Mefloquine Versus Proguanil
Mefloquine Versus Proguanil
Objective: To compare the efficacy and tolerability of mefloquine and proguanil in malaria prophylaxis in sickle cell anaemia.
Design: Nonblind, prospective, multicentre study.
Participants: The study population consisted of adults and children (aged ≥5 years) attending the sickle cell clinics in three centres in Nigeria.
Methods: Participants were treated with either a weekly dose of mefloquine (125 or 250mg) or a daily dose of proguanil (100 or 200mg) for 6 months. Complete physical examination and parasitology were performed for each patient at baseline and during and at the end of therapy. Efficacy was evaluated by the absence of parasitaemia during the course of the study; tolerability was evaluated by the incidence of adverse events. Laboratory safety parameters such as blood count, ALT and serum bilirubin were also monitored.
Results: The mean age of the 113 individuals enrolled into the study was 16.1 ± 8.3 years. The success rate was 89.2% with mefloquine and 81.8% with proguanil. The incidence of adverse events was 19.6% with mefloquine and 31.5% with proguanil. The difference in the efficacy and tolerability profile between the two treatment groups was not statistically significant (p > 0.05). None of the patients receiving mefloquine experienced a severe reaction, and of particular note was the very low incidence of CNS effects such as dizziness (1.8%) and headache (1.8%).
Conclusions: Malaria chemoprophylaxis with a weekly dose of mefloquine in Nigerians with sickle cell anaemia appears to be as effective as a daily regimen with proguanil. The tolerability profile of mefloquine in this group of patients appears promising.
The sickle cell trait (the inheritance of one normal and one sickle Hb gene) occurs at an incidence of between 20% and 40% in the Black population of Africa. It has been reported that the prevalence rises from the time of birth until about 5 years of age, after which there is no further change. It has been proposed that the sickle cell trait is a genetic modification for protection against malaria. However, sickle cell disease (a condition resulting from the inheritance of two abnormal Hb genes) has become one of the most important scourges of our time. Sickle cell disease was first observed by Dr JB Herricks in 1904 in the blood of an anaemic West Indian medical student, and described by him in a paper published in 1910. Since then, giant strides have been made in our understanding and knowledge of the disease. By 1982, it was estimated that in Nigeria alone, about 30 000 children are born each year with sickle cell disease. It is currently estimated that about 25% of adult Nigerians have the sickle cell trait.
Malaria has been identified as one of the most common causes of morbidity and mortality in individuals with sickle cell disease. Although malaria infection with Plasmodium falciparum is less prevalent in sickle cell disease than in normal individuals, the consequences of an infection are severe. It is a frequent precipitating cause of crisis (haemolytic, sequestration and infarctive) and a common cause of death in both Hb-SS and Hb-SC disease. Consequently, 'sicklers' are placed on malaria chemoprophylaxis on a lifetime basis. The current practice is to place all affected individuals on a daily dose of between 50mg and 200mg of proguanil (depending on the patient's age). Proguanil-resistant strains of P. falciparum had been identified in Nigeria as far back as 1949. In a study conducted in 1953, it was observed that of 435 non-immune individuals living in Nigeria treated for malaria, 74% had been on proguanil prophylaxis, thus suggesting some degree of inadequate prophylactic coverage by proguanil at the applied dose level (100 to 200mg daily).
Despite these earlier observations, no recent attempt has been made to reassess the efficacy of proguanil in malaria chemoprophylaxis in Nigeria; neither has the impact of a daily regimen on compliance been evaluated. The long-term use of chemoprophylaxis by sicklers invariably confers loss of immunity to malaria; hence, the consequence of non-compliance can be as grave as acute severe P. falciparum infection and haemolysis. In addition, despite the long-term use of malaria chemoprophylaxis in the management of sickle cell anaemia, no study has been conducted to evaluate the effectiveness of the current prophylactic regimen in sicklers. In a paper published in 1992, it was observed that malaria parasitaemia was present in 9% of children with sickle cell anaemia presenting to the emergency roomof the University of Benin Teaching Hospital with an acute episode of fever;[10] it was not clear, however, whether these children were on chemoprophylaxis or not.
The prophylactic efficacy of mefloquine in malaria has been established in various studies both in Nigeria and elsewhere, and these studies were conducted in both children and adult healthy volunteers. However, there is currently no known clinical experience with mefloquine prophylaxis in individuals with sickle cell anaemia, despite recent documentation of the efficacy of the drug in other special risk groups such as pregnant women.
This study was therefore planned to evaluate the efficacy and tolerability of a prophylactic once-daily treatment with proguanil in comparison with a once-weekly prophylactic treatment with mefloquine in Nigerian children and adults with sickle cell anaemia.
Objective: To compare the efficacy and tolerability of mefloquine and proguanil in malaria prophylaxis in sickle cell anaemia.
Design: Nonblind, prospective, multicentre study.
Participants: The study population consisted of adults and children (aged ≥5 years) attending the sickle cell clinics in three centres in Nigeria.
Methods: Participants were treated with either a weekly dose of mefloquine (125 or 250mg) or a daily dose of proguanil (100 or 200mg) for 6 months. Complete physical examination and parasitology were performed for each patient at baseline and during and at the end of therapy. Efficacy was evaluated by the absence of parasitaemia during the course of the study; tolerability was evaluated by the incidence of adverse events. Laboratory safety parameters such as blood count, ALT and serum bilirubin were also monitored.
Results: The mean age of the 113 individuals enrolled into the study was 16.1 ± 8.3 years. The success rate was 89.2% with mefloquine and 81.8% with proguanil. The incidence of adverse events was 19.6% with mefloquine and 31.5% with proguanil. The difference in the efficacy and tolerability profile between the two treatment groups was not statistically significant (p > 0.05). None of the patients receiving mefloquine experienced a severe reaction, and of particular note was the very low incidence of CNS effects such as dizziness (1.8%) and headache (1.8%).
Conclusions: Malaria chemoprophylaxis with a weekly dose of mefloquine in Nigerians with sickle cell anaemia appears to be as effective as a daily regimen with proguanil. The tolerability profile of mefloquine in this group of patients appears promising.
The sickle cell trait (the inheritance of one normal and one sickle Hb gene) occurs at an incidence of between 20% and 40% in the Black population of Africa. It has been reported that the prevalence rises from the time of birth until about 5 years of age, after which there is no further change. It has been proposed that the sickle cell trait is a genetic modification for protection against malaria. However, sickle cell disease (a condition resulting from the inheritance of two abnormal Hb genes) has become one of the most important scourges of our time. Sickle cell disease was first observed by Dr JB Herricks in 1904 in the blood of an anaemic West Indian medical student, and described by him in a paper published in 1910. Since then, giant strides have been made in our understanding and knowledge of the disease. By 1982, it was estimated that in Nigeria alone, about 30 000 children are born each year with sickle cell disease. It is currently estimated that about 25% of adult Nigerians have the sickle cell trait.
Malaria has been identified as one of the most common causes of morbidity and mortality in individuals with sickle cell disease. Although malaria infection with Plasmodium falciparum is less prevalent in sickle cell disease than in normal individuals, the consequences of an infection are severe. It is a frequent precipitating cause of crisis (haemolytic, sequestration and infarctive) and a common cause of death in both Hb-SS and Hb-SC disease. Consequently, 'sicklers' are placed on malaria chemoprophylaxis on a lifetime basis. The current practice is to place all affected individuals on a daily dose of between 50mg and 200mg of proguanil (depending on the patient's age). Proguanil-resistant strains of P. falciparum had been identified in Nigeria as far back as 1949. In a study conducted in 1953, it was observed that of 435 non-immune individuals living in Nigeria treated for malaria, 74% had been on proguanil prophylaxis, thus suggesting some degree of inadequate prophylactic coverage by proguanil at the applied dose level (100 to 200mg daily).
Despite these earlier observations, no recent attempt has been made to reassess the efficacy of proguanil in malaria chemoprophylaxis in Nigeria; neither has the impact of a daily regimen on compliance been evaluated. The long-term use of chemoprophylaxis by sicklers invariably confers loss of immunity to malaria; hence, the consequence of non-compliance can be as grave as acute severe P. falciparum infection and haemolysis. In addition, despite the long-term use of malaria chemoprophylaxis in the management of sickle cell anaemia, no study has been conducted to evaluate the effectiveness of the current prophylactic regimen in sicklers. In a paper published in 1992, it was observed that malaria parasitaemia was present in 9% of children with sickle cell anaemia presenting to the emergency roomof the University of Benin Teaching Hospital with an acute episode of fever;[10] it was not clear, however, whether these children were on chemoprophylaxis or not.
The prophylactic efficacy of mefloquine in malaria has been established in various studies both in Nigeria and elsewhere, and these studies were conducted in both children and adult healthy volunteers. However, there is currently no known clinical experience with mefloquine prophylaxis in individuals with sickle cell anaemia, despite recent documentation of the efficacy of the drug in other special risk groups such as pregnant women.
This study was therefore planned to evaluate the efficacy and tolerability of a prophylactic once-daily treatment with proguanil in comparison with a once-weekly prophylactic treatment with mefloquine in Nigerian children and adults with sickle cell anaemia.