Rafael Pardo, director of the Fundación BBVA, and Pedro Alonso, coordinator of the Centre of International Health of Hospital Clínic de Barcelona, have presented in the Fundación BBVA the results of a research project that will be published in the August issue of the Journal of Infectious Diseases on the efficiency and safety of the intermittent preventive treatment in Mozambican children of less than a year with sulfadoxine-pyrimethamine, a common and cheap anti-malarian. This work, that will be published in the prestigious journal of the American Society for the Infectious Disease, was presented in a press conference that had the participation of Clara Menéndez, also responsible for this work, and Eusebio Macete, the first signatory.
This research, promoted by the Fundación BBVA and the Hospital Clínic in Manhiça (Mozambique), demonstrates that the intermittent treatment with sulphadoxin-pirimetamine (SP) is safe, well tolerated and reduces by 22.2% the cases of clinical malaria in children under one year of age.
The project is also assessing, in a thousand of pregnant volunteers, the preventive value of the administration of the anti-malaria intermittent treatment on mother anaemia and parasitemia, and on the premature birth and low weight of newborns in mothers with malaria.
Malaria is one of the major causes of death in the world. It is estimated that it causes about 3,000 deaths every day and that more than 300 million people in the world are afflicted by severe malaria. This disease, with an especially high incidence among children, is responsible for 25-30% of deaths of children under five years of age in sub-Saharan Africa. To reduce the impact of this disease, it is indispensable to promote the development and eradicate poverty among the most vulnerable populations. The joint project of the Fundación BBVA and Hospital Clínic de Barcelona has the aim to fight the disease and poverty in developing countries.
Impact of the intermittent treatment of malaria in the mortality of Mozambican children
During children's visits in health centres for the WHO's vaccination programme (Expanded Programme of Immunization), researchers have administered three consecutive doses of sulfadoxine-pyrimethamine (SP). In this study, 1,503 children have been administered the drug on their third, fourth and ninth month of age. This drug is commercialised, inexpensive and has an extended use for the treatment of malaria. Works such as the one that today has been published evidence its possible preventive applications.
After receiving an informed consent, researchers codified the identity of children and divided them into two groups. The first was treated with SP, whereas the other received a placebo. This was a double-blind trial (neither the patient nor the physician knew if the drug or the placebo was administered), in order to assess the objectivity of the process. Parents were administered a card with a photo of the child for the child's identification during visits, and doctors insisted in the need to attend to the health centre if children fell ill. The safety of the treatment was registered with home care assistance after each SP dose, and a blood test was made a month after the second administration to assess the potential toxicity of treatment and the possible hepatic damage. After a temporary follow-up, specialists of the International Health Centre of Hospital Clínic de Barcelona compared contagion and mortality rates in both groups to assess the effectiveness of prophylaxis. The fact that the SP intermittent treatment did not interfere in the response of vaccinations administered in the WHO vaccination programme was tested in a in a subgroup of 600 children included in the study.
In this trial, promoted by Fundación BBVA and Hospital Clínic de Barcelona, children did not suffer from a potentially severe disease. Needless to say, the participation in this study did not prevent them from a medication they needed, since children were not malaria patients. In case they caught the disease during the study, they quickly received the drugs in order to fight it. The aim of this trial was to evaluate SP's potential ability to prevent the development of a disease. To get objective results, it was indispensable to set a control in order to compare the new therapy with the current situation. It is from this information that the International Health Agencies approve the generalised distribution of Malaria Intermittent Treatment throughout the world.
The possibilities this treatment has as a prophylactic to prevent the spreading of malaria were already demonstrated on a small scale in Tanzania, with a study that demonstrated that the intermittent treatment with sulfadoxine-pyrimethamine administered with the collaboration of the WHO's vaccination programme, improved survival. Now results obtained in Mozambique renew hope, after checking that the SP intermittent treatment has reduced the incidence of clinical malaria by 22.2% and the number of admissions by 19%.
On the other hand, there has been no rebound effect in the number of malaria cases after the third and last preventive SP administration. Although available data on the safety of SP treatment in children are scarce, no relevant side effects have been observed. Furthermore, no significant differences have been observed among the experimental and the control group in their immune response to the WHO's vaccination programme; the efficiency remained unaltered when the SP intermittent treatment was introduced. Another positive piece of data that deserves new studies is the effect of the SP administration on the overall health of children, since both gastrointestinal and respiratory symptoms were reduced during the month after the second SP dose.
One of the advantages of the treatment is that it proposes a simple oral administration, does not require a new infrastructure, and is cost-efficient compared to other options. Each SP administration has an approximated cost of 2 US dollar, including the cost of the drug, its transport and distribution.
This study will be discussed from September in the World Health Organisation, who is tutoring and monitoring the whole process. The intention of the WHO is to approve a resolution during its next 2007 General Assembly on the generalised use of the malaria intermittent treatment.
Effect of the administration of the intermittent treatment in pregnant women
Pregnant women are a group with an added risk in malaria infection. Malaria during pregnancy is, in the entire world, one of the most important causes of premature delivery, low weight of the newborn, and one of the main causes of severe mother anaemia. In all cases, this leads to an increase of mother and perinatal mortality. It is currently accepted that, during pregnancy, the kidnapping of erythrocytes infected by the parasite affects the functions of the placenta, interfering with the mother-foetus interchange.
Chloroquine chemoprophylaxis, which has been proposed during years, has not yielded positive results. This fact has two reasons: the lack of accomplishment of the medication by treated women and an increase of the resistance level of the parasite to the drug. The distribution of mosquito nets impregnated with insecticide, aimed to minimise the exposition of women to the mosquito transmitting the disease, has not yielded the expected results. That is why it is now needed to find an alternative system which protect pregnant women against malaria, above all in zones there it is endemic.
Pedro Alonso and Clara Menéndez's group is also studying the possibilities of the malaria intermittent treatment as a preventive strategy in pregnant women. Approximately 1,000 volunteer women of the Manhiça district, in the region of Maputo, collaborate in the study. These women have been divided into two groups: one group has received the SP treatment, and the other, a placebo. After their informed consent, medication was administered in their prenatal visit in the second trimester and early third trimester of gestation.
The trial is assessing the beneficial effects on the mother –reduction of anaemia and of premature and low weighted delivery– and the possible harmful effects –immune response disorder in mothers. Parallely, this study assesses if this treatment improves the protection provided by mosquito nets if both prophylaxis strategies are combined. Results will be soon published and will be the basis for new international health agencies strategic decisions.
First research centre on the infectious disease
In 1998, Hospital Clínic de Barcelona initiated in Manhiça (Mozambique) the first Spanish research centre on the infectious and tropical disease with the support of the Agencia Española de Cooperación Internacional. The WHO has not chosen this centre as a pilot centre to assess the application on the large scale of the Malaria Intermittent Treatment with a preventive aim.
The Centro de Investigaçao em Saude de Manhiça, directed by Pedro Alonso, controls the development of the research promoted by Fundación BBVA in the Mozambican region of Maputo (district of Manhiça). Barcelona was also the chosen city in 2004 by the Intermittent Preventive Treatment in Infants (IPTi) to set the headquarters of its executive secretariat, a decision influenced by the fact that the Fundación BBVA project was already in operation.
For further information, please contact the Communication Departments of Fundación BBVA (915 376 615 y 944 874 627) and IDIBAPS - Hospital Clínic de Barcelona (932 275 700)
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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