Outbreak of kala-azar in the Sudan

Beer, P.; Harith, AbdallahEl; Grootheest, ManjaVan; Winkler, Alex

doi:10.1016/0140-6736(90)90313-t

Cited by 45 publications

(18 citation statements)

References 1 publication

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“…Mortality and morbidity due to VL in these tribal groups was comparable only with the high level of mortality among the Nilotic Nuer in the Upper Nile province in southern Sudan. 9 An epidemic of VL in southern Sudan has moved northward into western Sudan with less grave consequences. 10 This difference has been attributed to the difference in nutritional status between the nomadic Bagara of western Sudan and the famine-stricken Nuer tribe.…”

Section: Discussionmentioning

confidence: 99%

Kala-azar in a high transmission focus: an ethnic and geographic dimension.

Ibrahim

Lambson²,

Yousif³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. In 1994-1996, we studied a group of 58 game wardens stationed in an area known to be highly endemic for visceral leishmaniasis (kala-azar) for evidence of infection with Leishmania donovani. Leishmania DNA was detected by the polymerase chain reaction in the peripheral blood of cases of active kala-azar, former patients with visceral leishmaniasis, patients, and asymptomatic subjects. Using the cloned antigen rk39, antibodies were detected in 44.2% of the game wardens while leishmanin skin test result was positive in 77% of our sample. It was shown that certain tribes from northern Sudan were more likely to develop subclinical infections, while those of the Baria tribe from southern Sudan and those of the Nuba tribe from western Sudan were more likely to develop visceral leishmaniasis. Whether this is due to genetic factors or previous exposure to Leishmania parasites remains to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Kala-azar in a high transmission focus: an ethnic and geographic dimension.

Ibrahim

Lambson²,

Yousif³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…The calamity brought kala-azar to the forefront as one of the greatest epidemics of the 20th century. 1,2 Longitudinal studies in Sudan show marked differences in incidence of clinical disease between adjacent villages inhabited by different ethnic groups. 3,4 Furthermore, when members of the different ethnic groups share the same immediate environment and exposure, certain ethnic groups remain at a higher risk of developing VL.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2003

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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 (Z lr scores 2.38 -2.55; 0.008pPp0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5 0 polymorphisms in the promoter (P ¼ 0.0145), exon 3 (P ¼ 0.0037) and intron 4 (P ¼ 0.0049), and haplotypes formed by them (P ¼ 0.0089), but not for 3 0 polymorphisms at exon 15 or the 3 0 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 þ 14G/C polymorphism. Although the two alleles for 469 þ 14G/C lie on haplotypes carrying different alleles for the functional promoter GT n 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 0 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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“…If untreated, the visceral form, principally caused by Leishmania donovani, is usually fatal. In addition, even in treated patients the fatality rate may be as high as 30% because of late or missed diagnoses (11). Due to the lack of vaccines, difficulties in vector control, and the development of parasite resistance to several treatments, leishmaniasis represents a significant clinical and public health problem (16).…”

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confidence: 99%

Topoisomerase I Amino Acid Substitutions, Gly185Arg and Asp325Glu, Confer Camptothecin Resistance in Leishmania donovani

Marquis

Hardy

Olivier

2005

Antimicrob Agents Chemother

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The antitumor compound camptothecin (CPT) is also recognized for its specific activity against Leishmania donovani topoisomerase I (Topo-I). In consequence, defining CPT resistance mechanisms represents an important strategic tool in the acquisition of a better understanding of its mode of action. In the present study, we selected a single highly resistant L. donovani strain termed LdRCPT.160 by stepwise exposure to CPT. Gene sequencing revealed two single nucleotide mutations in the LdRCPT.160 LdTOP1A gene, resulting in two amino acid substitutions (Gly185Arg and Asp325Glu) in the protein. Moreover, these two substitutions observed in the LdTOP1A protein were correlated with a decreased Topo-I DNA relaxation activity in these resistant parasites. Nevertheless, there was no change in the LdTOP1A gene expression level. Interestingly, transfection studies of the LdRCPT.160 LdTOP1A gene in its wild-type counterpart showed that it induced CPT resistance. Sitedirected mutagenesis studies demonstrated that, despite a substantial level of resistance conferred by the Gly185Arg and Asp325Glu substitutions separately, both were essential to reach a high-resistance phenotype. Of interest, the amino acid substitutions observed in LdRCPT.160 LdTOP1A protein occurred near the amino acids previously predicted to interact with CPT, providing new insight into the mechanism of CPT molecular action.

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Outbreak of kala-azar in the Sudan

Cited by 45 publications

References 1 publication

Kala-azar in a high transmission focus: an ethnic and geographic dimension.

Kala-azar in a high transmission focus: an ethnic and geographic dimension.

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

Topoisomerase I Amino Acid Substitutions, Gly185Arg and Asp325Glu, Confer Camptothecin Resistance in Leishmania donovani

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