Research in infectious disease control is heavily skewed towards high end technology; development of new drugs, vaccines and clinical interventions. Oft ignored, is the evidence to inform the best strategies that ensure the embedding of interventions into health systems and amongst populations. In this paper we undertake an analysis of the challenge in the development of research for the sustainable implementation of disease control interventions.We highlight the fundamental differences between the research paradigms associated with the development of technologies and interventions for disease control on the one hand and the research paradigms required for enhancing the sustainable uptake of those very same interventions within the communities on the other. We provide a definition for implementation research in an attempt to underscore its critical role and explore the multidisciplinary science needed to address the challenges in disease control.The greatest value for money in health research lies in the sustainable and effective implementation of already proven, efficacious solutions. The development of implementation research that can help provide some solutions on how this can be achieved is sorely needed.
Rapid diagnostic tests (RDTs) for visceral leishmaniasis (VL) based on rK39 antigen showed suboptimal sensitivity in East Africa. A prospective clinical cohort study in Sudan was designed to validate a novel rK28-based RDT for Leishmania donovani VL. Patients (n=285) suspected of VL by residency, fever for ≥2 weeks, splenomegaly with no prior reported VL, and negative for malaria were consecutively enrolled at three Sudanese sites in 2012–2013 and informed consent obtained. Two human readers, who were blinded to the clinical status and other RDT results, evaluated patient whole blood (WB) and serum on the rK28 RDT. Based on Leishmania parasite detection in lymph node or bone marrow aspirates (Giemsa-stained smears or culture in Novy-MacNeal-Nicolle medium), patients were categorized as VL cases (n=200) or VL controls (n=85). The rK28 RDT had high specificity using either WB (100% [85/85]) or serum (97.6% [83/85]) and exhibited greater sensitivity (WB, 92.5% [185/200]; serum, 94.5% [189/200]) than a direct agglutination test performed with the same sera (92.9% [79/85] and 83.5% [167/200] for specificity and sensitivity, respectively). Two blinded readers scored a given WB or serum sample the same on the rK28 RDT 99.6% and 100% of the time, respectively. A reader scored each individual donor's paired WB and serum rK28 RDT results the same 97.2% of the time. An inexpensive rK28 RDT that performs robustly with WB or serum will be valuable for diagnosing cases of VL in East Africa.
Post kala azar dermal leishmaniasis (PKDL) is a disease that appears after treatment of visceral leishmaniasis (VL). The highest incidence of PKDL in the world is in Sudan. Many patients heal spontaneously within 6 months but those who don't are difficult to treat, often requiring months of daily injections. These patients harbour parasite in their skin and are believed to be a source of infection and possibly epidemics. Present treatment modalities of PKDL are inadequate and impractical due to cost, duration of treatment required and side effects. New approach for treatment of PKDL is required. A joint meeting of the UNICEF/UNDP/World Bank/WHO Special Programme for research and training in Tropical Disease (TDR) and the Infectious Disease Research Institute (IDRI) Seattle, USA was held to review the progress of therapeutic vaccines and plan the development of treatment modalities for PKDL.The history of leishmaniasis vaccine development for prophylaxis and therapy was reviewed. Other than previous infection - simulated by inoculation of live Leishmania as a vaccine (leishmanization), none of the preparations of killed parasite with or without adjuvants have shown significant prophylactic efficacy. Killed L. major absorbed with alum and mixed with BCG remains to be tested as a prophylactic vaccine.Killed parasite preparations i.e. L. mexicana mixed with BCG and L. amazonensis (combined with low dose of antimonial), have shown efficacy in immunotherapy and immuno-chemotherapy, respectively. In addition combined full antimonial plus alum-absorbed autoclaved L. major vaccine has been shown to significantly improve therapy of refractory PKDL patients. These are all crude preparations of parasites and are difficult to define and standardize. However, there is now a new, second generation vaccine, Leish-111f + MPL-SE, composed of a recombinant protein comprising three leishmanial antigens and a defined adjuvant in clinical development.Immuno-chemotherapy has the potential of becoming a practical and affordable treatment modality for PKDL and other forms of leishmaniasis. The encouraging results with alum-autoclaved L. major + antimonial should be pursued. However, before further trials, availability of the vaccine and its production under Good Manufacturing Product, hence quality control must be assured. Following satisfactory safety profile of Leish-111f+MPL-SE, clinical trials using this vaccine initially with antimonials should be initiated. Similarly immunotherapy of VL should be considered with the view to controlling development of PKDL. Some immunological studies are required prior to initiation of immunotherapy in VL patients.
Journal Article Onchocerciasis in Sudan: the Southern Darfur focus Get access Hadi El Sheikh, Hadi El Sheikh 1Khartoum Eye Hospital, Khartoum, SudanaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar Hashim Ghalib, Hashim Ghalib 2Dept. of Microbiology and Public Health, Michigan State University, East Lansing, Michigan 48824, USAaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar Samir Mohamed Amin Hussein, Samir Mohamed Amin Hussein 1Khartoum Eye Hospital, Khartoum, SudanaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor Barbiero, Victor Barbiero 2Dept. of Microbiology and Public Health, Michigan State University, East Lansing, Michigan 48824, USAaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar Mustafa basheir Mustafa, Mustafa basheir Mustafa 2Dept. of Microbiology and Public Health, Michigan State University, East Lansing, Michigan 48824, USAaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar J.F. Wiluams J.F. Wiluams 2Dept. of Microbiology and Public Health, Michigan State University, East Lansing, Michigan 48824, USAaNIH/Sudan Project, Alamarat, P.O. Box 8273, Khartoum, Sudan, SudanbCommunicable Eye Disease Division, Ministry of Health, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 80, Issue 6, 1986, Pages 902–905, https://doi.org/10.1016/0035-9203(86)90252-X Published: 01 January 1986 Article history Accepted: 30 May 1985 Published: 01 January 1986
Patients with suspected kala-azar had aspirations of spleen, lymph node and bone marrow performed to compare the relative merit of each procedure. Splenic aspiration remains the method most likely to provide microscopic proof of leishmanial infection (18 of 19 samples) and was the only site positive in 5 patients. Lymph node aspirates contained parasites in 20 of 29 patients, whereas bone marrow aspirates provided the diagnosis in 18 of 28. Therefore, lymph node aspiration, with its minimal morbidity, is indicated as the primary diagnostic method in patients in the Sudan with suspected kala-azar. If negative, splenic aspiration should be performed.
Background Infection with Leishmania parasites causes mainly cutaneous lesions at the site of the sand fly bite. Inflammatory metastatic forms have been reported with Leishmania species such as L. braziliensis, guyanensis and aethiopica. Little is known about the factors underlying such exacerbated clinical presentations. Leishmania RNA virus (LRV) is mainly found within South American Leishmania braziliensis and guyanensis. In a mouse model of L. guyanensis infection, its presence is responsible for an hyper-inflammatory response driven by the recognition of the viral dsRNA genome by the host Toll-like Receptor 3 leading to an exacerbation of the disease. In one instance, LRV was reported outside of South America, namely in the L. major ASKH strain from Turkmenistan, suggesting that LRV appeared before the divergence of Leishmania subgenera. LRV presence inside Leishmania parasites could be one of the factors implicated in disease severity, providing rationale for LRV screening in L. aethiopica. Methodology/Principal Findings A new LRV member was identified in four L. aethiopica strains (LRV-Lae). Three LRV-Lae genomes were sequenced and compared to L. guyanensis LRV1 and L. major LRV2. LRV-Lae more closely resembled LRV2. Despite their similar genomic organization, a notable difference was observed in the region where the capsid protein and viral polymerase open reading frames overlap, with a unique −1 situation in LRV-Lae. In vitro infection of murine macrophages showed that LRV-Lae induced a TLR3-dependent inflammatory response as previously observed for LRV1. Conclusions/Significance In this study, we report the presence of an immunogenic dsRNA virus in L. aethiopica human isolates. This is the first observation of LRV in Africa, and together with the unique description of LRV2 in Turkmenistan, it confirmed that LRV was present before the divergence of the L. (Leishmania) and (Viannia) subgenera. The potential implication of LRV-Lae on disease severity due to L. aethiopica infections is discussed.
This study aims to describe the concept of fitrah as a paradigm of Islamic education according to the Koran. This qualitative research uses the descriptive-analytical method. All data from written materials related to the variables will be discussed and relevant. The concept of fitrah is a character, temperament, origin, religion, and all inherent potential, which is a gift from Allah Swt. Every human child born from his mother’s womb will always be accompanied by nature as the basis for personality formation in living his life. Human psychological components related to nature include human structure (physical, spiritual, nafsani, heart, reason, and lust), al-hayah (vitality), al-khuluq (character), al-sajiah (skills or talents), heredity (heredity), intuition (the ability to receive inspiration from god) and al-amal (behavior).
