International Journal of Infectious Diseases 14 (2010) e732e738

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Review

The global war against intestinal parasitesshould we use a holistic approach?

Absar Alum a, Joseph R. Rubino b, M. Khalid Ijaz b,*
a b

Department of Civil & Environmental Engineering, Arizona State University, Tempe, Arizona, USA Reckitt Benckiser Inc., One Philips Parkway, Montvale, NJ 07645, USA

A R T I C L E I N F O

A B S T R A C T

Article history: Received 23 December 2008 Received in revised form 27 October 2009 Accepted 26 November 2009 Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Personal hygiene Community hygiene Hand hygiene Prevention Intervention Intestinal parasites

Intestinal parasite infections have been known to compromise the quality of human life since prehistoric times. Throughout the ages, human civilizations have fought against parasitism, including intestinal parasites. During the second half of the last century, the focus of disease-combating efforts moved to other imminent public health issues, under the notion that the ght against infectious diseases had been won. However, the disease incidence data indicate that these diseases continue to wreak havoc on human productivity across the globe. Lately, chemotherapeutic intervention has been stressed for the control of intestinal parasitic infections. In this paper we evaluate the need for a holistic approach to address this issue and make recommendations for this cause. 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

1. Introduction Human societies have always been challenged by infectious diseases, some of which are caused by helminth and protozoan parasites. In fact, one fourth of the known human infectious diseases are caused by the helminth/protozoan group (Figure 1).1 Intestinal parasites have been known to infect humans since prehistoric times and they have evolved with humans throughout history. This association is still as strong as it was 10 000 years ago. In recent history, this relationship has been inuenced by global changes in the human socio-cultural spectrum. In the modern world, parasitic diseases are conveniently associated with underdeveloped countries, and the developed world has conventionally viewed itself as an island free of parasites/worms.2 However, with the emergence of immunocompromised populations, combined with an increase in life expectancy, parasitic infections have started to re-appear on the infectious disease radar in the developed world. The notion that human parasitic diseases are foreign to the developed world is an illusion; several new parasitic diseases were identied in the latter half of the last century. Since 1970, signicant improvements in public health conditions in developing and developed countries have been reported. However,

* Corresponding author. E-mail address: khalid.ijaz@reckittbenckiser.com (M.K. Ijaz).

the number of new protozoan and helminthic parasites that emerged between 1940 and 2000 indicates no change in the rate of emergence of new protozoan and helminthic parasites after the 1970 s (Figure 2).3 Even today, intestinal parasites are among the major contributors to the global disease load. A wide variety of intestinal parasites are prevalent in different parts of the world. Ascaris, Entamoeba, Toxoplasma, Cyclospora, Giardia, and Cryptosporidium are among the major contributors to the global intestinal parasitic disease burden. However, parasites like Enterobius are still ignored, even though they can impair the growth and learning capabilities of the young segment of our population. Global infections reported for some of the most common intestinal parasites are Ascaris (20%), hookworm (18%), Trichuris trichiura (10%), and Entamoeba histolytica (10%).4 Populations in different parts of the world face diverse parasitic challenges. For example, Enterobius vermicularis is more prevalent in temperate areas5 and Ascaris lumbricoides is more common in tropical regions.6 The highest rates of Ascaris infection have been reported in China, Southeast Asia, coastal regions of West Africa, and Central Africa. Trichuris infestation is at its highest rate in Central Africa, southern India, and Southeast Asia. Hookworm infections are most common in sub-Saharan Africa, South China, and Southeast Asia. In industrialized countries the prevalence of intestinal parasites such as Giardia ranges from 2% to 5%, whereas in developing countries it ranges from 20% to 40%.79

1201-9712/$36.00 see front matter 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2009.11.036

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pinworm infections.28 In a recent study, DALYs lost due to Ascaris, whipworm, and hookworm infections were estimated to be 1.2, 1.6, and 1.8 million, respectively.29 These DALY estimates were signicantly lower than those of previous reports: 10.5, 6.4, and 22.1 million, respectively.30 3. Survival of parasite eggs in the environment The factors affecting the survival of parasites in the environment can be categorized into biotic and abiotic factors. Biotic factors include other microorganisms and their by-products. El Hamouri et al. reported that the presence of algal species results in the increased removal and inactivation of helminth eggs in ponds.31 Bacterial contamination of Giardia stock results in decreased viability/infectivity of Giardia (personal communication, Dr Ramalangham, The Oregon Health and Sciences University, Portland, OR, USA). In ambient conditions, 97% of Cryptosporidium oocysts lose viability by 2 h,32 whereas oocysts in diarrheal stools smeared on a wooden surface survive for up to 72 h.32 The primary abiotic factors affecting the survival of parasites in the environment include temperature, relative humidity, and residence time. Although all intestinal parasites include eggs/ova/ (oo)cysts in their life cycle, some (e.g., Enterobius and Entamoeba) display a host-to-host cycle and their eggs do not need an environmental stage for maturation. Other groups of intestinal parasites (e.g., Ascaris and Trichuris) display a host-to-soil-to-host cycle and need an incubation period for their eggs to mature. In general, the parasite eggs that require an environmental incubation period are the most resistant. For example, Ascaris eggs are more resistant than other intestinal parasites to most types of inactivation processes. At a temperature range of 2030 8C, pH plays a signicant role in the survival of Ascaris eggs; however, above 50 8C, temperature becomes the single most important factor in their survival.33 When Ascaris eggs were stored for three months under anaerobic conditions, it had little effect on their viability.34,35 In Germany, an epidemic of roundworm was directly traced to the use of raw sewage to fertilize gardens.36 Humidity/moisture content also signicantly impacts the survival of parasite eggs/ova/(oo)cysts. In sandy loam soils at room temperature, E. histolytica can survive for 1842 h, 4272 h, and 810 days, under dry, moist, and damp conditions, respectively.37 Compared to open surfaces, eggs/ova/(oo)cysts present in soil are protected against radiation and desiccation, which helps them to survive for a long time. Storey and Phillips reported that viable eggs of Taenia saginata could still be found after 200 days on the soil surface, and that survival rates increased in proportion to how deep the eggs were found.38 However, this may be of little epidemiological signicance, because eggs buried deep in soil may have a lower chance of coming into contact with subjects. 4. Transmission factors The transmission routes of more than 400 parasites have been identied. Of these, many (45%) can be transmitted by close nonsexual contact, including the fecaloral route. Environmental artifacts play a pivotal role in such transmission by serving as vehicles of transmission.39 Intestinal parasites may be transmitted directly (hand-to-hand contact) or indirectly (contact with food or environmental surfaces). Regardless of route of transmission, the human hand acts as a common denominator in the transmission of intestinal parasites (Figure 3). These routes of transmission are of great importance in developing countries where poor hygiene conditions are prevalent.40 Socio-economic conditions and poor household hygiene practices have been associated with disease load in any household. Under such environmental conditions, a water faucet (tap) in the

Figure 1. Taxonomic distribution of etiological agents causing infectious diseases in humans (based on Cleaveland et al.1).

The diversity of parasites endemic in any area is inuenced by a variety of factors.1014 These factors can be divided into social, cultural, economic, and environmental factors and the life cycle features of parasites, such as the nature of the environmental stage. Transmission and spread of these parasites is inuenced by the availability of clean water, socio-economic conditions, education, personal and public hygiene practices, temperature, humidity, and survival of the environmental stages of the parasites. 2. Burden of disease due to neglected intestinal parasites Traditionally, epidemiological assessment of the public health signicance of intestinal parasites has been based on estimating the number of infections. After the release of the World Development Report in 1993,15 a paradigm shift occurred in the way in which the public health signicance of any disease is assessed. This report introduced the idea of burden of disease, which refers to the economic costs of disease, taking into consideration the disease impact at the individual level and at the societal level.16 The overall impact of any disease burden is quantied by the metric disability-adjusted life year (DALY).17 The accurate assessment of the global burden of disease (GBD) depends on robust epidemiological data. Traditionally, data from prevalence surveys of communities are extrapolated for the estimation of parasitic infections,18 and this is still practiced today.19 Despite the widespread incidence of these parasites, the nonacute nature of these infections has contributed to the perception of intestinal parasite infections being common but usually unimportant to the public health community. Over the years, several estimates of global and regional prevalence and of number of infections by intestinal parasites have been made, and these estimates project similar pictures.18,2027 Ascariasis still remains the most common intestinal parasite with 8071221 million infections globally. It is most prevalent in East Asia, sub-Saharan Africa, and India.28 Whipworm (Trichuris) and hookworm account for 604795 and 576740 million infections, respectively.28 SubSaharan Africa and East Asia have the highest incidence of these intestinal worms. Globally, an estimated 428% of children have

Figure 2. The number of new helminthic and protozoan parasites that emerged during 19412000 (based on Jones et al.3).

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5. Food Parasites are commonly associated with vegetable or fruitborne outbreaks of gastroenteritis. Protozoan and helminth parasites that have been implicated include Giardia48 and Ascaris.49 Some of the key factors in the vegetable and fruit-borne outbreaks include more global trade, the popular trend of eating raw or lightly cooked vegetables, and the increasing numbers of immunocompromised individuals. Protozoa and helminths are the parasites of primary public health concern with regard to wastewater reuse, which is becoming a favorite strategy for the economical management of wastewater and sludge. Produce can be contaminated in the eld or during harvesting, handling, transport, and storage. In recent years, increased interest in organic farming has been noted, which inherently carries a greater risk for contamination of food with intestinal parasites during farm operations and their dissemination during food processing operations.50 Erdogrul and Sener studied the seasonal trend in the contamination of intestinal parasites on various fruits and vegetables in Turkey.20 Samples of lettuce, parsley, cress, spinach, and strawberries and irrigation water were collected during different seasons. E. vermicularis was the most common parasite found, followed by Ascaris, E. histolytica, and Giardia. Strawberries were the most commonly contaminated, followed by lettuce, parsley, spinach, and cress. In general, contamination with Enterobius eggs was more prevalent during the fall season compared to spring, and an opposite trend was seen for Ascaris (Figure 5). In the USA, foods imported from Latin American countries have frequently been associated with gastroenteritis outbreaks. Cyclospora contamination has frequently been associated with raspberries imported from Guatemala.51 Idowu and Rowland studied the prevalence of direct transmission of parasites and the level of hygiene among food vendors in Nigeria and found that 97% of the vendors were infected with one or more intestinal parasites.52 The prevalence of E. histolytica was 72%, A. lumbricoides was 54%, E. vermicularis was 27%, and Giardia duodenalis was 13%. E. histolytica was more prevalent among the school food vendors (80%) than the street food vendors (69.3%) (p > 0.05). Other parasites were more prevalent among the street food vendors. 6. Implications of intestinal parasite infections Intestinal parasite infestation as a cause of malnutrition/ growth stunting is well documented and is caused by a decline in food intake and/or an increase in nutrient wastage.5355 Infestation with intestinal parasites is signicantly correlated with low levels of hemoglobin and the packed cell volume in blood.56,57

Figure 3. The human hand is a common denominator in intestinal parasite transmission. Hands can act as conduits to transfer parasites from surfaces (in the home or out of the home), currency, food, animals (pets or wild), and humans.

yard is a good predictor of hygienic excreta disposal.41 In sanitary homes, approximately 25% of houseies are likely to carry parasitic cysts.42 Houseies in unsanitary homes can carry higher numbers of parasitic cysts and helminth ova. A variety of personal habits have been shown to impact the risk of parasite transmission. General cleanliness of the home environment plays a signicant role in the transmission of intestinal parasites. The presence of E. vermicularis eggs in room dust brushes and vacuum cleaners has been reported. The presence of parasite eggs in house dust is highly correlated with the incidence of this parasite in young members of a house m et al. reported that nger sucking in young hold.43 Herrstro Swedish children is highly correlated with E. vermicularis infection.44 Defecation habits, use of footwear, and the presence of dirty nails have been reported as signicant factors in parasite infestation rates.45 The subjects who used open elds for defecation had markedly higher parasite infestation rates than those who used some type of latrine. A similar impact has been reported for the use of footwear and cleanliness of ngernails (Figure 4).45 In another study, increased risk of infection with intestinal parasites was reported for dirty, untrimmed nails and poor hand-washing habits (47.4% and 37.2%, respectively).46 Contact with animals (public, pet, or wild) is another source of transmission of intestinal parasites, and some of the pathogens transmitted through this route include Cryptosporidium and Giardia.47

Figure 4. Incidence of intestinal parasites according to living conditions and hygiene practices (based on Khan45).

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Figure 5. Contamination of fruits and vegetables with ova/(oo)cysts of intestinal parasites (based on Erdogrul and Sener20).

Parasitic infections can cause deciencies in vitamins (A, B6, B12) and minerals (iron, calcium, and magnesium), block nutrient absorption, and diminish immunity, predisposing subjects to serious diseases. Intestinal parasite infections often go undetected for years due to delayed onset of symptoms, which can exacerbate the effects of malnutrition. Parasitic infections are more common in children than adults and are a major cause of malnutrition. It is a point of concern, because malnutrition in children can compromise their learning capabilities in their formative years. Venkatachalam and Patwardhan studied the effect of ascariasis on the digestion of protein in school children in India.58 They reported that Ascaris in the small intestine interfered with the digestion and absorption of dietary protein. They further suggested that incomplete digestion, resulting from inefcient absorption, may be one of the etiological factors in nutritional edema syndrome in young children. El-Nofely and Shaalan investigated the effects of Ascaris infection on the nutritional status and the intellectual level of primary school children in Giza, Egypt.59 They reported that infected children had signicantly lower body weight, height, arm circumference, hemoglobin concentration, and IQ than the controls. Tarleton and colleagues compared verbal and nonverbal test scores with a health surveillance database (which tracks incidence of diarrhea and E. histolytica infection and nutritional status) for a group of Bangladeshi children.60 Cognitive scores were negatively associated with stunted growth in school age children. A positive correlation between E. histolytica-associated dysentery and lower test scores was reported, while dysentery of any other etiology was not identied to have any impact on test scores. Parasitic nematode infections not only cause diarrheal diseases, but have also been shown to be a signicant factor in the evolution of human metabolic genotype. Populations with thrifty genotypes are less vulnerable to the health implications of nematode infections.61 It has been shown that a strong TH2-mediated immune response facilitates the clearance of nematodes from the digestive track.62 Interestingly, helminth infection appears to afford protection from autoimmune diabetes and allergies by interfering with immune pathways.63,64 7. Intervention/prevention/control Intestinal helminthic and protozoan diseases impose a great burden on poor populations in the developing world. This segment of the population does not have purchasing power, political voice, or any clout in decision-making processes. Therefore, the public health and economic impact of these diseases have traditionally been given low priority in public health planning. This deaf ear attitude has resulted in the plight of people in endemic areas, left without any comprehensive effort to combat these diseases. The

history of infectious diseases has shown that changes in this attitude are provoked by highly visible phenomena (incidence/ outbreak). For example, Cryptosporidium had been a signicant public health threat even before 1987; however, the Milwaukee outbreak was the impetus for all the regulatory/scientic focus on Cryptosporidium in the USA.65 A variety of strategies has been used to combat these diseases. The most commonly reported strategies include hand-washing/personal hygiene/family hygiene and chemotherapeutic control. 8. Hand hygiene Hand-washing is one of the most important interventions that has proven to effectively intervene with fecaloral transmission of diseases. Hand-washing can interrupt parasite transmission by acting as a primary barrier (to remove fecal matter after contact with stools) or as a secondary barrier (before preparing food, handling uids, feeding, eating). The use of water and soap or similar agents is critical for effective removal of parasitic ova/ (oo)cysts from contaminated hands. The use of soap is determined by economic and logistic factors, and also by the perception of what is dirty and what is not. Therefore, hygiene plans must clearly indicate when hand-washing with soap is most needed for health protection. It has been shown that hands readily become contaminated after defecation even with the use of toilet paper.66 Hand-washing after defecation or stool contact is far from universal. Huttly and others reported that in Peru only 11% of people wash their hands after defecation.67 This habit is a high risk factor for parasite transmission. For example, dirty nails in school children have been associated with high parasite infestation.45 The ability of parasite ova/cysts to survive on environmental surfaces varies greatly among different groups of parasites. While Ascaris eggs are known to survive for a long time in the environment, eggs of other parasites (such as Enterobius) are relatively less resistant to environmental stresses. E. histolytica cysts contaminating ngers rarely survive air drying of more than ve minutes.68 A number of epidemiological studies have shown substantial reductions in gastrointestinal diseases by hand-washing; however, few make the distinction between hand-washing as a primary or secondary barrier. The effectiveness of hand hygiene in controlling infectious diseases has been widely shown.69 One month after hygiene education, a 63.6% to 78% reduction in load of intestinal parasites was reported among children practicing hand-washing with soap after defecation, without chemotherapy.46 In Indonesia, an 89% reduction in the incidence of gastrointestinal diseases was reported through the promotion of hand-washing in four different circumstances, including after defecation.70 In Burma, a 30% reduction in diarrheal morbidity was reported by regular hand-

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washing with soap.71 Variation in hand-washing practices can also impact the risk of disease transmission, and rigorous handwashing habits are effective in reducing the risk of contracting disease.72 9. Chemotherapy Chemotherapy is another intervention strategy that has been reported to reduce the incidence of intestinal helminth/protozoan diseases. It is an effective tool for the strategic control of these diseases as a short-term goal. This strategy has been used as a rapid-impact intervention method for controlling intestinal parasite infestation in households and communities.73 It was reported that after chemotherapy, the proportion of soil samples positive for helminth ova and the density of ova in soil declined over a two-month period.74 The results suggest that in the absence of continuing sources of contamination, the number of geo-helminth ova would be depleted from the surface of tropical soils. In general, chemotherapeutic intervention results in a rapidly decreased incidence of intestinal parasites; however, conicting results have been reported. For example, in northern Bangladesh, chemotherapeutic intervention was found to bear no signicant long-term impact, and even after 4 years of intervention more than half of the students were still infected with one or more intestinal parasites.75 One of the challenges of anti-parasitic therapeutic intervention for controlling parasitic infection or deworming is the emergence of drug resistance resulting from intensive control measures.76 Human helminth control programs mostly rely on praziquantel and there is increasing evidence that it may become virtually useless in the near future. Similar concerns have been shown for other therapeutic drugs such as mebendazole and pyrantel, which have been widely used for controlling hookworm infections. Various drug management strategies (cyclic use of drugs) have been suggested to address these issues; however, if drug resistance trends continue, they could doom global efforts to control parasitic diseases using drugs, a phenomenon well known in the use of antibiotics/antiviral drugs.76 South Korean efforts to control soil-transmitted helminths (STH) using chemotherapy is a success story. Mass chemotherapy was performed twice a year from 1969 to 1995 targeting school children all over the country. With the extensive chemotherapy program in South Korea, it took more than a quarter century to lower the STH incidence rate from 84% to less than 3% (Figure 6). These results cannot be attributed merely to chemotherapy, because rapid economic development during the time period resulted in signicant improvements in living standards, environmental sanitation, and agricultural and industrial hygiene. These improvements undoubtedly boosted the STH control efforts.77

Based on their experience, the Korean team concluded that improvement of environment and sanitation is of paramount importance for achieving the desired benets of chemotherapeutic intervention for STH control. The results of the Korean study point to the limitations of the chemotherapeutic intervention strategy. It is reasonable to assume that reliance on only chemotherapeutic intervention (without any signicant improvement in personal and public hygiene conditions) can diminish the efcacy of such a program. Such abatement in the efcacy of an STH control program would translate into a signicant increase in the time required for reducing the number of intestinal parasite infections among poor populations, and may lead to the emergence of drug-resistant parasites. 10. Gaps and future directions Currently available technical/scientic information on handwashing practices is primarily focused on preventing the transmission of bacterial and viral infectious diseases and little information on the impact of hand-washing on the (oo)cysts/ova of intestinal protozoan/helminthic parasites is available. Ironically, intestinal protozoan/helminthic parasites have largely been ignored in key policy documents, such as the World Health Organizations guideline document on hand hygiene.69 This is a serious scientic lapse because protozoan (oo)cysts and nematoidal ova are highly resistant in the environment and are expected to survive a long time on hands. Hands are of paramount importance in public health because they are easily contaminated in daily life and the contaminating pathogens are readily transferred to other surfaces. In the context of relative survival of different groups of pathogens, contamination of hands with ova/(oo)cysts presents a more perdurable public health threat than the contamination of hands with bacterial or viral pathogens. Chemotherapy as a rapid-impact intervention is a good strategy for immediately improving the lives of poor populations in developing countries. Effective chemotherapeutic drugs have been developed and extensively tested against most of these parasitic diseases. However, a few months after chemotherapeutic intervention, high re-infection rates for these parasites have been reported (Figure 7).78 In Kenya, a school-based anti-helminthic treatment program resulted in respective reductions of only 15%, 46%, 29%, and 27% in the number of hookworm, Ascaris, T. trichiura, and Schistosoma mansoni eggs excreted by the total population.79 In addition, the success of the chemotherapy program for controlling intestinal parasites relies on repeated and widespread administration of these drugs in endemic areas, which can lead to the emergence of drug resistance in these parasites. From the history of health education and sanitation interventions used for controlling neglected intestinal parasitic diseases around the world, it is obvious that while chemotherapy is the best option for rapid intervention and morbidity control, the role of hygiene interventions to sustain the long-term benets of chemotherapy should not be overlooked.19 In this regard we can benet from the lessons learned in the eld of bacteriology, where the indiscriminate use of antibiotics has resulted in the emergence of a large number of bacterial strains that are resistant to a wide range of antibiotics. The battle between human populations and infectious agents is eternal. As we are intensifying our war against infectious diseases, the number of new protozoan and helminthic parasites are emerging at a greater rate (Figure 2). Moreover, protozoan/ helminthic parasites should not be considered exempt from emergent drug-resistant strains of parasites, which will continue to afict the poverty-stricken/vulnerable masses around the globe.80 During the last few decades, more than ve drug-resistant protozoan parasites have emerged.3 Currently, a number of

Figure 6. Effect of chemotherapeutic intervention on helminthic parasite infections in South Korea.77

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Figure 7. Re-infection rates of intestinal nematodes after chemotherapeutic treatment (based on Narain et al.78).

agencies and organizations/foundations are participating in the ght against parasitic diseases. Some of the players are the Schistosomiasis Control Initiative, Partnership for Parasite Control, Human Hookworm Vaccine Initiative, International Trachoma Initiative, Global Alliance to Eliminate Lymphatic Filariasis, African Programme for Onchocerciasis Control, Drugs for Neglected Disease Initiative, WHO Programme to Eliminate Sleeping Sickness, and Neglected Tropical Disease Coalition.73 These organizations mostly focus on chemotherapeutic interventions to control a specic parasite or group of parasites. Recently, combination therapy (use of drugs with different modes of action) has been suggested to lower the development of resistance.81 In the context of a high probability of re-infection, chemotherapeutic interventions cannot ensure sustainable control of intestinal parasites. Vaccination could be a better choice for the sustainable control of intestinal parasites. Vaccination has been reported in the control of hookworm in animals.82 Currently, a hookworm vaccine (Na ASP2) is undergoing clinical development for use in human beings.83 While the efforts of these organizations to control intestinal parasites in poor countries are worthwhile, the incidence of such parasites in inner cities and rural/native communities requires closer investigation. The parasites, such as pinworm, which occur non-acutely, are still ignored because of the lack of data on their true occurrence. Therefore, unconventional strategies are required to assess the occurrence of neglected intestinal parasites. For example, surveys of public laundry facilities can provide good insight into the occurrence of pinworms in communities. Similarly, fresh produce can be surveyed to investigate the extent of foodborne STH. Likewise, an out-of-the-box approach is needed to control the incidence of intestinal parasites in the underdeveloped world. In our opinion, it is high time that a holistic approach is adopted to combat this global menace. In order to achieve a global and sustainable enteric parasite control program, we recommend ghting this war on multiple fronts, including: (1) mass education on hygiene practices, (2) improving personal and public health conditions, and (3) large-scale de-worming campaigns, along with efforts to develop effective vaccines against major intestinal parasites. The use of this integrated approach will not only result in the control of neglected intestinal protozoan/helminthic parasites, but also diseases caused by other (bacterial and viral) infectious agents.

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Acknowledgements Dr Alums research is supported by Reckitt Benckiser; JRR and MKI are engaged in R&D work at Reckitt Benckiser Inc., Montvale, New Jersey, USA. Conict of interest: No conict of interest to declare.

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