HIV infection, malnutrition, and invasive bacterial infection among children with severe malaria.

BACKGROUND Human immunodeficiency virus (HIV) infection, malnutrition, and invasive bacterial infection (IBI) are reported among children with severe malaria. However, it is unclear whether their cooccurrence with falciparum parasitization and severe disease happens by chance or by association among children in areas where malaria is endemic. METHODS We examined 3068 consecutive children admitted to a Kenyan district hospital with clinical features of severe malaria and 592 control subjects from the community. We performed multivariable regression analysis, with each case weighted for its probability of being due to falciparum malaria, using estimates of the fraction of severe disease attributable to malaria at different parasite densities derived from cross-sectional parasitological surveys of healthy children from the same community. RESULTS HIV infection was present in 133 (12%) of 1071 consecutive parasitemic admitted children (95% confidence interval [CI], 11%-15%). Parasite densities were higher in HIV-infected children. The odds ratio for admission associated with HIV infection for admission with true severe falciparum malaria was 9.6 (95% CI, 4.9-19); however, this effect was restricted to children aged 1 year. Malnutrition was present in 507 (25%) of 2048 consecutive parasitemic admitted children (95% CI, 23%-27%). The odd ratio associated with malnutrition for admission with true severe falciparum malaria was 4.0 (95% CI, 2.9-5.5). IBI was detected in 127 (6%) of 2048 consecutive parasitemic admitted children (95% CI, 5.2%-7.3%). All 3 comorbidities were associated with increased case fatality. CONCLUSIONS HIV, malnutrition and IBI are biologically associated with severe disease due to falciparum malaria rather than being simply alternative diagnoses in co-incidentally parasitized children in an endemic area.

[1]  K. Maitland,et al.  Defining Childhood Severe Falciparum Malaria for Intervention Studies , 2007, PLoS medicine.

[2]  M. Molyneux,et al.  Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. , 2007, The Journal of infectious diseases.

[3]  C. Newton,et al.  Role of viruses in Kenyan children presenting with acute encephalopathy in a malaria-endemic area. , 2006, The American journal of tropical medicine and hygiene.

[4]  M. Molyneux,et al.  The distribution and intensity of parasite sequestration in comatose Malawian children. , 2006, The Journal of infectious diseases.

[5]  J Thomson,et al.  Pocket book of hospital care for children: guidelines for the management of common illnesses with limited resources , 2006 .

[6]  R. Snow,et al.  Microscopy and outpatient malaria case management among older children and adults in Kenya , 2006, Tropical medicine & international health : TM & IH.

[7]  B. Lowe,et al.  Salmonella Bacteremia in Kenyan Children , 2006, The Pediatric infectious disease journal.

[8]  J. Scott,et al.  Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study , 2006, The Lancet.

[9]  A. Dicko,et al.  Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease. , 2005, The Journal of infectious diseases.

[10]  Brian G. Williams,et al.  Malaria Attributable to the HIV-1 Epidemic, Sub-Saharan Africa , 2005, Emerging infectious diseases.

[11]  K. Maitland,et al.  Assessment of severe malnutrition among hospitalized children in rural Kenya: comparison of weight for height and mid upper arm circumference. , 2005, JAMA.

[12]  R. Snow,et al.  Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. , 2005, The Journal of infectious diseases.

[13]  C. Mbogo,et al.  Anopheles gambiae s.l. and Anopheles funestus Mosquito Distributions at 30 Villages along the Kenyan Coast , 2005, Journal of medical entomology.

[14]  Robert E Black,et al.  WHO estimates of the causes of death in children , 2005, The Lancet.

[15]  K. Maitland,et al.  Bacteremia among children admitted to a rural hospital in Kenya. , 2005, The New England journal of medicine.

[16]  Chris Drakeley,et al.  Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study , 2004, BMJ : British Medical Journal.

[17]  D. Mack,et al.  High mortality of infant bacteraemia clinically indistinguishable from severe malaria. , 2004, QJM : monthly journal of the Association of Physicians.

[18]  L. Caulfield,et al.  Undernutrition as an underlying cause of malaria morbidity and mortality in children less than five years old. , 2004, The American journal of tropical medicine and hygiene.

[19]  Wenjiang J. Fu,et al.  Differentiating the pathologies of cerebral malaria by postmortem parasite counts , 2004, Nature Medicine.

[20]  N. French,et al.  Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence , 2003, The Pediatric infectious disease journal.

[21]  L. Seidlein,et al.  Increased risk for malaria in chronically malnourished children under 5 years of age in rural Gambia. , 2002, Journal of tropical pediatrics.

[22]  B. Lowe,et al.  Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa , 2001, The Lancet.

[23]  M. Quigley,et al.  Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study , 2000, The Lancet.

[24]  M. Molyneux,et al.  Clinical presentation of non-typhoidal Salmonella bacteraemia in Malawian children. , 2000, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[25]  B. Lowe,et al.  Bacteraemia complicating severe malaria in children. , 1999, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[26]  K. Marsh,et al.  Cerebral malaria versus bacterial meningitis in children with impaired consciousness. , 1999, QJM : monthly journal of the Association of Physicians.

[27]  B. Greenwood,et al.  Bacteraemia in cerebral malaria. , 1998, Annals of tropical paediatrics.

[28]  M. Alpers,et al.  Relation of anthropometry to malaria morbidity and immunity in Papua New Guinean children. , 1998, The American journal of clinical nutrition.

[29]  O. Sodeinde,et al.  Protein energy malnutrition and cerebral malaria in Nigerian children. , 1997, Journal of tropical pediatrics.

[30]  M. Ho,et al.  Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  R. Snow,et al.  Indicators of life-threatening malaria in African children. , 1995, The New England journal of medicine.

[32]  T. Smith,et al.  Attributable fraction estimates and case definitions for malaria in endemic areas. , 1994, Statistics in medicine.

[33]  P. Kremsner,et al.  Bacterial strains isolated from blood cultures of Nigerian children with cerebral malaria , 1993, The Lancet.

[34]  T. Theander,et al.  Loss of cellular immune reactivity during acute Plasmodium falciparum malaria. , 1991, FEMS microbiology immunology.

[35]  A. Greenberg,et al.  Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children. , 1991, The New England journal of medicine.

[36]  T. Quinn,et al.  Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. , 1987, Bulletin of the World Health Organization.

[37]  M. Murray,et al.  Diet and cerebral malaria: the effect of famine and refeeding. , 1978, The American journal of clinical nutrition.

[38]  A. Bryceson,et al.  Immunosuppression in children with malaria. , 1972, Lancet.

[39]  R. Hendrickse,et al.  Malaria in early childhood. An investigation of five hundred seriously ill children in whom a "clinical" diagnosis of malaria was made on admission to the children's emergency room at University College Hospital, Ibadan. , 1971, Annals of tropical medicine and parasitology.