Safety and immunogenicity of an autoclaved Leishmania major vaccine

Objective: To test the safety and immunogenicity of two doses of autoclaved L.major (ALM) vaccine mixed with BCG.Setting: Kala-azar endemic area of eastern Sudan.Design: This was a randomised, double blind and BCG controlled phase I/II study.Subjects: Eighty healthy volunteers (forty children and forty adults) with no past history of kala-azar, no reactivity to leishmanin antigen and with a reciprocal direct agglutination test (DAT) titre o

Spectrum of Leishmania donovani infection in the Southwest of Sudan: A rapid epidemiological mapping

This epidemiological survey was based on simple immunological techniques (leishmanin skin reactivity and the direct agglutination tests), combined with clinical history to obtain data about the spectrum of L. donovani infection in communities at risk of developing visceral Leishmaniasis. The data was depicted in map format to give an enhanced visual impact.</p

Leprosy in an endemic focus in the Sudan

Objectives: The objectives of this study were active case detection, provision of multidrug treatment in primary health care settings and evaluation of the accuracy of the clinical system of classification that was adopted by the Leprosy Control Program of Sudan. Design: The whole population of two villages in a remote area in eastern Sudan were examined initially and then followed up for three years in this prospective study. Patients from the surrounding villages, who were self reporting were also included in the study. Setting: The study was conducted in a primary health care setting, which was the only available form of health care facility in the study area. Subjects: Communal consent was obtained following explanation and discussion with the Sheikhs. The population of the two villages were interviewed and examined clinically with particular reference to skin lesions. Informed consents to participate in the study were obtained from individuals with skin lesions. Interventions: Skin biopsies were taken under local anaesthesia and aseptic conditions from suspicious lesions. Multi-drug therapy regimen (MDT) was given to those with proven disease. Out come measures: Response was measured by improvement in skin lesions and sensations every six months. Results: Compliance was around 90 %. According to the clinical classification 68.4% and 31.6% of the patients were multi-bacillary and pauci-bacillary respectively. There was 100 % agreement between the clinical classification and Ridley & Jopling classification where all Tuberculoid (TT) patients were correctly diagnosed as pauci-bacillary and borderline Lepromatous (BL) and Lepromatous (LL) patients were correctly diagnosed as multibacillary. Seventy BT patients were misclassified as multi-bacillary disease. Conclusions: The clinical classification is adequate for the diagnosis and treatment of leprosy patients in remote areas of eastern Sudan. Sudanese Journal of Dermatology Vol. 3(2) 2005: 73-7

Surrogate markers of subtle renal injury in patients with visceral leishmaniasis

Sudanese Visceral Leishmaniasis (VL) is a disease of children that is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and renal injury. Microalbumi-nuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. We report the prevalence of subtle renal injury in 88 para-sitologically confirmed VL patients in a cross-sectional and hospital-based study. Blood and urine were collected before treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal serum urea and creatinine levels and no detectable urRBP. However, 40&#x0025; of the patients had MA detected by ELISA, and 42&#x0025; were reactive with turbidometry. The sensitivity, specificity, positive and negative predictive values for MA turbidometric technique were calculated as 100&#x0025;; 96&#x0025;; 95&#x0025; and 100&#x0025;, res-pectively. In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for MA measurement is a simple, inexpensive, sensitive, and specific technique with high predictive values

Safety, immunogenicity & possible efficacy of immunochemotherapy of persistent post-kalasar dermal leishmaniasis

Background: Post kala-azar dermal leishmaniasis (PKDL) is a common skin condition that follows successful treatment of visceral leishmaniasis (VL) in Sudanese patients. Lesions persist for years in 15% of patients and are viewed as reservoirs for the disease. Drug treatment is protracted, toxic and costly. Cure is strongly correlated with conversion in the leishmanin skin test. Objective of the study: To determine safety, immunogenecity and possible efficacy of Alum-precipitated autoclaved L. major + BCG VL candidate vaccine combined with sodium stibogluconate (SSG) in patients with persistent PKDL. Methodology and results: Following informed consent, the vaccine mixture was administered in a stepwise manner as follows: 5 patients received a single intradermal injection of 10µg, 5 patients received a single dose of 100µg and 2 patients received 4 doses of 100µg at weekly intervals. Subsequently, the three groups of patients received means of 63.0 ± 8.0, 53.0 ± 5.0 and 40 days courses of SSG treatment respectively and were cured. Side effects were minimal and were confined to the vaccine injection site. Following completion of the safety study, eight patients were injected with 4-6 vaccine doses of 100µg/dose at weekly intervals in combination with SSG. Patients were closely followed up in hospital, with minimal side effects and complete clearance of the skin rash in forty days. Conclusion: Alum/ALM + BCG vaccine mixture plus SSG was safe and was apparently effective in healing persistent PKDL lesions. SSG treatment duration could be shortened with the SSG/vaccine combination. Keywords: PKDL, Immunochemotherapy, alum/ALM+BCG candidate vaccine Sudanese Journal of Dermatology Vol. 3(2) 2005: 63-7

Alum-precipitated autoclaved Leishmania major plus bacille Calmette-Guérrin, a candidate vaccine for visceral leishmaniasis: safety, skin-delayed type hypersensitivity response and dose finding in healthy volunteers.

In a previous efficacy study, autoclaved Leishmania major (ALM) + bacille Calmette-Guérrin (BCG) vaccine was shown to be safe, but not superior to BCG alone, in protecting against visceral leishmaniasis. From June 1999 to June 2000, we studied the safety and immunogenicity of different doses of alum-precipitated ALM + BCG vaccine mixture administered intradermally to evaluate whether the addition of alum improved the immunogenicity of ALM. Twenty-four healthy adult volunteers were recruited and sequentially allocated to receive either 10 microg, 100 microg, 200 microg, or 400 microg of leishmanial protein in the alum-precipitated ALM + BCG vaccine mixture. Side effects were minimal for all doses and confined to the site of injection. All volunteers in the 10 microg, 100 microg, and 400 microg groups had a leishmanin skin test (LST) reaction of > or = 5 mm by day 42 and this response was maintained when tested after 90 d. Only 1 volunteer out of 5 in the 200 microg group had a LST reaction of > or = 5 mm by day 42 and the reasons for the different LST responses in this group are unclear. This is the first time that an alum adjuvant with ALM has been in used in humans and the vaccine mixture was safe and induced a strong delayed type hypersensitivity (DTH) reaction in the study volunteers. On the basis of this study we suggest that 100 1 microg of leishmanial protein in the vaccine mixture is a suitable dose for future efficacy studies, as it induced the strongest DTH reaction following vaccination