BioStruct-Africa: empowering Africa-based scientists through structural biology knowledge transfer and mentoring - recent advances and future perspectives.

Being able to visualize biology at the molecular level is essential for our understanding of the world. A structural biology approach reveals the molecular basis of disease processes and can guide the design of new drugs as well as aid in the optimization of existing medicines. However, due to the lack of a synchrotron light source, adequate infrastructure, skilled persons and incentives for scientists in addition to limited financial support, the majority of countries across the African continent do not conduct structural biology research. Nevertheless, with technological advances such as robotic protein crystallization and remote data collection capabilities offered by many synchrotron light sources, X-ray crystallography is now potentially accessible to Africa-based scientists. This leap in technology led to the establishment in 2017 of BioStruct-Africa, a non-profit organization (Swedish corporate ID: 802509-6689) whose core aim is capacity building for African students and researchers in the field of structural biology with a focus on prevalent diseases in the African continent. The team is mainly composed of, but not limited to, a group of structural biologists from the African diaspora. The members of BioStruct-Africa have taken up the mantle to serve as a catalyst in order to facilitate the information and technology transfer to those with the greatest desire and need within Africa. BioStruct-Africa achieves this by organizing workshops onsite at our partner universities and institutions based in Africa, followed by post-hoc online mentoring of participants to ensure sustainable capacity building. The workshops provide a theoretical background on protein crystallography, hands-on practical experience in protein crystallization, crystal harvesting and cryo-cooling, live remote data collection on a synchrotron beamline, but most importantly the links to drive further collaboration through research. Capacity building for Africa-based researchers in structural biology is crucial to win the fight against the neglected tropical diseases, e.g. ascariasis, hookworm, trichuriasis, lymphatic filariasis, active trachoma, loiasis, yellow fever, leprosy, rabies, sleeping sickness, onchocerciasis, schistosomiasis, etc., that constitute significant health, social and economic burdens to the continent. BioStruct-Africa aims to build local and national expertise that will have direct benefits for healthcare within the continent.

Pierre Richet (1904-1983), fighting onchocerciasis and totalitarism.

While Eugène Jamot's name is associated with the combat against sleeping sickness, Pierre Richet is permanently linked to the battle against river blindness, which he first reported in 1936 in two neighboring households in Garango (Burkina Faso). Onchocerciasis remained a continuous interest, through his last article "The OCCGE and Onchocerciasis", written in 1983. Nonetheless over the course of these five decades, Richet's trajectory was far from that of a specialist dedicating his life to a single disease. After a decade essentially spent fighting trypanosomiasis, came a decade of war in which the specialist in endemism joined the Free French Army and put his organizational know-how at General Lerclerc's disposal, from Morocco to Indochina, via Germany. On his return to Africa in 1953, he extended the principle of mobile teams to the other major endemic diseases accessible to treatment and to vaccines. Richet organized first the combat against leprosy and launched vaccination programs. In 1955, he returned to the battle against onchocerciasis and deployed the first large-scale insecticide program in Chad. The intermediate term failure of this prototype fermented his scientific, interdisciplinary, and organizational thought, which flourished at Bobo-Dioulasso. At the dawn of the independence of French-speaking African countries, and against the political tides of the time, he obtained in 1960 the creation of a supranational organization, the OCCGE, common to 8 countries of West Africa, and he headed it for a decade. Drawing lessons from the past and in the absence of effective pharmaceutical treatment, Richet the physician played the entomological card with one hand, with technical support from Orstom (IRD); this detailed work enabled the development of a strategy. With the other hand, he played the multilateral card, which led in 1974 to the launching of the extraordinary Onchocerciasis Control Program (OCP). If it is Jamot who awakened Africa, Richet is the person who restored its view but also millions of hectares of cultivable land.

Organization of oversight for integrated control of neglected tropical diseases within Ministries of Health.

BACKGROUND: Neglected tropical diseases (NTDs) are communicable diseases that impact approximately 1 billion people, but receive relatively little research, funding, and attention. Many NTDs have similar treatments, epidemiology, and geographic distribution, and as a result, the integration of control efforts can improve accountability, efficiency, and cost-effectiveness of programs. Here, we examine the landscape of efforts towards NTD integration across countries with the highest burden of disease, and review the administrative management of integration in order to identify approaches and pathways for integration. METHODOLOGY AND PRINCIPAL FINDINGS: We utilized a standardized system to score countries for NTD endemnicity to create a list of 25 countries with the highest overall burden of NTDs. We then conducted a literature review to characterize the NTD control programs in the focus countries. Six countries were selected for key informant interviews to validate literature review results and gather additional data on opportunities and obstacles to NTD integration, from an administrative perspective. The majority of countries included in the study were located in Africa, with the remainder from Asia, North America, and South America. Multiple models and pathways were observed for the integration of NTD programs, in combination with other NTD programs, other diseases, or other health programs. Substantial heterogeneity existed with respect to the NTD control programs, and no country had integrated all of their NTD control efforts into a single program. NTDs that can be treated with preventative chemotherapy were frequently integrated into a single program. Leprosy control was also frequently integrated with those of other communicable diseases, and notably tuberculosis. Barriers to NTD integration may result from internal administrative obstacles or external obstacles. CONCLUSIONS: Although many countries have begun to integrate NTD control efforts, additional work will be required to realize the full benefits of integration in most of the countries examined here. Moving forward, NTD integration efforts must ensure that administrative structures are designed to maximize the potential success of integrated programs and account for existing administrative processes.

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.

Leprosy: a glossary.

Leprosy continues to afflict residents from a number of countries in Africa, South America, and southeast Asia, despite the marked reduction in the number of cases of leprosy worldwide, after the introduction of the multidrug regimens as recommended by the World Health Organization (WHO-MDT). With the increasing immigration of individuals from risk areas to Europe and the United States, knowledge of the basic concepts of leprosy would be helpful to clinicians caring for immigrants in nonendemic areas. We present a comprehensive, updated, and critical glossary of the most relevant terms related to leprosy.

African histoplasmosis: the first report of an indigenous case in India.

OBJECTIVES: African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is an invasive fungal infection endemic in Central and West Africa. Cases seen outside Africa are generally imported. We report a disseminated purely cutaneous form of this infection in an otherwise healthy person from Kerala, in southern India. METHODS: A 59-year-old farmer presented with asymptomatic, generalized, reddish skin lesions of five months in duration. Dermatologic examination revealed multiple erythematous papules and plaques of varying sizes, predominantly over the trunk and upper limbs. The patient was otherwise in good health. Systemic examination including the pulmonary and musculoskeletal systems revealed no abnormalities. RESULTS: Skin biopsy was performed from a lesion on the thigh. Histopathologic examination revealed epithelioid and suppurative granulomas in the upper dermis, with lymphocytes, neutrophils, and plenty of giant cells. Fite-Faraco staining for Mycobacterium leprae was negative. Fungus cultured from the specimen was identified as H. capsulatum var. duboisii, the rarer variant of H. capsulatum. The patient was treated with ketoconazole 200 mg/day for four months and attained complete clearance. No relapse has been detected over two years of follow-up. CONCLUSIONS: To the best of our knowledge, this case represents the first instance of African histoplasmosis to be reported from India. The occurrence of such a rare infection in an immunocompetent individual, who had not travelled elsewhere, raises the possibility of the indigenous existence of H. capsulatum var. duboisii in Kerala. Further studies of the ecology and epidemiology of this rare infection are essential.

Chemistry and biology of the genus Voacanga.

CONTEXT: Herbal remedies have been employed for the treatment and management of various ailments since the beginning of human civilization. Voacanga is an extensive genus of the family Apocynaceae and consists of small trees inhabiting the tropical and subtropical regions of Africa. Voacanga plants have been used in the treatment of leprosy, diarrhea, and generalized edema, convulsions in children as well as to treat cases of orchitis, ectopic testes and gonorrhea. OBJECTIVES: The aim of this review is to present as much information as was established from the available scientific literature. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of the plant genus Voacanga. METHODS: The present review reports on 111 natural products as found in 44 references compiled from the major databases, viz., Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr. Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An exhaustive survey of the literature revealed that indole alkaoids and steroids constitute the major classes of phytoconstituents of this genus. Pharmacological reports revealed that products derived from this genus have been used for the treatment of cancer, and for CNS, cardiotonic, antituberculosis, acetylcholinesterase (AChE), butyrylcholinesterase, antagonistic, anti-diarrheal activities.

[Present leprosy situation in the world in 2011].

The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2010 was reported. The Enhanced global strategy for further reducing the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing grade-2 disabilities among new cases. The burden of leprosy continues to decline globally as a result of sustained efforts carried out by national leprosy programmes along with continued support from both national and international partners. Improving the management of complications through the development of an effective referral service and increased community awareness about the disease will ensure that cases present for diagnosis at an early stage and will help reduce the disease burden further.

[Understanding current practice of clinical medicine in the tropics (II). Bacterial and viral diseases. Malnutrition]. / Aspectos básicos en la práctica actual de la medicina clínica en el trópico (II). Enfermedades bacterianas y virales. Malnutrición.

In recent years, a significant number of physicians want to spend part of their medical training in health facilities in developing countries. In this setting, clinical skills are extremely important due to the limited available diagnostic resources. Bacterial diseases are common, but bacterial cultures are rarely accessible. In Africa, tuberculosis affects over 200 cases per 100,000 persons, and more than 22 million people live with HIV infection; both diseases are a serious public health problem. Malnutrition is endemic in many countries in Africa and is compounded by the continuous humanitarian and food crisis. In this paper, basic concepts of epidemiology, clinical features, diagnosis and treatment of major diseases that can be found in a rural health post in the tropics are discussed.

A multi-centre study on quality of routine data collection on relapses.

OBJECTIVES: To assess the quality of routine data collection on relapses in leprosy programmes in six countries. DESIGN: Through a questionnaire for project managers. RESULTS: The number of reported relapse cases did not correlate with number of new cases in the individual projects. Even where available, skin smears were not always used for diagnosis of MB cases and relapses. The diagnosis of relapses in the participating projects was exclusively on clinical basis - in 91.8% on the basis of new lesions. CONCLUSION: Criteria for identification of relapses were not known or not applied in uniform manner in the projects involved in the research.

Immunogenicity of Mycobacterium leprae unique antigens in leprosy endemic populations in Asia and Africa.

Ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. Tools for early detection of Mycobacterium leprae (M. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. Following the sequencing of the M. leprae genome, many M. leprae-unique candidate proteins have been identified, several of which have been tested for induction of M. leprae specific T cell responses in different leprosy endemic areas. In this study, 21 M. leprae-unique proteins and 10 peptide pools covering the complete sequence of five M. leprae-unique proteins (ML0576, ML1989, ML1990, ML2283, and ML2567) were evaluated in 160 individuals in Nepal and Ethiopia. These included: tuberculoid and borderline tuberculoid (TT/BT), borderline borderline and borderline lepromatous (BB/BL) leprosy patients; healthy household contacts (HHC); tuberculosis (TB) patients and endemic controls (EC). Immunogenicity of the proteins was determined by IFN-gamma secretion via stimulation of PBMC in 6 days lymphocyte stimulation tests (LST) or in whole blood assays (WBA). In LST, BB/BL patients (40%) responded to ML0573 and ML1601 whereas ML1604 was most immunogenic in TT/BT (35%) and HHC (36%). Additionally, significant numbers of EC displayed IFN-gamma production in response to ML0573 (54%), ML1601 (50%) and ML1604 (54%). TB patients on the other hand, hardly responded to any of the proteins except for ML1989. Comparison of IFN-gamma responses to ML0121, ML0141 and ML0188 for TT/BT patients showed specific increase in diluted 6 days WBA compared to the undiluted 24 hours WBA, whereas EC showed a reduced response in the diluted WBA, which may indicate detection of disease-specific responses in the 6 days WBA. In summary, identification of multiple M. leprae proteins inducing M. leprae-specific T cell responses in groups at high risk of developing leprosy may contribute to improve early detection for M. leprae infection.

Buruli ulcer (Mycobacterium ulcerans infection).

Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Bone lesions may include reactive osteitis or osteomyelitis beneath skin lesions, or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. Pathogenesis is related to a necrotizing and immunosuppressive toxin produced by M. ulcerans, called mycolactone. The incidence of BU is highest in children up to 15 years old, and is a major public health problem in endemic countries due to disabling scarring and destruction of bone. Most patients live in West Africa, but the disease has been confirmed in at least 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against M. ulcerans infection and prevents osteomyelitis. HIV infection may increase risk for BU, and renders BU highly aggressive. Unlike leprosy and tuberculosis, BU is related to environmental factors and is thus considered non-communicable. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. The reemergence of BU around 1980 may be attributable to environmental factors such as deforestation, artificial topographic alterations and increased manual agriculture of wetlands. The first cultivation of M. ulcerans from nature was reported in 2008.

Leprosy Elimination: Progress Report

1. Leprosy is an infectious and disabling disease caused by the Mycobacterium leprae, which canlead to permanent disability. The chronic symptoms often afflict individuals in their most productivestage of life and therefore impose a significant social and economic burden on society. Leprosypatients are often shunned and become isolated within their own communities. They becomedependent on others for care and financial support, leading to further isolation and insecurity. At theend of 1993, the prevalence of the disease was 113 6501 cases in the African Region, correspondingto a rate of 2.1 per 10 000 inhabitants.2. In 1994, the WHO Regional Committee for Africa adopted Resolution AFR/RC44/R5 Rev.1 onthe elimination of leprosy, defined as a prevalence rate of less than one case per 10 000 inhabitants.At the end of 1999, the global leprosy prevalence dropped by 85% to reach 1.4 per 10 000inhabitants and leprosy was eliminated from 98 countries in the world; in the WHO African Region,the prevalence was 1.2 per 10 000 inhabitants—32 countries had achieved the elimination goal.2WHO together with countries and partners formed a Global Alliance for the Elimination of Leprosy3to reach the elimination goal at national level in each country worldwide by 2005.

Tore Godal: pragmatic opportunist championing global public health.

Recently retired as head of the Global Alliance for Vaccines and Immunization (GAVI) secretariat and as a health advisor to leading global entities, Tore Godal is now a Special Advisor to the Norwegian Prime Minister. He is nevertheless continuing to fight for better global health, cogently articulating the needs of the world's poor and disadvantaged. He is a leading leprosy expert, ex-director of the world's premier agency for research and training in tropical diseases, instigator and prime mover of some global innovative public-private health sector partnerships, adept fund mobilizer, and advocate of the 'let's get it done' school of leadership. Few individuals are, therefore, more experienced or better suited for such a crucial and much-needed role.