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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
There has been less progress in the development of anti-merozoite vaccines. Several complicating problems have dampened enthusiasm for such vaccines, including the brief time (a matter of seconds) that merozoites are free in the blood and vulnerable to antibodies before they invade new erythrocytes. Of the more than 30 blood-stage vaccines that have entered preliminary trials since 2000, few have shown even a small, statistically significant level of protection. One recently characterized blood-stage antigen, Plasmodium falciparum Glutamic Acid Rich Protein (PfGARP), may provide some hope of future success. PfGARP is expressed on the surface of infected erythrocytes. When engaged by antibodies, parasites within the erythrocyte are induced to undergo apoptosis and die. Non-human primates vaccinated with PfGARP develop partial immunity and it has been found that African children with circulating antibodies to PfGARP are 2.5 times less likely to suffer from severe malaria compared to children lacking these antibodies. It has been suggested that a PfGARP vaccine might function synergistically when used with vaccines targeting other life cycle stages and thus represent a new line of investigation in the continuing hunt for a truly protective malaria vaccine.
The Diseases – Malaria, Filariasis and Dengue
Published in Jacques Derek Charlwood, The Ecology of Malaria Vectors, 2019
Only a few (maybe 6–10) sporozoites are injected by the mosquito. Within 45 minutes they have either found refuge in a hepatocyte in the liver or have been killed by erythrocytes. In the liver, a phase of asexual reproduction takes place. (All reproduction in the human is asexual.) After 5.5 days for P. falciparum or 15 days for P. malariae, merozoites are released into the bloodstream. There they very quickly invade erythrocytes.
An Outbreak of Cryptosporidium sp. Associated with a Public Swimming Pool
Published in Meera Chand, John Holton, Case Studies in Infection Control, 2018
Christina J. Atchison, Rachel M. Chalmers
Cryptosporidium has a monoxenous life cycle completed within the gastrointestinal tract of a single host. Infection follows ingestion of the oocyst life-cycle stage, which is shed in faeces. Under conditions triggered in the intestine, the oocysts each release four motile infectious sporozoites in a process known as excystation. These actively probe, attach, invade, and become engulfed by host epithelial cells at the luminal surface. An asexual cycle follows, involving differentiation and, sequentially, trophozoites, Type I meront, and merozoite production. The parasite proliferates as six or eight merozoites are released to invade neighbouring epithelial cells, and they either develop into trophozoites, repeating the asexual cycle, or into Type II meronts. The sexual cycle is initiated following production of four merozoites by Type II meronts, which are then released to invade neighbouring host cells and differentiate into either macrogamonts (ova) or microgamonts. Microgamonts release microgametes (sperm) into the intestinal lumen. The microgametes attach and penetrate infected epithelial cells to fertilize the macrogamete, producing a zygote. Following meiosis, the zygote differentiates into four sporozoites as the oocyst matures and is released into the intestinal lumen. Sporulated oocysts are shed in the faeces, often in large numbers, and are immediately infectious for the next susceptible host. Autoinfection of the host can occur as sporozoites may be released directly into the intestinal lumen, and the life cycle continues.
Antimalarial drugs: what’s new in the patents?
Published in Expert Opinion on Therapeutic Patents, 2023
Elizabeth A. Lopes, Maria M. M. Santos, Mattia Mori
Remarkable efforts have been spent in the prevention of malaria transmission and infection using vaccines. Four types of vaccines have been developed so far: 1) pre-erythrocytic vaccines, 2) asexual blood-stage vaccines, 3) transmission blocking vaccines, and 4) multistage combination vaccines [82]. The pre-erythrocytic stage vaccines, also named circumsporozoite protein-based strategies, target sporozoites and/or schizont-infected hepatocytes. Targeting this stage confers immunity and prevents latent malaria infection. The asexual blood-stage vaccines act against the infected red blood cells or the merozoite. As this infection stage is responsible for the disease symptoms, these vaccines are designed to minimize clinical severity and/or prevent merozoites from invading erythrocytes [83]. Transmission blocking vaccines prevent the mosquitoes to become infected when feeding from malaria infected hosts. This strategy avoids the parasite to mature in the mosquito through antibodies [84]. The multistage combination malaria vaccines target multiple stages of the parasite life cycle [85].
Recent advances in quantitative structure–activity relationship models of antimalarial drugs
Published in Expert Opinion on Drug Discovery, 2021
Probir Kumar Ojha, Vinay Kumar, Joyita Roy, Kunal Roy
The life cycle of the parasites [3] completes in two stages such as asexual stage (liver and erythrocyte stages in human host) and sexual stage (inside the mosquito) [3]. The host infection starts with the bite of female Anopheles mosquito (taking the blood meal from infected human) and sporozoites injected into the human skin capillaries. This sporozoites make their way to the cells of the liver within 30 min of injecting and starts replicating asexually [3]. The schizonts rupture to give haploids form (merozoites) within 6 to 15 days in the blood stream [3]. The invasion of the merozoites gives rise to the erythrocytic stage [3,4]. In this stage, they multiply further mitotically and pass through ring forms then the feeding stage, i.e., trophozoites, then to the reproductive stage (schizonts) over the next 48 hours which gives birth of 16 new daughter merozoites for each schizont [3,4]. After maturation, the schizonts burst giving new merozoites to the blood stream [3]. The released merozoites further inject new erythrocytes to start new fever cycle that causes the clinical symptom of malaria [3]. After few cycles, the merozoites tend to develop male and female gametocytes, i.e., sexual forms (diploid zygotes) instead of new merozoites circulating into the blood stream [3,4]. They form oocyst and travel to the midgut wall of the mosquito and within 8 to 15 days sporozoites develop and migrate to the salivary glands of the mosquitoes [3]. The host infection begins when the mosquito takes blood meal and further injects sporozoites into the human blood stream [3].
Plasmodium infection and drug cure for malaria vaccine development
Published in Expert Review of Vaccines, 2021
Reshma J. Nevagi, Michael F. Good, Danielle I. Stanisic
Malaria is transmitted to humans through the bite of a Plasmodium spp.-infected female Anopheles mosquito. During a bloodmeal, sporozoites in the salivary glands of the mosquito are transferred into the dermis of human skin (Figure 1) [2]. They then migrate to the liver via the bloodstream, infect hepatocytes and mature into hepatic schizonts. P. vivax and P. ovale have dormant liver-stage parasites (hypnozoites) that may reactivate, leading to relapses months or even years after the recovery of patients from the first episode of malaria. Upon rupture of an infected hepatic schizont, tens of thousands of merozoites are released into the bloodstream where they invade erythrocytes and continue to develop through the different erythrocytic stages (rings, trophozoites and schizonts), before the erythrocyte ruptures to release daughter merozoites. These merozoites also invade erythrocytes and the ongoing cycles of asexual replication enable parasite growth in the blood. During each replication cycle, some of the parasites develop into sexual-stage gametocytes which are ingested by mosquitoes during a bloodmeal. In the mosquito, male and female gametocytes mate within the gut forming diploid zygotes, which then become ookinetes. The ookinetes migrate to the midgut of the mosquito, pass through the gut wall and form oocysts. Sporozoites are formed after meiotic division of the oocysts. Sporozoites migrate to the salivary glands of the female Anopheles mosquito, ready to transmit the infection to another human host and continue the cycle of transmission.