Publications by authors named "Ahmed Mohamed Hassan"

18 Publications

  • Page 1 of 1

Seroprevalence of Dromedary Camel HEV in Domestic and Imported Camels from Saudi Arabia.

Viruses 2020 05 18;12(5). Epub 2020 May 18.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels ( value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.
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http://dx.doi.org/10.3390/v12050553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290434PMC
May 2020

Evaluation of undergraduate psychiatric teaching in Sudan.

BJPsych Int 2019 Feb;16(1):13-15

Senior Specialist, Armed Forces Hospital Taif, Kingdom of Saudi Arabia.

Development of an undergraduate psychiatric teaching programme and curriculum is a challenge in the current atmosphere of increasing knowledge and vast literature. However, the curriculum remains the cornerstone for future doctors' development and career. Doctors need to have the abilities to recognise, assess and manage common psychiatric conditions presenting at different levels of health services. This paper aims to look at the current status of psychiatric teaching and evaluate the curricula through interviews with teaching staff, to make appropriate recommendations for the future. Teaching staff and psychiatrists involved in undergraduate teaching were interviewed using a data collection format.
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http://dx.doi.org/10.1192/bji.2017.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357528PMC
February 2019

WSES guidelines for management of Clostridium difficile infection in surgical patients.

Authors:
Massimo Sartelli Mark A Malangoni Fikri M Abu-Zidan Ewen A Griffiths Stefano Di Bella Lynne V McFarland Ian Eltringham Vishal G Shelat George C Velmahos Ciarán P Kelly Sahil Khanna Zaid M Abdelsattar Layan Alrahmani Luca Ansaloni Goran Augustin Miklosh Bala Frédéric Barbut Offir Ben-Ishay Aneel Bhangu Walter L Biffl Stephen M Brecher Adrián Camacho-Ortiz Miguel A Caínzos Laura A Canterbury Fausto Catena Shirley Chan Jill R Cherry-Bukowiec Jesse Clanton Federico Coccolini Maria Elena Cocuz Raul Coimbra Charles H Cook Yunfeng Cui Jacek Czepiel Koray Das Zaza Demetrashvili Isidoro Di Carlo Salomone Di Saverio Irina Magdalena Dumitru Catherine Eckert Christian Eckmann Edward H Eiland Mushira Abdulaziz Enani Mario Faro Paula Ferrada Joseph Derek Forrester Gustavo P Fraga Jean Louis Frossard Rita Galeiras Wagih Ghnnam Carlos Augusto Gomes Venkata Gorrepati Mohamed Hassan Ahmed Torsten Herzog Felicia Humphrey Jae Il Kim Arda Isik Rao Ivatury Yeong Yeh Lee Paul Juang Luis Furuya-Kanamori Aleksandar Karamarkovic Peter K Kim Yoram Kluger Wen Chien Ko Francis D LaBarbera Jae Gil Lee Ari Leppaniemi Varut Lohsiriwat Sanjay Marwah John E Mazuski Gokhan Metan Ernest E Moore Frederick Alan Moore Carl Erik Nord Carlos A Ordoñez Gerson Alves Pereira Júnior Nicola Petrosillo Francisco Portela Basant K Puri Arnab Ray Mansoor Raza Miran Rems Boris E Sakakushev Gabriele Sganga Patrizia Spigaglia David B Stewart Pierre Tattevin Jean Francois Timsit Kathleen B To Cristian Tranà Waldemar Uhl Libor Urbánek Harry van Goor Angela Vassallo Jean Ralph Zahar Emanuele Caproli Pierluigi Viale

World J Emerg Surg 2015 20;10:38. Epub 2015 Aug 20.

Clinic of Infectious Diseases, St Orsola-Malpighi University Hospital, Bologna, Italy.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.
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http://dx.doi.org/10.1186/s13017-015-0033-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545872PMC
August 2015

Head and neck mycetoma: the mycetoma research centre experience.

PLoS Negl Trop Dis 2015 Mar 13;9(3):e0003587. Epub 2015 Mar 13.

The Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan.

Mycetoma is a unique neglected tropical disease which is endemic in what is known as the "mycetoma belt". The disease has many devastating impacts on patients and communities in endemic area and is characterised by massive deformity, destruction and disability. Mycetoma is commonly seen in the foot and hand and less frequent in other parts of the body. Mycetoma of the head and neck is a rarity and is associated with high morbidity and even mortality if not treated early. In this communication we report on 49 patients with head and neck mycetoma followed up at the Mycetoma Research Centre in Khartoum. Most of the reported patients had actinomycetoma and the majority were young adult males from mycetoma endemic areas in the Sudan. Most of them were students, farmers and workers. Prior to presentation the majority had long disease duration and the cause was multifactorial. Advanced disease with massive lesion, deformity and disability was the common presentation. There was no obvious history of local trauma, familial tendency or other predisposing factor identified in this group of patients. MRI and CT scan were the most accurate diagnostic tools to determine the disease extent. The treatment outcome was rather poor and characterised by low cure rate, poor outcome and high follows-up dropout. Such a gloomy outcome calls for structured and objective health education programs.
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http://dx.doi.org/10.1371/journal.pntd.0003587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359145PMC
March 2015

A new model for management of mycetoma in the Sudan.

PLoS Negl Trop Dis 2014 Oct 30;8(10):e3271. Epub 2014 Oct 30.

Rotterdam Centre for Tropical Medicine, Rotterdam, The Netherlands.

Patients with mycetoma usually present late with advanced disease, which is attributed to lack of medical and health facilities in endemic areas, poor health education and low socio-economic status. With this background, an integrated patient management model at the village level was designed to address the various problems associated with mycetoma. The model was launched in an endemic village in the Sudan, between 2010 and 2013. This model is described in a prospective, descriptive, community-based study, aimed to collect epidemiological, ecological, and clinical data and to assess knowledge, attitude and practice (KAP) in order to design effective and efficient management measures. In this study, the prevalence of mycetoma was 14.5 per 1,000 inhabitants. The patients were farmers, housewives and children of low socio-economic status, and no obvious risk group was detected. All had surgery performed in a mobile surgical unit in the village which encouraged patients to present early with small early lesion leading to a good clinical outcome. The close contact with the Acacia tree thorns, animals and animal dung, walking bare footed and practising poor hygiene may all have contributed to the development of mycetoma in the village. Knowledge of mycetoma was poor in 96.3% of the study population, 70% had appropriate attitudes and beliefs towards interaction with mycetoma patients and treatment methods, and 49% used satisfactory or good practices in the management of mycetoma. Knowledge and practices on mycetoma were found to be significantly associated with age. Based on the KAP and epidemiological data, several health education sessions were conducted in the village for different target groups. The integrated management approach adopted in this study is unique and appeared successful and seems suitable as an immediate intervention. While for the longer term, establishment of local health facilities with trained health staff remains a priority.
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http://dx.doi.org/10.1371/journal.pntd.0003271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214669PMC
October 2014

Cytomorphologic patterns of breast lesions in Sudanese patients: lessons learned from fine needle aspiration cytology.

Asian Pac J Cancer Prev 2014 ;15(8):3411-3

Department of Pathology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan E-mail :

Background: Cytology for breast lesions is a safe, rapid and cost-effective with a high specificity and sensitivity.

Objective: To determine the cytomorphologic patterns of breast lesions identified among a group of Sudanese patients.

Materials And Methods: This study included 759 patients undergoing either a fine needle aspiration FNA, nipple discharge (ND) smears or breast skin scraping (SS) at a cytology clinic in Khartoum. Clinical and demographic data were reviewed. Stained smears were categorized into: inadequate sample, normal breast, benign lesion, suspicious, or malignant neoplasm.

Results: of the 759 cases, 734 (96.71%) were FNA, 18 (2.37%) ND and 7 cases (0.92%) SS. For 28 cases, FNA was done under ultrasound guidance. Females were 720 (94.86%). Benign lesions were 423(55.75%) and 248 (32.67%) were malignant and 77 (10.14%) of smears were normal without any detected abnormality. Ten (1.31%) cases were suspicious for malignancy, and only one case (0.13%) was reported as inadequate. Most lesions were observed among the age group 30 years and above.

Conclusion: Most patients investigated have benign lesions, one third of cytological smears were malignant. FNAC is a useful tool for investigating breast lesions in limited-resource settings.
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http://dx.doi.org/10.7314/apjcp.2014.15.8.3411DOI Listing
January 2015

Outcome of sublay mesh repair in non-complicated umbilical hernia with liver cirrhosis and ascites.

Int J Surg 2014 28;12(2):181-5. Epub 2013 Dec 28.

Radiology Department, Cairo University, Kasr El Ainy Hospitals, Cairo, Egypt. Electronic address:

Background: Umbilical hernia repair is often accompanied by complications in patients with liver cirrhosis and ascites. It appears that the early elective repair of umbilical hernias in these patients is safer and can be considered for selected patients. The objective of this study is to evaluate the feasibility, safety, complications and technical aspects of sublay mesh repair of umbilical hernia in cirrhotic patients with ascites.

Methods: Between October 2010 and April 2013, 70 patients with non-complicated umbilical hernia, liver cirrhosis and ascites were enrolled in this study. All patients underwent sublay mesh repair. Demographic data, preoperative variables, peri-operative course, and postoperative complications were recorded and analyzed.

Results: A total of 38 women and 32 men underwent operation at an average age 51.24 years. The patients mean MELD score was 18 (range 12-25). The mean operative time was 67.45 min and the average hospital stay was 3.8 days. 2 patients had wound infection, 3 patients developed seroma and 1 patient had an ascitic fistula. Recurrence occurred in 1 (1.4%) patient and no mortality related to the procedure.

Conclusion: elective sublay umbilical hernia mesh repair is a safe approach and feasible technique in selected non-complicated cirrhotic patients with ascites.
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http://dx.doi.org/10.1016/j.ijsu.2013.12.009DOI Listing
November 2014

Post-Kala-Azar Dermal Leishmaniasis: A Paradigm of Paradoxical Immune Reconstitution Syndrome in Non-HIV/AIDS Patients.

J Trop Med 2013 24;2013:275253. Epub 2013 Mar 24.

The Leishmaniasis Research Group, Sudan ; Institute of Endemic Diseases, University of Khartoum, P.O. Box 45235, 11111 Khartoum, Sudan ; The Central Laboratory, Ministry of Science & Communications, 7099 Khartoum, Sudan.

Visceral leishmaniasis (VL) is a parasitic disease characterized by immune suppression. Successful treatment is usually followed by immune reconstitution and a dermatosis called post-Kala-azar dermal leishmaniasis (PKDL). Recently, PKDL was described as one of the immune reconstitution syndromes (IRISs) in HIV/VL patients on HAART. This study aimed to present PKDL as a typical example of paradoxical IRIS in non-HIV/AIDS individuals. Published and new data on the pathogenesis and healing of PKDL was reviewed and presented. The data suggested that PKDL is a typical example of paradoxical IRIS, being a new disease entity that follows VL successful treatment and immune recovery. PKDL lesions are immune inflammatory in nature with granuloma, adequate response to immunochemotherapy, and an ensuing hypersensitivity reaction, the leishmanin skin test (LST). The data also suggested that the cytokine patterns of PKDL pathogenesis and healing are probably as follows: an active disease state dominated by IL-10 followed by spontaneous/treatment-induced IL-12 priming, IL-2 stimulation, and INF- γ production. INF- γ -activated macrophages eliminate the Leishmania parasites/antigen to be followed by LST conversion and healing. In conclusion, PKDL is a typical example of paradoxical IRIS in non-HIV/AIDS individuals with anti-inflammatory cytokine patterns that are superseded by treatment-induced proinflammatory cytokines and lesions healing.
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http://dx.doi.org/10.1155/2013/275253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619621PMC
May 2013

Misdiagnosis and mistreatment of post-kala-azar dermal leishmaniasis.

Case Rep Med 2013 21;2013:351579. Epub 2013 Feb 21.

Leishmaniasis Research Group, Institute of Endemic Diseases, University of Khartoum, Medical Campus, Qasr Avenue, P.O. Box 102, 11111 Khartoum, Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral leishmaniasis (VL) caused by L. donovani. It is rare in VL caused by L. infantum and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis of clinical appearance, distribution of the lesions, and past history of treated VL. The ideal diagnostic method is to demonstrate the parasite in smears, by culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL in the absence of previous history of visceral leishmaniasis. We describe a case of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were either misdiagnosed or mistreated as other dermatoses. This caused exacerbation of their disease leading to high parasite loads in the lesions and dissemination to internal organs in one of the patients, who was also diabetic. The latter patient had L. major infection. A fourth patient with papulonodular lesions on the face and arms of 17-year duration and who was misdiagnosed as having PKDL is also described. He turned out to have cutaneous leishmaniasis due to L. major. Fortunately, he was not treated with steroids. He was cured with intravenous sodium stibogluconate.
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http://dx.doi.org/10.1155/2013/351579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600135PMC
March 2013

Histopathological findings in appendectomy specimens: a retrospective clinicopathological analysis.

J Egypt Soc Parasitol 2012 Apr;42(1):157-64

Department of General Surgery, Theodor Bilharz Research Institute, Warak El-Hadar, Kornish El-Nile, Imbaba P.O. Box 30, Giza, 12411, Egypt.

The prevalence and clinical features of the various obstructive lesions in appendectomy specimens studied pathologically with special emphasis on unusualetiological findings were evaluated. The clinic-pathological data of 251 patients who underwent appendectomies for presumed acute appendicitis from January; 2008 to December; 2010; were reviewed retrospectively. Among all appendectomies performed, eleven (4.38%) specimens revealed incidental abnormal pathological diagnoses: Four cases (1.59%) of Enterobiusvermicularis, Ascaris lumbricoides two cases (0.79 %), schistosomiasis eggs in three cases (1.19%), and parasitic amebiasis in two cases (0.79%). None suffered tumor in any appendectomies specimens. Mean age was lower, perforated and gangrenous appendicitis was absent and negative appendectomy rate was higher in patients with unusual appendix pathology.
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http://dx.doi.org/10.12816/0006303DOI Listing
April 2012

Role of prophylactic antibiotic in elective laparoscopic cholecystectomy.

J Egypt Soc Parasitol 2012 Apr;42(1):129-34

Department of General Surgery, Theodor Bilharz Research Institute, Warak El-Hadar, Kornish El-Nile, Imbaba P.O. Box 30, Giza, 12411, Egypt.

This prospective study was conducted to investigate the efficacy of single-dose Ceftazidime as a prophylactic antibiotic to prevent surgical site infections in low-risk patients undergoing LC. Two hundred patients included in the study were randomly divided into two groups (100 each): G1: patients received intravenous Ceftazidime within 60 minutes prior to surgery and G2: received intravenous placebo (10 ml isotonic sodium chloride 0.9% solution). All patients were invited for examination 10, 20 and 30 days post-operatively and any post-operative complications were recorded and managed. Preoperatively; there was no significant differences existed between the 2 groups regarding sex, age; body mass index and ASA score. Also, the duration of LC surgery, incidence of intra-operative gallbladder perforations and spill of bile or stones, incidents of intra-operative bleeding from either cystic artery or gall bladder liver bed and mean postoperative hospital stay were found not significantly different between the 2 groups. Post operatively there was no statistical difference regarding the surgical site infection between the two groups.
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http://dx.doi.org/10.12816/0006301DOI Listing
April 2012

Effect of pancreatic biliary reflux as a cofactor in cholecystitis.

J Egypt Soc Parasitol 2012 Apr;42(1):121-8

Department of General Surgery, National Hepatology and Tropical Medicine Research Institution, Imbaba POB 30, Gizal2411, Egypt.

This study assessed the effect of pancreatico-biliary reflux (PBR) as co-factor in the process of chronic cholecystitis by measurement of the levels of active pancreatic enzyme amylase in gallbladder bile and serum of patients undergoing cholecystectomy. Pancreatic Amylase levels in bile from the gallbladder and serum were measured during surgery in 68 patients with chronic calcular cholecystitis subjected to elective open or laparoscopic cholecystectomy in the National Hepatology and Tropical Medicine Research Institution and Theodore Bilharz Research Institute. Bile amylase was detected in 64 patients (94.1%) indicating pancreatico-biliary reflux. Biliary amylase level ranged from 20-50 IU/L in 42 patients (61.76%), below 20 IU/l in 14 patients (20.59%), over 50 IU/L in 8 patients (11.76%) and undetectable in two patients. According to gallbladder bile amylase, the incidence of Occult PBR in patients operated upon for chronic calcular cholecystitis was 94.1%. The reason should be clarified by further research and wider scale study. Routinely investigating biliary amylase in every patient having cholecystitis can be a method for early detection of precancerous lesions.
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http://dx.doi.org/10.12816/0006300DOI Listing
April 2012

Single incision tans-umbilical laparoscopic cholecystectomy using conventional laparoscopic instruments: initial experience of single institute.

J Egypt Soc Parasitol 2011 Dec;41(3):675-84

Department of General Surgery, Theodor Bilharz Research Institute, Imbaba P.O. Box 30, Giza 12411, Egypt.

Laparoscopic cholecystectomy (LC) had been considered the gold standard treatment for symptomatic gall bladder (GB) stones. Single incision laparoscopic cholecystectomy (SILC) was emerged as a less invasive alternative with better cosmesis and less post operative pain. This study evaluated the feasibility, safety, advantages and complications of SILC using the conventional laparoscopic instruments. A total of 52 patients (47 females and 5 males) with symptomatic GB stones underwent elective SILC using the conventional laparoscopic instruments. The mean operative time was 61.75 min and the mean estimated blood loss was 17.21 ml. Gall bladder perforation occurred in 5 cases (9.6%) in which 3 cases calculi spillage occurred. Troublesome cystic artery bleeding occurred in 2 cases (3.8%) while gall bladder bed bleeding happened in 1 case (1.9%). An intraoperative cholangiogram was performed in 3 cases and a drain was inserted in one case. No conversions of the technique occurred. 49 patients discharged in the first post operative day and 3 patients (5.8 %) in the 2nd day. Three month post operative wound length was an average of 1.58 cm while patient satisfaction of the surgery was an average of 9.32.
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December 2011

Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment.

Trans R Soc Trop Med Hyg 2008 Jan 25;102(1):58-63. Epub 2007 Oct 25.

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) is a recognized dermatosis that follows successful treatment of visceral leishmaniasis in the Sudan. This randomized and double-blind study aimed to assess safety, immunogenicity and curative potentials of a novel immunochemotherapy regimen in patients with persistent PKDL. Following informed consent, 30 patients were randomized to receive alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine+Bacille Calmette-Guérin (BCG) and sodium stibogluconate (SSG) or vaccine diluent and SSG. The SSG+Alum/ALM+BCG proved safe with minimal local adverse events. In the SSG+vaccine group, 87% of the patients were cured by day 60 compared with 53% in the SSG alone group (SSG+vaccine efficacy=71%, 95% CI for risk ratio 0.7-1.16). On day 90 of follow-up there were two relapses in the SSG alone arm and none in the SSG+vaccine arm. Pre-treatment cytokines showed high IFN-gamma or high IFN-gamma/IL-10 levels and leishmanin skin test (LST) non-reactivity, while healing/clinical improvement were associated with LST reactivity and low IFN-gamma levels in both study groups (P=0.004). In conclusion, SSG+Alum/ALM+BCG is safe and immunogenic with significant healing potentials in persistent PKDL lesions. Immunochemotherapy probably augmented IFN-gamma production, which induced healing. Leishmanin skin reactivity is a good surrogate marker of cure in persistent PKDL lesions.
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http://dx.doi.org/10.1016/j.trstmh.2007.08.006DOI Listing
January 2008

Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study.

Ann Trop Paediatr 2006 Dec;26(4):357-61

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

Background: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions.

Methods: A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity.

Results: The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL.

Conclusion: Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.
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http://dx.doi.org/10.1179/146532806X152890DOI Listing
December 2006

SLC11A1 (formerly NRAMP1) and susceptibility to visceral leishmaniasis in The Sudan.

Eur J Hum Genet 2004 Jan;12(1):66-74

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence and clinical phenotypes between ethnic groups in Sudan. In mice, innate susceptibility to Leishmania donovani, the etiological agent of VL, is controlled by Slc11a1 (formerly Nramp1). We therefore examined polymorphisms at SLC11A1 in 59 multicase families of VL from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis in ALLEGRO shows a significant linkage across SLC11A1 (Zlr scores 2.38-2.55; 0.008< or =P< or =0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5' polymorphisms in the promoter (P=0.0145), exon 3 (P=0.0037) and intron 4 (P=0.0049), and haplotypes formed by them (P=0.0089), but not for 3' polymorphisms at exon 15 or the 3'UTR. Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families was consistent with main effects contributed by the intron 4 469+14G/C polymorphism. Although the two alleles for 469+14G/C lie on haplotypes carrying different alleles for the functional promoter GTn polymorphism, the latter did not itself contribute separate main effects. Sequence analysis of 36 individuals failed to identify new putative functional polymorphisms in the coding region, intron 1, intron/exon boundaries, intron 4/exon 4a, or in the 3'UTR. One novel promoter polymorphism (-86G/A) was located within a putative nuclear factor kappa B binding site that could be functional. Further work will determine whether additional polymorphisms occur upstream in the promoter, which could be in linkage disequilibrium with the intron 4 polymorphism. These studies contribute to knowledge of the role of SLC11A1 in infectious disease.
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http://dx.doi.org/10.1038/sj.ejhg.5201089DOI Listing
January 2004