ABSTRACT
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.
Subject(s)
Blackwater Fever/epidemiology , Blackwater Fever/genetics , Mannose-Binding Lectin/genetics , Polymorphism, Genetic , Adolescent , Alleles , Blackwater Fever/urine , Case-Control Studies , Child , Child, Preschool , Cohort Studies , DNA/genetics , DNA/isolation & purification , Democratic Republic of the Congo/epidemiology , Female , Gene Frequency , Genotyping Techniques , Haplotypes , Hemoglobinuria/diagnosis , Hemoglobinuria/urine , Humans , Logistic Models , MaleABSTRACT
Delayed haemolytic anaemia has been reported in association with intravenous artesunate treatment in patients with severe Plasmodium falciparum malaria, and furthermore, oral artemisinin-based combination therapies including artemether-lumefantrine (AL) have also been incriminated. However, definite cases of delayed haemolytic anaemia associated with AL appear to be scarce, as reported cases were often treated concomitantly with other anti-malarials. In this study, we report a severe case of delayed haemolytic anaemia following AL alone in a Japanese traveller with severe parasitaemia caused by numerous P. falciparum parasites and a few P. vivax parasites. We also stress the need by further studies to differentiate between delayed haemolytic anaemia and blackwater fever, the latter being another malaria-related haemolytic condition, more clearly than they are now.
Subject(s)
Anemia, Hemolytic/chemically induced , Antimalarials/adverse effects , Artemisinins/adverse effects , Ethanolamines/adverse effects , Fluorenes/adverse effects , Malaria, Falciparum/drug therapy , Administration, Intravenous , Administration, Oral , Anemia, Hemolytic/blood , Anemia, Hemolytic/drug therapy , Antimalarials/administration & dosage , Artemether , Artemisinins/administration & dosage , Artesunate , Blackwater Fever/blood , Blackwater Fever/drug therapy , Blackwater Fever/etiology , Blackwater Fever/urine , Drug Therapy, Combination , Ethanolamines/administration & dosage , Fluorenes/administration & dosage , Humans , Lumefantrine , Malaria, Falciparum/blood , Male , Plasmodium falciparum/isolation & purification , Plasmodium vivax/isolation & purification , Recurrence , Young AdultSubject(s)
Anemia, Hemolytic/etiology , Blackwater Fever/diagnosis , Glucosephosphate Dehydrogenase Deficiency/complications , Malaria/complications , Parasitemia/complications , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/urine , Adolescent , Anemia, Hemolytic/therapy , Aspirin/analogs & derivatives , Aspirin/therapeutic use , Blackwater Fever/blood , Blackwater Fever/etiology , Blackwater Fever/urine , Erythrocyte Transfusion , Glucosephosphate Dehydrogenase Deficiency/blood , Glucosephosphate Dehydrogenase Deficiency/diagnosis , Glucosephosphate Dehydrogenase Deficiency/urine , Hemoglobinuria/etiology , Hemolysis , Humans , Hyperbilirubinemia/etiology , Lysine/analogs & derivatives , Lysine/therapeutic use , Malaria/blood , Malaria/drug therapy , Male , Parasitemia/blood , Parasitemia/drug therapy , Quinine/therapeutic use , Renal Dialysis , TogoABSTRACT
During a prospective study of red cell variants and severe malaria in children, a surprising observation was the occurrence of dark urine. Children were grouped according to urine findings: 22 had dark urine that contained a haem protein (Group I), 93 had urine of normal colour that contained a haem protein (Group II) and 236 had normal urine (Group III). To investigate the cause of dark urine, haemolysis and muscle cell injury were assessed. Intravascular haemolysis was greater in Group I than in Groups II and III. However, anaemia was more severe in Group III and is likely to have resulted mainly from extravascular haemolysis. Median plasma myoglobin concentrations were greater in Groups I and II than Group III (P = 0.00060). Plasma myoglobin was greater in children with cerebral malaria, hyperlactataemia and those who died but was not associated with acidosis. Urine myoglobin was greater in Group I than Groups II and III (P = 0.00054). It is likely that both haemoglobin and myoglobin contributed to dark urine. The association between muscle cell injury and coma suggests sequestration of parasitized red cells as a common underlying pathology. In malaria, hyperlactataemia may result directly from breakdown of muscle protein as well as tissue hypoxia.
