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Biomedical subjects

A M el-Hassan

Publications and source records attributed to A M el-Hassan.

At least 19 recordsLinked to original sources
PubMed2003

Post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.

Africa, Eastern↗
PubMed2002

Socio-cultural aspects of leprosy among the Masalit and Hawsa tribes in the Sudan.

Social and cultural factors influencing knowledge, attitudes and practices (KAP) towards leprosy in two communities in eastern Sudan were studied to determine their effects on treatment seeking and compliance. The study was qualitative using focus small group discussions, personal interviews and direct observation. The target populations were Masalit and Hawsa, the two main tribes in the area. Knowledge about the pathological cause of leprosy was lacking but the clinical manifestations were well recognized, particularly among the Masalit, in whom the disease in more common than the Hawsa. Among the Masalit there was a widely held belief that leprosy was caused by eating meat of the wild pig and a certain type of fish. The Hawsa, who are more devout Muslims, do not eat pig and associate leprosy with consumption of two types of fish. Between both tribes, the stigma of leprosy was not strong and the degree of rejection was more towards those with severe disease, particularly patients with ulcerated lesions and severe deformities. Patients were cared for by the family and lived in a separate hut within the families' housing compounds. In this remote area where medical services are scarce or nonexistent, those interviewed did not realize that leprosy was treatable by modern medicine. This influenced the treatment-seeking behaviour of patients, who were often treated by spiritual healers and other traditional medicine practices. With the introduction of multidrug therapy and health education of patients and society, many more patients are now seeking medical treatment, indicating a change in health seeking behaviour.

Attitude to Health↗
PubMed2001

Leishmaniasis in Sudan. Cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) in Sudan is caused by Leishmania major, zymodeme LON-1. The disease is endemic in many parts of the country. The vector is Phlebotomus papatasi and the animal reservoir is probably the Nile rat Arvicanthis niloticus. Clinically, patients usually present with papules, nodules, or nodulo-ulcerative lesions, mainly on the exposed parts of the skin. In 20% of cases the parasite disseminates through the lymphatics, producing sporotrichoid-like lesions. The pathology of the lesion is described. Langerhans cells are the main antigen-presenting cells in CL. They pickup antigen from the dermis and migrate to regional lymph nodes where they present it to T cells. Antigen-specific activated T cells home to the dermis where they stimulate macrophages to eliminate the parasite. Peripheral blood mononuclear cells (PBMC) proliferate in response to Leishmania antigen in vitro and produce cytokines. PBMC of patients with mild and severe disease produce Th1- and Th2-like cytokine patterns, respectively. The criteria for the clinical diagnosis of CL are described. The diagnosis is confirmed by the demonstration of parasites in slit smears in 50-70% of cases and in histological sections in 70%. With primers specific for L. major, the polymerase chain reaction is positive in 86% of cases. Since CL is a self-limiting disease, treatment is confined to patients with severe disease.

Animals↗
PubMed2001

Leishmaniasis in Sudan. Mucosal leishmaniasis.

Sudanese mucosal leishmaniasis is a chronic infection of the upper respiratory tract and/or oral mucosa caused mainly by Leishmania donovani. The disease occurs in areas of the country endemic for visceral leishmaniasis, particularly among Masalit and other closely related tribes in western Sudan. The condition may develop during or after an attack of visceral leishmaniasis, but in most cases it is a primary mucosal disease. Unlike South American mucocutaneous leishmaniasis, mucosal leishmaniasis in Sudan is not preceded or accompanied by a cutaneous lesion. Pathologically, the lesions show a mixture of macrophages, plasma cells and lymphocytes. An epithelioid granuloma may also be found. Parasites are scanty. Diagnosis is established by demonstration of parasites in smears or biopsies, by culture or animal inoculation, or with the aid of the polymerase chain reaction. Most patients give positive results in the direct agglutination test and leishmanin skin test. Patients respond well to treatment with pentavalent antimony compounds.

Antiprotozoal Agents↗
PubMed2001

Leishmaniasis in Sudan. Visceral leishmaniasis.

From the early 1900s, visceral leishmaniasis (VL; kala-azar) has been among the most important health problems in Sudan, particularly in the main endemic area in the eastern and central regions. Several major epidemics have occurred, the most recent--in Western Upper Nile province in southern Sudan, detected in 1988--claiming over 100,000 lives. The disease spread to other areas that were previously not known to be endemic for VL. A major upsurge in the number of cases was noted in the endemic area. These events triggered renewed interest in the disease. Epidemiological and entomological studies confirmed Phlebotomus orientalis as the vector in several parts of the country, typically associated with Acacia seyal and Balanites aegyptiaca vegetation. Infection rates with Leishmania were high, but subject to seasonal variation, as were the numbers of sand flies. Parasites isolated from humans and sand flies belonged to three zymodemes (MON-18, MON-30 and MON-82), which all belong to the L. donovani sensu lato cluster. Transmission dynamics have not been elucidated fully; heavy transmission in relatively scarcely populated areas such as Dinder national park suggested zoonotic transmission whereas the large numbers of patients with post kala-azar dermal leishmaniasis (PKDL) in heavily affected villages may indicate a human reservoir and anthroponotic transmission. Clinical presentation in adults and in children did not differ significantly, except that children were more anaemic. Fever, weight loss, hepato-splenomegaly and lymphadenopathy were the most common findings. PKDL was much more common than expected (56% of patients with VL developed PKDL), but other post-VL manifestations were also found affecting the eyes (uveitis, conjunctivitis, blepharitis), nasal and/or oral mucosa. Evaluation of diagnostic methods showed that parasitological diagnosis should still be the mainstay in diagnosis, with sensitivities for lymph node, bone marrow and spleen aspirates of 58%, 70% and 96%, respectively. Simple, cheap serological tests are needed. The direct agglutination test (DAT) had a sensitivity of 72%, specificity of 94%, positive predictive value of 78% and negative predictive value of 92%. As with other serological tests, the DAT cannot distinguish between active disease, subclinical infection or past infection. The introduction of freeze-dried antigen and control sera greatly improved the practicality and accuracy of the DAT in the field. An enzyme-linked immunosorbent assay using recombinant K39 antigen had higher sensitivity than DAT (93%). The polymerase chain reaction using peripheral blood gave a sensitivity of 70-93% and was more sensitive than microscopy of lymph node or bone marrow aspirates in patients with suspected VL. The leishmanin skin test (LST) was typically negative during active VL and converted to positive in c. 80% of patients 6 months after treatment. Immunological studies showed that both Th1 and Th2 cell responses could be demonstrated in lymph nodes from VL patients as evidenced by the presence of messenger ribonucleic acid for interleukin (IL)-10, interferon gamma and IL-2. Treatment of peripheral blood mononuclear cells from VL patients with IL-12 was found to drive the immune response toward a Th1 type response with the production of interferon gamma, indicating a potential therapeutic role for IL-12. VL responded well to treatment with sodium stibogluconate, which is still the first line drug at a dose of 20 mg/kg intravenously or intramuscularly per day for 15-30 d. Side effects and resistance were rare. Liposomal amphotericin B was effective, with few side effects. Control measures have not been implemented. Based on observations that VL does not occur in individuals who have a positive LST, probably because of previous cutaneous leishmaniasis, a vaccine containing heat-killed L. major promastigotes is currently undergoing a phase III trial.

Adolescent↗
PubMed2001

Leishmaniasis in Sudan. Post kala-azar dermal leishmaniasis.

Post kala-azar dermal leishmaniasis (PKDL) is increasingly recognized in Sudan as a complication of visceral leishmaniasis (VL), occurring in c. 55% of patients after, or during treatment of, VL. The development of PKDL seems to be restricted to parasites of the Leishmania donovani sensu stricto cluster; no particular zymodeme has been found to be associated with it. In contrast to PKDL in India, PKDL in Sudan occurs within 0-6 months after treatment for VL. The rash may be macular, maculo-papular or nodular, and spreads from the perioral area to other parts of the body, depending on grade of severity. Young children are particularly at risk of developing more severe disease. In 16% of PKDL patients, parasites can be demonstrated by microscopy in lymph node or bone marrow aspirates and, with the aid of the polymerase chain reaction (PCR), in lymph nodes of 81% of patients, possibly indicating persistent visceralized infection. Diagnosis can be made by demonstration of parasites in skin smears or biopsies in 20-30% of cases; newer techniques, using PCR with skin smears, have higher sensitivity (83%). Monoclonal antibodies against L. donovani can detect parasites in 88% of biopsies. Serological tests are of limited value. The leishmanin skin test is positive in 50-60% of cases; there is an inverse relationship between the skin test result and severity of PKDL. In differential diagnosis, miliaria rubra is the most common problem; differentiation from leprosy is the most difficult. In biopsies, hyperkeratosis, parakeratosis, acanthosis, follicular plugging and liquefaction degeneration of the basal layer may be found in the epidermis; in the dermis there are varying intensities of inflammation with scanty parasites and mainly lymphocytes; macrophages and epithelioid cells may also be found. In 20% of cases discrete granulomas may be found. After VL, the immune response shifts from a Th2-type to a mixed Th1/Th2-type. High levels of interleukin-10 in skin biopsies as well as in peripheral blood mononuclear cells and plasma in patients with VL predict the development of PKDL. Treatment is needed only for those who have severe and prolonged disease; sodium stibogluconate (20 mg/kg/d for 2 months) is usually sufficient. (Liposomal) amphotericin B is effective, whereas ketoconazole, terbinafine and itraconazole are not.

Age Distribution↗
PubMed1997

Use of PCR on lymph-node sample as test of cure of visceral leishmaniasis.

When the polymerase chain reaction (PCR) was used to test lymph-node aspirates from 35 patients from eastern Sudan, who had had visceral leishmaniasis but were believed cured, leishmanial DNA was detected in samples from 14 of the patients. There were no significant differences between the PCR-positives and -negatives in terms of age, sex, spleen size, malaria status or presence of anti-Leishmania antibodies. However, PCR was more often positive in the patients who tested negative by the leishmanin skin test (LST) than in those who gave positive skin tests. Moreover, patients with a positive PCR and a negative LST converted more often to LST positivity than those with a negative PCR and a negative LST. The most important finding was that, during follow-up, eight (57%) of the PCR-positives, but none of the 21 negatives, developed post-kala-azar dermal leishmaniasis (PKDL) In conclusion, PCR-based testing of lymph-node aspirates after treatment may be used as a prognostic marker for the future development of PKDL and may be useful in the follow-up of patients.

Agglutination Tests↗
PubMed1995

IL-12 enhances Th1-type responses in human Leishmania donovani infections.

IL-12 is a pluripotent cytokine that interacts with NK and T cells to play a central role in the initiation and maintenance of Th1 responses and IFN-gamma production. Because of the interactive relationship between IL-12 and IFN-gamma response to infectious organisms, a study was undertaken to examine the role of IL-12 in the immune regulation of human visceral leishmaniasis (VL). Human (Hu) VL is associated with immune dysfunction and the appearance of IL-10 mRNA, not present in healed individuals. We found that PBMC from treated VL patients produced both IL-12 p40 and IFN-gamma in response to in vitro stimulation with Leishmania donovani. The production of both IL-12 p40 and IFN-gamma were interdependent and were abrogated by the addition of exogenous Hu rIL-10. In contrast, PBMC from active VL patients did not produce IL-12 p40 or IFN-gamma in response to L. donovani lysate. Neutralizing anti-IL-10 mAb led to the enhancement of IFN-gamma production by active VL PBMC cultured with L. donovani lysate, and this enhanced IFN-gamma production was blocked by anti-IL-12 mAb. The addition of exogenous Hu rIL-12 to PBMC from active VL patients resulted in the augmentation of IFN-gamma in response to L. donovani lysate. Therefore, treatment of active VL patient PBMC with anti-IL-10 or IL-12 shifted the response toward a Th1-type response with the production of IFN-gamma. These results indicate that IL-12 may play an important role in the regulation of the cellular immune responses in Hu VL.

Animals↗
PubMed1995

Endemic kala-azar in eastern Sudan: post-kala-azar dermal leishmaniasis.

In a longitudinal study between 1991 and 1993 in an endemic area in eastern Sudan, 85 cases of kala-azar (visceral leishmaniasis) were diagnosed, of whom 48 (56%) developed post-kala-azar dermal leishmaniasis (PKDL). Another four cases of PKDL had no clinical history of kala-azar. In children, PKDL was more frequent in the very young; seven of nine kala-azar cases (78%) in the group 0-1 years of age and 13 of 16 (81%) in the group 2-3 years of age developed PKDL. On the average, PKDL occurred 56 days (mean; range 0-180) after the end of treatment of kala-azar. To assess the severity of PKDL, a classification was developed using three grades of severity based on differences in density and distribution of lesions. In young children, PKDL was more severe. Incomplete treatment of kala-azar may be important in the pathogenesis of PKDL. Thirty-one patients were followed-up for at least six months; of these, 20 were not treated (17 healed, two improved, and in one, the condition was unchanged), three healed after incomplete treatment with sodium stibogluconate, and eight were cured after treatment but two required two courses. Considerable morbidity was caused by PKDL and should be taken into consideration in the management and follow-up of kala-azar patients. The high incidence of PKDL may have important implications in transmission.

Adolescent↗
PubMed1995

Recent observations on the epidemiology of kala-azar in the eastern and central states of the Sudan.

The main endemic area of kala-azar (visceral leishmaniasis) in the Sudan is in Eastern State and the Blue Nile area of Central State. In order to obtain more recent information about kala-azar in both States, the major hospitals and health centres were visited, the physicians and medical assistants interviewed and available records inspected. In Eastern State a cross-sectional survey of one village was carried out and a longitudinal population-based study of another village started. In this State, after a decline since 1985, a sharp increase in the number of cases was noted from 1991 onwards. This increase was seen in large areas, especially along the Rahad and Dinder Rivers. In contrast, in Central State, there was a decline in the frequency of the disease since the 1960s in the area around Sennar and Singa, which was regarded as a hyperendemic focus up to about 30 years ago. It was hypothesized that this decline may be related to the extensive agricultural development with regular insecticiding and the deforestation of the area. Several aspects with regard to transmission of kala-azar are discussed.

Adolescent↗
PubMed1994

Leishmania resistant to sodium stibogluconate: drug-associated macrophage-dependent killing.

A total of 17 Leishmania isolates, 6 of them isolated from antimony-resistant patients, were collected in the Sudan and tested for their sensitivity to sodium stibogluconate (Pentostam) as promastigotes. Six of those isolates were tested as amastigotes infecting a murine macrophage cell line. The results indicated that the conventional promastigote screening assay did not correlate with the clinical picture, whereas the amastigote/macrophage system produced results that pertained to the in vivo responses to the drug. A laboratory-generated resistant strain of L. major was adapted to grow at a high concentration of Pentostam (1000 micrograms/ml) as promastigotes but was quite sensitive to the drug at much lower concentrations in the amastigote/(macrophage system (20 micrograms/ml), thus suggesting that Pentostam's inhibitory action is mediated through the macrophage rather than through a direct toxic effect exerted on the parasite.

Animals↗
PubMed1994

Endemic kala-azar in eastern Sudan: a longitudinal study on the incidence of clinical and subclinical infection and post-kala-azar dermal leishmaniasis.

Between April 1991 and April 1993, a longitudinal study was performed in the village of Um-Salala (1,430 inhabitants) in the endemic area of kala-azar (visceral leishmaniasis) in eastern Sudan. During the two years, a total of 92 kala-azar cases were diagnosed (male:female ratio = 1.8:1, mean age 6.6 years). The annual incidence rates were 38.4/1,000 and 38.5/1,000 person-years, respectively. The ratio of clinical to subclinical cases was 1.6:1 in the first year and 2.4:1 in the second year. Post-kala-azar dermal leishmaniasis occurred in 48 (56%) of 85 kala-azar cases that were followed-up for at least six months. Kala-azar occurred only in previously leishmanin-negative individuals. The majority of the population had a positive leishmanin skin test result, probably due to previous exposure to Leishmania major causing cutaneous leishmaniasis in their homeland in western Sudan from which they had migrated in the 1980s. It was thus postulated that previous cutaneous leishmaniasis might protect against kala-azar but this could not be proved.

Adolescent↗
PubMed1994

Leishmaniasis of the nose caused by different species of Leishmania in the Sudan. Distinguishing features of the different clinical forms.

The nasal mucosa is affected in mucosal leishmaniasis and the skin of the nose, but not the mucosa, may be involved in cutaneous leishmaniasis (oriental sore) and in post kala-azar dermal leishmaniasis (PKDL). These clinical forms all occur in the Sudan and, particularly when advanced, may be confused with each other since mucosal leishmaniasis may extend to the skin of the upper lip and both cutaneous leishmaniasis and PKDL may spread to the anterior nares although they do not extend into the mucosa. Illustrative examples of the three conditions are described. Distinctive features of each form are given. The importance of making the correct diagnosis is stressed, since the different forms respond differently to anti-leishmanial drugs.

Adult↗
PubMed1993

Interleukin 10 production correlates with pathology in human Leishmania donovani infections.

We have found that an important Th2 cytokine, IL-10, is produced by tissues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. In contrast, both pre- and posttreatment lymph nodes had readily detected mRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on leishmania-induced proliferative responses was demonstrated when Hu rIL-10 was added to cultures of PBMC from clinically cured individuals. PBMC from individuals with acute visceral leishmaniasis responded to stimulation with leishmania lysate by producing IL-10 mRNA. Simultaneously cultured PBMC collected from the same patients after successful chemotherapy produced no detectable IL-10 mRNA after leishmania antigen stimulation. Neutralizing anti-IL-10 mAb added to PBMC from patients with acute visceral leishmaniasis markedly increased the proliferative response to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.

Animals↗
PubMed1993

Prevalence of cutaneous leishmaniasis along the Nile River north of Khartoum (Sudan) in the aftermath of an epidemic in 1985.

Based on a pilot clinical study of the prevalence of cutaneous leishmaniasis (CL) among school children in villages on both banks of the Nile River north of Khartoum, Sudan in the aftermath of a 1985 epidemic, we studied a random sample (303 individuals) from one of these villages to determine the prevalence of infection and exposure to CL. Four percent of the population had active CL lesions, 47% had healed lesions, and another 43% reacted positively to sensitization with leishmanin in the absence of past or active CL lesions. Ninety-one percent of the total population reacted positively to leishmanin. The present status of CL in the area and possible reasons for the emergence of the epidemic are discussed, and gaps in our knowledge about the epidemic are identified.

Adolescent↗
PubMed1992

Clinical aspects of kala-azar in children from the Sudan: a comparison with the disease in adults.

The clinical presentation of kala-azar in 43 children and 45 adults was compared. In both groups fever, left upper quadrant abdominal pain and swelling, and weight loss were equally the most common presenting symptoms. Lymphadenopathy was observed in 86 per cent of children and 76 per cent of adults. Splenomegaly was absent in 2 per cent of children and 7 per cent of adults. No significant difference was found in frequency distribution of symptoms and signs between children and adults. Haematological indices were compared in both children and adults with kala-azar and their control groups. In both children and adults with kala-azar, haemoglobin concentration, total white cell count, and platelet count were significantly lower before than after treatment. Only haemoglobin concentration was lower in children with kala-azar as compared with adults with the disease. Children in the control group had lower haemoglobin and higher total white cell count than adult controls. Response to therapy was evaluated in 693 patients. Two-hundred-and-fifty children and 373 adults were treated with sodium stibogluconate 10 mg/kg for 30 days; in both groups 12 per cent deaths and 4 per cent relapses occurred. Thirty children and 40 adults were treated with sodium stibogluconate 2 x 10 mg/kg for 15 days. In children, 3 per cent deaths and 7 per cent relapses were noted; in adults there were 8 per cent deaths and 5 per cent relapses. No significant difference in death rate or relapse rate was found between children and adults in both regimens. Both regimens performed equally well in children and adults with regard to death rate and relapse rate.

Adolescent↗
PubMed1992

Congenital kala-azar and leishmaniasis in the placenta.

During an epidemic of visceral leishmaniasis in the Sudan, two cases of congenital kala-azar were seen. The first child, whose mother had contracted kala-azar in southern Sudan, was born in Khartoum, where no transmission of leishmaniasis is currently occurring. At seven months, the child had fever, lymphadenopathy, and hepatosplenomegaly; leishmania parasites were detected in the bone marrow. The child died and an autopsy showed leishmania parasites in all tissues including the lungs, kidneys, and thymus. In the second case, parasites were found in the placenta of a five-month-old fetus. These two cases demonstrate the importance of follow-up of infants born to mothers with leishmaniasis.

Adult↗