High IgG1 Malaria Antibodies Level in Children is a Possible Risk Factor of Blackwater Fever: A Case-Control Study

peer reviewedContext: Pathogenesis of acute massive intravascular hemolysis in Blackwater fever is very complex. Mostly, Malaria immunity deficiency in expatriates, Quinine and Plasmodium are incriminated. The possible role of malaria IgG1 antibodies in BWF is not fully elucidated. Objectives: This study aimed to determine the profile of malaria IgG1 for malaria crude antigen in children developing blackwater fever compared to patients with uncomplicated malaria Methods: This case-control study was conducted in 4 medical institutions across Kinshasa. Cases were patients with Blackwater fever (BWF) whereas controls had uncomplicated Plasmodium falciparum malaria (UM). For each case, 2 controls were recruited and were matched for age, sex and the area of residence. Malaria IgG1 were assessed by standard ELISA and absorbance measured in an automated plate reader. Results: The majority of BWF cases (81.4%) were above 5 years old while only 18.6% were aged below 5 (OR: 1.33; 0.53-3.32). The level of malaria IgG antibodies in BWF children were significantly higher compared to uncomplicated malaria (p=0.002). Quinine was used by 95.3% of the BWF cases ([OR: 50.19 (10.75-234.42)] p<0.001) versus in uncomplicated malaria. There was no linear correlation between the age of patients and the logarithm of antibodies. R2 is totally null (p=0.335). Conclusion: Malaria IgG1 antibodies is significantly elevated in children with BWF and could trigger the occurrence of BWF. The absence of correlation with age suggests that BWF could not be age dependent

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.status: publishe

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children.

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF