Plasmodium falciparum
Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of "Plasmodium" that cause malaria in humans. It is transmitted through the bite of a female "Anopheles" mosquito. It is responsible for roughly 50% of all malaria cases. It causes the disease's most dangerous form called falciparum malaria. It is therefore regarded as the deadliest parasite in humans, causing 435,000 deaths in 2017. It is also associated with the development of blood cancer (Burkitt's lymphoma) and is classified as Group 2A carcinogen.
Epstein-Barr virus-associated lymphoproliferative diseases
Severe mosquito bite allergy (SMBA) is a rare disorder which occurs mainly in young East Asians (median age 6.7 years). In most cases, it is a manifestation of CAEBV infection of the EBV+ NK cell type: ~33% of all individuals with CAEBV develop this allergy. SMBA has also been reported to occur in rare cases of EBV positive Hodgkin disease, hydroa vacciniforme, aggressive NK‐cell leukemia (also termed aggressive NK-cell leukemia/lymphoma), and extranodal NK/T-cell lymphoma, nasal type, as well as in EBV negative LPD such as chronic lymphocytic leukemia and mantle cell lymphoma. EBV+ SMBA is an hypersensitivity reaction. In CAEV, the best studied or the predispositions to the disorder, SMBA is characterized by the development of skin redness, swelling, ulcers, necrosis and/or scarring at the site of a mosquito bite. This is often accompanied by fever and malaise; enlarged lymph nodes, liver, and/or spleen; liver dysfunction; hematuria; and proteinuria. Afflicted individuals have increased blood levels of immunoglobulin E (which plays an essential role in the development of type I hypersensitivity reactions of the skin and other tissues) and EBV+ NK cells. In severer cases, the disorder is complicated by hemophagocytosis, NK/T-cell lymphoma, or aggressive NK cell leukemia. Diagnostically, the skin lesions show infiltrating NK cells in the epidermis and subcutaneous tissue with a small fraction of these cells being EBV+ with the virus in its latency II phase. A very high density of EBV+ NK cells in these lesions suggests the disorder has progressed to NK/T cell lymphoma or NK cell leukemia. While the disorder's etiology is unclear, it is thought that the mosquito salivary gland allergenic proteins trigger reactivation of EBV in latently infected NK cells. Upon reactivation, EBV genes such as LMP1 express products that induce immortalization, proliferation, and in some cases malignancy of the EBV reactivated NK cells. The best treatment for SMBA remains unclear. Mild and clearly uncomplicated cases can be treated conservatively focusing on obtaining relief of symptoms such as skin irritation, fever, and malaise. However, cases with evidence of significant complications of CAEFV such as the development of hemophagocytosis, NK/T cell lymphoma, or aggressive NK cell lymphoma, support the use of the chemotherapeutic regimens directed at these complications. Cases of EBV+ SMBA associated with clear evidence of concurrent aggressive CAEBV have been treated with relative success by the 3 step regimen used to treat CAEBV. Rare cases of SMBA have been reported to occur in individuals who have no apparent predisposing disease but later develop CAEBV.. Such cases require careful evaluation and follow-up for development of a predisposing disorder.