• 1

    Gérardin P, Rogier C, Ka AS, Jouvencel P, Brousse V, Imbert P, 2002. Prognostic value of thrombocytopenia in African children with falciparum malaria. Am J Trop Med Hyg 66 :686–91.

    • Search Google Scholar
    • Export Citation
  • 2

    Ladhani S, Cole AO, Lowe B, Kowuondo K, Newton CJR, 2002. Non-erythrocytic blood components in children with falciparum malaria. Br J Haematol 119 :839–847.

    • Search Google Scholar
    • Export Citation
  • 3

    Lesi A, Meremikwu M, 2002. High first dose quinine regimen for treating severe malaria. Cochrane Database Syst Rev 3 : CD003341.

  • 4

    Marsh K, Snow RW, 1999. Malaria transmission and morbidity. Parassitologia 41 :241–246.

  • 5

    Imbert P, Sartelet I, Rogier C, Ka A, Baujat G, Candito P, 1997. Severe malaria among children in a low seasonal transmission area, Dakar, Senegal: influence of age on clinical presentation. Trans R Soc Trop Med Hyg 91 :22–24.

    • Search Google Scholar
    • Export Citation
  • 6

    Schellenberg D, Menendez C, Kahigwa E, Font F, Galindo C, Acosta C, Armstrong Schellenberg J, Aponte JJ, Kimario J, Urassa H, Mshinda H, Tanner M, Alonso P, 1999. African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death. Am J Trop Med Hyg 61 :431–438.

    • Search Google Scholar
    • Export Citation
  • 7

    World Health Organization, Division of Control of Tropical Diseases, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1):1–90.

    • Search Google Scholar
    • Export Citation
  • 8

    Grau GE, Mackenzie C, Carr R, Redard M, Pizzolato G, Allasia C, Cataldo C, Taylor TE, Molyneux ME, 2003. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 187 :461–466.

    • Search Google Scholar
    • Export Citation
  • 9

    Rigaud M, Leibovitz E, Quee CS, Kaul A, Nardi M, Pollack H, Lawrence R, DiJohn D, Krasinski K, Karpatkin M, 1992. Thrombocytopenia in children infected with human immunodeficiency virus: long term follow-up and therapeutic considerations. J Acquir Immune Defic Syndr 5 :450–455.

    • Search Google Scholar
    • Export Citation
  • 10

    Adewuyi J, Chitsike I, 1994. Haematologic features of the human immunodeficiency virus (HIV) infection in Black children in Harare. Cent Afr J Med 40 :333–336.

    • Search Google Scholar
    • Export Citation
  • 11

    UNAIDS/WHO/UNICEF, 2002. Epidemiological Fact Sheets on HIV/AIDS and Sexually Transmitted Infections, Senegal, July 2002 Update. Geneva: World Health Organization.

  • 12

    UNAIDS, 2000. Report on the Global HIV/AIDS Epidemic. UNAIDS/ 00.13E, June 2000. Geneva: World Health Organization.

  • 13

    Taha TE, Graham SM, Kumwenda NI, Broadhead RI, Hoover DR, Markakis D, van der Hoeven L, Liomba GN, Chiphangwi JD, Miotti PG, 2000. Morbidity among human immunodeficiency virus-1-infected and -uninfected African children. Pediatrics 106 :E77.

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    • Export Citation

 

 

 

 

LETTER TO THE EDITOR

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  • 1 Service des Maladies Infectieuses et Tropicales
 Hôpital d’Instruction des Armées Bégin
 69 Avenue de Paris
 94163 Saint-Mandé Cedex, France
 Telephone: 33-1-43-98-50-21
 Fax: 33-1-43-98-52-79

Dear Sir:

In our series of children living in a low, seasonal transmission setting for malaria (less than one infective bite per person per year), thrombocytopenia less than 100,000/mm3 was strongly associated with both severity and mortality.1 We have also proposed that thrombocytopenia can be a prognostic factor and independent predictor for death in P. falciparum malaria in African children living in areas of low transmission.1 However, in a large retrospective study from Kenya, Ladhani and others found no such associations and platelet counts were actually lower in mild cases than in severe ones.2

Given the extremely significant prognostic value of thrombocytopenia in our study, we doubt the differences are due to population size. Similarly, different care seems unlikely given that the superiority of loading doses of quinine on survival has not been proven,3 and that all severe cases in our series were treated in emergency wards, where mechanical ventilation and other intensive care supplies were available.1 We think that other reasons could explain the differences observed between our respective data.

First, in the series of Ladhani and others, the high upper limit of the normal platelet count reference range, i.e., 700,000/mm3, suggests confounding factors, e.g., iron deficiency (ruled out in our study) might have affected platelet counts and introduced a bias.

Second, we agree with Ladhani and Newton that geographic and patient population differences could explain the differences between the two studies. In Kilifi, Kenya, malaria transmission is higher and the patients are younger. This results in severe anemia predominating among severe forms of malaria and a much lower ratio of cerebral malaria to severe anemia than in Dakar, Senegal.4 In our series in Dakar, platelet counts were higher in those with severe anemia than in those with other manifestations of severe malaria, and the association between thrombocytopenia and death was not significant among severe cases of anemia (odds ratio [OR] = 3.55, 95% confidence interval [CI] = .3–46.4, P = 0.197; Table 3 in our paper), while it was highly significant in the other main severe forms of malaria, i.e., cerebral malaria and respiratory distress.1

Third, severe anemia has a better prognosis in hospitals where blood transfusions are available,5,6 which could explain the 2% death rate observed among their severe cases, a rate much lower than the 10–30% usually reported.7 However, we agree with Ladhani and Newton that fatality rate in their study was likely to be too low to detect significant differences in platelet counts between children who died and those who recovered.

Fourth, in Dakar, people are weakly immune against malaria, and severe forms occur irrespective of age.5 We have reported that cerebral malaria is more frequent among older children and has a greater inpatient mortality risk than severe anemia.5 In the present series, an admission thrombocytopenia less than 100,000/mm3 was associated with increased mortality, particularly in those with cerebral malaria (OR = 9.4, 95% CI = 2.3–54.4).1 We monitored platelet counts from the first to the seventh days in 208 children with severe malaria, and a retrospective analysis showed a significant association between improvement in the level of consciousness and an increase in the platelet count (P < 0.01, by chi-square test and P < 0.005, by Kruskal-Wallis test) (Table 1). Among survivors, an increase in platelet counts between admission and the first control was associated with a +0.64 mean improvement in the Blantyre coma score. Conversely, a decrease in platelets counts was associated with a smaller improvement (+0.34) in the coma score among survivors (P < 0.04, by Mann-Whitney test). No patients with a worsened level of consciousness had an increased platelet count (Table 1). These clinical results, as well as other findings from a recent pathologic study,8 suggest that the role of platelets in cerebral malaria is likely to be more important than previously thought.

We continue to believe that our data provide strong evidence for an association between thrombocytopenia and either severity or mortality in an area hypoendemic for malaria, such as Dakar, where neurologic disorders predominate. Discrepancies between our results and those of Ladhani and others highlight the need for analyzing clinical data separately, i.e., per clinical forms such as cerebral malaria, respiratory distress, and severe malaria, rather than globally. We agree with Ladhani and Newton on the need for additional studies in various settings of transmission to confirm the significance of thrombocytopenia in severe pediatric Plasmodium falciparum malaria.

Moerman and others have rightly underlined the association between infection with human immunodeficiency virus (HIV) and thrombocytopenia in childhood both in developed and developing countries.9,10 In our series, children had no history of HIV and were not systematically investigated for antibodies to this virus. However, prevalence rate of infection with HIV among children hospitalized in the Pediatric Unit of Hôpital Principal in Dakar was less than 0.2% (i.e., less than 10 new cases each year) during the period of the study. In Senegal, this rate was 0.05% among children (0–15 years old) at the end of 2001.11 Thus, infection with HIV cannot be considered a confounding factor in our Senegalese study.

What about other settings? In the absence of preventive interventions, the risk of mother-to-breastfed child transmission of HIV is generally estimated to be approximately 30% in developing countries. Most HIV-infected infants develop disease during the first year of life and have a high mortality rate,12 up to 89%, by three years of age, as was shown in a prospective study in Malawi.13 Consequently, it is unlikely that the prevalence rate of HIV infection among children 0–5 years of age exceeds 1% in countries where this prevalence is high among adults (e.g., 10%). Indeed, it has been estimated to be less than 0.1% in sub-Saharan Africa.12 Thus, it is unlikely that infection with HIV could have a significant confounding effect in the association between thrombocytopenia and poor outcome of P. falciparum malaria in children in most sub-Saharan African countries. However, we agree with Moerman and others that the validity of using thrombocytopenia as a prognostic indicator for P. falciparum malaria should be tested in settings other than the hypoendemic conditions prevailing in Dakar.

Table 1

Comparative evolution of consciousness level and platelet count between admission and first control of platelet count among 208 children with severe malaria in Dakar, Senegal

Evolution of platelet counts
Evolution of Consciousness level*No of patientsIncrease No. (%)Decrease No. (%)Mean variation (SE) of platelet counts
* The level of consciousness was divided in three classes: 1) normal (no prostration, Glasgow coma score = 15 or Blantyre coma score = 5); 2) prostate or mild consciousness impairment (Glasgow coma score >9 and <15 or Blantyre coma score = 4); 3) unrousable coma (Glasgow coma score ≤9 or Blantyre coma score ≤3).
P < 0.005, by Kruskal-Wallis test.
P < 0.01, by chi-square test.
Worsened303 (100)−99.000 (±49.153)†
Stationary11565 (56.5)‡50 (43.5)‡+1.435 (±9.847)†
Improved9070 (77.8)‡20 (22.2)‡+43.778 (±8.856)†
Total208135 (64.9)73 (35.1)

REFERENCES

  • 1

    Gérardin P, Rogier C, Ka AS, Jouvencel P, Brousse V, Imbert P, 2002. Prognostic value of thrombocytopenia in African children with falciparum malaria. Am J Trop Med Hyg 66 :686–91.

    • Search Google Scholar
    • Export Citation
  • 2

    Ladhani S, Cole AO, Lowe B, Kowuondo K, Newton CJR, 2002. Non-erythrocytic blood components in children with falciparum malaria. Br J Haematol 119 :839–847.

    • Search Google Scholar
    • Export Citation
  • 3

    Lesi A, Meremikwu M, 2002. High first dose quinine regimen for treating severe malaria. Cochrane Database Syst Rev 3 : CD003341.

  • 4

    Marsh K, Snow RW, 1999. Malaria transmission and morbidity. Parassitologia 41 :241–246.

  • 5

    Imbert P, Sartelet I, Rogier C, Ka A, Baujat G, Candito P, 1997. Severe malaria among children in a low seasonal transmission area, Dakar, Senegal: influence of age on clinical presentation. Trans R Soc Trop Med Hyg 91 :22–24.

    • Search Google Scholar
    • Export Citation
  • 6

    Schellenberg D, Menendez C, Kahigwa E, Font F, Galindo C, Acosta C, Armstrong Schellenberg J, Aponte JJ, Kimario J, Urassa H, Mshinda H, Tanner M, Alonso P, 1999. African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death. Am J Trop Med Hyg 61 :431–438.

    • Search Google Scholar
    • Export Citation
  • 7

    World Health Organization, Division of Control of Tropical Diseases, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1):1–90.

    • Search Google Scholar
    • Export Citation
  • 8

    Grau GE, Mackenzie C, Carr R, Redard M, Pizzolato G, Allasia C, Cataldo C, Taylor TE, Molyneux ME, 2003. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 187 :461–466.

    • Search Google Scholar
    • Export Citation
  • 9

    Rigaud M, Leibovitz E, Quee CS, Kaul A, Nardi M, Pollack H, Lawrence R, DiJohn D, Krasinski K, Karpatkin M, 1992. Thrombocytopenia in children infected with human immunodeficiency virus: long term follow-up and therapeutic considerations. J Acquir Immune Defic Syndr 5 :450–455.

    • Search Google Scholar
    • Export Citation
  • 10

    Adewuyi J, Chitsike I, 1994. Haematologic features of the human immunodeficiency virus (HIV) infection in Black children in Harare. Cent Afr J Med 40 :333–336.

    • Search Google Scholar
    • Export Citation
  • 11

    UNAIDS/WHO/UNICEF, 2002. Epidemiological Fact Sheets on HIV/AIDS and Sexually Transmitted Infections, Senegal, July 2002 Update. Geneva: World Health Organization.

  • 12

    UNAIDS, 2000. Report on the Global HIV/AIDS Epidemic. UNAIDS/ 00.13E, June 2000. Geneva: World Health Organization.

  • 13

    Taha TE, Graham SM, Kumwenda NI, Broadhead RI, Hoover DR, Markakis D, van der Hoeven L, Liomba GN, Chiphangwi JD, Miotti PG, 2000. Morbidity among human immunodeficiency virus-1-infected and -uninfected African children. Pediatrics 106 :E77.

    • Search Google Scholar
    • Export Citation

Author Notes

E-mail: hiabegin.mit@worldonline.fr
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