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Title:

Human schistosomiasis in Egypt: historical review, assessment of the current picture

and prediction of the future trends

Author:

Wael M. Lotfy

Parasitology Department, Medical Research Institute, Alexandria University

For correspondence:

Dr. Wael M. Lotfy. Email: waelotfy@alex-mri.edu.eg. Postal address: Parasitology Department,

Medical Research Institute, 165 El-Horreya Avenue, Alexandria, Egypt. P.O. Box 21561.

Abstract:

Schistosomiasis is a major source of morbidity affecting approximately 207 million people in 76

countries. The history of schistosomiasis in Egypt is longstanding over 5000 years. Since the

discovery of the parasite by Theodor Maximillian Bilharz in early 1851, the history of the major

discoveries related to the disease and the life cycle of the parasite was surprisingly linked to

Egypt. The past and current pictures of the disease in Egypt are covered in the form of a review.

Also the future trends are discussed in view of the effective control measures carried out by the

Egyptian government. These trends are the possibility of emergence of drug resistance, the

magnification of role of rodents in the transmission of the disease, and the possibility of

emergence of cercarial dermatitis by nonhuman schistosomes.

Schistosomiasis is one of the most prevalent human parasitic infections. It is a major source of

morbidity affecting more than 207 million people in 76 countries. It was estimated that 97% of

the infected cases are on the African continent.(1) The disease is caused by trematodes of the

genus Schistosoma, which exhibit dioecy and have complex life cycles comprising several

morphologically distinct phenotypes in definitive human and intermediate snail hosts.(2)

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The history of schistosomiasis in Egypt is longstanding for over 5000 years, with reports of

Schistosoma haematobium eggs in ancient mummies.(3-7) Schistosoma mansoni does seem to

be a relatively modern arrival as it has not been found in mummies. Jury is still out on when S.

mansoni first appeared in Egypt.(8) There have been numerous attempts to find descriptions of

the disease in the medical papyri.(9,10) The most debatable word is "aaa", which occurs in over

50 early papyri including the Ebers papyrus. In some papyri "aaa" occurs together with the initial

hieroglyph suggesting a penis discharging what has been interpreted as blood.(11) The

juxtaposition is the papyri of "aaa", antimony-based remedies, and possibly worms in the body

suggests urinary schistomiasis, and this interpretation is widely quoted in textbooks.

Unfortunately, things are not as simple as this because no passages from the papyri link "aaa"

with the bladder or urine and the discharge from the penis might represent semen and not

blood. It is to be mentioned here that there have been a number of other suggestions about

what "aaa" might be, including hookworm disease.(12) This topic is discussed in detail by Nunn

and Tapp (2000), who rejected "aaa" as a possible ancient Egyptian word for

schistosomiasis.(13) However, since schistosomiasis was almost certainly common and

widespread in ancient Egypt, it is strange that the Egyptians did not have a word for it unless it

was so common that it was ignored.(12) Probably the first authoritative description of hematuria in

the earliest medical literature is by Avicenna (c1000) in his famous book “Al Kanon fi al Tib”.(14)

Centuries later, an epidemic among soldiers in Napoleon’s army in Egypt in 1798 was described

by a French army surgeon, A. J. Renoult.(15) However, the cause of the disease was unknown.

In early 1851, Theodor Maximillian Bilharz, a German physician working at Kasr El Ainy Hospital

in Cairo, discovered the causative agent of hematuria while performing an autopsy on a young

Egyptian man. He named the parasite Distomum haematobium and reported his discovery in a

series of letters to his old teacher, Carl Theodor Ernst von Siebold. In 1853, extracts from these

letters with von Siebold comments were published in the German Zoological Journal.(16) At the

time when Bilharz wrote his letters, he did not know that he was dealing with two species of

schistosomes. He regarded these lateral-spined eggs as abnormalities.(16,17) Bilharz made the

connection between schistosomiasis and hematuria later.(18) The peculiar morphology of the

worm (the presence of the gynaecophoric canal or the schist) made it clear that it could not be

included in the genus Distomum. The parasite was described in 1856 as Bilharzia

haematobium, after its discoverer, by Meckel von Hemsbach in a thesis entitled “The Geology of

the Human Body”. This work was published but had a limited circulation.(19) In 1858, Weinland,

apparently not knowing of this thesis, described the worm as Schistosoma haematobium.(20) In

1948 the International Commission on Zoological Nomenclature established the name

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Schistosoma and it is thus the current name of the parasite.(21) However, both bilharzia and

schistosomiasis are used to denote the various diseases caused by the numerous species of

the genus in man and animals. Our knowledge of the history of intestinal schistosomiasis

caused by S. mansoni dates back to 1902, Sir Patrick Manson saw in London a case of

intestinal bilharziasis, contracted in the West Indies, in which lateral-spined eggs only were

present. He concluded there are two species of Schistosoma in humans.(22) Sambon (1907)

named the new species as S. mansoni after Sir Patrick Manson.(23) The name was officially

accepted in 1913.(24) Although it was known that other digeneans employed a snail intermediate

host, a number of experienced parasitologists including Arthur Looss, Prospero Sonsino, and

Thomas Cobbold, working at the end of the 19th century, all failed to infect snails and reveal the

life cycle of schistosomes;(12) it was not until 1915 that Robert Leiper demonstrated the complete

life cycle in the snail host. In February 1915, Leiper was sent to Egypt to investigate the life

cycle of the schistosomes and to advise the British troops on preventive measures. He

established experimentally that there were two species of Schistosoma in Egypt, a urinary form

with terminal-spined eggs (S. haematobium) and an intestinal form with lateral-spined eggs (S.

mansoni), and that the former is transmitted by Bulinus truncatus and the latter is transmitted by

Biomphalaria alexandrina snails.(25,26) Audouin in 1826 described Physa truncate (Synonym B.

truncatus)  in Savigny's “Description of Egypt”. The snail occurs throughout the whole length of

the Nile Valley in Egypt, in irrigation channels and drains and in many places in the River Nile

itself. It is especially common in the region of the Nile Delta, and also occurs in the Baharia,

Dakhla and Kharga oases.(27) Ehrenberg in 1831 described Planorbis alexandrina (Synonym B.

alexandrina) which he collected from the brackish water of Lake Maryut near Alexandria.(28) The

snail has historically been confined to the Nile Delta especially the area between Alexandria and

Rosetta.(29) There are some indications that a larger geographic range existed in wetter periods,

as fossilized shells of B. alexandrina were detected in a Paleolithic site in the Egyptian Western

Desert(30) and in a Neolithic site in Sinai.(31) However, at late Paleolithic sites in the Nile valley in

Upper Egypt (Edfu and Esna), fossilized shells of other freshwater snails, including B. truncatus,

but not B. alexandrina, have been recovered,(32) which may indicate that B. alexandrina was not

present in Upper Egypt in that time.

In 1856, Bilharz noted that schistosomiasis is one of the most frequent helminthic infections

among Egyptians. He estimated that it will be rather low when he assumes that half of the adult

population of Egypt harbor the worm or traces of it.(18) According to Abdel-Azim (1935) there

were not any reliable surveys conducted to detect the prevalence of schistosomiasis in Egypt

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until 1915.(32) A survey was made by MacCallan during 1913-1915. He was the first to introduce

microscopic examination in population studies.(33,34) From 1933 to 1935, Dr. John A. Scott

carried out an extensive country-wide house-to-house schistosomiasis survey. It was the first

accurate epidemiological study in Egypt's long history of schistosomiasis. Scott examined

40,000 persons from different governorates and analyzed the data from two million

examinations at government treatment centers. His paper published in 1937, offers unique

information on the various aspects of the epidemiology of the disease in Egypt. He reported that

S. haematobium was the only species transmitted along the Nile Valley in Middle and Upper

Egypt, south of Cairo, and both species of schistosomes were endemic in the Nile Delta (under

perennial system for several years before that time). The perennial system had also been

established for some time in most of Upper Egypt as far south as Assiut. South to Assiut, the

ancient basin system was still in use except in a few, relatively small districts where sugar

plantations had been established. Scott estimated that 47% of the Egyptian population which

was 15.23 million persons were infected with either one or both species of Schistosomes.(35) In

1955, about 20 years after Scott survey, the Egyptian Ministry of Health performed a

randomized survey utilizing the same diagnostic methods as Scott and in the same villages

surveyed by him. The overall S. haematobium prevalence was 38%, with only 9% infected with

S. mansoni in the Delta. Schistosoma mansoni was not locally transmitted in Upper Egypt until

the time of that survey. The overall prevalence of S. haematobium south of Assiut was

dramatically rose from 3 to 42% following the change from basin irrigation to perennial

irrigation.(36) Khalil and Abdel-Azim in 1938 demonstrated a remarkable impact of conversion of

the ancient form of basin irrigation to perennial irrigation in Aswan on the transmission of S.

haematobium.(37) It is to be noted here that Aswan Low Dam was completed in 1902. More than

two-thirds of Egypt had been converted to perennial irrigation by the 1930s and by the 1950s

most of the arable land in the Egyptian Nile valley had been converted to perennial irrigation

including much of old Nubia.(38,39) El-Zawahry in 1963 reported that S. haematobium had

increased strikingly in those areas of old Nubia where perennial irrigation systems had been

constructed.(40) Farooq et al., in 1966 estimated that about half of the population was already

infected (14 million out of 30 million). In areas that were to be converted or reclaimed, Farooq

expected the prevalence to increase from 5 to 70 % and calculated that 2.65 million new cases

of schistosomiasis would result from the completion of the Aswan High Dam in 1970.(41) Abdel-

Wahab et al., in 1979 reported an inversion from Scott’s survey in prevalence of S. mansoni and

S. haematobium (from 3% and 73% to 74% and 2%) in a Nile Delta rural community. Most

probably this is due to the changes in the irrigation system after the construction of the High

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Dam which affected the freshwater ecology and snail fauna.(42) In very recent times, B.

alexandrina appears to be expanding its range upstream in Egypt. In the late 1970s and 1980s,

the snail was found at increasing distances upstream, as far as Aswan City and Abu Simbel at

Lake Nasser, respectively.(43,44) However, Lotfy et al., in 2005 reported that B. alexandrina snails

were widely distributed in the Nile Delta and along the Nile Valley as far south as Aswan City

only.(45) Changes in the hydrology of the Nile basin, controlled water flow, and new irrigation

networks following construction of the Low and High Dams at Aswan, have been implicated in

increasing appropriate habitats for the snail.(44,46)

In 1976, the Ministry of Health started the National Schistosomiasis Control Programme

(NSCP), based on case detection and treatment. The objectives of the NSCP were: control of

morbidity by reduction of the prevalence and intensity of infection, thereby limitation of

complications; protection of young age groups and other at risk populations; protection of

settlers in newly reclaimed lands; and prevention of the spread of S. mansoni to Upper Egypt.

By 1989, the distribution of PZQ doses, free of charge, to all diagnosed schistosomiasis cases

was implemented through different health facilities including the network of rural health units.

Chemotherapy was frequently supplemented with focal snail control with chemical molluscicides

(niclosamide at 1-2 ppm).(47) In 1988, under sponsorship of the Ministry of Health and the United

States Agency for International Development (USAID), the Schistosomiasis Research Project

(SRP) was started. This ten-year program supported the investigation of prevalence and

intensity of Schistosoma infection, the prevalence and magnitude of morbidity caused by

schistosomiasis, the changing pattern of distribution of S. mansoni and S. haematobium, and

the determinants of infection and morbidity in a random sample of the rural inhabitants of nine

governorates in the country, selected as representative of each area (Upper and Lower Egypt)

and of governorates with both high and low infection rates. The program is the second national

house-to-house survey for schistosomiasis in Egypt after J. A. Scott’s work which was

conducted 60 years previously.(48) The SRP results showed that although a significant progress

was undeniably made in the control of schistosomiasis, particularly urinary schistosomiasis, one

of the striking findings of this study was that in parts of Egypt, especially in the Nile Delta, the

prevalence of the related schistosome, S. mansoni, remains quite high.(49) Furthermore, it is

replacing S. haematobium in the Delta and has become well established in Middle Egypt(50) and

has been reported in parts of Upper Egypt.(51,52) By 1997, the Ministry of Health started to

distribute praziquantel (PZQ) to endemic populations without prior diagnosis. These populations

included schoolchildren (4.3 million) in 11 governorates and the entire population (2.9 million)

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living in 535 villages with estimated prevalence of schistosomiasis (intestinal and/or urinary)

higher than 20%. The prevalence rate level at which mass chemotherapy was offered to a

village has decreased over time, being 10% in 1999, 5% in 2000 and 3.5% in 2002.

Consequently, the overall prevalence of both S. haematobium and S. mansoni declined steadily

year by year. By the end of 2006, S. haematobium has virtually disappeared from the Nile Delta,

however, still present in Upper Egypt with a prevalence rate of 1.2%. The overall prevalence

rate of S. mansoni in the Nile Delta declined to 1.5% (Figure 1). All endemic villages (744

villages) have prevalence rates 1%-3%, however 68 villages (mainly in Behira and Sohag

governorates) remained with slightly higher prevalence (range 3%-5%). No morbidity associated

with schistosomiasis has been seen in recent years in Egypt. The NSCP has succeeded to

significantly decrease the prevalence and intensity of schistosomiasis (intestinal and/or urinary)

to a low level such that the disease is no longer a major public health problem.(47)

The situation with respect to Biomphalaria in Egypt has become complicated in recent years by

the introduction of Biomphalaria glabrata.(53-57) This large snail is the most widespread and

important intermediate host of S. mansoni in the Neotropics. In 1996, snails identified as B.

glabrata by conchological and morphologic criteria were found along many kilometers of

irrigation canals and drains in Giza, in Qalyoubia Governorate in the south of the Nile Delta, and

in Kafr El-Sheikh Governorate in the north-central Nile Delta.(54) In 1999, snails considered to be

hybrids between B. glabrata and the indigenous B. alexandrina were reported to be widespread

throughout the Nile Delta.(55,56) Experimentally, both B. glabrata and hybrids were found to be

susceptible to Egyptian strains of S. mansoni but showed lower susceptibilities than B.

alexandrina. However, the duration of cercarial shedding was longer and the numbers of

cercariae shed per snail were higher in B. glabrata and hybrid snails than in B. alexandrina.(56)

This may indicate that the introduced B. glabrata and the hybrid snails are more hazardous than

B. alexandrina in the transmission of S. mansoni. In addition to complicating the epidemiology of

schistosomiasis in Egypt, B. glabrata can also be viewed as an invasive exotic that threatens

the integrity of the African aquatic biota.(58) Recent advances in molecular technology have

made possible large scale surveys at the DNA sequence level. By using known nuclear and

mitochondrial sequences for Biomphalaria spp. and newly developed polymerase chain reaction

(PCR) based assays by Lotfy et al., (2004),(59) a molecular survey was carried out from regions

between Alexandria and Ismailia in the north of the Nile Delta, to as far south as Abu Simbel at

Lake Nasser. The aim of the study was to identify the species of Biomphalaria present in Egypt,

to assess the current distribution of B. alexandrina, B. glabrata, and their possible hybrids, and

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to examine further the nature and extent of hybridization if hybrids were found. Also, sequence

data were used to assess the extent of genetic variation in B. alexandrina. They found no

evidence for B. glabrata, but B. alexandrina does remain common, and no evidence for

hybridization with B. glabrata was found.(45) They mentioned that after the presence of B.

glabrata in the Nile Delta was reported,(53-57) the Snail Control Section in the Ministry of Health

was alerted and reacted strongly by applying molluscicides in putative B. glabrata habitats.(45)

Molecular approaches have become an increasingly important way to study the epidemiology of

schistosomiasis, enabling more rigorous examination of schistosome population structure and

genetic subdivision and response to control efforts. Microsatellite markers have been used with

increasing frequency in population genetics studies of schistosomes. Among the applications of

microsatellite markers, and other molecular markers, is the identification of Schistosoma

genotypes among individual infected snails. The distribution of S. mansoni genotypes among

snails can have significant consequences for the transmission dynamics of the parasite and on

the distribution of genetic diversity of schistosomes among the definitive host population.(60) To

confirm the current epidemiological picture of intestinal schistomiasis in Egypt, Lotfy et al. (in

press),(61) studied the distribution of Schistosoma genotypes among a snail population. A survey

of B. alexandrina from an endemic focus in Damietta (Nile Delta, Egypt), an area subjected to

persistent schistosomiasis control efforts, provided only 17 snails infected with S. mansoni, each

shown by microsatellite analysis to have a single genotype infection. By contrast, recent studies

of uncontrolled S. mansoni transmission foci in Kenya revealed that 4.3% Biomphalaria pfeifferi

and 20-25% Biomphalaria sudanica snails had multiple genotype infections.(62,63) Compared with

the 3 Kenyan populations, the Egyptian population of S. mansoni also showed a lesser degree

of genetic variability and was genetically differentiated from them. Although the focal

persistence of snail infections indicates transmission has not been eliminated in Damietta,

mono-genotypic snail infections, along with an overall low degree of genetic variability, could

serve as adjuncts to human infection or prevalence rates to monitor the impact of

schistosomiasis control programs in Egypt and elsewhere.(61)

Praziquantel is now considered as the drug of choice for treatment of schistosomiasis and a

major advance in the treatment of most trematode and cestode infections.(64,65) This

pharmaceutical product is the first anthelminthic drug to fulfill the World Health Organization’s

requirements for population-based chemotherapy of a broad range of parasitic infections.(66)

PZQ was first released by Bayer A.G. in 1979, after the mandatory toxicological tests and

clinical trials had been completed.(67) In 1987, formulation of PZQ in Egypt under a licensing

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agreement from Shin Poong was started. Before 1987, PZQ was being produced in Egypt under

license from Bayer, but sold at a very high price. Shin Poong’s licensee competition with Bayer’s

licensee in Egypt contributed to major reductions in the private market price for PZQ.(68) From

1988 onward, Egypt's Ministry of Health began providing PZQ free of charge in its national

schistosomiasis control program. It is well documented that during the SRP, over a 10 year

period, the Egyptian Ministry of Health dispensed almost 30 million doses of PZQ.(69) Heavy use

of PZQ continues to this day as it remains the drug of choice for treatment of schistosomiasis,(70)

therefore, if PZQ-resistance were to emerge, Egypt would be a likely place. Ismail et al. (1994a,

1994b, 1996), reported that during a survey in some villages of the Nile Delta some cases

remained infected in spite of the PZQ three treatment regimens.(71-73) Several factors may be

responsible for such result. Some of the infections resisted chemotherapy because of host

factors, while others are attributable to the worms themselves. Pharmacokinetic parameters

were the same in patients treated successfully after a single dose versus those not treated

successfully following two or three doses, thus eliminating the possibility that poor cure rates

among infected villagers was due to a decrease in PZQ bioavailability.(73) The in vitro action of

the drug on schistosomes was related to its in vivo action confirming that these isolates were

PZQ-resistant strains.(74-76) Recently, some of these PZQ-resistant isolates maintained in the

laboratory for years reverted to a PZQ-sensitive phenotype when they were passaged in mice in

the absence of PZQ pressure.(77) Moreover, after one decade of the first report of PZQ

resistance in the Nile Delta,(73,74) the same villages were investigated for the current sensitivity of

S. mansoni infection to PZQ. There has not been an increase of drug failure, despite ten years

of therapeutic pressure in these villages where there had been resistant infections and worms

with decreased response to PZQ.(78) Lotfy et al., (2009), by comparing field isolates of S.

mansoni cercariae from Alexandria with those of a laboratory strain never exposed to PZQ

before, concluded that PZQ resistance may not constitute a real problem in the studied field

isolates.(79)

A second issue that may emerge in the future is the role of the animal host in transmission of

the disease. Kuntz and Malakatis (1955) reported that the Nile rat, Arvicanthis niloticus, is a

satisfactory host for S. mansoni  in Egypt.(80) Experimentally, it gave satisfactory yields of well-

developed schistosomes which deposit numerous eggs in the wall of the lower intestine as well

as in other organs of the body. It is frequently found near or even in the water of irrigation

systems in areas where schistosome infection is common in snails and in man.(80,81) There are

several reports of natural infection of A. niloticus with S. mansoni.(82-84) In the past the role of the

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Nile rat in transmission of S. mansoni was minimal because of the high prevalence and intensity

of infection among humans. However, after the great success of the NSCP in Egypt the role of

the Nile rat must be revised and highlighted.

A third issue that may emerge in the future is cercarial dermatitis. It is a cosmopolitan water-

borne disease which has been recently regarded as an emerging infection of increasing

concern.(85) Early reports associated the disease with infection by cercariae of bird

schistosomes.(86) More recent reports indicated that larval stages of other genera and species of

the family Schistosomatidae are also able to produce cercarial dermatitis. Dermatitis-producing

cercariae have been reported also in brackish and salt water.(87) However, to date, the most

frequently reported causative agents of the infection are cercariae of bird schistosomes from

freshwater bodies.(88) Usually cercarial dermatitis often goes unrecognized in endemic areas.(89) 

In the past, human  infection with Schistosoma japonicum was endemic in Japan.(90,91) Control

programs have successfully eradicated the parasite from Japan.(92) On the other hand, the bird

schistosome Gigantobilharzia sturniae has emerged as a serious cause of dermatitis in the

paddy fields of the country.(93) Species known to cause cercarial dermatitis were reported from

Egypt.(94,95) After control of human schistosomes in Egypt, probably cercarial dermatitis will

become of more public health concern for people in contact with freshwater bodies.

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Figure 1. Overall prevalence of schistosomiasis in Egypt during the period 1935-2006

(Source: the National Schistosomiasis Control Program, quoted from WHO, 2007)

11  

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