Relapsing Fever

The kinetoplastid infections are transmitted by insect vectors, and the three major kinetoplastid infections of humans, human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis, kill approximately 70,000 people annually, making them among the most lethal neglected tropical diseases (NTDs). HAT, also known as sleeping sickness, is caused by two different species of trypanosomes. Trypanosoma brucei gambiense is the cause in West Africa, while T. b. rhodesiense occurs in East Africa. It results from the bite of tsetses of the genus Glossina. Control of West African HAT relies largely on case detection and treatment as well as vector control, while fighting East African HAT relies on control in animal reservoirs and vector control. Chagas disease, also known as American trypanosomiasis, is caused by T. cruzi, which has the ability to invade host cells and replicate as amastigotes. The infection is transmitted by kissing bugs, primarily of the genus Triatoma. Control of Chagas disease in the Southern Cone has been highly effective through indoor spraying that targets the vector, T. infestans. Leishmaniasis is transmitted by the bite of a sandfly. Cutaneous leishmaniasis (CL) is a disfiguring, pizza-like lesion, which often self-heals but can leave a scar. The scar is often deeply stigmatizing for women in developing countries. Visceral leishmaniasis (VL), or kala-azar, produces a febrile wasting syndrome with signs and symptoms that resemble leukemia. Drugs containing antimony are still widely used for the treatment of CL and VL, but are toxic and difficult to administer.

Depending on the life cycle, a number of parasites may be recovered in a blood specimen, either whole blood, buffy coat preparations, or various types of concentrations. These blood parasites include Plasmodium, Babesia, and Trypanosoma species, Leishmania donovani, and microfilariae. Blood films can be prepared from fresh, whole blood collected with no anticoagulants, anticoagulated blood, or sediment from the various concentration procedures. The recommended stain of choice is Giemsa stain; however, the parasites can also be seen on blood films stained with Wright’s stain, a Wright-Giemsa combination stain, or one of the more rapid stains such as Diff-Quik. Delafield’s hematoxylin stain is often used to stain the microfilarial sheath; in some cases, Giemsa stain does not provide sufficient stain quality to allow differentiation of the microfilariae. It is important to report the level of parasitemia when blood films are reviewed and found to be positive for malaria parasites. Due to the potential for drug resistance in some of the Plasmodium species, particularly P. falciparum and P. vivax, it is important that every positive smear be assessed and the parasitemia reported exactly the same way on follow-up specimens as on the initial specimen. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. There are a number of new approaches to the diagnosis of malaria, including the use of fluorescent stains (QBC), dipstick antigen detection of histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) PCR, and automated blood cell analyzers.

The discovery that Plasmodium falciparum-infected erythrocytes can bind to uninfected erythrocytes to form rosette-like clumps of cells was first made in the late 1980s. Some of the parasite ligands and host uninfected erythrocyte receptors that mediate rosette formation have been identified, and work has begun to determine the potential for a rosette-inhibiting antidisease vaccine. Despite this progress, the function of rosetting remains unknown, and the exact role of rosetting in the pathogenesis of severe malaria remains controversial. In falciparum malaria it may be the combination of rosetting and cytoadherence, together with high parasite burdens, that is particularly obstructive to microvascular blood flow and could lead to hypoxia, tissue damage, and severe malaria. Skeptics of rosetting claim that there is no evidence that rosettes form in vivo. A number of different red blood cell rosetting receptors have been described, including CR1, heparan sulfate-like molecules, ABO blood group sugars, and CD36. The CD36 glycoprotein, which is an important endothelial receptor for cytoadherence, is expressed at low levels on red blood cells but only rarely acts as a rosetting receptor in field isolates. The development of rosette-inhibiting immune responses in natural malaria infections has received relatively little attention. There is lack of proof that rosetting causes severe malaria. However, evidence does support a direct role for rosetting in the pathogenesis of some cases of life-threatening malaria.