Proc. West. Pharmacol. Soc. 51: 38-41 (2008) 38 Oral Calcium Administration Attenuates Thrombocytopenia in Patients With Dengue Fever. Report of a Pilot Study Jorge Isaac Cabrera-Cortina 1 , Emilio Sánchez-Valdéz 2 , Dora Cedas-DeLezama 3 , María Dolores Ramírez-González 4 School of Medicine, Northeastern University (UNE, Tampico) 1 ; Community Center “Las Americas”, Tampico 2 ; Civil Hospital, Ciudad Madero, Tamaulipas 3 ; and Department of Pharmacology, School of Medicine, National Autonomous University of Mexico (UNAM) 4 E-mail: mdrg@servidor.unam.mx ABSTRACT Global climate change is one of the instigating and contributing factors for epidemic outbreaks of infectious diseases in human populations. In the years 2003 to 2005 the city of Tampico, in the northern state of Tamaulipas, Mexico, experienced recurrent outbreaks of dengue virus infections (DV) and the resulting dengue fever (DF). One of the hallmark symptoms of DF, which appears to worsen as the environmental temperature increases, is thrombocytopenia. In as much as it is a hallmark for hemorrhagic manifestations, thrombocytopenia is a useful sign to monitor the course of infected patients. Extracellular calcium (Ca 2+ o ) plays a key role in blood clotting; its chelation in vitro with ethylenediamine- tetracetic acid (EDTA) or citrate prevents clotting, while exogenous recalcification of plasma leads to shortening of clotting time. In vivo, Ca 2+ o is essential for platelet function and for the regulation of the immune response. In this work we report a significant increase (p<0.05) in the number of blood platelets of patients with clinical signs and symptoms of DF following oral administration of calcium carbonate (CAL, 1.2 to 1.8 g/day; n=10) when compared with a control group (CTL, n=10): 89 (46–132) versus 206 (155–257). Data expressed as mean value (95% confidence interval, C.I.) for x1000 cells/mm 3 . CAL also improved overall clinical condition and reduced by 36 % the duration of signs and symptoms of DF: 6.7-11.3 days, versus 11.5 – 16.6 days (95 % C.I., p<0.05) when compared with CTL patients. The possible mechanism of calcium attenuated thrombocytopenia and clinical improvement is discussed. INTRODUCTION Dengue fever (DF) is a self-limiting febrile illness characterized by the sudden onset of fever over 38 ºC, myalgia, headache, joint pain, increased capillary permeability, and loss of appetite lasting for 2 to 3 weeks. The steady drop in peripheral blood platelet counts below 100 x 1000 cells/mm 3, may occur 3 to 5 days before and continue after defervescence [1, 2]. DF, an arthropod-borne disease is caused by four serotypes of dengue virus (DV) and transmitted through the byte of several species of Aedes mosquitoes. Infection with one serotype confers immunity for a long period, but not to other serotypes; and thus patients with a history of DF may be re- infected, with an additional risk for developing other life-threatening forms of the disease such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Worldwide DV is one of the most frequent causes of arboviral diseases and is highly endemic in more than 100 tropical countries. It is estimated that, at the present time, two and a half billion people are at risk of infection, with 50 – 100 million cases of DF and several hundred cases of DHF per year [2]. Definite diagnosis of DV infection is important for epidemiological recording and can be done by detection of virus-specific antibody, detection of the genomic sequence by RT-PCR, by viral isolation, or by hemagglutination inhibition testing [2]. These tests, although important, provide little help and even when conducted in the correct time frame subsequent to infection do not change the reality that there is currently no specific treatment against DV infections. Treatment of DF is done according to case severity and it is traditionally limited to electrolytic solutions and rest. When fever is too high, bathing in warm water or administration of antipyretics like paracetamol can be used, but NSAID’s are to be avoided due to the risk of bleeding. Patient monitoring is limited to measurements of blood pressure, body temperature, hematocrit, platelet count and assessment of the level of consciousness. After defervescence, treatment is limited to intravenous fluids, measurement of hematocrit, blood pressure and urine output. Additional treatments including intravenous immune globulin or platelet transfusions may shorten the duration or decrease the severity of thrombocytopenia [1-3]. Thrombocytopenia appears 2-3 days before defervescence, and may last for 3-5 days thereafter; the major problem being high risk for progression to severe vascular permeability syndrome, which may