title: Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study.
abstract: BACKGROUND
  The hyperreactive malarial splenomegaly (HMS) represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly (e-HMS). The main research questions was: does "e-HMS" tend to evolve to the full-blown syndrome? And if so, what are the main factors influencing this evolution?
  
  
  METHODS
  Retrospective, longitudinal study. The patient database was searched to retrieve all potentially eligible patients. e-HMS was defined by splenomegaly of any size (with or without raised IgM), high anti-malarial antibody titre and exclusion of other causes of splenomegaly. The clinical outcome at following visits was analysed in relation to re-exposure to malaria, and to treatment (only part of the patients with e-HMS were treated with a single anti-malarial treatment and advised to follow an effective anti-malarial prophylaxis, if re-exposed). The association of the outcome with the main independent variables was first assessed with univariate analysis. A stepwise logistic regression model was then performed to study the association of the outcome with the main independent variables.
  
  
  RESULTS
  One hundred and twenty-six subjects with e-HMS were retrieved. Eighty-one had at least one follow-up visit. Of 46 re-exposed to malaria for a variable period, 21 (46 %) had progressed, including 10/46 (22 %) evolving to full-blown HMS, while of 29 patients not re-exposed, 24 (93 %) had improved or cured and five (7 %) progressed (p < 0.001). At logistic regression re-exposure was confirmed as a major risk factor of progression (OR 9.458, CI 1.767-50.616) while treatment at initial visit was protective (OR 0.187, CI 0.054-0.650).
  
  
  CONCLUSIONS
  e-HMS should be regarded as a clinical condition predisposing to HMS. Although the case definition may include false positives, e-HMS should be treated just as the full-blown syndrome. A single anti-malarial treatment is probably adequate, followed by effective prophylaxis for patients exposed again to malaria transmission.
authors.affiliation: Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, 37024, Negrar, Verona, Italy. zeno.bisoffi@sacrocuore.it.
authors.forename: Zeno
authors.initials: Z
authors.lastname: Bisoffi
authors.affiliation: Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, 37024, Negrar, Verona, Italy. dott.stefania.leoni@gmail.com.
authors.forename: Stefania
authors.initials: S
authors.lastname: Leoni
authors.affiliation: Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, 37024, Negrar, Verona, Italy. dora.buonfrate@sacrocuore.it.
authors.forename: Dora
authors.initials: D
authors.lastname: Buonfrate
authors.affiliation: Medici senza Frontiere Italia, Via Magenta 5, 00186, Roma, Italy. claudia.lodesani@libero.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lodesani
authors.affiliation: Ospedale dell'Angelo, Via Don Federico Tosatto, 147, 30174, Venezia Mestre, Italy. Franklyn.Eseme@ulss12.ve.it.
authors.forename: Franklin Esoka
authors.initials: FE
authors.lastname: Eseme
authors.affiliation: Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, 37024, Negrar, Verona, Italy. geraldo.monteiro@sacrocuore.it.
authors.forename: Geraldo Badona
authors.initials: GB
authors.lastname: Monteiro
authors.affiliation: Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, 37024, Negrar, Verona, Italy. stefania.marocco@sacrocuore.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marocco
authors.affiliation: Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy. massimo.guerriero@univr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Guerriero
mesh_terms: D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008137:Longitudinal Studies; D008288:Malaria / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013163:Splenomegaly / Q000453:epidemiology* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D007075:Immunoglobulin M