WikiJournal Preprints/Combating intestinal parasitic infections: The need to initiate control strategies targeting intestinal protozoa infections and integrate the strategies with the ongoing mass deworming programmes

Background
Intestinal parasitic infections are among the most prevalent parasitic infections worldwide, especially in low-income countries. IPIs are caused by protozoa and helminths species and are responsible for high morbidity and mortality especially in resource-limited places. Globally, it's estimated that 3.5 billion people are affected of which more than 450 million people are sick as a result of IPIs. The major intestinal parasites that infect human beings are; Giardia lamblia, Entamoeba histolytica, Cystoisospora belli, Balantidium coli, Cryptosporidium spp., Ascaris lumbricoides, Trichuris trichiura, hookworms, Enterobius vermicularis, Strongyloides stercoralis, Schistosoma mansoni, Taenia solium, Taenia saginata, Dipyllidium caninum, Hymenolepis nana, Diphyllobothrium latum, Metagonimus yokogawai, Heterophyes spp. and Fasciolopsis buski. Among the vulnerable groups for IPIs, children (preschoolers and school-age children) are the most affected, and infection can lead to several complications such as anemia, nutrient deficiency and malabsorption, stunting, intestinal obstruction, intestinal bleeding, low academic performance, and mental and physical development retardation.

Due to the burden of IPIs, the ongoing interventions have been focusing on periodic mass deworming of people at risk and improvement of water, sanitation and hygiene (WASH). The drugs used for mass deworming are albendazole or mebendazole for soil-transmitted helminths (STH) and praziquantel for schistosomiasis. However, the praziquantel has a very broad-spectrum activity against cestodes and trematodes that makes mass deworming with albendazole or mebendazole and praziquantel beneficial in controlling intestinal helminths only. The aim of mass deworming is to reduce and maintain the burden of IPIs, in order to protect the infected population from morbidity and prevent further transmission. The implementation of interventions such as the improvement of water, sanitation and hygiene (WASH) is done but on a small scale due to the lack of resources. Regular mass deworming of at least 75% of at higher-risk populations such as school-age children have been successful in reducing the STH and schistosomiasis burden. In all countries with ongoing mass deworming programmes for more than five years, it has resulted in the elimination of morbidity caused by the STH. Further, in countries with regular administration of praziquantel, it has resulted in low worm burden and morbidity reduction despite the high continued schistosomiasis transmission.

However, despite the success of the ongoing interventions, we think that these interventions are not enough to prevent and control IPIs. This paper aims to express our opinions on the ongoing interventions to combat IPIs in endemic countries. The paper also highlights the challenges of the ongoing interventions and recommends strategies to be integrated into the ongoing mass deworming programmes to accelerate the rate of IPIs prevention and control.

Why the mass deworming is not enough to control IPIs
We think the ongoing mass deworming is not enough to prevent and control IPIs due to various factors. Mass deworming using albendazole or mebendazole and praziquantel target only intestinal helminths (intestinal nematodes, cestodes and trematodes), leaving out intestinal protozoa which highly contribute to the morbidity in the vulnerable population. The effort to control intestinal helminths alone, without simultaneously controlling intestinal protozoa, makes elimination of IPIs difficult. The challenge for integrating deworming of intestinal protozoa in the ongoing mass deworming programme could be attributable to different intestinal protozoa which requires different drugs. However, a drug known as nitazoxanide has shown the potential to be used in mass drug administration to control intestinal protozoa.

The ongoing mass deworming practices must be done regularly (moreso than current practices) because reinfection after treatment is inevitable. To ensure sustainable control, mass deworming must be supported with other interventions such as improvement of WASH services. However, the challenge with the implementation of WASH remains inadequate water supplies, poor sanitation and hygiene practices. It has been proven that basic hygienic measures such as handwashing with water and soap at critical moments lower the IPIs by 68% but the problem has been limited access to water that makes the implementation of hygienic measures difficult.

The ongoing mass deworming might not be enough to prevent and control IPIs because it is currently targeted to pre-school children, school-age children and pregnant women compared to the rest of the population that includes adolescents and adults in certain high-risk occupations who might serve as the source for transmission in the community. Furthermore, the drugs used for deworming have been used for several years in the mass population thus limiting it is effectiveness over time alerting the emergence of parasitic drug resistance.

Possibility of integration of nitazoxanide into the ongoing mass deworming programme
Nitazoxanide has shown to be effective in the protection and treatment of intestinal parasites such as G. lamblia, E. histolytica, I. belli, B. coli, Cryptosporidium spp., A. lumbricoides, T. trichura, T. saginata, H. nana, and F. hepatica when integrated with albendazole. The dose should be administered twice daily for three consecutive days at a dose of 200 mg for children less than 12 years and 500 mg for 12 years and above. The integration of nitazoxanide with albendazole will broaden the fight against intestinal protozoa. However, the challenges of integrating nitazoxanide to the ongoing deworming could be the administration of the drugs, as the current drugs are administered as a single dose, but nitazoxanide will require prolonged administration, hence increased cost. Furthermore, mass administration of nitazoxanide without specific diagnosis could cause emergence of drug resistance.

Recommended strategies to accelerate the rate of IPIs prevention and control
We are therefore recommending the following strategies to be emphasized to accelerate the rate of IPIs prevention and control namely;


 * 1) The use of combination drugs that are proven to be safe, the combination of drugs should target both intestinal protozoa and helminths. It's time we start thinking about the possibility of integrating nitazoxanide in the ongoing deworming programmes in order to broaden the coverage against intestinal protozoa infections. However more clinical studies are required to establish how they can be integrated safely without altering the efficacy of drugs ;
 * 2) More studies should be conducted to identify new potential drug compounds that can be used in mass deworming in case if resistance happens we will have drugs to replace the existing one;
 * 3) Modification of the existing programmes for prevention and control of IPIs to reach other at risk groups such as women of reproductive age;
 * 4) Improvement  of WASH interventions to support deworming programmes. Although the implementation of WASH is challenging, the emphasis should be done first in areas with a high prevalence of IPIs then expanded to areas with low prevalence; and
 * 5) Health education programmes should continue to be given to raise awareness of IPIs. Health education programmes lead to behavioral change thus reducing the incidence of IPIs.

Conclusion
In conclusion, there is a need to integrate the ongoing mass deworming with drugs that will target intestinal protozoa. Although the prevalence of intestinal protozoa infections is considered low, it contributes to significant morbidity to children and immunocompromised individuals. It’s now the opportune time for endemic countries to emphasize the recommended prevention and control measures to accelerate the fight against IPIs.

Abbreviations
IPIs: Intestinal Parasitic Infections

STH: Soil Transmitted Helminths

WASH: Water, Sanitation and Hygiene

Author contributions
VM conceptualized the idea, reviewed the literature, and prepared the first draft of the manuscript. AZ and TM reviewed the manuscript.

Acknowledgements
None.

Competing interests
The authors declare that they have no competing interests.

Funding
Not applicable.

Ethics statement
Not applicable.