Eltahir Awad Gasim Khalil | University of Khartoum (original) (raw)
Papers by Eltahir Awad Gasim Khalil
Emerging Infectious Diseases, Mar 1, 2020
T uberculosis (TB) remains a major global health problem; 10 million new cases were reported in 2... more T uberculosis (TB) remains a major global health problem; 10 million new cases were reported in 2018 (1). In Sudan, the estimated national TB incidence in 2018 was 71/100,000 persons; a total of 20,638 cases were reported (1). However, the TB burden is by no means homogeneous across the country. For instance, in eastern Sudan, TB notifications reached 275/100,000 persons in 2012 (2,3). Prevalence of multidrug-resistant TB (MDR TB) (i.e., resistant to isoniazid and rifampin) was estimated at 2.9% in new and 13% in retreatment cases; however, studies have reported MDR TB rates of 6%-22% (1,4-10). Ongoing transmission is one of the key challenges for TB control programs, especially in countries with a high TB burden (1,11). In recent years, molecular techniques have been increasingly used to clarify and trace transmission of Mycobacterium tuberculosis complex (MTBC) strains and to direct and guide targeted TB control actions (12,13). However, availability of molecular techniques is limited in many countries in Africa with a high TB burden (11). In Sudan, drug-resistant TB often goes undetected, resulting in inadequate treatment, illness, death, and ongoing transmission (1,14). Local laboratories have limited access to mycobacterial culture and drug susceptibility testing (DST) or DNA-based techniques (14). Therefore, MDR TB rates might be underestimated in eastern Sudan. In addition, mutations that mediate drug resistance have not been investigated. Taken together, these factors indicate that, although TB is a huge health problem in eastern Sudan, precise data on the phylogeny and transmission dynamics of MTBC strains, as well as on resistance patterns, is sparsely available (2,3,7,8,15). Studies using molecular epidemiologic tools are rare and have used classical genotyping techniques, such as
Journal of tuberculosis research, 2016
Drug susceptibility testing (DST) plays a pivotal role in TB patients' management leading to the ... more Drug susceptibility testing (DST) plays a pivotal role in TB patients' management leading to the selection of most effective drugs. This study aimed to determine resistance patterns to first line anti-TB drugs in Mycobacterium tuberculosis isolates from retreated patients from Sudan. A total of 239 sputum specimens were collected from smear positive re-treatment TB patients during the period from July 2009 to July 2010. Specimens were pre-treated according to Petroff method. The recovered isolates were tested for sensitivity to first line anti-TB drugs by the 1% proportion method. One hundred and forty three (143/239, 59.8%) mycobacterial isolates were successfully recovered. The majority (98.6%, 141/143) of the isolates were Mycobacterium tuberculosis complex strains. Two strains (2/143, 1.4%) were identified as RIF/INH-resistant MOTT, while fifty four isolates (38.3%, 54/141) were MDR. Multidrug resistant Mycobacterium tuberculosis complex (MDR-TB) among re-treatment patients from national referral centers for tuberculosis diagnosis and management was considerably high in the study isolates.
The Open Microbiology Journal, Dec 18, 2020
Ovarian cancer is the leading cause of mortality from female reproductive cancer. No definite sym... more Ovarian cancer is the leading cause of mortality from female reproductive cancer. No definite symptoms related with early-stage disease and no effective screening methods make its early detection difficult, which results in about two-third patients with advanced-stage ovarian cancer at the diagnosis. In this study, the overall mean age of patients was 46.5 ± 27.5 years. The vast majority of women [90.0%] in this cohort were with the age groups 30–70 years. Ovarian cancer is not common (p = 0.5) below 30 years (frequency = 4.5%) and above 70 years (frequency = 1.7%), the common age group is above 60 years. More than forty percent (50/112, 44.6%) of the patients had symptoms of abdominal discomfort, pelvic pain and irregular bleeding during the last 6 months. A third (38/112, 33.9%) had symptoms for more than a year, while 5.4% (6/112) and 14.3% (16/112) had symptoms for two and three years respectively. The majority of patients (80%, 89/112) were childless. A third (44/112, 39.3%) we...
Revue d’élevage et de médecine vétérinaire des pays tropicaux, 2018
Tuberculosis (TB) is a chronic bacterial disease of humans and animals. It is characterized by th... more Tuberculosis (TB) is a chronic bacterial disease of humans and animals. It is characterized by the progressive development of specific granulomatous lesions in affected organs. Human TB is endemic in Eastern Sudan. However, knowledge on the epidemiology of TB in ruminants is scarce. In a six-month study from June to November 2014, a total of 2304 carcasses of cattle, sheep, goats and camels slaughtered at the East and West Gaash slaughterhouses of Kassala were inspected to investigate TB prevalence. Only 0.1% (n = 2) of the carcasses had suspicious TB lesions. These lesions were solely found in carcasses of sheep, in the liver, lungs, and peritoneal cavity. The samples collected from the lesions were investigated for the presence of mycobacteria, which were found in one of the two carcasses. The grown bacteria were subjected to a line probe assay (GenoType Mycobacterium CM), and to 16S rDNA and ITS gene sequencing, and whole genome sequencing (WGS). However, none of these methods id...
![Research paper thumbnail of Toxic Effects and Safety of Bee Venom Protein [Melittin] in Mice: Search for Natural Vaccine Adjuvants](https://attachments.academia-assets.com/117358068/thumbnails/1.jpg)
](Melittin protein is the main component of Bee venom (BV) that contains twenty-six amino acids. It... more Melittin protein is the main component of Bee venom (BV) that contains twenty-six amino acids. It constitutes 40% to 50% of dry bee venom by weight and is used in traditional medicine to inhibit infection and reduce inflammation. This study aimed to determine the toxic effects of melittin in CD-1 Swiss albino mice. The study also aimed to determine the lowest safe melittin dose to be used as a potential vaccine adjuvant. One hundred and sixty mice were injected intra-dermally with increasing doses of melittin [9000, 4500, 2250, 900, 450, 250, 100, 50 and 30 μg/dose]. The mice were followed for toxicity with respect to body temperature, body movement, weight, function/ anatomical structure of vital organs [brain, liver, bone marrow, kidneys]. Injected mice with high doses [9000, 4500, 2250 μg/dose] died with hypothermia, ataxia and loss of weight. Thirty μg /dose of melittin was found to be the lowest safe dose with minimum side effects and no abnormalities in histological sections o...
Clinical Pharmacokinetics, 2021
Introduction Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been ... more Introduction Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been shown to be effective for Indian patients, while a similar regimen resulted in lower efficacy in Eastern Africa, which could be related to differences in paromomycin pharmacokinetics. Methods Pharmacokinetic data were available from two randomized controlled trials in VL patients from Eastern Africa and India. African patients received intramuscular paromomycin monotherapy (20 mg/kg for 21 days) or combination therapy (15 mg/kg for 17 days) with sodium stibogluconate. Indian patients received paromomycin monotherapy (15 mg/kg for 21 days). A population pharmacokinetic model was developed for paromomycin in Eastern African and Indian VL patients. Results Seventy-four African patients (388 observations) and 528 Indian patients (1321 observations) were included in this pharmacokinetic analysis. A one-compartment model with first-order kinetics of absorption and elimination best described paromomycin in plasma. Bioavailability (relative standard error) was 1.17 (5.18%) times higher in Kenyan and Sudanese patients, and 2.46 (24.5%) times higher in Ethiopian patients, compared with Indian patients. Ethiopian patients had an approximately fourfold slower absorption rate constant of 0.446 h-1 (18.2%). Area under the plasma concentration-time curve for 24 h at steady-state (AUC τ,SS) for 15 mg/kg/day (median [interquartile range]) was higher in Kenya and Sudan (172.7 µg•h/mL [145.9-214.3]) and Ethiopia (230.1 µg•h/mL [146.3-591.2]) compared with India (97.26 µg•h/mL [80.83-123.4]). Conclusion The developed model provides detailed insight into the pharmacokinetic differences among Eastern African countries and India, however the resulting differences in paromomycin exposure do not seem to explain the geographical differences in paromomycin efficacy in the treatment of VL patients.
Annals of Systems Biology, 2021
In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment o... more In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment of leishmaniasis and in vaccine and drug development studies. There is no information about the effects of urine within culture on the infectivity of Leishmania parasites. In this study we used two culture media with different overlays to enhance the in vitro growth rates of Leishmania donovani. In this study we used two culture media with different overlays to enhance the in vitro growth rates of Leishmania donovani. Addition of female human urine to these media enhanced the growth of the promastigotes by at least 40 times when compared to the classical Novy-MacNeal-Nicole medium (NNN). Analysis of the effect of urine have showed that proliferation indexes were signifi cantly increased in culture medium supplemented with human urine to 12.84×10 6 parasite / ml in day 12. On the other hand, when 5% fresh human urine was overlaid, the promastigotes' count was increased to 32.8×10 6 parasite / ml on day 4 and further increase to 58.5 x 10 6 parasite / ml on day 8 was signifi cantly (p=0.002) noted) to 137.8×10 6 parasite / ml on day 12. In conclusion, human urine in parasite cultures differentially affected the infectivity and proliferation of L.donovani species promastigotes. Further identifi cation of components found in urine that play a role in infectivity of parasites may be important for understanding transmission mechanisms of parasites into infective stages.
Clinical Infectious Diseases, 2021
Background To expedite the development of new oral treatment regimens for visceral leishmaniasis ... more Background To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months. Results The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a c...
Clinical Diagnostic Laboratory Immunology, 1998
The rK39 enzyme-linked immunosorbent assay (ELISA) was compared with the direct agglutination tes... more The rK39 enzyme-linked immunosorbent assay (ELISA) was compared with the direct agglutination test (DAT) for Leishmania donovani infection in the Sudan. rK39 ELISA proved more sensitive than DAT in diagnosis of kala-azar (93 and 80%, respectively); both tests may remain positive up to 24 months after treatment. For patients with post-kala-azar dermal leishmaniasis and individuals with subclinical infection, rK39 ELISA performed as well as DAT but could detect infection 6 months earlier in ∼40% of patients. Conversion in DAT and rK39 ELISA also occurred in leishmanin skin test (LST)-positive individuals, suggesting active parasite replication (rK39 is an amastigote antigen) in these presumably immune individuals. In contrast to DAT, rK39 ELISA also detected infection in randomly selected LST-positive individuals (in four of six) and endemicity (LST-negative) controls (in one of five). rK39 ELISA appears more sensitive than DAT and may prove an important tool in epidemiological studies.
Journal of Clinical Microbiology, 1998
Microscopy and PCR were compared for use in the diagnosis of post-kala-azar dermal leishmaniasis ... more Microscopy and PCR were compared for use in the diagnosis of post-kala-azar dermal leishmaniasis (PKDL) in 63 patients. Aspirates of lymph nodes (samples from 52 patients), skin (23 samples), and bone marrow (18 samples) were used. For 11 patients lymph node aspiration could be repeated 6 months after they recovered from PKDL. During active PKDL, PCR was positive for 42 of 52 (80.8%) lymph node aspirates and 19 of 23 (82.7%) skin aspirates, whereas microscopy was positive for only 9 of 52 (17.3%) lymph node aspirates and 7 of 23 (30.4%) skin aspirates. PCR was always positive when parasites were seen by microscopy. When the results obtained with lymph node and skin aspirates from the same patient ( n = 16) were compared, there was complete agreement. Bone marrow samples were negative by microscopy and PCR for 16 patients and positive by both methods for 1 patient; for one sample only the PCR was positive. PCR confirmed the co-occurrence of visceral leishmaniasis and PKDL in one pati...
Universal Journal of Public Health, 2019
Journal of Human Virology & Retrovirology, 2018
Hepatitis C virus infection is a global public health problem and a leading cause of acute and ch... more Hepatitis C virus infection is a global public health problem and a leading cause of acute and chronic liver disease. HCV is a small, single-stranded RNA virus of the Flaviviridae family that can infect hepatocytes, lymphocytes and monocytes. It is classified into eleven genotypes and 67 subtypes on genetic differences. Hepatitis C infections can be concentrated in certain populations and/or in general populations.1–4 HCV is transmitted through needle sharing, contaminated surgical equipment, blood transfusion, sexual contact and from infected mothers to babies. Variable low to high prevalence (1.3%-55%) of HCV in patients with hepatocellular carcinoma or chronic liver disease have been reported form different African countries.5–7 The global prevalence of anti-HCV has been estimated at 2.0% (1.7–2.3%) among adults and 1.6% (1.3–2.1%) for all ages with an estimated 115 million people infected mainly adults. HCV infection is not preventable by vaccination, so improved surveillance and access to screening and treatment at national and regional levels are strongly recommended.8–14 Sudan is the largest country in the Nile valley with a land mass about the size of Europe with HCV infection prevalence among asymptomatic male Sudanese blood donors of 1.5%-4.4%. This is definitely an under-estimate since females do not usually donate blood in Sudan. The highest prevalence [66.7%] of HCV infection in Sudan was noted in patients with end-stage renal disease on regular hemodialysis.2,15 Early diagnosis and treatment of HCV infection minimize risks of both long-term complications and transmission of infection. HCV infection is usually diagnosed by the detection of anti-HCV antibodies in a patient’s serum that react to recombinant HCV proteins in ELISA or chemiluminescence immunoassays.16,17 However, various biochemical and molecular markers are now available that can be used in screening for hepatitis C infection, for both diagnosis and monitoring chronic HCV infection. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are routinely employed for the initial assessment and monitoring of hepatic disease.7,16–20
Annals of Medicine & Surgery, 2017
Subtotal laparoscopic cholecystectomy (SLC) is the safest procedure of choice for difficult cases... more Subtotal laparoscopic cholecystectomy (SLC) is the safest procedure of choice for difficult cases of the elderly and prolonged symptoms. Postoperative retained stones were statistically significant in subtotal laparoscopic cholecystectomy. The conversion rate of 5.5% was recorded. Subtotal laparoscopic cholecystectomy is feasible and safe for patients with obscure Calot's especially those with acute cholecystitis in meager resource settings.
Annals of Tropical Medicine & Parasitology, 1996
The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Su... more The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Sudan was compared with that caused by L. major zymodeme LON 4 in Saudi Arabia and with that already described for L. tropica infections in Iran and for localized CL in the New World. The lesions were classified according to Ridley&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s five histological types. Most of the lesions in the Sudan and Saudi Arabia were of types B and C, characterized, respectively, by diffuse macrophage necrosis and focalized necrosis. B was the most common type in Nicaragua and Guyana whereas responses of types A (in which there are heavily parasitized macrophages without necrosis) and D (reactive tuberculoid) were the most frequent in Iran. The type-E response, which is similar to D but with virtual absence of plasma cells, was uncommon in all areas. The type-D reaction is a chronic relapsing disease when associated with L. tropica but not when associated with L. major. The major differences in the pathology of CL in different geographical areas most probably relate to differences in the Leishmania species involved. Minor differences, however, not only occur between patients from the same area but may also occur, with time, in the same patient. Detailed comparison between areas is therefore difficult; lesions on one patient may heal asynchronously and show different histological types at any point in time and rebiopsy from the same lesion during healing reveals changes from one histological type to another.
Advances in Clinical Chemistry and Laboratory Medicine
African Journal of Primary Health Care & Family Medicine, 2013
Background: Tuberculosis is a major health problem in developing countries. The distinction betwe... more Background: Tuberculosis is a major health problem in developing countries. The distinction between tuberculous lymphadenitis, non-specific lymphadenitis and malignant lymph node enlargement has to be made at primary health care levels using easy, simple and cheap methods.Objective: To develop a reliable clinical algorithm for primary care settings to triage cases ofnon-specific, tuberculous and malignant lymphadenopathies.Methods: Calculation of the odd ratios (OR) of the chosen predictor variables was carried out using logistic regression. The numerical score values of the predictor variables were weighed against their respective OR. The performance of the score was evaluated by the ROC (ReceiverOperator Characteristic) curve.Results: Four predictor variables; Mantoux reading, erythrocytes sedimentation rate (ESR),nocturnal fever and discharging sinuses correlated significantly with TB diagnosis and were included in the reduced model to establish score A. For score B, the reduced ...
Journal of the Neurological Sciences, 2013
Clinical Infectious Diseases
Background This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninfer... more Background This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. Methods An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. Results Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], −6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91....
Emerging Infectious Diseases, Mar 1, 2020
T uberculosis (TB) remains a major global health problem; 10 million new cases were reported in 2... more T uberculosis (TB) remains a major global health problem; 10 million new cases were reported in 2018 (1). In Sudan, the estimated national TB incidence in 2018 was 71/100,000 persons; a total of 20,638 cases were reported (1). However, the TB burden is by no means homogeneous across the country. For instance, in eastern Sudan, TB notifications reached 275/100,000 persons in 2012 (2,3). Prevalence of multidrug-resistant TB (MDR TB) (i.e., resistant to isoniazid and rifampin) was estimated at 2.9% in new and 13% in retreatment cases; however, studies have reported MDR TB rates of 6%-22% (1,4-10). Ongoing transmission is one of the key challenges for TB control programs, especially in countries with a high TB burden (1,11). In recent years, molecular techniques have been increasingly used to clarify and trace transmission of Mycobacterium tuberculosis complex (MTBC) strains and to direct and guide targeted TB control actions (12,13). However, availability of molecular techniques is limited in many countries in Africa with a high TB burden (11). In Sudan, drug-resistant TB often goes undetected, resulting in inadequate treatment, illness, death, and ongoing transmission (1,14). Local laboratories have limited access to mycobacterial culture and drug susceptibility testing (DST) or DNA-based techniques (14). Therefore, MDR TB rates might be underestimated in eastern Sudan. In addition, mutations that mediate drug resistance have not been investigated. Taken together, these factors indicate that, although TB is a huge health problem in eastern Sudan, precise data on the phylogeny and transmission dynamics of MTBC strains, as well as on resistance patterns, is sparsely available (2,3,7,8,15). Studies using molecular epidemiologic tools are rare and have used classical genotyping techniques, such as
Journal of tuberculosis research, 2016
Drug susceptibility testing (DST) plays a pivotal role in TB patients' management leading to the ... more Drug susceptibility testing (DST) plays a pivotal role in TB patients' management leading to the selection of most effective drugs. This study aimed to determine resistance patterns to first line anti-TB drugs in Mycobacterium tuberculosis isolates from retreated patients from Sudan. A total of 239 sputum specimens were collected from smear positive re-treatment TB patients during the period from July 2009 to July 2010. Specimens were pre-treated according to Petroff method. The recovered isolates were tested for sensitivity to first line anti-TB drugs by the 1% proportion method. One hundred and forty three (143/239, 59.8%) mycobacterial isolates were successfully recovered. The majority (98.6%, 141/143) of the isolates were Mycobacterium tuberculosis complex strains. Two strains (2/143, 1.4%) were identified as RIF/INH-resistant MOTT, while fifty four isolates (38.3%, 54/141) were MDR. Multidrug resistant Mycobacterium tuberculosis complex (MDR-TB) among re-treatment patients from national referral centers for tuberculosis diagnosis and management was considerably high in the study isolates.
The Open Microbiology Journal, Dec 18, 2020
Ovarian cancer is the leading cause of mortality from female reproductive cancer. No definite sym... more Ovarian cancer is the leading cause of mortality from female reproductive cancer. No definite symptoms related with early-stage disease and no effective screening methods make its early detection difficult, which results in about two-third patients with advanced-stage ovarian cancer at the diagnosis. In this study, the overall mean age of patients was 46.5 ± 27.5 years. The vast majority of women [90.0%] in this cohort were with the age groups 30–70 years. Ovarian cancer is not common (p = 0.5) below 30 years (frequency = 4.5%) and above 70 years (frequency = 1.7%), the common age group is above 60 years. More than forty percent (50/112, 44.6%) of the patients had symptoms of abdominal discomfort, pelvic pain and irregular bleeding during the last 6 months. A third (38/112, 33.9%) had symptoms for more than a year, while 5.4% (6/112) and 14.3% (16/112) had symptoms for two and three years respectively. The majority of patients (80%, 89/112) were childless. A third (44/112, 39.3%) we...
Revue d’élevage et de médecine vétérinaire des pays tropicaux, 2018
Tuberculosis (TB) is a chronic bacterial disease of humans and animals. It is characterized by th... more Tuberculosis (TB) is a chronic bacterial disease of humans and animals. It is characterized by the progressive development of specific granulomatous lesions in affected organs. Human TB is endemic in Eastern Sudan. However, knowledge on the epidemiology of TB in ruminants is scarce. In a six-month study from June to November 2014, a total of 2304 carcasses of cattle, sheep, goats and camels slaughtered at the East and West Gaash slaughterhouses of Kassala were inspected to investigate TB prevalence. Only 0.1% (n = 2) of the carcasses had suspicious TB lesions. These lesions were solely found in carcasses of sheep, in the liver, lungs, and peritoneal cavity. The samples collected from the lesions were investigated for the presence of mycobacteria, which were found in one of the two carcasses. The grown bacteria were subjected to a line probe assay (GenoType Mycobacterium CM), and to 16S rDNA and ITS gene sequencing, and whole genome sequencing (WGS). However, none of these methods id...
Melittin protein is the main component of Bee venom (BV) that contains twenty-six amino acids. It... more Melittin protein is the main component of Bee venom (BV) that contains twenty-six amino acids. It constitutes 40% to 50% of dry bee venom by weight and is used in traditional medicine to inhibit infection and reduce inflammation. This study aimed to determine the toxic effects of melittin in CD-1 Swiss albino mice. The study also aimed to determine the lowest safe melittin dose to be used as a potential vaccine adjuvant. One hundred and sixty mice were injected intra-dermally with increasing doses of melittin [9000, 4500, 2250, 900, 450, 250, 100, 50 and 30 μg/dose]. The mice were followed for toxicity with respect to body temperature, body movement, weight, function/ anatomical structure of vital organs [brain, liver, bone marrow, kidneys]. Injected mice with high doses [9000, 4500, 2250 μg/dose] died with hypothermia, ataxia and loss of weight. Thirty μg /dose of melittin was found to be the lowest safe dose with minimum side effects and no abnormalities in histological sections o...
Clinical Pharmacokinetics, 2021
Introduction Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been ... more Introduction Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been shown to be effective for Indian patients, while a similar regimen resulted in lower efficacy in Eastern Africa, which could be related to differences in paromomycin pharmacokinetics. Methods Pharmacokinetic data were available from two randomized controlled trials in VL patients from Eastern Africa and India. African patients received intramuscular paromomycin monotherapy (20 mg/kg for 21 days) or combination therapy (15 mg/kg for 17 days) with sodium stibogluconate. Indian patients received paromomycin monotherapy (15 mg/kg for 21 days). A population pharmacokinetic model was developed for paromomycin in Eastern African and Indian VL patients. Results Seventy-four African patients (388 observations) and 528 Indian patients (1321 observations) were included in this pharmacokinetic analysis. A one-compartment model with first-order kinetics of absorption and elimination best described paromomycin in plasma. Bioavailability (relative standard error) was 1.17 (5.18%) times higher in Kenyan and Sudanese patients, and 2.46 (24.5%) times higher in Ethiopian patients, compared with Indian patients. Ethiopian patients had an approximately fourfold slower absorption rate constant of 0.446 h-1 (18.2%). Area under the plasma concentration-time curve for 24 h at steady-state (AUC τ,SS) for 15 mg/kg/day (median [interquartile range]) was higher in Kenya and Sudan (172.7 µg•h/mL [145.9-214.3]) and Ethiopia (230.1 µg•h/mL [146.3-591.2]) compared with India (97.26 µg•h/mL [80.83-123.4]). Conclusion The developed model provides detailed insight into the pharmacokinetic differences among Eastern African countries and India, however the resulting differences in paromomycin exposure do not seem to explain the geographical differences in paromomycin efficacy in the treatment of VL patients.
Annals of Systems Biology, 2021
In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment o... more In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment of leishmaniasis and in vaccine and drug development studies. There is no information about the effects of urine within culture on the infectivity of Leishmania parasites. In this study we used two culture media with different overlays to enhance the in vitro growth rates of Leishmania donovani. In this study we used two culture media with different overlays to enhance the in vitro growth rates of Leishmania donovani. Addition of female human urine to these media enhanced the growth of the promastigotes by at least 40 times when compared to the classical Novy-MacNeal-Nicole medium (NNN). Analysis of the effect of urine have showed that proliferation indexes were signifi cantly increased in culture medium supplemented with human urine to 12.84×10 6 parasite / ml in day 12. On the other hand, when 5% fresh human urine was overlaid, the promastigotes' count was increased to 32.8×10 6 parasite / ml on day 4 and further increase to 58.5 x 10 6 parasite / ml on day 8 was signifi cantly (p=0.002) noted) to 137.8×10 6 parasite / ml on day 12. In conclusion, human urine in parasite cultures differentially affected the infectivity and proliferation of L.donovani species promastigotes. Further identifi cation of components found in urine that play a role in infectivity of parasites may be important for understanding transmission mechanisms of parasites into infective stages.
Clinical Infectious Diseases, 2021
Background To expedite the development of new oral treatment regimens for visceral leishmaniasis ... more Background To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months. Results The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a c...
Clinical Diagnostic Laboratory Immunology, 1998
The rK39 enzyme-linked immunosorbent assay (ELISA) was compared with the direct agglutination tes... more The rK39 enzyme-linked immunosorbent assay (ELISA) was compared with the direct agglutination test (DAT) for Leishmania donovani infection in the Sudan. rK39 ELISA proved more sensitive than DAT in diagnosis of kala-azar (93 and 80%, respectively); both tests may remain positive up to 24 months after treatment. For patients with post-kala-azar dermal leishmaniasis and individuals with subclinical infection, rK39 ELISA performed as well as DAT but could detect infection 6 months earlier in ∼40% of patients. Conversion in DAT and rK39 ELISA also occurred in leishmanin skin test (LST)-positive individuals, suggesting active parasite replication (rK39 is an amastigote antigen) in these presumably immune individuals. In contrast to DAT, rK39 ELISA also detected infection in randomly selected LST-positive individuals (in four of six) and endemicity (LST-negative) controls (in one of five). rK39 ELISA appears more sensitive than DAT and may prove an important tool in epidemiological studies.
Journal of Clinical Microbiology, 1998
Microscopy and PCR were compared for use in the diagnosis of post-kala-azar dermal leishmaniasis ... more Microscopy and PCR were compared for use in the diagnosis of post-kala-azar dermal leishmaniasis (PKDL) in 63 patients. Aspirates of lymph nodes (samples from 52 patients), skin (23 samples), and bone marrow (18 samples) were used. For 11 patients lymph node aspiration could be repeated 6 months after they recovered from PKDL. During active PKDL, PCR was positive for 42 of 52 (80.8%) lymph node aspirates and 19 of 23 (82.7%) skin aspirates, whereas microscopy was positive for only 9 of 52 (17.3%) lymph node aspirates and 7 of 23 (30.4%) skin aspirates. PCR was always positive when parasites were seen by microscopy. When the results obtained with lymph node and skin aspirates from the same patient ( n = 16) were compared, there was complete agreement. Bone marrow samples were negative by microscopy and PCR for 16 patients and positive by both methods for 1 patient; for one sample only the PCR was positive. PCR confirmed the co-occurrence of visceral leishmaniasis and PKDL in one pati...
Universal Journal of Public Health, 2019
Journal of Human Virology & Retrovirology, 2018
Hepatitis C virus infection is a global public health problem and a leading cause of acute and ch... more Hepatitis C virus infection is a global public health problem and a leading cause of acute and chronic liver disease. HCV is a small, single-stranded RNA virus of the Flaviviridae family that can infect hepatocytes, lymphocytes and monocytes. It is classified into eleven genotypes and 67 subtypes on genetic differences. Hepatitis C infections can be concentrated in certain populations and/or in general populations.1–4 HCV is transmitted through needle sharing, contaminated surgical equipment, blood transfusion, sexual contact and from infected mothers to babies. Variable low to high prevalence (1.3%-55%) of HCV in patients with hepatocellular carcinoma or chronic liver disease have been reported form different African countries.5–7 The global prevalence of anti-HCV has been estimated at 2.0% (1.7–2.3%) among adults and 1.6% (1.3–2.1%) for all ages with an estimated 115 million people infected mainly adults. HCV infection is not preventable by vaccination, so improved surveillance and access to screening and treatment at national and regional levels are strongly recommended.8–14 Sudan is the largest country in the Nile valley with a land mass about the size of Europe with HCV infection prevalence among asymptomatic male Sudanese blood donors of 1.5%-4.4%. This is definitely an under-estimate since females do not usually donate blood in Sudan. The highest prevalence [66.7%] of HCV infection in Sudan was noted in patients with end-stage renal disease on regular hemodialysis.2,15 Early diagnosis and treatment of HCV infection minimize risks of both long-term complications and transmission of infection. HCV infection is usually diagnosed by the detection of anti-HCV antibodies in a patient’s serum that react to recombinant HCV proteins in ELISA or chemiluminescence immunoassays.16,17 However, various biochemical and molecular markers are now available that can be used in screening for hepatitis C infection, for both diagnosis and monitoring chronic HCV infection. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are routinely employed for the initial assessment and monitoring of hepatic disease.7,16–20
Annals of Medicine & Surgery, 2017
Subtotal laparoscopic cholecystectomy (SLC) is the safest procedure of choice for difficult cases... more Subtotal laparoscopic cholecystectomy (SLC) is the safest procedure of choice for difficult cases of the elderly and prolonged symptoms. Postoperative retained stones were statistically significant in subtotal laparoscopic cholecystectomy. The conversion rate of 5.5% was recorded. Subtotal laparoscopic cholecystectomy is feasible and safe for patients with obscure Calot's especially those with acute cholecystitis in meager resource settings.
Annals of Tropical Medicine & Parasitology, 1996
The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Su... more The pathology of cutaneous leishmaniasis (CL) caused by Leishmania major zymodeme LON 1 in the Sudan was compared with that caused by L. major zymodeme LON 4 in Saudi Arabia and with that already described for L. tropica infections in Iran and for localized CL in the New World. The lesions were classified according to Ridley&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s five histological types. Most of the lesions in the Sudan and Saudi Arabia were of types B and C, characterized, respectively, by diffuse macrophage necrosis and focalized necrosis. B was the most common type in Nicaragua and Guyana whereas responses of types A (in which there are heavily parasitized macrophages without necrosis) and D (reactive tuberculoid) were the most frequent in Iran. The type-E response, which is similar to D but with virtual absence of plasma cells, was uncommon in all areas. The type-D reaction is a chronic relapsing disease when associated with L. tropica but not when associated with L. major. The major differences in the pathology of CL in different geographical areas most probably relate to differences in the Leishmania species involved. Minor differences, however, not only occur between patients from the same area but may also occur, with time, in the same patient. Detailed comparison between areas is therefore difficult; lesions on one patient may heal asynchronously and show different histological types at any point in time and rebiopsy from the same lesion during healing reveals changes from one histological type to another.
Advances in Clinical Chemistry and Laboratory Medicine
African Journal of Primary Health Care & Family Medicine, 2013
Background: Tuberculosis is a major health problem in developing countries. The distinction betwe... more Background: Tuberculosis is a major health problem in developing countries. The distinction between tuberculous lymphadenitis, non-specific lymphadenitis and malignant lymph node enlargement has to be made at primary health care levels using easy, simple and cheap methods.Objective: To develop a reliable clinical algorithm for primary care settings to triage cases ofnon-specific, tuberculous and malignant lymphadenopathies.Methods: Calculation of the odd ratios (OR) of the chosen predictor variables was carried out using logistic regression. The numerical score values of the predictor variables were weighed against their respective OR. The performance of the score was evaluated by the ROC (ReceiverOperator Characteristic) curve.Results: Four predictor variables; Mantoux reading, erythrocytes sedimentation rate (ESR),nocturnal fever and discharging sinuses correlated significantly with TB diagnosis and were included in the reduced model to establish score A. For score B, the reduced ...
Journal of the Neurological Sciences, 2013
Clinical Infectious Diseases
Background This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninfer... more Background This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. Methods An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. Results Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], −6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91....