title: Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe.
abstract: BACKGROUND
  Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort).
  
  
  METHODS
  HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR. We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54A>G), C (codon 57A>G), and D (codon 52T>C) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test.
  
  
  RESULTS
  We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection.
  
  
  CONCLUSIONS
  Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S. haematobium infection.
authors.affiliation: Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Medical Research Council of Zimbabwe, Ministry of Health and Child Welfare, Harare, Zimbabwe; Letten Research Foundation, Harare, Zimbabwe.
authors.forename: Rutendo B L
authors.initials: RB
authors.lastname: Zinyama-Gutsire
authors.affiliation: Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Charles
authors.initials: C
authors.lastname: Chasela
authors.affiliation: Tissue typing Laboratory, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.affiliation: Letten Research Foundation, Harare, Zimbabwe; University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe.
authors.forename: Simbarashe
authors.initials: S
authors.lastname: Rusakaniko
authors.affiliation: Centre for Global Health, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Kallestrup
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
authors.forename: Exnevia
authors.initials: E
authors.lastname: Gomo
authors.affiliation: Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: Tissue typing Laboratory, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Erikstrup
authors.affiliation: Biomedical Research and Training Institute, Harare, Zimbabwe.
authors.forename: Shungu
authors.initials: S
authors.lastname: Munyati
authors.affiliation: Letten Research Foundation, Harare, Zimbabwe; University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe.
authors.forename: Edith N
authors.initials: EN
authors.lastname: Kurewa
authors.affiliation: Division of Women and Children, Rigshospitalet Oslo University Hospital and University of Oslo, Oslo, Norway, and Letten Research Foundation, Harare, Zimbabwe; University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe.
authors.forename: Babill
authors.initials: B
authors.lastname: Stray-Pedersen
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Copenhagen University, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.affiliation: University of Zimbabwe, Biochemistry Department, Harare, Zimbabwe, and Department of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Takafira
authors.initials: T
authors.lastname: Mduluza
mesh_terms: D000293:Adolescent; D000328:Adult; D060085:Coinfection / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012424:Rural Population; D012553:Schistosomiasis haematobia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D012555:Schistosomiasis mansoni / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult; D015030:Zimbabwe / Q000453:epidemiology
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin
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