Effect of chlorpyrifos on healing of cutaneous leishmaniasis lesions after treatment with Pentostam®

Abstract

The insecticide chlorpyrifos (CPF) is widely used in the Kingdom of Saudi Arabia (KSA) to control agricultural pests. The present work is a preliminary investigation of the effect of CPF on healing of cutaneous leishmaniasis (CL) lesions, caused by Leishmania major in farmers exposed to this insecticide, after treatment with Pentostam(®). Lesion diameters were measured and CPF concentrations in the blood plasma of farmer and non-farmer CL patients in Al-Ahsa were detected by gas chromatography/mass spectrometry/mass spectrometry before and 6 weeks after treatment with Pentostam(®). CPF concentrations in the blood of farmer patients ranged between 4.570 and 7.096 ng/μl (mean = 6.19 ± 0.881 ng/μl) before and after treatment with Pentostam(®). The mean lesion diameter in these patients decreased by a factor of 2.21 after treatment with Pentostam(®); they measured 1.85-11.75 mm, (mean = 6.165 ± 3.500 mm) before treatment and 0.22-6.10 mm (mean = 2.796 ± 2.102 mm) after treatment. Lesion diameter increased exponentially with the increase of CPF concentration in the patients' blood. CPF was not detected in the non-farmer patients before or after treatment. Their mean lesion diameter decreased by a factor of 6.86 after treatment with Pentostam(®); they measured 1.33-7.10 mm (mean = 2.882 ± 1.764 mm) before treatment and 0.11-0.92 mm (mean = 0.425 ± 0.277 mm) after treatment. The mean lesion diameter in farmer patients was much greater than that of non-farmer patients both before (2.14×) and after (6.657×) treatment with Pentostam(®). Chronic exposure to low levels of the pesticide aggravates the development and delays the healing of CL lesions due to immunotoxicity and/or peripheral neurotoxicity caused by CPF. Further detailed studies would assess CPF effect on the severity of infection with CL in agricultural workers continuously exposed to this insecticide in different areas of KSA in conformity of their finding.

Increased heart fibrosis and acute infection in a murine Chagas disease model associated with organophosphorus pesticide metabolite exposure

“…We suggest that the elimination of parasites is reduced because MΦ are subsequently reprogrammed to switch to the immunosuppressive/tissue-repairing phenotype of M2 cells (mainly M2a and M2d), which contributes to uncontrolled parasite replication. These results are consistent with those observed in some human populations 17 , where chronic exposure to low levels of the OP pesticide chlorpyrifos exacerbated infection with Leishmania sp . and delayed the healing of cutaneous leishmaniasis lesions due to alterations in the immune response.…”

“…Some epidemiological studies report that exposure to OP pesticides may increase the rate and risk of infections in rural populations 16 , exacerbating cutaneous leishmaniasis and inducing a low response to treatment in farmers exposed to chlorpyrifos, an OP pesticide that generates DETP and DEP 17 . In vivo studies showed that these effects on the immune response may be due to a decrease in the levels of plasma nitric oxide (NO) and interferon (IFN)-γ and to the increase in the activity of arginase, which explains the inability of macrophages (MΦ) to control the parasites or induce an adequate immune response against them 18 .…”

Adverse Effects of Organophosphorus Insecticides on Macrophage Activity in Persons at High Risk for Parasitic Infection

“…It has been revealed that induction of arginase enzyme favored the replication of leishmania inside the macrophages, but inhibition of arginase reduces the number of parasites found in macrophages [15]. Furthermore, Al-Dawood et al, 2009 [12] reported that leishmaniasis persons exposed to CPF exhibited a delay in the healing of their skin lesions as compared to leishmaniasis persons not exposed to CPF. Therefore, high level of arginase activity as a result of CPF exposure associated with adding curcumin directly on the insect bites may explain the delayed healing of skin lesions in our patients.…”

“…Furthermore, Arginase activity is induced by cytokines secreted by T helper-2 lymphocyte, while iNOS is activated by gamma interferon (IFN-gamma) secreted by T helper-1 lymphocyte [7]. Recent studies reported that chronic exposure to low levels of the pesticide aggravates and delays the healing of cutaneous leishmaniasis lesions [12]. In Tabouk region, North of KSA, farmers are inevitably exposed to high amount of chlorpyrifos (CPF) insecticide.…”