PZQ Therapy: How Close are we in the Development of Effective Alternative Anti-schistosomal Drugs?

Abstract

Today schistosomiasis, caused mainly by the three major schistosome species (S. mansoni, S. haematobium and S. japonicum), has for many decades and still continues to be on a rapid and swift rise globally, claiming thousands of lives every year and leaving 800 million people at the risk of infection. Due to the high prevalence of this disease and the steady increase in the infection rates, praziquantel (PZQ) remains the only effective drug against this acute disease although it has no effect on the juvenile schistosome parasite. However, no significant approaches have been made in recent years in the discovery of new or alternative drugs and unfortunately, resistance to this drug has been reported in some parts of the world. Therefore, it is imperative to develop a new drug for this debilitating disease. In this review, a brief history of past, present, and new promising anti-schistosomal drugs is presented.

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

“…Urman et al, 1975;Katz, 1977;Nare et al, 1992;Thetiot-Laurent et al, 2013 Oxamniquine Oxamniquine has also been used in the past, but it is ineffective against all schistosomes type, only effective to S. mansoni, and due to cost effectiveness, drug resistance and some side effects, the drug has been replaced by praziquantel in treating schistosomiasis. Saconato and Atallah, 2000;Morgan et al, 2001;Richter, 2003;El Ridi and Tallima, 2013;Aruleba et al, 2018 interacting with proteins and glycans via the extracellular loops of the tetraspanins protein, this depicts tetraspanins as a probable target for nano-delivery systems. The initiation of heptalaminate membrane surface alongside dyneins protein starts from the outer membrane of the cercarial trilaminate 30 min after invasion of cercarial into the host skin, and within 3 h, the change in cercarial membrane from the trilaminate to the heptalaminate mature membrane structure is accomplished in an immature schistosome (schistosomulum) (Mansour and Mansour, 2002), with the help of several molecules which are potential target for nano-delivery systems.…”

“…Metrifonate is selective to only S. haematobium and due to medical standards and economic operations, the drug has been withdrawn from the market. Eissa et al, 2011;de Moraes, 2012;Aruleba et al, 2018 Oltripaz Oltripaz is another anti-schistosomal drug which has been used in the past, but not in the market again and discontinued in treating schistosomes infection due to its photosensitivity induction and longer time in curing the infections; approximately 2 months. Nare et al, 1992 Niridazole Niridazole was jettisoned due to its unpleasant adverse effects which include non-specificity destruction to the T waves electrocardiogram (ECG), toxicity to the renal and central nervous system, it has also been revealed to be a carcinogenic material.…”

Polymeric Nano-Biomaterials for Medical Applications: Advancements in Developing and Implementation Considering Safety-By-Design Concepts

“…The membranocalyx can be active by Urman et al, 1975;Katz, 1977;Nare et al, 1992;Thetiot-Laurent et al, 2013 Oxamniquine Oxamniquine has also been used in the past, but it is ineffective against all schistosomes type, only effective to S. mansoni, and due to cost effectiveness, drug resistance and some side effects, the drug has been replaced by praziquantel in treating schistosomiasis. Saconato and Atallah, 2000;Morgan et al, 2001;Richter, 2003;El Ridi and Tallima, 2013;Aruleba et al, 2018 interacting with proteins and glycans via the extracellular loops of the tetraspanins protein, this depicts tetraspanins as a probable target for nano-delivery systems.…”

The Effect of Climate Change and the Snail-Schistosome Cycle in Transmission and Bio-Control of Schistosomiasis in Sub-Saharan Africa

“…More so, there is a need for control measures for the disease in sub-Saharan Africa such as infrastructural development that can mitigate the effects of floods and development of vaccines and new drug formulations that will be capable of blocking re-infection of schistosomiasis and effectively overcome drug resistance. Since multidrug resistance to the worm has been reported [11,149] due to: the parasitic load; poor treatment compliance; co-infections of different strains of the parasites; and the rate of mutation of the parasite, as well as the ineffectiveness of praziquantel against the juvenile schistosomes [150]. Moreover, other measures that need to be put in place in order to lessen the burden of schistosomiasis in SSA include: an improvement and consistency in climate surveillance systems, execution of vaccination campaigns in target regions once vaccines are developed, sensitization of the public about the disease and its impacts on public health and public health policies, as well as improvement in support towards schistosomiasis research in order to better understand the current and possible future distribution of the disease.…”