The Effect of Helminth Infections and Their Treatment on Metabolic Outcomes: Results of a Cluster-Randomized Trial

Abstract

Background Helminth infection may influence cardiometabolic risk through effects on inflammation and metabolism. We hypothesised that helminths are protective and their treatment detrimental to metabolic outcomes. Methods We conducted a cluster-randomised trial in 26 fishing communities, Lake Victoria, Uganda. We investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple dose albendazole) versus standard (annual single-dose praziquantel, six-monthly single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminth infection and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes (including blood pressure, fasting blood glucose and lipids) were assessed in a survey conducted after four years of intervention among individuals ≥10 years. Results We analysed 1898 participants. The intervention had no effect on HOMA-IR (adjusted geometric mean ratio [95%CI] 0.96 [0.86,1.07] p=0.42) but resulted in higher mean LDL-cholesterol in the intensive arm (2.86 vs 2.60 mmol/L, adjusted mean difference [95%CI] 0.26 [-0.03,0.56] p=0.08). Lower LDL-cholesterol levels were observed in S. mansoni (2.37 vs 2.80 mmol/L, -0.25 [-0.49,-0.02] p=0.04) and Strongyloides infected (2.34 vs 2.69mmol/L, -0.32 [-0.53,-0.12] p=0.003) participants compared with uninfected. S. mansoni infection was associated with lower total cholesterol levels (4.24 vs 4.64 mmol/L, -0.25 [-0.44,-0.07] p=0.01). Participants with moderate to heavy S. mansoni infection had lower triglycerides, LDL-cholesterol and diastolic blood pressure levels. Conclusions Helminth infections improve lipid profiles and may lower blood pressure. Further studies to confirm causality and investigate mechanisms will contribute to understanding the epidemiological transition and may suggest new approaches to prevent cardiometabolic disease. Clinical trials registration ISRCTN47196031

Schistosoma haematobium infection is associated with lower serum cholesterol levels and improved lipid profile in overweight/obese individuals

“…LDL-c levels were significantly lower in lean Chinese subjects with chronic S. japonicum infection when compared to uninfected individuals [24]. Finally, during the preparation of the manuscript, the results of a study investigating the effects of S. mansoni infection on metabolic outcomes in the framework of the LaVIISWA trial conducted in the highly-endemic region of Lake Victoria in Uganda became available [25]. Interestingly, a negative association between the intensity of S. mansoni infection and serum TC, HDL-c, LDL-c and TG levels was found [25].…”

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

“…58 Two others studies in Indonesia and Uganda demonstrated similar outcomes after treatment against STHs and S. mansoni, respectively. 59,60 Finally, a cross-sectional analyses of several studies linking helminth infection and metabolic syndrome confirmed the trend towards a decreased prevalence of metabolic syndrome in people with past or present helminth infection. 61 Although this emerging literature is intriguing, further work is certainly required to show exactly how these effects are mediated.…”

“…More importantly, they could show a significant deterioration of these parameters after anthelmintic therapies . Two others studies in Indonesia and Uganda demonstrated similar outcomes after treatment against STHs and S. mansoni, respectively . Finally, a cross‐sectional analyses of several studies linking helminth infection and metabolic syndrome confirmed the trend towards a decreased prevalence of metabolic syndrome in people with past or present helminth infection .…”

Contrasting impact of rural, versus urban, living on glucose metabolism and blood pressure in Uganda

“…Diabetes and impaired fasting glucose were defined, according to the WHO classification, as fasting plasma glucose of ≥7.0 mmol/L and 6.1-6.9 mmol/L, respectively 31,32 . Hypertension was defined as diastolic blood pressure of ≥90 mmHg or systolic blood pressure of ≥140 mmHg in participants ≥18 years of age 33 . Participants <18 years old were categorised to be hypertensive if their systolic or diastolic blood pressures were above the 95 th percentile using the Centers for Disease Control blood pressure charts for children and adolescents 34 .…”