Impact of human schistosomiasis in sub-Saharan Africa

(1)

www .e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Review

article

Impact

of

human

schistosomiasis

in

sub-Saharan

Africa

Abiola

Fatimah

Adenowo

a

_,

_Babatunji

_Emmanuel

_Oyinloye

a,b

_,

Bolajoko

Idiat

Ogunyinka

a

_,

_Abidemi

_Paul

_Kappo

a,∗

a_{Biotechnology}_and_Structural_Biology_(BSB)_Group,_Department_of_Biochemistry_and_{Microbiology,}_University_of_Zululand,

KwaDlangezwa3886,SouthAfrica

b_Department_of_{Biochemistry,}_College_of_Sciences,_Afe_Babalola_University,_Ado_Ekiti,_Nigeria

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received28September2014

Accepted12November2014

Availableonline27January2015

Keywords:

Neglectedtropicaldiseases

Praziquantel Schistosomiasis

Sub-SaharanAfrica

a

b

s

t

r

a

c

t

Schistosomiasis,a neglectedtropicaldiseaseofpovertyrankssecondamong themost

widespreadparasiticdiseaseinvariousnationsinsub-SaharanAfrica.Neglectedtropical

diseasesarecausesofabout534,000deathsannuallyinsub-SaharanAfricaandanestimated

57milliondisability-adjustedlife-yearsarelostannuallyduetotheneglectedtropical

dis-eases.Theneglectedtropicaldiseasesexertgreathealth,socialandﬁnancialburdenon

economiesofhouseholdsandgovernments.Schistosomiasishasprofoundnegativeeffects

onchilddevelopment,outcomeofpregnancy,andagriculturalproductivity,thusakey

rea-sonwhythe“bottom500million”inhabitantsofsub-SaharanAfricacontinuetolivein

poverty.In2008,17.5millionpeopleweretreatedgloballyforschistosomiasis,11.7million

ofthosetreatedwerefromsub-SaharanAfrica.Thisenervatingdiseasehasbeen

success-fullyeradicatedinJapan,aswellasinTunisia.MoroccoandsomeCaribbeanIslandcountries

havemadesigniﬁcantprogressoncontrolandmanagementofthisdisease.Brazil,China

andEgyptaretakingstepstowardseliminationofthedisease,whilemostsub-Saharan

countriesarestillgroaningundertheburdenofthedisease.Variousfactorsareresponsible

forthecontinuousandpersistenttransmissionofschistosomiasisinsub-SaharanAfrica.

Theseincludeclimaticchangesandglobalwarming,proximitytowaterbodies,irrigation

anddamconstructionaswellassocio-economicfactorssuchasoccupationalactivitiesand

poverty.Themorbidityandmortalitycausedbythisdiseasecannotbeoveremphasized.

Thisreviewisanexpositionofhumanschistosomiasisasitaffectstheinhabitantsof

vari-ouscommunitiesinsub-SaharaAfricancountries.Itishopedthiswillbringare-awakening

towardseffortstocombatthisimpoverishingdiseaseintermsofvaccinesdevelopment,

alternativedrugdesign,aswellasnewpoint-of-carediagnostics.

∗ _{Corresponding}_author.

E-mailaddresses:KappoA@unizulu.ac.za,bidemi2k@gmail.com(A.P.Kappo).

http://dx.doi.org/10.1016/j.bjid.2014.11.004

(2)

Introduction

Humanschistosomiasisotherwisecalledbilharzia,isa

fresh-water snail transmitted intravascular debilitating disease

resultingfrom infection bythe parasitic dimorphic

Schisto-somatrematode worms,which lives inthe bloodstream of

humans.1,2_The_World_Health_Organization_(WHO)_regards_the

disease as a neglected tropical disease,with an estimated

732millionpersonsbeingvulnerabletoinfectionworldwide

inrenownedtransmissionareas.3_Steinmann_and_co-workers

documented that over 200million individuals from Africa,

Asia,andSouthAmericaareinfectedwiththisdisease.1_The

WHOfurtherestimatedthatschistosomeinfectionsand

geo-helminthsaccountsforover40%oftheworldtropicaldisease

burdenwiththeexclusionofmalaria.4_Humans_get_infected

withthis diseasewhentheymakecontactwithwater

con-taminatedwiththeskin-penetratingcercariae.Prevalenceof

schistosomiasis,atpresent,isstillhighinsub-SaharanAfrica.

In2008,17.5millionpeopleweretreatedgloballyfor

schisto-somiasis,11.7millionofthosefromsub-SaharanAfricaonly.3

Approximately120millionindividualsinsub-SaharanAfrica

haveschistosomiasis-relatedsymptomswhileabout20

mil-lionundergohardshipasaresultofchronicpresentationsof

thedisease.5

SchistosomiasishasbeensuccessfullyeliminatedinJapan

andTunisia.MoroccoandsomeCaribbeanIslandscountries

have made signiﬁcant progress on controlling the disease

whileBrazil,China,andEgyptaretakingstepstowards

elim-ination of the disease.6 _{Schistosomiasis} _is _more _rampant

in poor rural communities especially places where ﬁshing

andagriculturalactivitiesaredominant.Domesticactivities

suchaswashingclothesandfetchingwaterininfectedwater

exposewomenandchildrentoinfection.Recreational

activ-ities like swimming and poor hygiene also make children

vulnerabletoschistosomiasis.3Humansareusuallyinfected

byﬁvespeciesofschistosomes,namelySchistosomamansoni,

Schistosoma haematobium, Schisosoma japonicum, Schistosoma mekongi, and Schistosomaintercalatum, but the main burden

of disease in sub-Saharan Africa is usually attributed to

twospecies,namely,S.mansoniandS.haematobiumandare

referredtoasthemajorhumanschistosomes.6

Biomphalariasnails are responsible forthe transmission ofS.mansoniwhich isthe sourceofhepatic andintestinal

schistosomiasisinplaceslike theArabian countries, South

America,andAfrica.Bulinussnails transmitS.haematobium

whichisthechiefcauseofurinaryschistosomiasisinAfrica

andintheArabworld.2_The_Biomphalaria_snails_comprise_many

speciesincludingB.alexandrina,B.sudanica,B.pfeifferi,andB.

hoanomphala,whilethe genusBulinuscomprisesthe

follow-ingspecies;B.tropicus,B.globosus,B.truncatus,B.forskalli,and

B.africanus.7_Schistosoma_japonicum_is_spread_by_the

freshwa-tersnailOncomelaniaanditisresponsibleforintestinaland

hepatosplenicschistosomalinfectionsinIndonesia,Peoples

RepublicofChina,andthePhillipines.Itisazoonotic

para-siteinfectinganimalsincludingpigs,dogs,cattle,androdents.

Someotherspeciesofschistosomeareparasitesofdifferent

animals,butoccasionallyinfecthumans.S.mansonicanalso

befoundinprimatesandrodentsbutthemainhostarehuman

beings.2

Maturedschistosomesareusuallygreyishorwhiteworms

with alength of7–20mm, havingacylindrical shape with

twoendingsuckers,ablinddigestivetract,acomplex

tegu-ment,and reproductive organs.Adistinguishing featurein

thistrematodecomparedwithothertrematodesisits

exist-ence intwosexes.Themalehasagyneaphoricchannelor

agroove,whereinitgripsthefemalewhichisusuallylonger

andthinner.Themaleandfemaleschistosomesliveas

perma-nentlyembracedcouplesintheperivesicalvenousplexus(inS.

haematobium)orinthemesentricvenousplexus(inS.mansoni

andS.japonicumspecies).Theschistosomesgetnourishment

fromthehostbloodandglobulinsbymeansofanaerobic

gly-colysisandexcretethewastebackintothebodyofthehosts.2

Afemaleschistosomehasthecapacitytoproducehundreds

ofeggsperdayasdiscoveredintheAfricanspecies,andabout

thousandsofeggsperdayintheorientalspecies.The

individ-ualovumishometomiracidiumlarvawithciliathatproduce

proteolyticenzymeswhichaidtheeggstomoveeithertowards

thelumenofthebladderortowardsthehostintestine.2

Subsequently,theparasiteseggsarereleasedintothe

fae-cesorurine wheretheyremainaliveforaboutsevendays.

When theyget into freshwater,the miracidium isreleased

fromtheegg.Withtheaidofchemicalstimuliandlight,the

miracidiumseeksthefreshwatersnailwhichisits

intermedi-atehost.Onlocatingthesnail,themiracidiumpenetratesit

andundergoesasexualreproductiontoproducemulticellular

sporocyteswhichdeveloptocercariallarvaehaving

embry-onicsuckersaswellasatwo-branchedtail.2_After_4–6_weeks

ofinfectingthesnail,thecercariaeleavethesnailandgyrates

aroundforabout72hlookingoutfortheskinofaprospective

host.Oncereleasedfromthesnailthecercariaeareinstigated

bylight mainlyduringthe daytime. On locatingahuman

hostskin,thecercariaeburrowintoit,migrateintotheblood

throughtheliverandlungsandundergotransformationinto

schistosomulaalsocalledyoungworms.2

Theschistosomulamaturewithin4–6weeksinsidethe

por-talvein,mate,andmigratetotheirdestination,whichiseither

the perivesicularor mesentericvenousplexus, tostart the

cycleagain(Fig.1).Asingleinfectedsnailhasthepotentialof

sheddingthousandsofcercariaedailyformanymonths.An

adultschistosomehasanaveragelifespanofbetweenthree

toﬁveyears,butitcanaswelllivefor30years.Asingle

schis-tosomepairhasatheoreticalreproductionpotentialofupto

600billionschistosomes.2_The_intermediate_freshwater_snail

inhabitcalmorslowlymovingfreshwaterlakes,rivers,ponds,

orstreams.Therateofinfectioninhumanincreaseswiththe

durationoftimespentincontaminatedwater.8_Microscopic

examinationofstoolsandurineisthegold-standardfor

detec-tion (diagnosis)ofschistosomal infection.Theschistosome

eggsareeasilyseenandidentiﬁedonmicroscopyduetoits

peculiarsizeandshape,andpossessionofalateralorterminal

spine.8

Schistosomiasis:

a

neglected

tropical

disease

of

poverty

Neglectedtropicaldiseases (NTDs)aregenerallyreferredto

asacollectionofchronic,disabling,andphysicallydisﬁguring

(3)

5

4

3

2

6

1

Fig.1–LifecycleofSchistosoma1.Definitivehost,2.Schistosomeeggsreleasedinurineorfaecesofdefinitivehost,3. Free-swimmingmiracidiafromeggs,4.Intermediatehost,5.Cercaria(penetratesskin,losesitstailandtransformsinto schistosomulum),6.Pairedadultworm(schistosomulummigratestothehepaticportalsystem;adultwormsmaturein pairsintheveinssurroundingthebladder,intestinesorliver.Theyproducedeggs,themajorityofwhichareeliminatedin urineorfaecesofdefinitivehosttotheenvironment.Theeggshatchliberatingmiracidiatorestartthelifecycle.71

dwellersandsomeurbanpopulation.Studies haverevealed

thatthe NTDsaremoreprominentinsub-SaharanAfrican

communities.NTDshaveprofoundnegativeeffectson

chil-dren development, outcome ofpregnancy, and agricultural

productivity,thusakeyreasonwhythe“bottom500million”

inhabitantsofsub-SaharanAfricacontinuetobeinpoverty.

ThisledtotheconcernforeliminationoftheNTDsasamajor

elementoftheMillenniumDevelopmentGoalsMDGs.9

Morethan17diseasesarereferredtoasNTDsbutsevenof

themhaveattractedmoreattentionduetotheirhigh

preva-lenceandresistancetocontrolworldwide.10_NTDs_poses_great

healthaswellaseconomicchallengesforthepoordwellers

ofAfrica,LatinAmericaaswellasAsia.Thesediseasesare

thecauseofabout534,000deathsannually;anestimated57

milliondisability-adjustedlife-years(DALYs)arelostannually

duetotheNTDs.Theseneglectedtropicaldiseasesputgreat

health,social,andﬁnancialburdenoneconomiesof

house-holdsandgovernments.11

Schistosomiasisisthesecond mostcommonNTDsafter

hookworminSub-SaharanAfrica.Childrenandyoungadults

bearmostoftheburdenresultingfromthisdiseaseinAfrica.

Sub-SaharanAfricaaccountsfor93%(192million)oftheworld

estimated207millioncasesofschistosomiasis.Thehighest

prevalenceofthis infection isseen inNigeria (29million),

whichiscloselyfollowedbyUnitedRepublicofTanzania(19

million),Ghana,andDemocraticRepublicofCongo(15million)

makingupthetopﬁvecountriesinAfricawithschistosomal

infection(Fig.2).However,underestimationofthetrue

preva-lenceofschistosomiasishasbeenreported;itisproposedthat

theprevalenceofschistosomal-relateddiseasesmaybemore

than400–600millionglobally.12

Prevalenceofschistosomiasisinsomesub-SaharanAfrica countries

S. mansoniisthe chiefcause ofclinical abnormalitiessuch

as hepatomegaly, splenomegaly, and periportal ﬁbrosis in

various sub-Saharan Africa countries. A study innorthern

Ethiopia in Alamata district revealed an alarming 73.9%

prevalence of schistosomal infection, with presentation of

3.7% hepatomegaly, 7.4%splenomegaly,and 12.3%

peripor-talﬁbrosis.13_A_{cross-sectional}_study_carried_out_among₃₆₂

school age children inMachakos districtin Kenya showed

varying intensitiesofS.mansoniinfections and its

associa-tionwithhepatomegaly.Itwasobservedthatinfectedchildren

exhibitedstuntedgrowthandwastedmusclescomparedwith

childrenwithoutinfection.14_Cases_of_{appendicitis-related}_to

schistosomalinfectionshavebeenreportedinvarious

stud-ies.SchistosomalappendicitiscausedbyS.mansoniinfection

is an unusual complication in endemic communitieswith

0.02–6.3%prevalence,whichrepresents28.6%ofsevere

(4)

Schistosomiasis burden in subSaharan Africa Ghana 15 Nigeria 29 Tanzania 19 Mozambique 13 Congo, DRC 15 N Legend Country_Prevalence Prevalence / SubSaharan_total 0.0069 Prevalence SubSaharan_total Africa_countries 0 1125 2250 4500 Kilometers

Fig.2–MapofAfricashowingrankingofestimatedschistosomiasisburdeninsub-SaharanAfrican(SSA)countries. SchistosomiasisprevalenceinSSAisdocumentedtobe192million,whichis93%ofthetotalglobalprevalenceofthe disease.Atotalof29millionpeopleareinfectedbythisdiseaseinNigeria,19millioninTanzania,15millioneachin DemocraticRepublicofCongoandGhana,whileMozambiquewith13millionpeoplecompletesthetopfivecountrieswith thehighestprevalenceinSSA.Thisprevalencefiguresbycountryarerepresentedbyapiechartasaratioofthetotal diseaseburdeninSSAusinganormalizationfigureof0.0069.TheprevalencefiguresaretakenfromHotezandKamath,9 whiletheprevalencemapwasgeneratedusingtheArcGISsoftware.

AstudycarriedoutinNigeriareportedthat2.3%ofover

1000casesofappendicitishadschistosomeeggsdiscovered

inhistologicalsections,with56%ofthecasesattributableto

S.mansoni,26.0%toS.haematobium,and19.0%tocoinfection

bybothspecies.16_In_another_study,_4.2%_of_appendicitis_cases

wereclassiﬁedasschistosomiasisoftheappendix.17

Schisto-somiasisduetoS.mansoniisontopofthelistofthecausesof

pulmonaryhypertensionworldwide,especiallyinareaswhere

schistoasomiasisisendemic.18

Asurveyofschoolchildrenaged5–19yearsinMbitaand

someIslandsclose toLake VictoriainKenyarevealed that

thecommunitieswerehighlyendemicforS.mansoniinfection

withprevalence ashigh as 60.5%.19 _Another _survey

cover-ingtheinhabitantsofLakeRweruinRwandaindicatedthat

21.1%ofthepopulationscreenedhadintestinal

schistosomia-sis.Thissuggestsalikelyhighprevalenceofschistosomiasis

inthecommunitiesevaluated.Outofthreecommunities

vis-ited,onecommunity had asingle caseofinfection,which

could beattributedto the presenceofpiped waterinthat

commmunity.20

Astudycarried outinYewaNorth LocalGovernmentof

OgunState,Nigeriabuttressedthefactthatschistosomiasis

exists among pregnant women. The study population

consisted of pregnant womenof age range 15–42 years.A

prevalenceof20.8%ofS.haematobiuminfectionwasobserved,

withtheyoungerpregnantwomenatgreaterriskofthe

infec-tion, which is in consonance with a previous report from

Tanzania.Itwasalsoobservedthattheprevalencerecorded

withinpregnantmothersinYewaNorthwasobviouslylower

comparedwithearlierreportsfromsimilarpopulationgroups

duetoataboointhatpartofthecountryrestrictingpregnant

womenfromvisitingnaturalwaterbodies.21

Across-sectionalstudyofschoolchildrenaged8–17years

inSengeremaDistrict,NyamatongowardofNorth-West

Tan-zania, revealed analarmingprevalenceof64.3%S.mansoni

infection. Thisprevalencewas remarkably high inspiteof

previous control efforts in the ward such as mass drug

administration.22_An_{investigative}_study_of_in-school_and

not-in-schoolchildrenaged6–15yearslivingincommunitiesalong

theTonoIrrigationCanalinNorthGhana revealeda

preva-lenceof33.2%ofS.haematobiuminfectionanda19.8%forS.

mansoni.Anoverallschistosomiasisprevalenceof47.7%was

reported.Itwasalsoobservedthattherewashigherinfection

(5)

whichmightbeduetolongerperiodofcontactwith

contam-inatedwater.23

Astudyconsistingofadultmaleandfemalesubjects

resid-ingintheVoltaBasinofGhanarevealeda46.5%prevalence

ofurinary schiatosomiasis;this reportis agood indication

thatschistosomalinfectionprevalenceisnottransientamong

adults.24 _An_{investigative} _study _carried_out _in_Zenu, _a

sur-burb community of the capital city of Ghana, revealed a

prevalence of30.7% ofurinary schistosomiasis amongthe

studypopulationofschoolchildrenaged3–16years.

Demo-graphic analysisshowed that the proximityof households

to a dam was associated with the prevalence observed

amongthechildren.25 _A_high _prevalence_(57.6%)_of_urinary

schistosomiasis and elevated intensity of S. haematobium

infection (185eggs/ml) was also reported among

school-age children in Niakhar District, Senegal. This endemicity

couldbeattributedtotheinhabitants’greatdependenceon

backwaterandpondsforvariousdomesticandrecreational

activities.26

Thereportofapilotstudy in2010,inthe EasternCape

ProvinceofSouthAfrica,withschool-agestudentsrevealed

analarmingprevalenceof73.3%.Theauthorsobservedthat

duetothestudypopulationsizebeingsmall,therewasneed

forfurtherstudy to determinethe extentof

schistosomia-sisinthearea.27 _A_nation-wide_survey_of_the_prevalence_of

schistosomal infections and soil helminths in school

chil-dren from Mozambique reported a prevalence of 47.0% S.

haematobium infection and 1.0% S. mansoni infection.

Fur-ther observation from this study showed that infection

increaseswith age,with the agegroup 10–14years having

the highest prevalence of S. haematobium infection. Itwas

also observed that across the districts, male children had

higherprevalencecomparedtotheirfemalecounterparts.The

high prevalenceofschistosomiasis was attributedto

inad-equate water supply in the districts, poor sanitation, and

alowlevelofsocioeconomic developmentinmostpartsof

Mozambique.28

Across-sectionalstudycarriedoutinZarimatown,

north-westEthiopiaamong319elementaryschoolchildrenrevealed

aprevalenceof37.9%S.mansoniinfection.Theresearchers

observedan increased prevalencecompared withprevious

studiesintheareadespiteschooldewormingprogrammes.

A study done at Barombi Kotto focus, SouthWest

Camer-oun,revealedanalarming69.17%prevalenceofS.haematobium

infectionconﬁrminghighendemicityinthearea.Itwasnoted

that mostlakes in the area were habitatsfor the B.

globo-sus intermediate host required for disease transmission.29

Addedtothis,another study carriedout inAgboville, Cote

d’Ivoire among school-aged children showed a very high

prevalenceof85.3%and53.8%forS.haematobiumandS.

man-sonirespectively.30

Schistosomal

morbidity

and

mortality

in

sub-Saharan

Africa

Thesigniﬁcanceofmorbidity and mortalityresulting from

helminthic infections including schistosomiasis has been

grossly underestimated in most developing countries.12

School-agedchildren, teenagers, womenand young adults

are mostlyhit withthemorbidityand mortalityassociated

with schistosomiais.31 _Population _studies _of

schistosoma-infected children revealed that schistosomiasis can cause

growthretardation,fatigue,weakness,impairmentof

mem-oryandcognitivereasoning,andincreasedriskofanaemia,

leading to poor academic performance, thus limiting the

potential of infected children.8 _These _negative _outcomes

in children add to the socioeconomic burden of the

society.11

Thoughschistosomiasisisrarelyfatal,itcauseslongterm

morbiditysuchasanaemiawhichresultsfrombleedingfrom

the urinaryandintestinaltractsduetoworminvasionand

movements;irondeﬁciencyisalsoanoutcomeofthedisease

sequel to nutritional impairment such as nutrient

malab-sorption anddigestive disorderlike diarrhoea.32 Astudyin

Daekena,intheRepublicofNigeranareaendemicforurinary

schistosomiasis,revealed41.7%ofthe174schoolchildren

hav-ingirondeﬁciencywhile57.7%exhibitedanaemiarelatedto

irondeﬁciency.33_A_longitudinal_study_in_Burkina_Faso_among

1727Burkinabechildrenaged6–17yearsrevealedadramatic

increaseinhaemoglobinconcentrationfollowing

chemother-apyofS.haematobiumcomparedwithbaselineconcentration

ayearearlier.34

Clinical observation and autopsy strongly indicate that

people, speciﬁcally elderly patients, die as a result of

schistosomal-inducedkidneydamage.2_Urogenital

schistoso-miasisisakeypredisposingagentforHuman

Immunodeﬁ-ciency Virus(HIV) transmission.Urogenital schistosomiasis

in HIV-infectedwomen increases the ease oftransmission

to male sexual partners, as well as transmission from an

HIV-infected male to his sexual partner. It also hastens

the progression of the disease in people already infected

with the virus by increasing the plasma concentration of

the HIV RNA (viral load).35 _A _study _among _Zimbabwean

women showed that women with S. haematobium eggs in

their pap smear had a risk three times higher of having

HIV.36

Studiesonanimalmodelsandhumansubjectshave

estab-lishedadverseconsequencesofschistosomiasisonpregnancy

outcomes.S.haematobiuminfection hasbeenlinkedto

pla-cental inﬂammation, leading to poor birth-outcomes as a

result of placental incompetency. Heavy S. mansoni

infec-tion has also been linked to higher risk of anaemia that

mightsubsequentlyleadtomaternalmortalityorlowbirth

weight(LBW)babies.Theanaemiamaybeduetourinaryiron

loss and faecalwaste.Proinﬂammatorycytokines resulting

from schistosomiasis infection leadsto anorexiaor lossof

appetite ofpregnantwomenwhichmight ultimatelyresult

in reduced maternal weight gain and thus lead to a LBW

baby.37_An_{observational}_study_in_Tanzania_showed_that_there

was a high prevalence of S. mansoni infection among the

pregnantwomenandthehighintensityofinfectionexposes

thewomentoahigherriskofanaemiaduringpregnancy.38

AnotherstudyinTanzanialinkedthedeliveryofLBWbabies

toinfection withparasiticdiseases including

schistosomia-sis during pregnancy.39 _The _study _has _shown _an _elevated

progressionofliverﬁbrosis inpeopleco-infectedwith

sch-istosomiasisandhepatitisCvirusincomparisonwithcases

ofsingleinfections,which ultimatelyled toadvancedliver

(6)

Factors

determining

the

continuous

transmission

of

schistosomiasis

in

sub-Saharan

Africa

The continuous transmission of schistosomiasis in

sub-SaharanAfricaisattributabletovariousenvironmentaland

socio-economicfactorssuchas:

Climaticchanges

Thereisan establishedlinkbetweenclimaticchanges and

infectiousdiseasetransmission.Schistosomiasisisatypical

example of diseases whose local infection and

geographi-calexpansionisinﬂuenced byclimaticchangesand global

warming.41 _Mangal _and _co-workers _showed _that _a _rise _in

ambienttemperaturefrom20◦Cto30◦Cwillleadtoover

ten-foldincreaseinthemean burdenofS.mansoniinfection in

endemicareas.Nonetheless,attemperaturesabove 30◦C a

decreaseinthediseaseburdenwasobserved,probablydue

to higher death rate of the intermediate snail host. They

observedthatalthoughanincreaseindiseaseburdenleads

toincreasedmorbidityandmortality,theremightbea

negli-gibleincreaseinprevalenceofthedisease.17_Rainfall_patterns

alsohaveaneffectonthetransmissionofschistosomiasis;in

Senegal,thesnailspecieBiomphalariapfeifferiisresponsiblefor

S.mansonitransmissionduringtherainingseason,while

dur-ingthedryseasonS.haematobiuminfectionistransmittedby

Bilunusglobosus.42

Proximitytowatersources

Theschistosomeparasiterequiresanavenuewhereinthereis

directcontactbetweenthemolluscanintermediatesnailand

theﬁnalhumanhostfortransmissionofschistosomiasisto

takeplace.43 _An_estimated_76%_of_the_sub-Saharan

popula-tionliveclosetovariousopenwaterbodieswhichareinfested

withtheintermediatesnailhostnecessaryforthe

transmis-sionofthedisease.1_Various_studies_have_established_a_direct

associationbetweentheintensityofthediseaseand

proxim-ityofinfectedindividualstonaturalwatersourcessuchas

lakes,rivers,andponds.44,45_A_study_carried_out_in_Blantryre

districtinMalawi,showedthatchildrenwhoseschoolwere

closertoopenwaterbodieshadincreasedriskofinfection,44

aﬁndinginconsonancewiththatreportedbyClennonand

co-workers.45

Man-madeecologicalchanges

Ecological changes due to man-made construction of

irrigationschemes,reservoirsanddamsforagricultural

pur-poses and electricity generation are also responsible for

continuedtransmission ofschistosomiasis insomein

sub-Saharan African countries.46 _Construction _of _dams _led _to

remarkableincrease incasesofurinary schistosomiasis as

experiencedinsomesub-Saharan Africa countriessuch as

Senegal,Coted’Ivoire,Ghana,Mali,Namibia,andCameroun.4

Steinmann and co-workers estimated that 13.6% (106

mil-lion)ofpeoplevulnerabletoschistosomiasisresidecloseto

irrigationschemesandlargedamreservoirs.1

Socio-economicfactors

Socio-economicfactorsinﬂuencingthecontinuous

transmis-sion of the debilitating disease in sub-Saharan countries

includepovertyoccupationalactivities,poorsanitationand

hygiene, andnon-availability ofpotable waterfordomestic

use.2_A_World_Bank_analysis_conﬁrmed_that_the_majority_of_the

sub-SaharanpopulationsurviveonbetweenUS$1.25–2per

day.9_King_postulated_a_vicious_cycle_between_poverty_and

sch-istosomiasis.Heexplainedthatpovertycompelsanindividual

toutilizingcontaminatedwatersourcesforhisdomestic

activ-itiestherefore gettinginfectedwiththe disease,on getting

sick dueto theinfection, hebecomesunable toengage in

activitiestoearnhislivelihoodandthus,povertypersists.12

Ugbomoikoandco-workersestablishedthelinkbetween

sch-istosomiasisandpovertyintheircross-sectionalstudyintwo

peri-urbancommunitiesinOsunState,Nigeria.Analarming

62%prevalencewasrecordedamong1023individualsunder

study.47

AnanalysisbyEsreyandco-workersreportedontheroleof

improvedwatersupplyandhygieneondiseasetransmission

andincidence.Theyconcludedthatavailabilityofsafewater

andsanitationarenecessaryforreducingtheincidenceand

prevalenceofschistosomiasisandsomeotherwaterrelated

diseases.48Manyinhabitantsofsub-Saharancountrieshave

limitedaccesstopotablewaterfordomesticuse,leavingthem

withtheoptionofusingnaturalwaterbodiessuchaslakes,

rivers, ponds, and other watersources contaminated with

developmental stages ofthe schistosomeparasite. Astudy

carriedoutinnorthernNigeriashowedthelinkbetweensafe

waterandintensityofurinaryschistosomiasis.Ahigherrate

ofinfection(88.57%)wasrecordedinacommunitythatonly

hadapondassourceofwaterfordomesticuseincomparison

with0.59%inaneighbouringcommunitywithborehole.49

Occupational activities such asﬁshing and farmingare

alsoriskfactorsfortransmissionofthedisease.Contactwith

infectedwaterisavitalfactorintransmissionofinfection;

womenandchildrengetexposedtoinfectionduringactivities

suchaslaundry,platewashing,waterfetchingfordomestic

useandbathing.Recreationalactivitiessuchasswimmingand

divingalsoexposeanindividualtoinfection.3

Chemotherapy

for

schistosomiasis

and

associated

fallout

SeveraldrugshavebeenusedinthetreatmentofSchistosoma

infection,andnotableamongthemareoxamniquine,

metri-fonate,artemisininderivatives,andpraziquantel.Artemisinin

is an antimalarial, which has been shown to have

anti-schistosomal properties, with the best outcomes with

artesunateandartemether.Thesedrugshavethecapacityto

killjuvenilewormsofbothS.mansoniandS.japonicum.

Tri-alsdoneinChinaandCoted’Ivoireestablishedtheefﬁcacyof

artemisininderivatives.However,thereiswidespreadconcern

ontheuseofthesedrugsinareaswheremalariaisendemic

duetofearofraisingPlasmodiumresistance.50

Praziquantel, apyrazinoisoquinoline derivativehasbeen

shown in randomized controlled trials to be a very safe

(7)

variousschistosomespecies.49_This_drug_is_made_of_a_white

crystallinebittertastingcompoundwhichisstableinnormal

storageconditionandinsolubleinwater.Commercially,the

drugisavailableasaracematemixturewithequal‘levo’and

‘dextro’isomers.The‘levo’parthasschistosomicidalactivity

invivoandinvitro.Itismainlyavailableas600mgcrystalline

tablets,butthegenerally recommendeddosageis40mg/kg

bodyweightinasingledose.A600mg/5mlsyrupisalso

avail-ableforsmallchildren.51 _Praziquantel_is_still_the _best_drug

forcombatinginfectionsfromallﬁvespeciesofschistosomes

afﬂictinghumans,withacurerateof60–90%invarious

epi-demiologicalsettings.52

Millionsofpeoplearegiventhedrugyearlyinsub-Saharan

African nations, courtesy of various mass chemotherapy

controlprogrammes,especiallyundertheBillandMellinda

GatesFoundationsponsoredSchistosomiasisControl

Initia-tive(SCI).53_In_the_year_2002,_WHO_endorsed_the_drug_safety_for

treatingpregnantwomenaswellaslactatingmothers.

How-ever,100%curerateshavescarcelybeenrecordedinendemic

areas.54 _Praziquantel _acts_within_an _hour_of _oral_ingestion

butitsactualmechanismofactionontheadultwormisnot

yetknown.Laboratory studies haverevealed that thedrug

causescontractionoftegumentalvacuolesmakingtheworm

todisengagefromthewalloftheveinsanddie.Thecalcium

ion channel of the schistosome worm has been indirectly

establishedasthemoleculartargetofthedrug.8Oneofthe

hypothesesofthemodeofactionofthisdrugstatesthatit

insertsitselfintotheparasitesmembraneandproduceslipid

phasetransitionthusdestabilizingthemembrane.52

Praziquantel negative effects are very mild and these

includenausea, vomitting,abdominalpain, malaise,andin

seriousinfections, intensecolicand bloodydiarrhoeasoon

aftertreatment,whichmaybeattributedtowormmass

move-mentandantigenrelease.2_Praziquantel_does_not_have_effect

onyoungwormsbothinvivoandinvitro.Thissigniﬁcant

short-comingisresponsibleforpoorcurerateaswellastreatment

failurereported insomestudies,especially inareas where

transmissionrateisveryhigh.Toovercomethis,twocourses

ofdrugadministrationhasbeenadvocatedwhichgavea

bet-tercurerate.51_Extensive_and_intensive_usage_of_the_drug_gave

risetoconcernsontheemergenceofdrug-resistantmutants

oftheschistosomalparasitesandthus,theneedforresearch

intoevolvementofnewanti-schistosomaldrugs.8

Schistosomiasisandcancer

StudiesinAfricaandintheMiddleEasthavebeencarriedout

aimingatestablishingtherelationshipbetweeninﬂammation

resultingfromschistosomiasisandsquamouscellcarcinoma

ofthebladder.55_The_{International}_Agency_for_Cancer_Research

inassociationwiththeWorldHealthOrganizationcategorized

S.haematobiuminfection as carcinogenic.S.mansoni andS. japonicumareassociatedwithcervical,liver,aswellas

colo-rectalcarcinomas.56_Deposition_of_parasite_ova_in_the_bladder

leadstointenseinﬂammatoryreactionsthatarelinkedtothe

releaseofoxygen-derivedfreeradicals,whichaidsthe

pro-ductionofcarcinogenicN-nitrosamines,andthusmalignant

transformation. N-nitrosamine formation has been linked

tochronicbacterialinfection intheurinary bladder dueto

schistosomalinfections.57_Groeneveld_and_co-workers_stated

intheirworkthateradicationofschistosomiasisaswellasa

timelydetectionofbladdercancerwillgiveroomforefﬁcient

managementofsquamouscellcarcinomaofthebladderin

Africanpatients.58

Combating

schistosomiasis

in

sub-Saharan

Africa

Preventivechemotherapeuticapproachusingpraziquantelis

themostcommonstrategytocontrolschistosomiasis.It

actu-ally leads to decreased schistosomal-related morbidity but

highdiseasere-occurrenceandtransmissionofinfectionstill

persisted.Hence,inordertosupportthebeneﬁtsofthedrug,it

mustbeadministeredatregularintervalsforlimitlessperiod

oftimetopreventrecurrencyofmorbidity.8_The_WHO_reported

thatasat2010,34.8millionpeopleweretreatedwith

prazi-quantelin30countries;thedrugwasmadeavailablethrough

yearly donation of 250 million tablets. The WHO set the

goalofcontrollingschistosomiasis-associatedmorbidityinall

endemiccountriesbytheyear2020.Itaimedateliminatingthe

diseaseinallendemiccountriesbytheyear2025andto

inter-rupttransmissionofschistosomalinfectionsinnon-endemic

regionssuchasAmerica,Europe,EastMediterrranean,

South-EastAsia,aswellassomeselectedAfricancountries.53

Despitesub-Saharan Africacountrieshavingthehighest

burdenofmorbidityandmortalityassociatedwiththe

dis-ease, limited efforts havebeen made inthe control ofthe

diseaseuntiltheintroductionofSchistosomiasisControl

Ini-tiativesin2002(SCI).59_The_SCI_successfully_instituted_national

schistosomiasis control programmes in some sub-Saharan

nationslikeZambia,Mali,Tanzania,BurkinaFaso,Nigerand

Uganda.However,theseprogrammeswerenotsuccessfuldue

toincompleteverticalmassdrugdistribution.Thecoverage

oftheprogrammewasineffective,infantsandpreschool

chil-drenwerenotadministeredthedrug.46_More_so,_below_50.0%

ofthehighriskpopulationweregiventhedrugwhile

indi-vidualswhowerenotinfectedwiththediseasereceivedthe

drugasthefocuswasontreatingeveryonewithoutcase

ﬁnd-ing.Thus,morbidityreductionwasverylowandcessationof

transmissionvery limited.60 _Before_2013,_over _US$₁₅₀

mil-lionhavebeenexhaustedonschistosomiasisandotherNTDs

insub-Saharan Africannations,and by2013,therewasan

increaseaftertheUnitedStatesofAmericaannouncedafresh

fundingforainitiativeforcombatingNTDs.61

Realistically,mostsub-SaharanAfricancountriescannot

affordtheestimated1.2billiontabletsofPraziquantelrequired

totreat400millionindividualsperannum forﬁveyearsat

atotalcostofUS$100million.62_Thus,_{schistosomiasis}

con-trol in thesecountries cannot beachieved without foreign

donor fundings.60 _Over_the _decades, _the _approach _used_in

sub-Saharan countries hasaimed atreducing morbidityof

infection,46_however,_there_is_dire_need_for_sustainable

strate-giesgearedtowardstransmissioncontrolandeliminationof

this impoverishingdisease.Vaccines are known tobevital

in disease controland eradication;this wasevidentin the

1978eradicationofsmallpox.63_There_is_a_consensus_among

researchersintheﬁeldthateffectivecontroloftransmission

(8)

introductionofanti-schistosomalvaccinescapableofbuilding

humanimmuneresponsestoparasiteinvasion.61,64

Improvementinwatersupply,sanitationandhygiene

Improvedsanitationandaccesstosafewatersupplyarekey

factorsinschistosomiasiscontrolandelimination.31

Advance-mentinwatersupplyand sanitationplayarole ingeneral

economicdevelopmentandgrowthofacountry.65_Campbell

andcolleagues66_opined_that_there_is_need_to_progress_from

emphasisontreatmentofmorbidityduetoinfectiontowards

reductioninexposuretoinfectionthroughthe

implementa-tion ofWater, Sanitationand Hygiene(WASH)intervention

policy.Manyauthoritiesinsub-SaharanAfricaarenot

ded-icated to making available clean water sources for their

communities,andwithoutaccessibilitytocleanwater,

eradi-cationofschistosomiasisinsub-SaharanAfricawillcontinue

tobeamirage.

Educatingpeopleonbehaviouralchanges

Thereis aneedtoeducate people, bothyoung andold on

theimplicationofvoidingtheirbladderandfaecalwasteinto

waterbodies. This behavioural change will go a long way

inreducing contamination ofwatersourcesand thus lead

toreductioninthe rateoftransmission ofschistosomiasis

and someother water-transmitted diseases.An intensiﬁed

effortateducatingpeopleontheriskofschistosomalinfection

and transmission is necessary to assist in achieving

posi-tive behavioural changes regarding waste elimination and

personal exposure to open water sources.9 _Inhabitants _of

endemicareasneedtobeencouragedtoreducewater

con-tactasmuchaspossibleinabidtoreduceschistosomiasis

transmission.67

Snailcontrol

Thoughnotinuseinsub-SaharanAfrica,theuseof

mollus-cicidesreducessnailpopulationbutrarelyeliminatesthem.

This is because the snails recolonize their habitat after a

while,soregularandlong-termapplicationofthechemicalis

required.Although,thiscontrolmethodwassuccessfullyused

toachieveeradicationofthisdiseaseinMoroccoandJapan,it

wasalsousedincontrolprogrammestrategiesinEgyptand

China. Toxicityof the chemical toﬁsh aswell asto other

water-dwellingorganismsisofgreatconcernecologicallyand

economically. Alternatives tochemical-based molluscicides

includethe use ofplant-based derivatives(e.g. endod)and

biologicalcontrolwithsnailcompetitors.31

Advances

in

schistosomal

vaccine

candidates

Sub-Saharan African researchers need to be aggressively

involvedintheongoingsearchforalternativedrugsor

anti-schistosomalvaccinestoovercometheinherentchallenges

posedbythis neglected but destructive disease ofpoverty.

Theforegoingaresomeadvancesinvaccinediscovery.

Vac-cinecandidatesforschistosomalinfections areindifferent

phases of development. Some vaccines are in pre-clinical

trial phase whileothers are inphase oneand two clinical

trials.Examplesincludefattyacidbindingprotein(FABP),

Cal-pain,Triose-phosphateisomerase,andTetraspanins,GST,and

Paramyosin.6 _The _Calpain_subunit _called _Sm-p80_has _been

experimentallytestedforitsanti-fecundityandanti-infective

efﬁcacy. Experimentalmicevaccinated with DNA plasmids

with Sm-p80 and interleukin-2 (IL-2)provided 59%

protec-tion,whilevaccinationusingplasmiddesignedwithSm-p80

and interleukin-12 (IL-12) gave 45% protection. The study

indicatedthat Sm-p80isagood vaccinecandidatefor

sch-istosomiasis and furtheradvancement and optimizationis

neededforhumantrials.68_{Triose-phosphate}_isomerase_(TPI)

andtetraspaninsareanothergroupofantigenswith

promis-ing vaccine potential; trials havebeen done onbuffalos to

determinetheefﬁcacy levelsofbothvaccinesontheirown

andfusedtogetherwithheat-shockprotein70(Hsp70).The

vaccine constructs are SjCTP1-Hsp70 and SjC23-Hsp70; the

formerwasreportedtobemoresuccessfulasitproduceda

wormburdendecreaseof51.2%,livereggdecreaseof61.5%,

faecalwaste eggreductionof52.1%,and52.1% decreasein

hatchingfaecalmiracidia.69

Pearson andcolleagues70 _also_succeeded_in_producing _a

chimericvaccinenamedSm-TSP-2.Theirstudyindicatedthat

thisvaccineantigencouldbesafelyusedagainstschistosome

adultwormsandlivereggsaswellasforthehookworm

par-asite. The28kDaGSTrecombinant protein(Sh28GST)from

S. haematobium has been experimentally tested regarding

safety,immunogenicity,aswellastoxicity.Thevaccine

can-didate molecule, paramyosin (rSj97) recombinant fraction

has also been discovered to give protection together with

immunogenicityinBALB/cmice.Thefulllengthrecombinant

paramyosin proteinelicited antibodyresponsesinhumans

withre-infectionresistance.6_However,_till_the_moment,

sci-entiﬁc hurdles and socioeconomic factors remain major

challenges towardssuccessfultransitionofthe above

men-tionedvaccinecandidatesintoformsthatcouldbeusedfor

schistosomiasisinterventioninsub-SaharanAfricaandother

regionsoftheworld.64

Conclusion

Formanydecadeshumanschistosomiasishasbeenofgreat

healthconcerngloballyandmostlyincommunitiesof

sub-Saharan Africa. The economic loss, disability and agony

caused by the various species of schistosomes cannot be

over-emphasized.Concertedeffortsshouldbemadetowards

theeliminationofthisdiseaseofpovertyinallcountriesin

sub-SaharanAfrica.Thevariousauthoritiesinsub-Saharan

countriesshouldmakeprovisionofcleanandsafewater

avail-able for the citizens.There should be constant awareness

programmestoeducatethepopulationontheprominenceof

sanitationandhygieneinachievingdiseasecontrolandthe

effect ofschistosomiasison the qualityoflifeand general

well-beingofpeople.

Most importantly, it is hoped that this review will

generate new interest among researchers in sub-Saharan

Africa towardsfurtherscientiﬁcdiscoveriestocombat

sch-istosomiasis, in terms of alternative drugs to address

(9)

point-of-carediagnostics,snail control, and othergermane

discoveriesthatwillserveasguidetovoting-off

schistosomia-sisinsub-SaharanAfricaandsomeotherendemicregionsof

theworld.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgements

Theauthors wouldliketothankMr HenokSolomonofthe

DepartmentofEarthSciences,UniversityoftheWesternCape,

Bellvilleforthehelpreceivedingeneratingthe

schistosomia-sisburdeninsub-SaharanAfricamap.

r

e

f

e

r

e

n

c

e

s

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