Neglected diseases

The classification relative to diseases proposed by OMS and by Médicos sem Fronteiras is divided in: global, those that affects all the world; neglected, which prevails in developing countries; and more neglected, which occurs exclusively in developing countries. Between them are malaria, Chagas disease, yellow fever, leishmaniasis and dengue. Most of the time, the microorganisms which cause these diseases are transmitted by mosquitoes, and in the tropics they have optimum conditions of growth.

The insects that are vectors of diseases are responsible for thousands of deaths and afflict millions of people in the world, especially the Culicidae family. This family comprises vectors of neglected diseases that affect approximately 700 million of people annually. The malaria, for example, causes more than one million of deaths every year; dengue, 24 thousand deaths between the 50 million of people afflicted by this disease yearly, according to data from the World Health Organization.

Besides the transmitted diseases, the insects’ bites cause allergy and discomfort. The diversity of habits and interspecific cycles are the main difficulties to counter the occurrence of these bites, and consequently, the transmission of diseases.

The pursuit for ways to avoid bites and the risk of transmitting diseases including all habitats, habits and cycles from different species of insects is already known (STEFANI et al., 2009; SORGE et al., 2007; FRADIN et al., 2002). As vaccines and chemoprophylaxis are not available in all cases, and a single insect bite can cause a disease, it is important to create new repellents, more efficient and with a prolonged activity (FRADIN et al., 2002).

Epidemic of neglected diseases are occurring lately, unfortunately without forecast for efficient prevention. There are 3 main flaws comprising repellents that corroborate with the persistency of neglected diseases epidemics (MAHONEY & MOREL, 2006). Science flaws, when research is not efficient to solve the problem; market flaws, when there are answers to the problem, but it has a cost that prevents treatment; and public health policy flaws, when there is a cheap and efficient product, but there are no mechanisms to facilitate the population to get it.

DEET

The N,N-diethyl-m-toluamide (DEET) is a compound from toluene family that has the following molecular formula: C12H17NO. It was one of the first synthetic repellents, originally developed by the United States Department of Agriculture for military uses. In 1957 it was released to the public and it is still the repellent compound most used in the world (BARNARD, 2000).

Figure 1: DEET structure.

The concerns with safety involved in DEET usages arouse for the first time in the 80’s, with encephalopathy reports after exposition to the product; especially in children. In response to these cases, many safety analysis and investigations related to DEET were done (CHEN-HUSSEY et al., 2014; ROBBINS et al., 1986).

A study about DEET, done to analyze the prevention of malaria transmission in pregnant women in Thailand, evaluated the health of the participants. As results, DEET was not detected in urine; however, it was detected on women’s blood and in umbilical cord of about 8% of the analyzed patients, indicating that DEET is capable to pass through placenta (MCGREADY et al., 2001). This feature was already confirmed in a study of toxic compounds in umbilical cord blood of pregnant women in New Jersey (BARR et al., 2010).

Being a self-administered drug that exhibit risks if taken in high concentrations, the incidence of deaths continues to indicate it as dangerous for domiciliary uses. A recent example is the case of a patient that died after ingesting of 177 mL of repellent containing 40% of DEET in its composition (WILES et al., 2014).

Considering the uses on children and pregnant women, a 2010 directive of the European Union recommends that the percentage of DEET in the composition of repellents do not pass 15%. However, this percentage would result in a sub-therapeutic activity; leading to a situation which are necessary more frequent applications of the product. The concentration of DEET is related to the length of its protection (FRADIN et al., 2002).

The Brazilian legislation discusses about DEET. It is not allowed to use it on children younger than 2 years old; it is allowed to use on children from 2 to 12 years old, as long as the DEET concentration is below 10%, restricting it to three applications per day; for last, formulas containing DEET with concentrations superior to 30% are allowed to use by people older than 12 years old, as long as studies evaluating risks for humans are done, considering the frequency of application.

Studies that tested the relation between DEET concentration and the duration of protection against insects showed a significant correlation between them. The formula containing 4,75% of DEET provided a mean of 88,4 minutes of complete protection; the formula containing 23,8% of DEET provided a protection of approximately 301,5 minutes (FRADIN et al., 2002).

The same study still tested some repellents made from natural oils. They showed a protection equal or inferior in one hour and half of the duration compared to DEET based repellent (FRADIN et al., 2002).

In this way, following the recommendations of European Union or from Brazilian legislation would result in an inadequate individual protection, especially to children from 2 to 12 years old. This potentially raises the number of cases of diseases transmitted by insects, requiring many daily applications, which also raise the accumulated toxicity.

References

STEFANI G. P., PASTORINO A. C., CASTRO A. P. B. M., FOMIN A. B. F., JACOB C. M. A. Insect repellents: recommendations for use in children. Rev Paul Pediatr 2009

SORGE F., IMBERT P., LAURENT C., MINODIER P., BANERJEE A., KHELFAOUI F. Children arthropod bites protective measures: insecticides and repellents. Arch Pediatr 2007

FRADIN M. S., DAY J. F. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002

MAHONEY R. T., MOREL C. M. A Global Health Innovation System (GHIS). Innovation Strategy Today, 2006

CHEN-HUSSEY V., BEHRENS R., LOGAN J. G. Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET). Parasit Vectors. 2014

ROBBINS P. J., CHERNIAK M. G. Review of the biodistribution and toxicity of the insect repellent N, N-diethyl-m-toluamide (DEET). J Toxicol Environ Health. 1986

MCGREADY R., HAMILTON K. A., SIMPSON J. A., CHO T., LUXEMBURGER C., EDWARDS R., LOOAREESUWAN S., WHITE N. J., NOSTEN F., LINDSAY S. W. Safety of the insect repellent N, N-diethyl-m-toluamide (DEET) in pregnancy. Am J Trop Med Hyg. 2001

BARR D. B., ANANTH C. V., YAN X., LASHLEY S., SMULIAN J. C., LEDOUX T. A., HORE P., ROBSON M. G. Pesticide concentrations in maternal and umbilical cord sera and their relation to birth outcomes in a population of pregnant women and newborns in New Jersey. Sci Total Environ, 2010

WILES D., YEE J., CASTILLO U., RUSSELL J., SPILLER H., CASAVANT M. A Lethal Case of DEET Toxicity Due to Intentional Ingestion. Journal of Analytical Toxicology, July 6, 2014