3 60 3.4 <0.001  Death 35 1.8 0 0 35 2.0 0.07  No improvement 15 0.8 0 0 15 0.8 0.6  Voluntary discharge 15 0.8 0 0 15 0.8 0.2 Note: A: adults. C: Children and adolescents. The median length of hospital stay in all patients was 58 days [interquartile range (IQR) 31, 96]; however, in the younger group, it was 73 days (IQR 44, 113), significantly higher than in adults (57 days, IQR 30, 94) (p < 0.001). Most children and adolescents (88.7%) were discharged to their home after their condition improved, while the rest (11.3%) were transferred to other centres; none of the patients died, saw their condition worsen or were voluntarily discharged. The rate of referral to other centres was lower in adults at 3.4% (p < 0.001), but the mortality among adult patients was higher at 2% (p = 0.07). DISCUSSION It is notable that in our series, 1 of every 10 patients admitted to hospital with leprosy was aged ≤18 years. The ratio of males to females is 1.2:1 in the younger age group, compared with 1.9:1 in adults. The ratio that we found in our study is higher than that reported by other studies on childhood leprosy [5, 6, 14]. This difference may be attributable to a higher admission rate for complications or morbidity among girls [4, 16–19]. One of every three patients aged ≤18 years had a new case of leprosy, usually MB leprosy. Proportionally, admission of new cases is higher in children and adolescents than in adults. This can be explained by the fact that all children (<12 years of age) newly diagnosed with leprosy must be admitted, and clinicians prefer to also admit adolescent patients to monitor the evolution of the treatment [4, 15]. In contrast, adults who are newly diagnosed with leprosy are only admitted in case of a severe leprosy reaction or complicated lepromatous ulcer [4]. Of all the reasons for admission, leprosy reaction and neuritis were the most common in the younger age group, which is logical given the associated risks and the need to admit these patients to avoid central nervous system sequalae. Leprosy reactions are a major cause of nerve damage and morbidity in these patients. Reactions are immunologically mediated and can occur even after successful completion of MDT. There are two types of leprosy reaction: Type 1 reaction (or reverse reaction) and Type 2 reaction (or ENL). Moreover, neuritis leads to nerve function impairment, which in turn can lead to permanent loss of nerve function. Thus, nerve function impairment is considered a risk factor for the development of deformities [20]. In our study, the percentage of admissions corresponding to leprosy reaction in young people was 29.4%. This is higher than the proportions reported in some studies, which range from 1.36 to 8.33% [7, 21–24] but more consistent with the findings in others, where estimates range from 18.0 to 29.7% [9, 6, 11, 12, 14, 25–27]. The high rate of admissions because of leprosy reaction in our study is attributable to the fact that the hospital is a reference centre, and many patients presumably come from other areas to be admitted for case management and follow-up. The appearance of neuropathy is considered to be a risk factor for the development of deformities [20, 26]. In our study, this occurs more frequently among those aged ≤18 years, necessitating a more rigorous follow-up to avoid disabilities. Other studies report proportions of neuritis of 6.4% [6] or estimates that range from 13.63 to 40.62% (affecting a single nerve) or from 4.54 to 59.38% (affecting several nerves) [28]. Clinical variability may be one reason for such wide ranges in the estimated prevalence. Variability may also exist in the data given the different cut-off ages used to define childhood, so it is preferable to perform a stratified study that is more in line with natural age groups in children. In any case, we know that there is a peak in new cases among young people aged 10–14 years and that the disease is rare in those aged ≤5 years. Ulcers are a serious problem in people with long-term leprosy [16, 19, 29]. Admissions for lepromatous ulcers that were secondary to neuropathic damage from leprosy were less frequent in young people, perhaps because the disease in these patients has had less time to evolve and to produce neuropathic damage or because of the better care now available for young people, which enables the prevention of lepromatous ulcers [16, 19]. Also, young patients are logically admitted less frequently for other medical problems than adults. Length of hospital stay was also longer in young people, which could mean that these patients require closer follow-up that translates to a longer stay. No young patients died from leprosy, and a higher proportion was referred to other centres for disease control compared with adults, who are transferred for management of complications. Patients were referred to the ALERT reference centre in Addis Ababa for surgery and for several complications that are not dealt with in our centre [30, 31]. Our study has the limitations inherent to retrospective data collection. The data from the registers in the admission books for leprosy were incomplete, at times lacking information on neurological assessment or type of leprosy reaction. Moreover, the register does not necessarily include all patients with leprosy, as clinical record-keeping has been heterogeneous. Another limitation is that the patient register is for episodes of hospital admissions and does not contemplate the possibility of a re-admission; this is because of the difficulties in normalizing the clinical records during the study period. Despite the study limitations, we see clear differences in the patient characteristics of children and adolescents admitted to the leprosy unit of the Gambo Rural Hospital. Compared with adults, this group presents with a lower ratio of males to females and a higher proportion of neuritis and leprosy reaction. Young people are more frequently referred to other reference centres. 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Google Scholar CrossRef Search ADS PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Journal of Tropical PediatricsOxford University Press

Published: Jun 22, 2017

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