Musa M. Kheir

Immunocompetence may be important in the effectiveness of Mectizan® (ivermectin) in the treatment of human onchocerciasis

Mectizan (Ivermectin) has been proved to be central to the control of onchoceriasis through self-sustainable community-based treatment. The possibility of parasitological unresponsiveness to this treatment or selection for drug resistance has emerged recently in many occasions. The reason for the reduced ability of Mectizan to maintain low levels of dermal microfilariae and early recurrent pruritus can only be speculated upon. Here, we report our own findings to address this particular issue.

Epidemiology of visceral leishmaniasis in Atbara River area, eastern Sudan: the outbreak of Barbar El Fugara village (1996-1997).

An outbreak of visceral leishmaniasis (VL) started in 1995 in the Atbara River area in eastern Sudan. This article reports on this outbreak and on the clinical and immunological studies that were carried out in a village, with the highest incidence of VL cases, from 1996 to 1997. A significant increase in VL incidence was recorded in a dozen villages in this area; one village, Barbar El Fugara accounted for half of the total number of cases recorded at the regional hospital. A total of 152 VL and 61 post kala-azar dermal lesion (PKDL) cases were diagnosed and treated in Barbar. Household (n = 671) and school (n = 276) surveys were performed using the leishmanin skin test (LST) and the direct agglutination test (DAT). LST positivity was 23.1 and 15.7%, whereas DAT positivity was 8.9 and 26.4% in both surveys, respectively. No gender differences were observed in either test. Unlike DAT, LST positivity was predominant in the higher age groups that also exhibited lower prevalence of VL. Few individuals were positive by both tests (1.3%, 5.2%) while the majority (68.8%, 64.8%) had no evidence of acquired immune response, suggesting either a role of innate immunity in preventing parasite establishment or, unexpectedly, lack of exposure to Leishmania. Subclinical parasitism was also demonstrated, as evidence of both acquired humoral and cellular immune responses was observed in individuals with no past history of the disease. The wide spectrum of L. donovani/human interactions may be explained by differential exposure to environmental risk factors, parasite strain polymorphisms or host genetic makeup.

A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease

PARK2 and PINK1 gene mutations are involved in recessive early onset Parkinson’s disease (EOPD). In order to determine the causative mutations in three affected sibs from a consanguineous Sudanese family with EOPD, multiplex ligation-dependent probe amplification was performed and revealed that the patients were homozygous for a deletion of PINK1 exons 4 to 8. Breakpoint analysis revealed a complex rearrangement combining a large deletion and the insertion of a sequence duplicated from the DDOST gene intron 2, located near the PINK1 gene. As breakpoint sequences displayed only three base pairs of homology, this rearrangement may result from Fork Stalling and Template Switching mechanism. This third large rearrangement of PINK1 enlarges the mutation spectrum and, together with recent published data in Tunisian patients with EOPD, points out that PINK1 gene analysis, including search for large rearrangement, should be considered in early onset recessive PD patients, particularly those from Arab origin.

Antileishmanial antibodies in an outbreak of visceral leishmaniasis in eastern Sudan: high antibody responses occur in resistant subjects and are not predictive of disease

A 3-year longitudinal survey was carried out from 1998 to 2000 in a village in eastern Sudan where a visceral leishmaniasis (VL) outbreak occurred. Leishmania-specific antibodies were analysed by enzyme-linked immunosorbent assay and immunoblotting. Immunoblot analysis detected antibodies to Leishmania in 80% of the healthy subjects and half of them harboured high immunoglobulin (Ig) G antibody levels, similar to those of VL patients. These antibodies belonged to the IgG1 and IgG3 subclasses but neither their respective levels nor the immunoblot recognition patterns were predictive of VL. During this epidemic, a large proportion of subjects had a high antileishmanial antibody response, indicating that they were infected by Leishmania though most of them remained healthy during the whole study period. These results obtained in the context of an outbreak contrast with those obtained from studies performed in endemic areas characterized by lower parasite transmission levels. Furthermore, the clinical and serological follow-up of our study subjects showed that VL occurred mainly in subjects who had been serologically positive for 5-24 months rather than resulting from primo infection by the parasite.

Cortisol and uncomplicated Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan.

OBJECTIVE To investigate the levels of serum cortisol in patients with uncomplicated Plasmodium falciparum (P. falciparum) malaria in an area of unstable malaria transmission in eastern Sudan. METHODS The concentrations of cortisol were measured in sera of 25 patients with uncomplicated P. falciparum malaria (at presentation, 24 h and 7 d later) and 25 healthy volunteers using radioimmunoassay gamma counter. RESULTS There was no significant difference in mean (SD) of total cortisol levels in patients with malaria in comparison with the control group; 602.2 (369.6) vs. 449.2(311.7) ng/mL, P=0.12. In patients with uncomplicated P. falciparum malaria, the mean (SD) presenting cortisol levels were significantly higher in comparison to the levels on day 7; 602.2 (369.6) vs. 373.6(139.1) ng/mL, P=0.009. In the patients with uncomplicated P. falciparum malaria (on presentation) cortisol levels were not correlated with initial temperature or the presenting parasitaemia. CONCLUSIONS Thus, cortisol levels were not significantly different between the patients and the controls.

First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients.

Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug.

Exome sequencing identifies two variants of the alkylglycerol monooxygenase gene (AGMO) as a cause of relapses in visceral leishmaniasis in children, in Sudan.

Background Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly, and lymphadenopathy. During an outbreak of KA in Babar El Fugara (Sudan), 5.7% of cured patients displayed relapses, with familial clustering in half the cases. Methods We performed whole-exome sequencing on 10 relapsing individuals and 11 controls from 5 nuclear families. Results Rare homozygous and compound-heterozygous nonsense (c.1213C > T, rs139309795, p.Arg405*) and missense (c.701A > G, rs143439626, p.Lys234Arg) mutations of the alkylglycerol monooxygenase (AGMO) gene were associated with KA relapse in 3 families. Sequencing in additional family members confirmed the segregation of these mutations with relapse and revealed an autosomal dominant mode of transmission. These mutations were detected heterozygous in 2 subjects among 100 unrelated individuals with KA who never relapsed after cure, suggesting incomplete penetrance of AGMO deficiency. AGMO is expressed in hematopoietic cells, and is strongly expressed in the liver. AGMO modulates PAF production by mouse macrophages, suggesting that it may act through the PAF/PAF receptor pathway previously shown to have anti-Leishmania activity. Conclusions This is the first demonstration that relapses after a first episode of KA are due to differences in human genetic susceptibility and not to modifications of parasite pathogenicity.

First report on Leishmania major/HIV coinfection in a Sudanese patient

This case report emerged from a large study on biotechnological typing of leishmania parasites in Sudan. Thetyp -ing study was approved by the National Ethical Committeeof the Federal Min-istry of Health, Sudan. The approved protocol included obtaining consent of the participants for sample collection and HIV testing for unusual and severe clinical presentations to assist effective treatment and control. Thepatient in this case report gave writtenconsent for HIV testing and enrolment in the typing study. Based on the severity of the presenting lesions he was suspected of HIV coinfection and was referred to the national HIV control programme for pre-counselling and HIV testing. Following the diagnosis of