Journal Article

Hormones in malaria infection: influence on disease severity, host physiology, and therapeutic opportunities

Das, Aleena, Suar, Mrutyunjay, Reddy, K Sony

2024

Overview

Human malaria, caused by Plasmodium parasites, is a fatal disease that disrupts the host’s physiological balance and affects the neuroendocrine system. This review explores how malaria influences and is influenced by hormones. Malaria activates the Hypothalamus-Pituitary-Adrenal axis, leading to increased cortisol, aldosterone, and epinephrine. Cortisol, while reducing inflammation, aids parasite survival, whereas epinephrine helps manage hypoglycemia. The Hypothalamus-Pituitary-Gonad and Hypothalamus-Pituitary-Thyroid axes are also impacted, resulting in lower sex and thyroid hormone levels. Malaria disrupts the renin-angiotensin-aldosterone system (RAAS), causing higher angiotensin-II and aldosterone levels, contributing to edema, hyponatremia and hypertension. Malaria-induced anemia is exacerbated by increased hepcidin, which impairs iron absorption, reducing both iron availability for the parasite and red blood cell formation, despite elevated erythropoietin. Hypoglycemia is common due to decreased glucose production and hyperinsulinemia, although some cases show hyperglycemia due to stress hormones and inflammation. Hypocalcemia, and hypophosphatemia are associated with low Vitamin D3 and parathyroid hormone but high calcitonin. Hormones such as DHEA, melatonin, PTH, Vitamin D3, hepcidin, progesterone, and erythropoietin protects against malaria. Furthermore, synthetic analogs, receptor agonists and antagonists or mimics of hormones like DHEA, melatonin, serotonin, PTH, vitamin D3, estrogen, progesterone, angiotensin, and somatostatin are being explored as potential antimalarial treatments or adjunct therapies. Additionally, hormones like leptin and PCT are being studied as probable markers of malaria infection.

• Publisher: Portland Press Ltd The Biochemical Society
• Subject: Aldosterone / Anemia / Angiotensin / Angiotensin II / Animals / Antiparasitic agents / Blood parasites / Brain research / Calcitonin / Cortisol / Deficiency diseases / Dehydroepiandrosterone / Dopamine / Edema / Epinephrine / Erythrocytes / Erythropoietin / Estrogens / Glucagon / Glucose / Growth hormones / Hepcidin / Homeostasis / Hormones / Hormones - metabolism / Humans / Hyperglycemia / Hyperinsulinemia / Hypertension / Hypocalcemia / Hypoglycemia / Hyponatremia / Hypothalamo-Hypophyseal System - metabolism / Hypothalamus / Infections / Inflammation / Insulin / Iron / Malaria / Malaria - drug therapy / Malaria - metabolism / Malaria - parasitology / Melatonin / Metabolism / Neuroendocrine system / Pancreas / Parasites / Peptides / Physiology / Pituitary-Adrenal System - metabolism / Plasmodium - metabolism / Plasmodium - pathogenicity / Proteins / Renin / Renin-Angiotensin System - drug effects / Serotonin / Testosterone / Thyroid / Thyroid gland / Vector-borne diseases / Vitamin D3