Profile of the leprosy endemic in the district of Murrupula, Nampula, Mozambique: A population-based study.

BACKGROUND: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. METHODS: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. RESULTS: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. CONCLUSIONS: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

Development of a questionnaire to determine the case detection delay of leprosy: A mixed-methods cultural validation study.

BACKGROUND: Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient's indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A 'Question-by-Question Guide' was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. CONCLUSIONS/SIGNIFICANCE: It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

PEP4LEP study protocol: integrated skin screening and SDR-PEP administration for leprosy prevention: comparing the effectiveness and feasibility of a community-based intervention to a health centre-based intervention in Ethiopia, Mozambique and Tanzania.

INTRODUCTION: Leprosy, or Hansen's disease, remains a cause of preventable disability. Early detection, treatment and prevention are key to reducing transmission. Post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) reduces the risk of developing leprosy when administered to screened contacts of patients. This has been adopted in the WHO leprosy guidelines. The PEP4LEP study aims to determine the most effective and feasible method of screening people at risk of developing leprosy and administering chemoprophylaxis to contribute to interrupting transmission. METHODS AND ANALYSIS: PEP4LEP is a cluster-randomised implementation trial comparing two interventions of integrated skin screening combined with SDR-PEP distribution to contacts of patients with leprosy in Ethiopia, Mozambique and Tanzania. One intervention is community-based, using skin camps to screen approximately 100 community contacts per leprosy patient, and to administer SDR-PEP when eligible. The other intervention is health centre-based, inviting household contacts of leprosy patients to be screened in a local health centre and subsequently receive SDR-PEP when eligible. The mobile health (mHealth) tool SkinApp will support health workers' capacity in integrated skin screening. The effectiveness of both interventions will be compared by assessing the rate of patients with leprosy detected and case detection delay in months, as well as feasibility in terms of cost-effectiveness and acceptability. ETHICS AND DISSEMINATION: Ethical approval was obtained from the national ethical committees of Ethiopia (MoSHE), Mozambique (CNBS) and Tanzania (NIMR/MoHCDEC). Study results will be published open access in peer-reviewed journals, providing evidence for the implementation of innovative leprosy screening methods and chemoprophylaxis to policymakers. TRIAL REGISTRATION NUMBER: NL7294 (NTR7503).

Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations.

Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.

Frequency and distribution of neglected tropical diseases in Mozambique: a systematic review.

BACKGROUND: Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. MAIN TEXT: Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. CONCLUSIONS: This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.

Hansen's disease deformities in a high risk area in Mozambique: A case study.

INTRODUCTION: Hansen's disease is no longer a public health problem in Mozambique, since 2008 (incidence under 1 / 10,000 inhabitants). The country is one of the most affected in the world and Nampula province's Murrupula district (incidence 1.7 / 10,000) has a high deformity rate (22% in 2010). This study aimed to identify high deformity rate associated determinants and proposals for better health program results. METHODS: This study involved a descriptive quantitative survey, systematic observation of patients and health professionals, and a survey of community volunteers. Data were analyzed using Epi Info 7.2. Pearson's chi-square and Fisher's exact test were used to assess statistical association with deformity, with a significance level of 5% and 95% confidence interval. Ethical procedures followed the Helsinki declaration (2013). RESULTS: Among 238 subjects, 175 were patients and 63 leprosy health staff. Most patients relied on subsistence agriculture facing social exclusion (43, 25%). The waiting time from first symptoms to diagnosis was over one year for 63%. Deformity affected 116 subjects (68%), particularly those who considered the disease as God's desire (p = 0.01), and practiced traditional treatments (p = 0.001). Among leprosy health staff, 35 (52%) were not trained on diagnosis and management. CONCLUSIONS: High deformity rate is associated with low economic status, the belief that the disease is God's desire, the use of traditional healers, late diagnosis, and poor disease management. A health education program targeting professionals and population, with infection screening and self-care groups can prevent deformities.

Hansen's disease deformities in a high risk area in Mozambique: A case study

Abstract INTRODUCTION: Hansen's disease is no longer a public health problem in Mozambique, since 2008 (incidence under 1 / 10,000 inhabitants). The country is one of the most affected in the world and Nampula province's Murrupula district (incidence 1.7 / 10,000) has a high deformity rate (22% in 2010). This study aimed to identify high deformity rate associated determinants and proposals for better health program results. METHODS: This study involved a descriptive quantitative survey, systematic observation of patients and health professionals, and a survey of community volunteers. Data were analyzed using Epi Info 7.2. Pearson's chi-square and Fisher's exact test were used to assess statistical association with deformity, with a significance level of 5% and 95% confidence interval. Ethical procedures followed the Helsinki declaration (2013). RESULTS: Among 238 subjects, 175 were patients and 63 leprosy health staff. Most patients relied on subsistence agriculture facing social exclusion (43, 25%). The waiting time from first symptoms to diagnosis was over one year for 63%. Deformity affected 116 subjects (68%), particularly those who considered the disease as God's desire (p = 0.01), and practiced traditional treatments (p = 0.001). Among leprosy health staff, 35 (52%) were not trained on diagnosis and management. CONCLUSIONS: High deformity rate is associated with low economic status, the belief that the disease is God's desire, the use of traditional healers, late diagnosis, and poor disease management. A health education program targeting professionals and population, with infection screening and self-care groups can prevent deformities.

Lepra: doença, isolamento e segregação no contexto colonial em Moçambique / Leprosy: disease, isolation, and segregation in colonial Mozambique

Resumo A partir de documentação produzida entre a primeira metade do século XIX e a primeira metade do século XX, prioritariamente relatórios médicos, o artigo aponta as concepções vigentes na comunidade médica colonial e entre as populações locais sobre a lepra, suas manifestações e seu enfrentamento. Enfoca as tensões quanto à prática de segregação dos leprosos e suas implicações sanitárias e sociais. Para compreender as raízes dos discursos e estratégias no meio médico português e colonial, recupera-se a trajetória das definições de isolamento, segregação, lepra e suas aplicações, ou ausência de referência, na literatura de missionários, cronistas e médicos em Angola e Moçambique a partir da segunda metade do século XVII.

Abstract Drawing on documents produced between the early nineteenth and mid-twentieth centuries, mainly medical reports, this paper indicates the prevailing conceptions in the colonial medical community and local populations about leprosy, its manifestations, and how to deal with it. It focuses on the tensions concerning the practice of segregating lepers and its social and sanitation implications. To comprehend the roots of the discourses and strategies in the Portuguese and colonial medical environment, the trajectory of the definitions of isolation, segregation, and leprosy are traced, as are their use in or absence from the writings of missionaries, chroniclers, and doctors in Angola and Mozambique as of the second half of the seventeenth century.

Leprosy: disease, isolation, and segregation in colonial Mozambique. / Lepra: doença, isolamento e segregação no contexto colonial em Moçambique.

Drawing on documents produced between the early nineteenth and mid-twentieth centuries, mainly medical reports, this paper indicates the prevailing conceptions in the colonial medical community and local populations about leprosy, its manifestations, and how to deal with it. It focuses on the tensions concerning the practice of segregating lepers and its social and sanitation implications. To comprehend the roots of the discourses and strategies in the Portuguese and colonial medical environment, the trajectory of the definitions of isolation, segregation, and leprosy are traced, as are their use in or absence from the writings of missionaries, chroniclers, and doctors in Angola and Mozambique as of the second half of the seventeenth century.

Lepra: doença, isolamento e segregação no contexto colonial em Moçambique / Leprosy: disease, isolation, and segregation in colonial Mozambique

A partir de documentação produzida entre a primeira metade do século XIX e a primeira metade do século XX, prioritariamente relatórios médicos, o artigo aponta as concepções vigentes na comunidade médica colonial e entre as populações locais sobre a lepra, suas manifestações e seu enfrentamento. Enfoca as tensões quanto à prática de segregação dos leprosos e suas implicações sanitárias e sociais. Para compreender as raízes dos discursos e estratégias no meio médico português e colonial, recupera-se a trajetória das definições de isolamento, segregação, lepra e suas aplicações, ou ausência de referência, na literatura de missionários, cronistas e médicos em Angola e Moçambique a partir da segunda metade do século XVII.(AU)

Onchocerciasis, an undiagnosed disease in Mozambique: identifying research opportunities.

BACKGROUND: The objective of this paper is to summarise and critically review the available data about onchocerciasis in Mozambique, in order to report epidemiological and clinical aspects related to the disease and identify gaps in knowledge. The paper is intended to raise awareness of the existence and importance of this disease and to define research priorities. METHODS: We examined the scarce epidemiological data at our disposal: two diagnostic studies in 1997 and 1998 (first reports on the existence of onchocerciasis in Mozambique), and two Rapid Epidemiological Mapping of Onchocerciasis (REMO) surveys in 2001 and 2007. We examined differences in study designs and methodologies as well as the differing geographical locations to explain the divergence in findings among the studies. RESULTS: Evidence indicates that onchocerciasis is hypoendemic in Mozambique (with national and imported cases), but still largely remains an undiagnosed illness. There is no awareness of the clinical aspects of the disease and nor of the differential diagnosis with lepromatous leprosy and dermatitis caused by Scabies spp. The use of skin biopsy and a symptom screening questionnaire, combined with nodule rate, in the first two studies may have captured even atypical or subacute presentations. Both REMO surveys relied solely on nodule detection and in the six years between the two studies, the prevalence of nodules detected more than doubled. CONCLUSIONS: The epidemiology and clinical aspects of the disease are unknown in Mozambique. Since the last REMO took place in 2007 and since the population is subject to large-scale movement and displacement, it is important to develop tools to identify and analyse populations that are at high risk for onchocerciasis. Cases of onchocerciasis may be misdiagnosed as leprosy or scabies that fail to improve despite being subjected to treatment against leprosy. Techniques to enable a differential diagnosis need to be established by training health professionals on the recognition of this undiagnosed disease. It is equally necessary to identify the blackfly vectors and where they breed.

Epidemiology of lobomycosis-like disease in bottlenose dolphins Tursiops spp. from South America and southern Africa.

We report on the epidemiology of lobomycosis-like disease (LLD), a cutaneous disorder evoking lobomycosis, in 658 common bottlenose dolphins Tursiops truncatus from South America and 94 Indo-Pacific bottlenose dolphins T. aduncus from southern Africa. Photographs and stranding records of 387 inshore residents, 60 inshore non-residents and 305 specimens of undetermined origin (inshore and offshore) were examined for the presence of LLD lesions from 2004 to 2015. Seventeen residents, 3 non-residents and 1 inshore dolphin of unknown residence status were positive. LLD lesions appeared as single or multiple, light grey to whitish nodules and plaques that may ulcerate and increase in size over time. Among resident dolphins, prevalence varied significantly among 4 communities, being low in Posorja (2.35%, n = 85), Ecuador, and high in Salinas, Ecuador (16.7%, n = 18), and Laguna, Brazil (14.3%, n = 42). LLD prevalence increased in 36 T. truncatus from Laguna from 5.6% in 2007-2009 to 13.9% in 2013-2014, albeit not significantly. The disease has persisted for years in dolphins from Mayotte, Laguna, Salinas, the Sanquianga National Park and Bahía Málaga (Colombia) but vanished from the Tramandaí Estuary and the Mampituba River (Brazil). The geographical range of LLD has expanded in Brazil, South Africa and Ecuador, in areas that have been regularly surveyed for 10 to 35 yr. Two of the 21 LLD-affected dolphins were found dead with extensive lesions in southern Brazil, and 2 others disappeared, and presumably died, in Ecuador. These observations stress the need for targeted epidemiological, histological and molecular studies of LLD in dolphins, especially in the Southern Hemisphere.

Self-care groups of leprosy-affected people in Mozambique.

INTRODUCTION: In 2011, the national leprosy control programme in Mozambique decided to promote the setting up of self-care groups (SCGs) for prevention and care of disabilities. OBJECTIVES: To present an overview of the national SCG strategy and to understand the perceptions of people with leprosy regarding the benefits and challenges of participating in the SCGs in Mozambique. METHODS: Semi-structured group interviews were carried out with 22 SCGs involving 299 leprosy affected people in Nampula and Manica provinces. RESULTS: SCGs are involved in different activities and do not limit themselves to activities related to disability care. The majority of respondents expressed satisfaction about their participation in SCGs. Apart from perceived benefits in relation to their disabilities, the majority of SCG members also reported benefits in social participation. Lack of training, insufficient resources for income generation and long distances were the major challenges for SCGs, especially in the Manica province. CONCLUSIONS: People affected with leprosy perceive SCGs as useful in self-care for prevention of disabilities and social participation.

Characteristics and treatment outcomes of leprosy patients detected during a leprosy elimination campaign in Mozambique compared with routinely detected patients.

The objective of this study is to assess whether the case-finding method is a determinant for diagnostic characteristics and treatment outcome of newly diagnosed leprosy patients in Northern Mozambique. This is a retrospective cohort study of 3202 patients on the differences between entrance characteristics and treatment outcome in self-reporting patients and patients detected during a leprosy elimination campaign (LEC) in 1999 in Northern Mozambique. As a consequence of LEC activities, 3 times more patients were found compared with the same period 1 year earlier. After the LEC, case detection remained higher in the years 2000-2002 compared with the years preceding the LEC. More young (<15 years) paucibacillary (PB) cases were diagnosed during LEC activities with, surprisingly, equal percentage of disability grades. No gender imbalance was found in diagnosed LEC patients contrary to self-reporting patient groups. Comparing patients detected during a LEC in 1999 with the passive group of 1998 and 1999 showed a slight but statistically significant better treatment result for the passive group. The classification of leprosy (in favour of PB) and age (in favour of older age groups) were also determinants for favourable treatment outcomes. Volunteers had a significantly better result of treatment compared with trained nurses and regardless of detection method. LEC proved to be a useful addition to the National Leprosy and Tuberculosis Programme in Northern Mozambique. As a result, many new cases were diagnosed and put on treatment and their treatment results were very satisfactory. LEC had a lasting impact on case finding. Volunteers make a valuable contribution to leprosy control in Mozambique because they have consistently better treatment results compared with nurses.

Defaulting patterns in a provincial leprosy control programme in Northern Mozambique.

Cohort-based multidrug therapy (MDT) completion rates are used to assess adherence to MDT. However this measure gives no information about when during the treatment period defaulting occurs. Two districts in Cabo Delgado province in Northern Mozambique were selected for evaluation of multibacillary patient defaulter data between 1993 and 1997 to examine when patients default during the treatment penod. In all, 548 (59.2%) of 926 MB patients completed treatment and 378 (40.8%) defaulted between 1993 to 1997. The percentage of defaulters fell steadily from 59.8% in 1993 to 23.2% in 1997. Of the 378 defaulters 57.7% defaulted treatment within 6 months and 83.1% within 1 year of starting treatment. It was observed that patients tend to default early rather than late in the treatment period and that this pattern is maintained over time despite a fall in defaulter rates. Patients established early into a treatment routine were more likely to complete treatment. A comprehensive effort to improve and maintain leprosy control services will probably influence adherence more than any single, specific strategy. Shortening MDT treatment from 2 years to 1 year is unlikely to affect the defaulter rate.