CHAPTER ONE

INTRODUCTION

1.1 Background to the Study

Malaria and schistosomiasis are the two most prevalent parasitic infections in tropical and sub-

tropical regions, accounting for a considerable proportion of global morbidity and mortality

(Kamau et al., 2021). Malaria and schistosomiasis are common in tropical and sub-tropical

areas, causing high burden of morbidity and mortality, particularly in children. In 2015, about

214 million people were infected and 438,000 estimated to have died globally due to malaria.

Additionally, more than 261 million people required preventive treatment for schistosomiasis

and close to 200,000 are estimated to die due to this disease annually (Degarege et al., 2016)

about 90% of the malaria deaths and 90% of those who require treatment for schistosomiasis live

in sub-Saharan Africa (SSA), with children being the most affected group.

Plasmodium falciparum (P. falciparum) is responsible for most malaria cases and deaths due to

the disease in SSA. Likewise, two schistosome species, Schistosoma mansoni (S. mansoni)

and S. haematobium are responsible for almost all of schistosomiasis cases in

SSA. S. mansoni causes intestinal and hepatic schistosomiasis and S. haematobium causes

urogenital Schistosomiasis. Both Schistosoma spp. cause inflammation that leads to anaemia

growth stunting or cognitive impairment (Degarege et al., 2016). Social, economic, and

environmental factors are important determinants in the patterns and prevalence of malaria and

schistosomiasis including co-infections, with poor and rural communities highly impacted.

Further, individuals who engage in certain activities and occupations such as anglers are at

increased risked due to increased environmental exposures. (Kamau et al., 2021)

According to the World Health Organization (WHO), both parasitic diseases are endemic to Sub-

Saharan Africa with more than 194 million malaria cases, and an estimated 91.4% requiring

preventive chemotherapy. In 2016, more than 100,000 malaria deaths were reported in Nigeria

with Plasmodium falciparum responsible for all malaria cases. Infected individuals exhibit mild

symptoms ranging from fever, fatigue, chills to severe complications including cerebral malaria,

austere anaemia or renal failure (Ojo et al., 2019). Plasmodium falciparum accounts for more

than 99% of malaria cases in Africa (Iliyasu et al., 2020). These infections cause a spectrum of

clinical illness ranging from asymptomatic to severe disease with immune status acting as a

critical determinant of disease progression and they can be either microscopic or submicroscopic

(Ojo et al., 2019). Malaria infection can lead to hematologic abnormalities such as anemia,

leucopenia, and thrombocytopenia, which are important in disease pathophysiology. After

repeated exposure, premunition may lead to persistent, asymptomatic infections which are

characterized as subclinical due to lack of overt clinical symptoms. However, it is now evident

that asymptomatic infections may cause harm to the individual and are reservoirs for

transmission (Ojo et al., 2019).

Schistosomiasis is caused by five identified Schistosoma species and is ranked second to malaria

as a neglected tropical disease. In Nigeria, Schistosoma haematobium and Schistosoma mansoni

are responsible for almost all the cases of schistosomiasis, causing urogenital and intestinal

schistosomiasis, respectively. People infected with Schistosoma spp (S. haematobium or S.

mansoni) display various symptoms and pathologies including anaemia, growth retardation

(prevalent among school aged children), dysuria, nutritional deficiencies, haematuria,

hepatosplenomegaly, pelvic discomfort, infertility (in prolonged cases in females) and bladder

cancer. Several epidemiological and immunological studies have indicated high rates of co-
infection with soil transmitted helminths and Plasmodium falciparum in conditions of poverty,

where they frequently overlap. Schistosomiasis and malaria exhibit almost similar distribution

patterns, making schisto-malaria coinfection a predominant occurrence in malaria endemic

countries (Ojo et al., 2019). Studies conducted in Nigeria have reported conflicting results about

whether Schistosoma coinfection with Plasmodium falciparum regulates the outcome of malaria

infections, by altering the pathophysiological and immune responses of the disease (Ojo et al.,

2019).

1.2 STATEMENT OF PROBLEM

Nigeria faces a significant health burden due to malaria and schistosomiasis, two prevalent

parasitic diseases. Studies have shown a high occurrence of co-infection with soil-transmitted

helminths and Plasmodium falciparum in poverty-stricken regions where the diseases overlap.

The co-distribution of schistosomiasis and malaria makes schisto-malaria co-infection a

predominant occurrence in malaria-endemic countries like Nigeria. However, the impact of

Schistosoma coinfection on the outcome of malaria infections remains controversial, with

conflicting results reported in studies. Nigeria bears the greatest malaria burden globally,

accounting for approximately 30% of all malaria cases in Africa. Annually, the country reports

around 51 million malaria cases and 207,000 related deaths. The vast majority of the populations

(97%), roughly 173 million people, are at risk of infection. Malaria significantly impacts

healthcare facilities, with 60% of outpatient hospital visits attributed to the disease. It also

contributes to maternal and child mortality rates, particularly among children under the age of

five. The impact of malaria extends beyond public health, negatively affecting Nigeria's

economic productivity. The disease incurs substantial monetary losses estimated at

approximately 132 billion Naira (700 million USD). This cost encompasses treatment,
prevention efforts, and indirect expenses associated with malaria's debilitating effects on

individuals and communities. In specific regions, like the Local Government Areas of Benue

State, schistosomiasis poses a significant health threat, especially to local farmers. Infected

individuals experience illness, lethargy, and reduced productivity, hindering farming activities,

school attendance, and other daily tasks. In severe cases, schistosomiasis can lead to

malignancies that may prove fatal. There is little information about the prevalence of

Schistosoma co-infection with Plasmodium falciparum in Adoka, Benue state. Hence, this

research work seeks carryout epidemiological studies and the current prevalence of Schistosoma

and Plasmodium falciparum co-infection in Nigeria.

1.3 AIM

The aim of this research is to investigate the co-endemicity of malaria and schistosomiasis in

Adoka district of Benue State.

1.4 OBJECTIVES

 To determine the prevalence of Plasmodium falciparum and Schistosoma haematobium

in the study area.

 To investigate factors responsible for co-endemicity of Plasmodium falciparum and

Schistosoma haematobium.

 To investigate the use of mosquito nets and water contact activities in study.

 To investigate the knowledge, attitude and beliefs on malaria and schistosoma in the

study area.
 CHAPTER TWO

LITERATURE REVIEW

2.1 Prevalence of Malaria and Schistosomiasis

Malaria and schistosomiasis are among the most important diseases of enormous public health

burdens in tropical and subtropical countries of the globe (Doumbo et al., 2014). Malaria is a

complex and life-threatening parasitic disease caused by the protozoan parasite of the genus

Plasmodium (Getie et al., 2015). Malaria is associated with anaemia, which causes severe

morbidity and mortality in vulnerable groups infected with Plasmodium falciparum (Ajakaye and

Ibukunoluwa, 2020).Other Species that affect humans include: P. vivax, P. ovale, and P.

malariae. Schistosomiasis is a chronic and debilitating disease caused by flukes (digenetic

Trematode flatworms) known as Schistosomes (Okpala et al., 2004). Schistosomiasis also known

as (biharziasis or snail fever) ranking second to only malaria in terms of its socio-economic and

public health importance in tropical and subtropical areas (Ogbe, 2002). It is also the most

prevalent of the waterborne diseases and one of the greatest risks to health in rural areas of

developing countries (Ofoezie et al., 1998; Ogbe, 2002).

An analysis, based on African studies, showed that there is a risk ratio of 2.4 and 2.6 for urinary

schistosomiasis (caused by S. hematobium) and intestinal schistosomiasis (caused by S.

mansoni), respectively, among persons living adjacent to reservoirs. The analyses also showed

that persons living near land that had been irrigated for agricultural use had an estimated risk

ratio of 1.1 for urinary schistosomiasis and an estimated risk ratio of 4.7 for intestinal

schistosomiasis (Steinmann et al., 2006). Infection occurs through contact with water infested

with the free swimming larval stages of parasitic worms (cercariae) that penetrate the skin and

develop in the human body to maturity. Parasite eggs leave the human body with urine or
excreta. They hatch in freshwater and infect the appropriate aquatic snail intermediate hosts.

Bulinus snails are intermediate host for S. haematobium (Okoli and Iwuala, 2004). Within the

snails they develop into cercariae, which are, in turn, released into the water to infect new human

hosts. Transmission can take place in almost any type of habitat from large lakes or rivers to

small seasonal ponds or streams (WHO, 2001; Akue et al., 2011). In urinary Schistosomiasis, it

is the eggs and not the worm which cause damage to the intestines, the bladder and other organs

(Brooker et al., 2007). Schistosomiasis appears to be a neglected tropical disease. However, due

to irrigation programs and hydroelectric power development, the incidence of infections is

increasing in endemic areas of Africa and the near east, and the risk of infection is highest

amongst those who lived near lakes or rivers (Kabatercine et al., 2004; Brooker et al., 2007).

More than 207 million people are infected worldwide, with 75% of them living in Africa alone

(WHO, 2011). Recent estimates from sub-Saharan Africa have indicated that approximately

280,000 deaths each year can be attributed to schistosomiasis (Van der Werfet et al., 2003). In

Nigeria S. haematobium infection is widespread, constituting a public health problem

particularly in children (Sulyman et al., 2009; Griffiths et al., 2011; Doumbo et al., 2014).

Although there is no current estimate of the disease in the country, past estimates have put the

infection at about 25 million people, and 101 million at risk of infection (Chitsulo et al., 2000).

The distribution of the disease is focal, aggregated and usually related to water resources and

development schemes such as irrigation projects, rice/fish farming and dams. It occurs in all the

states of the federation, with a high infection rate among school children (Okpala et al., 2004;

Mafe et al., 2005; Akue et al., 2011).

In Nigeria, Schistosomiasis due to S. haematobium is widespread, constituting a public health

problem particularly in children (Okpala et al., 2004; Sulyman et al., 2009 and Griffiths et al.,
2011). The distribution of the disease is focal, aggregated and usually related to water resources

and development schemes such as irrigation projects, rice/fish farming and dams. It occurs in all

the states of the federation, with a high infection rate among school children (Mafe et al., 2000;

Okpala et al., 2004).There are reports of Bilharziasis in Benue State (Amali, 1989; Atu and

Galadima, 2003; Houmsou, et al., 2012), Four species of Schistosomes are responsible for

human schistosomiasis: Schistosoma mansoni, S. haematobium, S. japonicum and S.

intercalatum (Swai et al., 2006; Dawaki et al., 2015; Dawaki et al., 2016). Infection with multiple

Species of parasites is often the norm in developing countries (Griffiths et al., 2011). Malaria and

schistosomiasis are highly endemic in tropical and sub-tropical areas and their epidemiologic co-

existence is frequently observed (Adegnika and Kremsner, 2012; Anchang-Kimbi et al., 2017).

The prevalence of malaria-schistosomiasis co-infection reported to be 15 % and caused high

prevalence of anemia, as compared to those infected only with malaria (Degarege et al., 2012).

Schistosomiasis plays an antagonistic role against malaria, but the egg intensity of Schistosoma

species and the age of infected individuals could determine the type of interaction (Briand et al.,

2005; Sangweme et al., 2010). Although most studies were conducted, reported that Schistosoma

co-infection contributes to severe malaria presentation. Schistosoma co-infection resulted in high

Plasmodium parasitemia and increased susceptibility of infection to mortality (Yoshida et al.,

2000; Legesse et el., 2004; Laranjeiras et al., 2008; Sangweme et al., 2009). In contrast, others

illustrated that Schistosoma co-infection contributed to low Plasmodium parasitemia and

inhibited cerebral malaria (Lwin et al., 1982; Waknine-Grinberg et al., 2010; Bucher et al.,

2011). Both Malaria and schistosomiasis are endemic in Nigeria (Terer et al., 2013). Malaria

environmental risk factors include: low utilization of nets, low utilization of indoor residual

spray, and availability of multiple mosquitoes breeding site or stagnant water near the home and
staying outdoor overnight. Schistosomiasis risk factors are: lack of access to safe water,

contact/exposure to fresh water bodies, outdoor activities, low Socio-economic status, and poor

educational access for schistosomiasis (FMOH, 2007; Getie et al., 2015).

2.2 Malaria

Malaria affected an estimated 219 million people causing 435,000 deaths in 2017 globally. This

burden of morbidity and mortality is a result of more than a century of global effort and research

aimed at improving the prevention, diagnosis, and treatment of malaria (WHO 2018). Malaria is

the most common disease in Africa and some countries in Asia with the highest number of

indigenous cases. The malaria mortality rate globally ranges from 0.3–2.2%, and in cases of

severe forms of malaria in regions with tropical climate from 11–30% (White et al., 2014).

Different studies showed that the prevalence of malaria parasite infection has increased since

2015 (Dhiman 2019). The causative agent of malaria is a small protozoon belonging to the group

of Plasmodium species, and it consists of several subspecies. Some of the Plasmodium species

cause disease in human (Walker et al., 2017). The genus Plasmodium is an amoeboid

intracellular parasite which accumulates malaria pigment (an insoluble metabolite of

hemoglobin). Parasites on different vertebrates; some in red blood cells, and some in tissue; of

the 172 of Plasmodium species, five species can infect humans. These are P. malariae, P.

falciparum, P. vivax, P. ovale, and P. knowlesi. In South-East Asia, the zoonotic malaria P.

knowlesi is recorded. Other species rarely infect humans (Ashley et al., 2018). All the mentioned

Plasmodium species cause the disease commonly known as malaria (Latin for Malus aer—bad

air). Likewise, all species have similar morphology and biology. The Plasmodium life cycle is

very complex and takes place in two phases; sexual and asexual, the vector mosquitoes and the

vertebrate hosts. In the vectors, mosquitoes, the sexual phase of the parasite’s life cycle occurs.
The asexual phase of the life cycle occurs in humans, the intermediate host for malaria (Soulard

et al., 2015). Human malaria is transmitted only by female mosquitoes of the genus Anopheles.

The parasite, in the form of sporozoite, after a bite by an infected female mosquito, enters the

human blood and after half an hour of blood circulation, enters the hepatocytes (Ashley et al.,

2018). The first phase of Plasmodium asexual development occurs in the hepatocytes, and then

in the erythrocytes as shown in figure 1. All Plasmodium species lead to the rupture of

erythrocytes. The most common species in the Americas and Europe are P. vivax and P.

malariae, while in Africa it is P. falciparum.

Figure 1: Malaria Stages (Source: Nilsson et al., 2015)

2.3 Discovery of Malaria

It is believed that the history of malaria outbreaks goes back to the beginnings of civilization. It

is the most widespread disease due to which many people have lost lives and is even thought to

have been the cause of major military defeats, as well as the disappearance of some nations The

first descriptions of malaria are found in ancient Chinese medical records of 2700 BC, and 1200

years later in the Ebers Papyrus . The military leader Alexander the Great died from malaria. The

evidence that this disease was present within all layers of society is in the fact that Christopher

Columbus, Albrecht Dürer, Cesare Borgia, and George Washington all suffered from it (Moss et

al., 2008). Although the ancient people frequently faced malaria and its symptoms, the fever that

would occur in patients was attributed to various supernatural forces and angry divinities. It is,

thus, stated that the Assyrian-Babylonian deity Nergal was portrayed as a stylized two-winged

insect, as was the Canaan Zebub (‘Beelzebub, in translation: the master of the fly’). In the 4th

century BC, Hippocrates described this disease in a way that completely rejected its demonic

origins and linked it with evaporation from swamps which, when inhaled, caused the disease.

That interpretation was maintained until 1880 and Laveran’s discovery of the cause of the

disease; Laveran, a French military surgeon, first observed parasites in the blood of malaria

patients, and for that discovery he received the Nobel Prize in 1907. Cartwright and Biddis

(2006), state that malaria is considered to be the most widespread African disease. The causative

agent of malaria is a small protozoon belonging to the group of Plasmodium species, and it

consists of several subspecies. The Development of Diagnostic Tests for Proving Malaria

through History Malaria can last for three and up to five years, if left untreated, and depending

on the cause, may recrudesce. In P. vivax and ovale infections, the persistence of the merozoites

in the blood or hypnozoites in hepatocytes can cause relapse months or years after the initial
infection. Additionally, relapse of vivax malaria is common after P. falciparum infection in

Southeast Asia. Relapse cases were observed in P. falciparum infections, which can lead to a

rapid high parasitemia with subsequent destruction of erythrocytes (Chu and White 2016).

Children, pregnant women, immunocompromised and splenectomized patients are especially

vulnerable to malaria infection, as well as healthy people without prior contact with Plasmodium.

A laboratory test for malaria should always confirm clinical findings. The proving of malaria is

carried out by direct methods such as evidence of parasites or parts of parasites, and indirect

methods that prove the antibodies to the causative agents (figure 2).

Figure 2: Diagnostic tests for proving malaria (Murphy et al., 2013)

The gold standard method for malaria diagnosis is light microscopy of stained blood films by

Giemsa. Due to a lack of proper staining material and trained technicians, this method is not

available in many parts of sub-Saharan Africa. The sensitivity of the method depends on the

professional expertise, and it is possible to detect an infection with 10–100 parasites/µL of blood.
A negative finding in patients with symptoms does not exclude malaria, but smears should be

repeated three times in intervals of 12–24 h if the disease is still suspected (Tangpukdee et al.,

2009). Diagnosis of malaria using serologic testing has traditionally been done by

immunofluorescence antibody testing (IFA). IFA is time-consuming and subjective. It is

valuable in epidemiological studies, for screening possible blood donors. It also demands

fluorescence microscopy and qualified technicians (Tangpukdee et al., 2009). Rapid Diagnostic

Tests (RDT) for the detection of antigens in the blood are immunochromatographic tests to prove

the presence of parasite antigens. No electrical equipment, and no special experience or skills are

required to perform these tests. The RDTs are now recommended by WHO as the first choice of

test all across the world in all malaria-endemic areas.

The FDA approved the first RDT test in 2007. It is recommended that the results of all RDT tests

should be confirmed by microscopic blood analysis (WHO 2015). It is known that antigens

detected with RDT test remain in the blood after antimalarial treatment, but the existence of

these antigens varies after treatment. The false-positive rates should be less than 10%. Several

RDT tests in the eight rounds of testing revealed malaria at a low-density parasite (200

parasites/µL), had low false-positive rates and could detect P. falciparum or P. vivax infections

or both. False-positive rates of P. vivax were typically small, between 5% and 15%. On the other

hand, the false-positive rates of P. falciparum range from 3–32% (Ranadive et al., 2017). Good

RDTs might occasionally give false-negative results if the parasite density is low, or if variations

in the production of parasite antigen reduce the ability of the RDT to detect the parasite. False

negative results of the RDT test for P. falciparum ranged between 1% and 11% . The overall

sensitivity of RDTs is 82% (range 81–99%), and specificity is 89% (range 88–99%). Polymerase

chain reaction (PCR) is another method in the detection of malaria. This method is more
sensitive and more specific than all conventional methods in the detection of malaria. It can

detect below one parasite/µL. PCR test confirms the presence of parasitic nucleic acid

(Tangpukdee et al., 2009). PCR results are often not available fast enough to be useful in malaria

diagnosis in endemic areas. However, this method is most helpful in identifying Plasmodium

species after diagnosis by microscopy or RDT test in laboratories that might not have

microscopic experts. Additionally, PCR is useful for the monitoring of patients receiving

antimalaria treatment (Mathison and Pritt 2017). Indirect methods are used to demonstrate

antibodies to malaria-causing agents. Such methods are used in testing people who have been or

might be at risk of malaria, such as blood donors and pregnant women. The method is based on

an indirect immunofluorescence assay (IFA) or an ELISA Microorganisms 2019, 7, 179 4 of 17

test. The IFA is specific and sensitive but not suitable for a large number of samples, and the

results are subjective evaluations. For serological testing, ELISA tests are more commonly used.

Rapid and accurate diagnosis of malaria is an integral part of appropriate treatment for affected

person and the prevention of the further spread of the infection in the community.

2.4 Malaria Treatment through History

Already in the 2nd century BC, a sweet sagewort plant named Qinghai (Latin Artemisia annua)

was used for the treatment of malaria in China (Hsu 2006). Much later, in the 16th century, the

Spanish invaders in Peru took over the cinchona medication against malaria obtained from the

bark of the Cinchona tree (Latin Cinchona succirubra). From this plant in 1820 the French

chemists, Pierre Joseph Pelletie, and Joseph Bienaimé Caventou isolated the active ingredient

quinine, which had been used for many years in the chemoprophylaxis and treatment of malaria.

In 1970, a group of Chinese scientists led by Dr. Youyou Tu isolated the active substance

artemisinin from the plant Artemisia annua, an antimalarial that has proved to be very useful in
treating malaria. Most of the artemisinin-related drugs used today are prodrugs, which are

activated by hydrolysis to the metabolite dihydroartemisinin. Artemisinin drugs exhibit its

antimalarial activity by forming the radical via a peroxide linkage (Guo 2016). WHO

recommends the use of artemisinin-based combination therapies (ACT) to ensure a high cure rate

of P. falciparum malaria and reduce the spread of drug resistance. ACT therapies are used due to

high resistance to chloroquine, sulfadoxine-pyrimethamine, and amodiaquine. Due to the unique

structure of artemisinins, there is much space for further research. Extensive efforts are devoted

to clarification of drug targets and mechanisms of action, the improvement of pharmacokinetic

properties, and identifying a new generation of artemisinins against resistant Plasmodium strains.

The German chemist Othmer Zeidler synthesized dichlorodiphenyltrichloroethane (DDT) in

1874 during his Ph.D. At that time, no uses of DDT was found, and it just became a useless

chemical. The insecticide property of DDT was discovered in 1939 by Paul Müller in

Switzerland. DDT began to be used to control malaria at the end of the Second World War.

During the Second World War, the success of DDT quickly led to the introduction of other

chlorinated hydrocarbons which were used in large amounts for the control of diseases

transmitted by mosquito (Ray 2010). From the late Middle Ages until 1940, when DDT began to

be applied, two-thirds of the world’s population had been exposed to malaria, a fact that

represented a severe health, demographic, and economic problem. DDT is an organochlorine

pesticide which was applied in liquid and powder form against the insects. During the Second

World War people were sprayed with DDT. After the war, DDT became a powerful way of

fighting malaria by attacking the vector (Ray 2010).

Five Nobel Prizes associated with malaria were awarded: Youyou Tu in 2015. Ronald Ross

received the Nobel Prize in 1902 for the discovery and significance of mosquitoes in the biology
of the causative agents in malaria. In 1907, the Nobel was awarded to the already-mentioned

Charles Louis Alphonse Laveran for the discovery of the causative agent. Julius Wagner-Jauregg

received it in 1927 for the induction of malaria as a pyrotherapy procedure in the treatment of

paralytic dementia. In 1947 Paul Müller received it for the synthetic pesticide formula

dichlorodiphenyltrichloroethane. Attempts to produce an effective antimalarial vaccine and its

clinical trials are underway. Over the past several decades’ numerous efforts have been made to

develop effective and affordable preventive antimalaria vaccines. Numerous clinical trials are

completed in the past few years. Nowadays are ongoing clinical trials for the development of

next-generation malaria vaccines. The main issue is P. vivax vaccine, whose research requires

further investigations to identify novel vaccine candidates. Despite decades of research in

vaccine development, an effective antimalaria vaccine has not yet been developed (i.e., with

efficacy higher than 50%).

The European Union Clinical Trials Register currently displays 48 clinical trials with a EudraCT

protocol for malaria, of which 13 are still ongoing clinical trials. The malaria parasite is a

complex organism with a complex life cycle which can avoid the immune system, making it very

difficult to create a vaccine. During the Microorganisms 2019, 7, 179 5 of 17 different stages of

the Plasmodium life cycle, it undergoes morphological changes and exhibits antigenic variations.

Plasmodium proteins are highly polymorphic, and its functions are redundant. Also, the

development of malaria disease depends on the Plasmodium species. That way, a combination of

different adjuvants type into antigen-specific formulations would achieve a higher efficacy

(Arama and Troye-Bloomberg 2014). Drugs that underwent clinical trials proved to be mostly

ineffective. However, many scientists around the world are working on the development of an

effective vaccine. Since other methods of suppressing malaria, including medication,

insecticides, and bed nets treated with pesticides, have failed to eradicate the disease, and the

search for a vaccine is considered to be one of the most important research projects in public

health by World Health Organization (WHO). The best way to fight malaria is to prevent insect

bite.
Figure 3: Summary of drugs used in Malaria treatment (Talapko et al., 2019)
2.5 Malaria Trends in the World

The WHO report on malaria in 2017 shows that it is difficult to achieve two crucial goals of a

Global Technical Strategy for Malaria. These are a reduction in mortality and morbidity by at

least 40% by 2020. Since 2010, there has been a significant reduction in the burden of malaria,

but analysis suggests a slowdown, and even an increase in the number of cases between 2015

and 2017. Thus, the number of malaria cases in 2017 has risen to 219 million, compared to 214

million cases in 2015 and 239 million cases in 2010. Figure 4 presents the reported number of

malaria cases per WHO region from 1990–2017 (WHO 2018). The most critical step in the

global eradication of malaria is to reduce the number of cases in countries with the highest

burden (many in Africa). The number of deaths from disease is declining, thus, in 2017 there

were 435,000 deaths from malaria globally, compared with 451,000 in 2016, and 607,000 deaths

in 2010. Figure 5 presents the number of malaria deaths from 1990-2017 (WHO 2010). Despite

the delay in global progress, there are countries with decreasing malaria cases during 2017. Thus,

India in 2017, compared with 2016, recorded a 24% decline of malaria cases. The number of

countries reporting less than 10,000 malaria cases is growing, from 37 countries in 2010, to 44 in

2016, and to 46 in 2017. Furthermore, the number of countries with fewer than 100 indigenous

malaria cases growing from 15 in 2010, to 26 countries in 2017 (WHO 2018).

18
Figure 4: presents the reported number of malaria cases per WHO region from 1990–2017

(WHO 2018).

19
Figure 5: presents the number of malaria deaths from 1990-2017 (WHO 2010).

20
Funding in malaria has not changed much. During 2017, US$3.1 billion was invested in malaria

control and elimination globally. That was 47% of the expected amount by 2020. The USA was

the largest single international donor for malaria in 2017 (WHO 2018). The most common global

method of preventing malaria is insecticide-treated bed nets (ITNs). The WHO report on

insecticide resistance showed that mosquitoes became resistant to the four most frequently used

classes of insecticides (pyrethroids, organochlorines, carbamates, and organophosphates), which

are widespread in all malaria-endemic countries (WHO 2018). Drug resistance is a severe global

problem, but the immediate threat is low, and ACT remains an effective therapy in most malaria-

endemic countries (WHO 2018).

According to the WHO, Africa still has the highest burden of malaria cases, with 200 million

cases (92%) in 2017, then Southeast Asia (5%), and the Eastern Mediterranean region (2%). The

WHO Global Technical Strategy for Malaria by 2020 is the eradication of malaria from at least

ten countries that were malaria-endemic in 2015 (WHO 2018). The march towards malaria

eradication is uneven. Indigenous cases in Europe, Central Asia, and some countries in Latin

America are now sporadic. However, in many sub-Saharan African countries, elimination of

malaria is more complicated, and there are indications that progress in this direction has delayed.

Elimination of vivax and human knowlesi malaria infections are another challenge (WHO 2018).

The campaign to eradicate malaria began in the 1950s but failed globally due to problems

involving the resistance of mosquitoes to the insecticides used, the resistance of malaria parasites

to medication used in the treatment, and administrative issues. Additionally, the first eradication

campaigns never included most of Africa, where malaria is the most common. Although the

majority of forms of malaria are successfully treated with the existing antimalarials, morbidity

and mortality caused by malaria are continually increasing. This issue is the consequence of the

21
ever-increasing development of parasite resistance to drugs, but also the increased mosquito

resistance to insecticides, and has become one of the most critical problems in controlling

malaria over recent years (Ashley et al., 2018). Resistance has been reported to all antimalarial

drugs. Therefore, research into finding and testing new anti-malarials, as well as a potential

vaccine, is still ongoing, mainly due to the sudden mass migration of humans (birds, parasite

disease vector insects) from areas with a large and diverse infestation. The process towards

eradication in some countries confirms that current tools could be sufficient to eradicate malaria.

The spread of insecticide resistance among the vectors and the rising ACT failures indicate that

eradication of malaria by existing means might not be enough. Thus, given the already

complicated problem of overseeing and preventing the spread of the disease, it will be necessary

to supplement and change the principles, strategic control, and treatment of malaria.

2.6 Malaria risk factors

Malaria is enhanced by certain factors which either increases the chance of vector breeding or

vector to host transmission. These factors are referred to as risk or causal malaria factors. Risk

factors of malaria in urban areas are complex in nature and were not fully understood in the last

decades (Donnelly et al., 2005). The complex nature of urban risk factors is based on the fact that

the set of factors generally understood as risk are more of natural factors and often do not apply

to urban areas. De Silva & Marshall (2012) explains, that natural risk factors such as vegetation,

clean water surfaces such as lakes, rivers and swamps, known breeding malaria sites are fewer in

urban areas and more in rural areas. This explains the heavy burden of malaria in rural areas

compared to urban areas. Though some of these natural factors are present in urban areas, a

greater percentage of risk factors are artificial and man-made.

22
Present malaria studies such as De Silva & Marshall (2012) & Ngom & Siegmund (2015) have

attempted to identify artificial risk factors inherent in the urban environment. These studies

revealed that the risk factors of urban malaria do not only lie on factors that favour the growth

and existence of the vector species, but on a wide range of social and environmental factors that

enables vector to host contact. The subsequent sections make a comprehensive review of the risk

factors in urban areas as identified in literature. Discussion is made in two groups: vector-based

urban risk factor and host-based factor.

2.6.1 Vector based risk factors

These are factors that favour breeding of the malaria vector. Factors are both natural (climatic

and topographic) and artificial or man-made factors.

2.6.1.1 Climatic factors

Rainfall and temperature are the climatic factors that affect the breeding of the malaria vector.

Both factors are needed at suitable conditions to increase the breeding of mosquitoes (Tanser et

al., 2003).

2.6.1.2 Rainfall

The abundance of anopheles mosquitos is strongly affected by rainfall events. A high

precipitation increases water surfaces that harbour malaria vector. Mosquitoes breed in standing

waters such as freshwater pools or marshes (Martens et al., 1999) and also in temporal and

polluted water surface (De Silva & Marshall, 2012). The capacity of these water surfaces is

saturated by the outpour of rain. Consequently, this results in a larger pool of surface water that

favours breeding of the vector and the longevity of the adult mosquito.

23
The study of Afrane et al. (2012) proves a negative correlation between rainfall and adult and

larval abundance. They explain that higher amounts of rainfall wash larvae out of its habitat and

thus, reduce the abundance of mosquito larvae. This consequently, leads to a reduced number of

positive larval habitats during rainy season.

2.6.1.3 Temperature

Temperature has a direct effect on the duration of the sporogonic (larvae) life cycle of the

malaria parasite and vector survival (Tanser et al., 2003). At a minimum temperature reaching

freezing level, the population of anopheles vector radically reduced. Though it has been proven

by the study of Petersen et al. (2013) that malaria vector can develop in temperate zones even in

zones with freezing temperature. The plasmodium vivax was dominant in the temperate zones of

the world before the 1950’s and presently in temperate zones of Italy and South Korea. Malaria

in temperate zones is as a result of the long incubation period of the genotype of plasmodium

vivax and the migration of people from malaria endemic regions. Vector density increases at a

warmer temperature of 19.5°C and above. A consistent temperature of 19.5°C prolongs the

duration of the sporogonic cycle of the plasmodium falciparum parasite and guarantees- 4% of

the total vector cohort surviving (Tanser et al., 2003). Temperature of over 32–34°C rapidly

reduces the survival rate of parasite. The minimum temperature for both parasite development

and transmission lies between 14.5 and 15°C in the case of Plasmodium vivax and between 16

and 19°C for Plasmodium falciparum (Martens et al., 1999; Petersen et al., 2013).

It is reviewed by studies such as Craig et al. (1999) & Tanser et al. (2003) that climatic factors

(rainfall and temperature) have serious impact on malaria occurrence. The results of the temporal

analysis conducted by these studies show that climatic condition in Nigeria for almost all the

24
monthly period (7-12 months) of the year are suitable for Plasmodium falciparum transmission.

Despite the impact of climatic conditions in malaria transmission, the studies of Ngom &

Siegmund (2015) &Robert et al (2003) emphasize the significant impact of socio-demographic

and socio-environmental factors on urban malaria. These factors are discussed in section 2.3.2.

2.6.1.4 Topographic factors

Altitude: Altitude is generally considered to play an important role in limiting malaria in the

tropical highlands by negatively influencing the breed of vector species (De Silva & Marshall,

2012). Areas at a high altitude have low transmission when compared to areas at low altitude.

The increased water run-off downstream and warmer temperature in lowlands makes low altitude

areas a preferred breeding location for malaria parasite. However, the studies of Ernst et al.

(2006) & Peterson et al. (2009) show the possibility of malaria transmission in highland areas.

These studies confirm a clustered pattern of malaria in the highlands of Ethiopia and Kenya with

altitudes above 1600m and 2000 meters. Areas that were prone to malaria risk in highlands are

lower altitude areas within high plains. These include valleys and lower depressed areas. Vector

density could form clusters in these depressed areas causing risk to the inhabitants living at close

distance to these sites.

Urban agriculture: Urban agriculture has been used as a measure to enhance food security and

to alleviate poverty in urban areas. Besides these foreseen benefits, they have been found optimal

sites for vector breeding (Klinkenberg et al., 2008). Irrigated agricultural fields are the most

attractive habitats for mosquitoes. Dug out wells present in these fields, foot prints, furrows and

seepages contain the largest amount of mosquito larvae which consequently increases the vector

population (Afrane et al., 2012; Klinkenberg et al., 2008). Hamilton et al. (2013) asserts that the

25
proportion of habitats containing Anopheline larvae and adult anopheles is 1.7 times greater in

urban areas with agriculture than those without agricultural fields. The abundance of larvae and

adult mosquito in urban agricultural fields has serious implication on those who live and work in

urban agricultural areas, irrespective of other factors such as urban or peri-urban location (De

Silva & Marshall, 2012). Children living in close proximity to agricultural areas, especially

irrigated fields, are at high risk of contracting malaria. The study of (Klinkenberg et al., 2006)

conducted in the urban area of Accra, Ghana show a significant malaria epidemic on children

living close to urban agriculture. Animal husbandry is another aspect of agriculture that increases

the presence of the malaria vector. Animals increase the attraction of zoophilic mosquitoes under

the stimulus of CO2 and octanol. When mosquitoes are both zoophilic and anthropophlic such as

the Anopheles Albimanus, children living or playing close to livestock farms becomes

vulnerable to malaria (Rosas-Aguirre et al., 2015).

Natural water surfaces: Natural water surfaces such as rivers and floodplains provide great

breeding grounds for mosquitoes in riverside urban communities (De Silva & Marshall, 2012).

River banks are rich in aquatic plants and these plants retain sunlight, resulting in lower

temperature conducive for vector breeding. However, vectors could be reduced by the presence

of predators such as fish species, tadpoles and aquatic insects of the order coleopteran and

hemipteran species (Akono et al., 2015).

2.6.2 Artificial/made-made factors

Urban areas have several artificial sites that favour the breeding of the mosquito vector. These

sites are in the form of artificial surface water in the surrounding of residential communities and

waste dumpsites. Artificial surface water as pointed by De Silva & Marshall (2012) &

26
Klinkenberg, et al (2008) include: blocked and stagnant drainage channels, road surfaces with

tyre tracks and potholes, stagnant swimming pools, domestic water reservoir, broken water pipes

and pools at construction sites. Blocked drains are often due to poor sanitation which leads to a

reduced water flow. Consequently, stagnant water pools accumulate, forming suitable sites for

the breed of mosquitoes. Unsurfaced roads and poorly maintained road network raise the risk of

tyre tracks and potholes. They create shallow surfaces having temporal pools of water that are

saturated during rainfall. Tyre tracks are more common in areas of high socioeconomic status,

which tend to house more vehicle owners having poor conditioned roads. Poor waste

management has serious implications on malaria transmission. Solid waste in Nigeria and in

most Sub-African countries is generated in proportionately large amounts without adequate

management set in place. A large proportion of solid waste is dumped either in poorly managed

landfills or in open dumps and this constitutes a source of health risk to surrounding residents

(Ogunrinola & Adepegba, 2012).

Waste sites provide a favourable breeding site for the malaria vector due to the dampness of

biodegradable waste and the contaminated effluence that is discharged, especially during the

downpour of rain (Wachukwu & Eleanya, 2007). It has been proven that people living or

working at close distance to waste disposal sites are of greater risk of contracting the

plasmodium virus than those living further away. The study of Afon (2012) reports a

significantly higher level of malaria parasitaemia on scavengers (informal collectors of valuable

waste from dump sites) working in the waste dump sites. Similar findings were made by

Wachukwu & Eleanya (2007) in Lagos where malaria prevalence was found to be higher

amongst regular on-site workers than off-site or unexposed workers of the open waste dump site

in Lagos. The study of Rahman (2006) identified waste as one of the strongly associated factors

27
to the prevalence of malaria inAligarh city of India. The implication of these findings on children

is that infants attending schools close to waste dump sites or living and playing close to these

sites could be prone to malaria infection.

2.6.3 Host based risk factors

Host based factors are those socio-environmental, socio-demographic and metric factors that

enables malaria transmission from malaria vector to their host, humans. They have been assessed

by Ngom & Siegmund (2015) & Robert et al. (2003) as key influences to malaria epidemics and

have a larger impact than the vector based factors previously discussed. The prevalence of

malaria is strongly based on host factors because without them, there is no malaria transmission

and no account of malaria epidemic or incidence.

2.6.4 Socio environmental risk factors

2.6.4.1 Housing quality and condition

The quality of housing is one of the socio-environmental risk factors of malaria. Quality is

assessed by the type of material used in housing construction which could be durable or natural.

Houses built with durable materials comprise of: brick, cement, tile for walls and asbestos or

metals for roofs. Houses built with natural building materials comprise of thatched or mud walls

and thatched or other plant materials for roofs (Leandro-Reguillo et al., 2015). The findings of

Konradsen et al. (2003) & Lwetoijera et al. (2013) show that houses built with durable materials

have better resistance to the entrance of mosquitoes indoors than houses built with natural

materials. These authors explain that houses made of mud walls and grass roofs often have

crevices used by mosquitoes to enter the house. Also of major importance is the cool and dark

28
condition that characterizes mud wall and grass roof houses which provides hiding and resting

place for mosquitoes.

Housing quality has also been viewed in relation with condition of building materials

(Konradsen et al., 2003; Lwetoijera et al., 2013). Houses built with durable materials can

deteriorate in quality over time due to poor maintenance. This is seen by cracks in walls, opening

or gaps in the eaves and lack or damaged screening over windows. Houses in these deplorable

conditions provide access points for mosquitoes to enter indoors (Lwetoijera et al., 2013). The

study of (Yé et al., 2006) shows that children living in houses with natural roofing materials and

open eaves had a higher malaria infection than children living in suitable roofed houses. These

children are 30% more at risk of malaria transmission than their counterpart (Konradsen et al.,

2003).

2.6.5 Socio-demographic risk factors

2.6.5.1 Income level

Income level plays a profound role in the transmission of malaria in children. Infants from low

income or poor families are more susceptible to the risk of contracting malaria than those from

average and wealthy families. It is clear from findings such as (Nriagu et al., 2008) that low

income families are more likely to live in overcrowded areas with open and contaminated

sewers. They also tend to reside in poorly constructed buildings which are porous for the entry of

mosquitoes indoors. Poor households are faced with inadequate water supply and poor sanitation

which increases vector breeding and contact. Also from an economic viewpoint, low income

families have a lower capacity of using health care services and preventive malaria control

measures (Robert et al., 2003).

29
2.6.5.2 Educational level

Lower education level of parents and caregivers contribute to malaria transmission in infants. A

possible reason for this is that uneducated parents tend to respond late to malaria symptoms and

they lack awareness of malaria control measures used in the protection against malaria

(Abdulkadir et al., 2015; Robert et al., 2003). Also, children having low educated parents might

not attend schools and hence tend to play more often outside. This increases exposure levels of

infants to vector bites, especially when the surrounding environment is prone to vector

proliferations (Nriagu et al., 2008).

2.6.5.3 Household size and density

This factor has been identified as a significant demographic factor in the transmission of malaria.

Houses with more occupants tend to attract more mosquitoes than households with fewer

occupants. The relation between household size and malaria is merely not based on the numeric

composition of a household (number of occupants) but on spatial composition (the number of

occupants per room space). Ngom & Siegmund (2015) explains that a high sleeping density

room favours the emanation of human odour that attracts the malaria vector. Mosquitoes identify

and find their host through olfaction. Substances such as lactic acid and ammonia present in the

human skin and carbon dioxide exhaled through breathing attract mosquitoes to their host

(Rosas-Aguirre et al., 2015).

30
2.6.6 Metric risk factors

2.6.6.1 Distance to vector breeding site

The presence of vector breeding sites is of no effect in malaria transmission except when such

sites are in close distance to the location of host. Distance plays an important role in the vector-

host malaria transmission and it has been found a reoccurring risk factor in all malaria studies.

There is a consensus in all malaria studies that people living in close proximity to vector

breeding site are at higher risk of contracting malaria parasites than those living further away.

However, variations vary in the exact distance in meters that poses serious risk to malaria

transmission. DeSilva & Marshall (2012) and Ogunrinola & Adepegba(2012) specify a threshold

distance of 250 meters to vector sites as hazards prone areas. Konradsen et al (2003) in his

analysis sets a threshold distance of 750 meters.

2.6.6.2 Distance to health centre

Access to health centre especially for children under the age of 5 has the potential of reducing

significantly the number of malaria cases and death(Rutherford et al., 2010). This with reason

that they have access to effective health care services such as: treated bed nets (Larson et al.,

2012). The study of Feikin et al. (2009) show that for every 1 km increase(up to 4km) in the

distance from health centre, there was a corresponding increase in the number of malaria cases.

Although distance to health centre plays a role in the reduction of malaria, there are also barriers

that could limit its impact. Barriers such as: educational, cultural and financial factors (Kizito et

al., 2012).

31
2.6.6.3 Migration pattern

The prevalence of malaria in urban areas can be increased by two types of movement: rural to

urban migration; this is often a permanent relocation to urban areas for purposes of jobs and

studies and urban to rural migration; this is often temporal and is referred to as rural travel

(Robert et al., 2003). In both cases, migrants bring infection from rural endemic areas to urban

areas where they reside. Children involved in rural travel for vacation for instance, could be at

risk of exposure to mosquitoes. The result of Klinkenberg et al. (2008) conducted in Ghana show

that children that travelled to rural areas within the 3 weeks of sample period had a higher chance

of malaria parasite than those who did not embark on rural travel.

2.6.7 Clinical factors

IRS (Indoor residual spray) and ITN (Insecticide treated nets) are the clinical control measures

used in the prevention of malaria. The lack of use or ineffective use of these measures could lead

to malaria (Esimai & Aluko, 2015). The study of Lwetoijera et al. (2013) shows that these

control measures are not effective in reducing malaria transmission, especially in poor quality

houses with open eaves and roofs. Their study shows a high number of malaria vectors indoors

in poor conditioned houses despite the use of IRS and ITN control measures. Ineffectiveness of

IRS and ITN is also linked to its lack of protection from outdoor mosquito bites since they are

only used indoors. The implication of this on children is that clinical measures do not protect

children playing close to vector prone areas and even when measures are used indoors, children

living in poor quality homes are still at risk.

32
2.6.8 Individual factors

The vulnerability to malaria has been linked to biological components such as immunity. Infants

generally have a low level of immunity, especially during the first and second year of life

(Umeh, 2013). This makes them highly susceptible to malaria infection. Besides low immunity

levels, factors such as nutrient deficiency and existing illness might decrease considerably, the

immune response of children to malaria (Deguen & Zmirou-Navier, 2010). The study of (Nriagu

et al., 2008) raises counter claim to immune deficiency and existing illness. Their study shows

that a high blood level of lead provides immunity against malaria infection in children. Though

presumptively, lead may affect the effectiveness of malaria vaccines due to the changes lead

poisoning has on the immune regulatory function.

2.7 Schistosomiasis

Schistosomiasis also known as bilharzias is an infectious disease that affects more than 230

million people worldwide, according to conservative estimates (Gryseels et al., 2006). It is

caused by trematode parasites of the genus Schistosoma; the adult male and female worms live

within the veins of their human host, where they mate and produce fertilised eggs. The eggs are

either shed into the environment through faeces or urine, or are retained in host tissues where

they induce inflammation and then die. The eggs that reach freshwater will hatch, releasing free-

living ciliated miracidia that then infect a suitable snail host. In the snail, the parasite undergoes

asexual replication through mother and daughter sporocyst stages, eventually shedding tens of

thousands of cercariae (the form infectious for human beings) into the water. The asexual portion

of the lifecycle in the snail (figure 6) requires 4–6 weeks before infectious cercariae are released.

After cercariae penetrate the skin of the mammalian host, the maturing larvae (schistosomula)

33
need about 5–7 weeks before becoming adults and producing eggs (Gryseels et al., 2006). These

intervals (in both the snail and human being) are termed prepatent periods, when the infection is

ongoing but release of cercariae (from snails) or eggs (from humans) cannot be detected.

Cercariae can remain infective in freshwater for 1–3 days, but deplete their energy reserves

greatly over a few hours. Eggs whether excreted or retained in the body die within 1–2 weeks

after being released by the female worm.

Figure 6: Lifecycles of Schistosoma mansoni, Schistosoma haematobium, and Schistosoma

japonicum. (A) Paired adult worms (larger male enfolding slender female). (B) Eggs (left to right, S
haematobium, S mansoni, S japonicum). (C) Ciliated miracidium. (D) Intermediate host snails (left to right,
Oncomelania, Biomphalaria, Bulinus). (E) Cercariae. (Gryseels et al., 2006).

34
Three main species of schistosomes infect human beings, Schistosoma haematobium,

Schistosoma mansoni, and Schistosoma japonicum. S haematobium and S mansoni both occur in

Africa and the Middle East, whereas only S mansoni is present in the Americas. S japonicum is

localised to Asia, primarily the Philippines and China. Three more locally distributed species

also cause human disease: Schistosoma mekongi, in the Mekong River basin, and Schistosoma

guineensis and Schistosoma intercalatum in west and central Africa (figure 7). Each species has

a specific range of suitable snail hosts, so their distribution is defined by their host snails’ habitat

range. S mansoni and S haematobium need certain species of aquatic freshwater Biomphalaria

and Bulinus snails, respectively. S japonicum uses amphibious freshwater Oncomelania spp

snails as its intermediate host (Gryseels et al., 2006).

Figure 7: Global prevalence of Schistosomiasis (Gryseels et al., 2006).

35
Schistosomes live an average of 3–10 years, but in some cases as long as 40 years, in their

human hosts. Adult male and female worms live much of this time in copula, the slender female

fitted into the gynaecophoric canal of the male, where she produces eggs and he fertilises them

(appendix). Adult worms digest erythrocytes and although most of their energy is obtained by

glucose metabolism, egg production is dependent on fatty acid oxidation both glucose and fatty

acids being derived from the host (Gryseels et al., 2006). They live within either the perivesicular

(S haematobium) or mesenteric (S mansoni, S japonicum, and others) venules. Schistosomes

have no anus and cannot excrete waste products, so they regurgitate waste into the bloodstream.

Some of these expelled products are useful for blood-based and urine-based diagnostic assays. S

japonicum and S mekongi are zoonoses that also infect a wide range of mammalian hosts,

including dogs, pigs, and cattle, which greatly complicates control and elimination efforts.

Although S mansoni can infect rodents and non-human primates, human beings are thought to be

its predominant mammalian reservoir. Understanding the schistosome lifecycle (figure 6) and the

parasite's movement between intermediate (snail) and definitive (mammalian) hosts is

fundamental to the control and elimination of human schistosomiasis. Environmental changes

can either increase or decrease transmission (Gryseels et al., 2006). Changes in snail habitat and

predators are crucial determinants of transmission, and prepatent periods can affect the efficacy

of treatment regimens. Effective treatment of people (such that their excreta do not contain eggs),

the prevention of sewage contamination of freshwater, the elimination of intermediate host

snails, and the prevention of human contact with water containing infected snails can help to

prevent transmission (Gryseels et al., 2006).

36
2.8 Epidemiology

Several isolated studies on the prevalence of the disease in Nigeria have been reported with

various studies carried out to show prevalence and intensity of schistosomiasis in various States

in Nigeria; (Akinwale et al., 2009; Amuta and Houmsou, 2014; Dawaki et al., 2016;Anchang-

kimbiet al., 2017; Abdulkareem et al., 2018). Since 1881 the presence of two forms of human

schistosomiasis, caused either by Schistosoma haematobium or by Schistosoma mansoni has

been known in Nigeria. A report by the WHO in 1987 indicated that the urinary form of the

disease (caused by S. haematobium) is widespread throughout Nigeria, while intestinal

schistosomiasis (caused by S. mansoni) is less prevalent and was not reported in the South-

Eastern and some south-western parts of Nigeria. An overview of the number of surveys with

details given regarding sampling period, diagnostic technique, survey type, and prevalence,

stratified (Ezeh et al., 2019). Past estimates have calculated infection rates of about 25 million

people and 101 million at risk of infection with the highest prevalence and intensities of disease

occurring in school-aged children, adolescents, and young adults who also suffer from the

highest morbidity and mortality (Houmsou, 2012). In terms of urinary schistosomiasis

endemicity, Nigeria has been divided into three zones: a hyperendemic zone, a moderately

endemic zone, and a zone with low or no endemicity (Ezeh et al., 2019)

2.9 Pathogenesis and morbidity

All evidence suggests that schistosome eggs, and not adult worms, induce the morbidity caused

by schistosome infections (Hatz 2005). Many eggs are not excreted and become permanently

lodged in the intestines or liver (for S mansoni, S japonicum, and S mekongi) or in the bladder

and urogenital system (for S haematobium). Acute schistosomiasis occurs most often in

travellers or immigrants to schistosome-endemic regions who are exposed to schistosome

37
antigens for the first time at an older age than usual. It occurs weeks to months after infection, as

a consequence of worm maturation, egg production, release of egg antigen, and the host's florid

granulomatous and immune complex responses. Acute schistosomiasis is sometimes referred to

as Katayama syndrome and the typical clinical presentation is a sudden onset of fever, malaise,

myalgia, headache, eosinophilia, fatigue, and abdominal pain lasting 2–10 weeks. This aspect of

schistosomiasis has been reviewed in detail (Cheever et al., 2000). The limited presentation of

this syndrome in residents of endemic regions is probably a result of in-utero priming of T-

lymphocyte and B-lymphocyte responses of babies born to mothers with helminthic infections

(Gryseels et al., 2006).

Over time, the granulomatous response to eggs is down regulated through several mechanisms in

most individuals, leading to progression to the chronic intestinal form of the disease for S

mansoni, S japonicum, and S mekongi. This form of the disease presents as non-specific

intermittent abdominal pain, diarrhoea, and rectal bleeding, with the frequency of symptoms

often related to the intensity of infection (Gryseels et al., 2006). Such gastrointestinal features are

often focal with isolated mucosal hyperplasia, pseudopolyposis, and polyposis interspersed with

normal bowel. Some people with intestinal schistosomiasis only poorly immunoregulate their

response to parasite egg antigens and consequently develop extensive fibrosis and subsequent

hepatosplenic disease with periportal fibrosis. Patients with periportal fibrosis also called

Symmer's pipe-stem fibrosis retain hepatocellular function, differentiating the disease from

cirrhosis and other liver diseases. Clinical features include upper abdominal discomfort with

palpable nodular and hard hepatomegaly, often with splenomegaly. Ascites and haematemesis

from oesophageal varices as a complication of portal hypertension can rapidly lead to death

(Fenwick et al., 2003).

38
Substantial pulmonary hypertension caused by granulomatous pulmonary arteritis can also occur

in patients with advanced hepatic fibrosis disease. The time from initial infection to advanced

fibrosis is usually 5–15 years. However, periportal fibrosis can occur in children as young as 6

years, showing the need for screening and treatment of preschool children. By contrast, the

defining symptom for urogenital schistosomiasis (S haematobium) is haematuria, often

presenting with urinary frequency, burning micturition, and suprapubic discomfort. In endemic

regions, haematuria is so widespread that it is thought a natural sign of puberty for boys, and is

confused with menses in girls (Gryseels et al., 2006). As with severe intestinal schistosomiasis,

severe urogenital schistosomiasis results from poor immunoregulation of antischistosome-egg

responses, leading to chronic fibrosis of the urinary tract presenting as obstructive uropathy

(hydroureter and hydronephrosis), which along with resulting bacterial superinfection and renal

dysfunction can have lethal consequences. Squamouscell carcinoma of the bladder is also

strongly associated with S haematobium infection (Gryseels et al., 2006).

This tumour is often multifocal, and in regions endemic for S haematobium, occurs at a younger

age than do transitional-cell bladder carcinomas. Female genital schistosomiasis caused by S

haematobium strongly affects women's reproductive health. Eggs in the vesical plexus migrate to

the genital tract causing inflammatory lesions in the ovaries, fallopian tubes, cervix, vagina, and

vulva. Lower genital tract sandy patches are pathognomonic for female genital schistosomiasis

and are associated with neovascularisation and friable mucosa that can result in contact bleeding.

Female genital schistosomiasis causes pain and has been associated with stress incontinence,

infertility, and increased risk of abortion. Unfortunately, treatment might not resolve these

advanced forms of genital tract damage and there is growing evidence that such lesions can

increase transmission of HIV (Gryseels et al., 2006).

39
For men, urogenital schistosomiasis can present with haematospermia, orchitis, prostatitis,

dyspareunia, and oligospermia. These conditions resolve more readily after antischistosomal

treatment than do those of female genital schistosomiasis. S mansoni and S japonicum rarely

affect the genital tract. All Schistosoma species cause non-specific but disabling systemic

morbidities including anaemia, malnutrition, and impaired childhood development, as a result of

the effect of continued inflammation on normal growth, iron metabolism, physical fitness, and

cognitive function. Most anaemia in patients with schistosomiasis is anaemia of inflammation,

linked with blood loss (and high parasitic loads), that contributes to total-body iron deficiency

(Gryseels et al., 2006). Anaemia of inflammation is caused by iron trapping within the body

mediated by the hepatic hormone hepcidin, the release of which is stimulated by infection related

production of the pro-inflammatory cytokine interleukin. As a downstream consequence of

chronic anaemia, decreased aerobic capacity negatively affects physical work output in regions

endemic for schistosomes. Reduced intellectual function scores and acute and chronic

undernutrition in children are also significantly associated with schistosomiasis. Fortunately,

these deficits lessen with treatment, although the effective window for preventive treatment is

probably short (Booth et al., 2004).

2.10 Comorbidities

Schistosomiasis often occurs alongside other infectious diseases, with a wide range of

coinfecting organisms. In addition to its direct morbidities, schistosomiasis can affect

immunological and physiological relations between the host and co-infecting pathogens. Thus,

better control of schistosomiasis could provide adjunctive benefits in such areas. The most

compelling example might be the effect of schistosomiasis on susceptibility to HIV infection.

Among women with female genital schistosomiasis, the inflammation, friability, and

40
neovascularisation of the genital epithelial tissue can lead to a compromised physical barrier to

exposure to HIV through sexual activity. In population-based studies, female genital

schistosomiasis has been associated with a three to four times increased risk of HIV infection

(Gryseels et al., 2006). This effect is compounded by increased concentrations of CD4-positive

cells in semen of men with high intensity S haematobium infection. Furthermore, during active

schistosomiasis, CD4-positive cells express increased concentrations of HIV coreceptors,

providing more targets for HIV infection. HIV-positive people who have delayed treatment for

schistosomiasis have a more rapid increase of viral load and CD4 Tcell loss than do those treated

early for schistosomiasis. However, a randomised trial detected no significant effect of

schistosome or other helminth infection on the length of time before patients with HIV became

eligible for antiretroviral therapy. So far no studies have been done of paediatric HIV and

schistosomiasis co-infection, in which perinatally acquired HIV infection would normally

precede schistosomiasis.

2.11 Diagnosis

Examination of stool and/or urine for ova is the primary method of diagnosis for suspected

schistosome infections. The choice of sample to diagnose schistosomiasis depends on the species

of parasite likely causing the infection. Adult stages of S. mansoni, S. japonicum, S. mekongi,

and S. intercalatum reside in the mesenteric venous plexus of infected hosts and eggs are shed in

feces; S. haematobium adult worms are found in the venous plexus of the lower urinary tract and

eggs are shed in urine. (CDC 2020)

Careful review of travel and residence history is critical for determining whether infection is

likely and which species may be causing infection. It is important to remember that both S.

41
mansoni and S. haematobium are endemic in some areas of sub-Saharan Africa; patients with

freshwater exposures in those areas should have both stool and urine samples examined for eggs.

Testing of stool or urine can be of limited sensitivity, particularly for travelers who may have

lighter burden infections. To increase the sensitivity of stool and urine examination, three

samples should be collected on different days. For S. haematobium, presence of hematuria can

suggest infection but this test is more useful for population studies in Africa and is not

sufficiently sensitive or specific for individual patient diagnosis. The eggs are shed intermittently

and in low amounts in light-intensity infections. (CDC 2020)

Serologic testing for antischistosomal antibody is indicated for diagnosis of travelers or

immigrants from endemic areas who have not been treated appropriately for schistosomiasis in

the past. Commonly used serologic tests detect antibody to the adult worm. For new infections,

the serum sample tested should be collected at least 6 to 8 weeks after likely infection, to allow

for full development of the parasite and antibody to the adult stage. Serologic testing may not be

appropriate for determination of active infection in patients who have been repeatedly infected

and treated in the past because specific antibody can persist despite cure. In these patients,

serologic testing cannot distinguish resolved infection from active infection. An antigen test has

been developed that can detect active infection based on the presence of schistosomal antigen,

but this test is not commercially available in the United States and at this time is undergoing field

evaluations for accurate diagnosis of low-intensity infections. (CDC 2020)

Better diagnostic tests for schistosomiasis are still needed—both in the field and in the clinic —

and new technologies are being studied. For example, PET scans have been used experimentally

to detect adult parasites in vivo and microfluidics now offer the potential to miniaturise both

antibody and parasite antigen detection assays. In addition to the importance of diagnostic

42
improvements for clinical diagnoses, such advances will also be essential for drug development,

elimination programmes, and vaccine assessment, in which infection must be accurately

monitored over time. For the present, the absence of a true gold standard for quantitative

correlations to actual worm burden remains a significant challenge.

An important public health aspect of monitoring control and elimination programmes is detection

of schistosome infections in the snail host. Snail xenodiagnosis enables the identification of

environmental contamination during control and elimination programmes, whether through the

use of so-called sentinel snails or wild caught snails. Fully patent snail infections are detected by

inducing cercarial shedding and prepatent infections can be identified by histological

examination of snail tissues and by molecular parasitological techniques such as PCR or loop-

mediated isothermal amplification assays. Comparisons of molecular assays and shedding assays

show that most schistosome-infected snails do not progress to patency. (Lengeler et al., 2002)

2.12 Treatment

Praziquantel, a pyrazinosoquinolone derivative, is an anthelminthic drug targeting a broad range

of parasitic infections, and thus is advocated by the World Health Organization (WHO) for

population-based mass chemotherapy. Its antihelminthic activity was discovered in 1972 and it

was initially developed for use in animals. Subsequently, it has been shown to be effective

against all the various schistosome species known to infect humans and against cestodes, and is

well tolerated by humans (Inobaya et al., 2014). Approximately 80% of the drug is rapidly

absorbed from the gastrointestinal tract. It is metabolized by the liver and excreted through the

urine and feces. Multicenter trials conducted by the WHO and Bayer found a single dose of 40

mg/kg body weight to be effective against S. haematobium and S. mansoni, and two doses of 30

mg/kg body weight for S. japonicum, with cure rates of 75%–100%.Studies on praziquantel

43
against S. mansoniand S. haematobium among schoolchildren, at a dosage of 40 mg/kg body

weight, resulted in cure rates of 60.9%–88.6% and 39.8%–88.9%, respectively (Inobaya et al.,

2014). In children aged ≥7 years, 77.6% of treatment-naïve children were cured of S. mansoni

infection, with lower rates among children who had been previously treated with praziquantel.

Multiple doses of praziquantel 40 mg/kg resulted in cure rates of 41.9% to as high as 100%

among individuals infected with S. mansoni, while the cure rates for S. haematobium infection,

i.e, 53.1%–88.0%, did not vary much from that of the single dose. The benefits of praziquantel

are its high efficacy, ease of administration, relative safety, and mild to moderate side effects,

including nausea, dizziness, rash, pruritus, headache, drowsiness, and abdominal pain. (Inobaya

et al., 2014)

2.13 Prevention of Schistosomiasis

The basic means of preventing Schistosoma infection is avoiding contact with fresh water

infested with Schistosomeparasites. Swimming, wading, or any other aquatic activities in these

bodies of water exposes the skin to possible penetration by the cercariae. In cases when there is

brief accidental contact with infected water, vigorous towel drying is advised to help prevent the

cercariae from penetrating the skin.In using water from these fresh water sources for bathing,

water must be brought to the boil for at least 1 minute to kill the parasite that may be present in

the water. Allowing the water to stand for 24 hours or more before using it may also help in

preventing infection. Fine-mesh filters may also be used to filter the cercariae possibly contained

in the water. Insect repellants such as DEET (N,N-Diethyl-meta-toluamide) may be applied

topically to prevent cercariae from penetrating the skin, but this is not a very reliable measure.

(Inobaya et al., 2014). The immunopathology and immunoregulation associated with morbidity

of schistosomiasis has been studied extensively. However, the immune mechanisms related to

44
resistance, to reinfection, or in response to candidate vaccines are much less defined. Although

adult worms are refractory to immune attack, immature, developing worms (skin-stage and

lungstage schistosomulae) are the probable targets of protective immunity. Whether a protective

resistance to reinfection exists is subject to ongoing debate, but several lines of evidence suggest

that such resistance does develop, albeit slowly.

2.14 Burden of disease

Official estimates of the prevalence of Schistosoma infection were based on insensitive egg-

detection techniques, which substantially under-represent active infection. Schistosomiasis

initiated by infection in early life persists into adulthood, even after infection terminates (Mutapi

et al., 2003). Thus, although more than 230 million people are thought to be actively infected

with schistosomes, 1 a similar number are in a post-infection stage but continue to have residual

morbidity. As a result, the number of people with schistosomiasis (ie, infection-related disease)

could be closer to 440 million. Classic descriptions of schistosomiasis-related morbidity focus on

the pathologies unique to schistosome infection: periportal fibrosis for intestinal schistosomiasis

and bladder deformity and hydronephrosis for urogenital schistosomiasis. In fact, these

morbidities are much less common (5–10% of cases) than the less obvious, but disabling

complications of anaemia, growth stunting, cognitive impairment, and decreased aerobic

capacity. These morbidities are systemic, associated with continuous inflammation during the

first decades of life as a child has multiple, recurrent schistosome infections. (Mutapi et al.,

2003) These disabling complications are particularly relevant in low-income countries, where

they contribute to impaired physical performance and limited educational attainment disabilities

that become irreversible if infection cannot be prevented or suppressed throughout childhood.

Schistosomiasis does not occur in isolation. It is a disease of poverty that often occurs where

45
other parasites are prevalent and food insecurity is common. Thus, fully determining the global

attributable fraction of schistosomiasis toward these morbidities is difficult. However,

schistosomiasis alone is clearly a sufficient cause of these morbidities in many endemic

locations. (Mutapi et al., 2003)

2.15 Mapping and surveillance

Implementation of population-based control programmes by WHO guidelines requires

prevalence estimates, to decide where to use school-based versus community-based delivery of

praziquantel. A crucial consideration for the effective integration of preventive chemotherapy for

neglected tropical diseases is whether schistosoma infection overlaps with filariasis,

onchocerciasis, intestinal worm infections, and trachoma, (Pearce, 2005) which are all targeted

for control through preventive chemotherapy. Climate measures and digital topography linked

with data from past population-based surveys can broadly predict where schistosome

transmission is possible. But schistosome prevalence can be focal, resolving into a patchwork

mosaic of high-prevalence, medium-prevalence, and low-prevalence villages across a permissive

landscape. (Hewitson et al., 2005) Therefore, random cluster sampling across districtlevel

administrative units can substantially overestimate or underestimate infection risk in individual

communities and schools. (Mwanakasale et al., 2003) Randomised subsampling could be

improved by testing paired locations at various distances apart to estimate the controlling

distance factor for autocorrelation of infection prevalence within a given region.128 However,

because prevalence can vary significantly over 2–5 km, it might be best to briefly survey all

intended treatment locations (implementation units) with rapid sampling techniques (limited to

15–50 people per site). For initial allocation of S haematobium treatment, the WHO's Red Urine

Group consortium showed that a prevalence of visible (gross) haematuria of 10% or greater

46
effectively identifies high-prevalence communities. However, for S mansoni infection, symptom

scores or occult blood testing although indicative of severe disease (Fernando and Miller 2002)

are not sufficient to map levels of infection for preventive chemotherapy. Instead, Lot-Quality

Assurance or Multiple Category Lot-Quality Assurance approaches are used for limited testing

of a single stool to classify communities as having high or low prevalence. (Kallestrup et al.,

2005) Point of-care urine assays might supplant stool testing for this crucial mapping and

decision process. A shortcoming of rapid testing strategies is that test sensitivity will probably

fall as programmes succeed and prevalence and intensity falls. More sensitive testing of more

residents will be needed to define regions that still have high transmission and to establish if

elimination has been achieved. For S haematobium infection, dipstick diagnosis of microscopic

haematuria still seems to be adequate to detect low-level infection. However, for S mansoni and

S japonicum new elimination diagnostic tests are needed. (Gryseels et al., 2006)

2.16 Control and elimination

It is an exciting time for control and elimination of schistosomiasis. In 1984, the WHO endorsed

a strategy to control morbidity caused by schistosomiasis through preventive chemotherapy with

praziquantel. (Gryseels et al., 2006) Because of its excellent tolerability and generally good

ability to either cure or drastically reduce egg output (70–90%), praziquantel can be distributed

yearly (or in alternate years) by moderately trained school teachers or community health workers

to obtain sufficient coverage to control morbidity in children, even despite the possibility of

reinfection, resulting in prevention of severe hepatosplenic or urogenital disease. (Gryseels et al.,

2006) WHO has recommended the inclusion of preschool children in preventive chemotherapy

efforts. In 2012 through World Health Assembly Resolution the WHO recommended that

countries, if possible, aim beyond control of morbidity toward elimination of schistosomiasis.

47
This change of policy was a bold and important step. It is partly predicated on the pledge by

Merck Serono (Geneva, Switzerland) to donate up to 250 million tablets of praziquantel per year

(Gryseels et al., 2006) and the demonstration by the Schistosomiasis Control Initiative, that

nationwide rollout of preventive chemotherapy with praziquantel can be accomplished. The

decision by a country to move towards elimination should not be made lightly. It must be based

on years of extensive control and reliable prevalence mapping that justifies the decision.

Countries will need diagnostic tests suitable for use in the field, suitable survey sampling

schemes, and the human capacity to implement the necessary interventions. Meeting these

requirements needs a strong platform of government commitment over a substantial period. After

elimination, the programme must provide an adequately designed surveillance scheme based on

sound epidemiological and statistical techniques and improved diagnostic instruments. Aside

from drug donations, many countries will need international and binational assistance for

implementation of elimination interventions. (Gryseels et al., 2006)

Because preventive chemotherapy alone will not eliminate schistosomiasis from most regions,

additional control measures should be integrated into national and regional programmes. For the

first 60 years of large-scale efforts to control schistosomiasis, snail control was the primary

method used to prevent infection because no drugs were suitable for mass distribution. Although

chemicals, habitat change, predators, and biological competitors have been used to reduce snail

populations, efforts at present primarily use the molluscicide niclosamide, which kills snails at

low concentrations and is non-toxic to people. However, it is toxic to some freshwater fish and

amphibians. Niclosamide is a licensed pesticide in the USA, and is widely used for control of

snails and sea lampreys. When used properly in suitable habitats, it has been an important

contributor to schistosomiasis elimination campaigns. (Gryseels et al., 2006)

48
Behavioural modification is a possible, but challenging, approach to management of any health

problem. However, with proper community involvement, it could be useful for reduction of both

exposure of people to schistosome-containing water and contamination of snail habitat by human

excreta containing schistosome eggs. Behavioural modification without provision of feasible

alternatives is destined to fail, but in conjunction with improvements in water and sanitation, it

could prove successful. Provision of schistosomesafe water for washing, bathing, and recreation

is effective but expensive. (Gryseels et al., 2006)

Ongoing studies of the Schistosomiasis Consortium for Operational Research and Evaluation in

five African countries will help determine the regimens needed to gain and sustain control of

morbidity. The coordination and logistics needed at national, regional, and continental scales to

reach sustained control of morbidity, then elimination, are daunting. Nevertheless, now is the

time to move towards this goal. World Health Assembly resolution calls on all countries to

intensify interventions to control schistosomiasis and to strengthen surveillance of

schistosomiasis transmission. It also recommends that endemic countries embark on elimination

programmes and develop means to document their progress. The resolution calls on WHO to

report on progress towards elimination of schistosomiasis to the Executive Board and the World

Health Assembly every 3 years. The ultimate vision is a world free of schistosomiasis, with the

intermediate goals of controlling morbidity caused by schistosomiasis by 2020, eliminating

schistosomiasis as a public health problem by 2025, and interrupting transmission of

schistosomiasis in most regions and in selected countries in Africa by 2025. (Gryseels et al.,

2006) Schistosomiasis is an ancient human disease with effects worldwide, particularly in the

poorest communities. Effective early treatment is possible, thereby preventing the substantial

immune-mediated effects of Schistosoma infection on human health. New diagnostic tests and

49
new approaches to treatment implementation are aimed at local, then regional elimination, thus

changing the public health agenda from curative approaches to a truly preventive strategy.

2.17 Co-endemicity of Malaria and Schistosomiasis

In the current study, we performed a combined analysis of more than 6000 individuals from 14

retrieved research articles on co-infection of malaria and schistosomiasis in Nigeria Adeola et al.,

2012. Estimated co-infection rate was 15% (1SD=9%-39%). There was wide variability in the

reports of the co-infection and sample sizes across the studies. Extreme co-infection rates may

reach as high 96.4% in small-sized, child-focused studies. The low level of co-infection research

across the country retrieved was surprising, and almost 60% (10/17) of those retrieved were

carried out in the southwest. An overview of the studies retrieved from the literature search

showed that studies involving children had higher co-infection rates. This finding of a higher

prevalence of P. falciparum infection among children infected with Schistosoma could result

from social or environmental factors. In some of the children-based reports, more than one-third

of the analysed study population had both schistosomiasis and malaria. There are previous

reports on co-infection dynamics in children. The different intensities of Schistosoma and P.

falciparum co-infection have been surmised to be based on the age of the host and intensity of

Schistosoma infection Adeola et al., 2012. School aged children co-infected with S. mansoni may

be more susceptible to P. falciparum infection because anaemia associated with Schistosoma

infection may cause hyperventilation of carbon dioxide and increased lactates, making infected

individuals more attractive for mosquitoes and thus increasing their risk for Plasmodium

infection Ewunyenga et al., 2001. Despite the fact that concomitant parasitic infections are a

common occurrence in different regions of the world, the small number of research articles

retrieved was surprising, especially since schistosomiasis and malaria are among parasitic

50
infections with high prevalence in Sub-Saharan Africa Eleng et al, 2015. The high level of co-

infection of these two has been attributed to similar factors: poor sanitation, lack of toilet

facilities, unsafe drinking water, and ineffective public health enlightenment programme.

Therefore, WaSH (safe water, Sanitation and Hygiene) strategies remain valuable against these

highly prevalent tropical pathologies. Three cross-sectional studies included in our work

investigated the modulating effect of Schistosomiasis infection on the parasitaemia level of

Plasmodum falciparum. Schistosoma co-infection with Plasmodium in a patient can alter the

development of acquired immunity associated with the resistance or pathology of

schistosomiasis activating varied cytokine responses. The type of immune responses depends on

the Schistosoma species, host age, worm burden and Plasmodium spp. involved. Schistosoma

infection induces helper T cell (Th2) responses which alter cellular responses against malaria

parasites Ngoa et al, 2014. Adedoja et al. 2017 found higher levels of IL-10 among children with

only schistosomiasis and there was no significant association between pro-inflammatory

cytokines in co-infected children. Similar results were found in Kenya Bustinduy et al., 2015 and

in Senegal Lemaitre et al., 2014. The concomitant infection of two parasites may modulate the

effects of each other within their host. This has been reported extensively in different studies

where pre-existing infection alters the effect of other (reviewed in Degarege et al., 2016).

Conversely, Schistosoma haematobium exerts a persistent stimulatory effect on the host immune

system, protecting children against uncomplicated P. falciparum malaria Lyke et al, 2018. This

modulation effect has not been widely studied in Nigeria. In some studies, proxies for

modulation were used, and often not correctly. Bustinduy et al. 2015 studied age-stratified

profiles of IL-6, IL-10 and TNF-α cytokines in Schistosoma haematobium, Plasmodium

falciparum and other chronic parasitic co-infections in Kenyan children. They correlated these

51
cytokine levels with schistosomiasis and interactions with concurrent co-infections. After

controlling for sex, malaria, anaemia, wasting, stunting and other cytokines, it was shown that

IL-6, IL-10 and TNF-α levels were higher among children infected with S. haematobium,

regardless of S. haematobium co-infection status. Morenikeji et al. 2015 showed that anti-

Schistosoma IgG produced during co-infection with Plasmodium spp. among infected

individuals in Ijoun, Nigeria, were higher than in malaria mono infection but not in S.

haematobium mono infection; while Anumudu et al. 2012 reported high levels of schistosome

specific antibody IgG3 in children co-infected with malaria and schistosomiasis in Ibadan. Co-

infection of the two endemic parasitic diseases has socio-economic and health impact on the

population according to authors. Higher prevalence of schistosomiasis and malaria co-infection

recorded in some articles included in this review was attributed to poverty, lack of potable water,

limited access to health care, lack of protective clothing, poor hygiene, poverty and poor sanitary

conditions. The geographical harmony of socio-economic and climatic conditions was also

indicative of the overlap in the distribution of Schistosoma and P. falciparum co-infection;

indeed, socio-economic factors were not greatly improved in the communities through the period

of studies included in this review. In this review, we find that school aged children are more

prone to schisto-malaria co-infection with severe anaemia, probably due to high worm load and

low immunity [Atanda 2014]. Females had higher co-infection rates than males and this was

attributed to daily exposures to water contact related activities including fetching water and

swimming Adedoja et al., 2015. In addition, the poor socio- economic status of the people

encourages poor nutrition, and lack of adequate medical attention complicates the infections.

When lower prevalence of co-infection was reported, authors indicated that this may reflect

increased health awareness and improved sanitary conditions due to gradual urbanization

52
Oloyede et al., 2017 or it may be just the reality faced in rural Nigerian communities. Indeed, the

co-infection studies reported indicate that a greater impact is due to prevailing social factors,

which could be more visible within certain societal demographics. Studies also reported the

impact of coinfection on the overall host responses. Inyang-Etoh et al. 2017 indicated that

schistosomiasis can have a negative effect on host response to malaria, including increased

susceptibility to plasmodium infection and increased severity of disease especially among

children. These co-infected school aged children also had malnutrition, impaired cognitive

development, splenomegaly and fatigue resulting in poor school performance and overall

physical work capacity. Lower haemoglobin levels were seen among pregnant women with co-

infection than in those with single infection of S. haematobium or P. falciparum Oloyede et al.,

2017. Co-infection with these two parasites could aggravate renal related disorders due to excess

haematuria and proteinuria inducing kidney complications. In treatment, modulation may even

occur such that treatment of schistosomiasis may reduce the risk of malaria infection Atanda

2014. At the moment, there is no treatment policy for the co-infection, and often the sufferers

don’t even count on the co-infection when treating the individual infections. However, Oloyede

et al. 2017 suggested that artemether-lumefantrine, an antimalarial may be a possible treatment

against schistosomiasis in uncomplicated P. falciparum co-infected individuals, as it also reduces

the intensity of Schistosoma, severe anaemia and parasitemia. Morenikeji et al. 2015 emphasized

the possibility of re-infection with S. haematobium among the same individuals following mass

chemotherapy for schistosomiasis carried out five years previously. Schistosomiasis influences

the production of anti-inflammatory cytokines in children co-infected with malaria. Low levels

of circulating T reg memory cells in co-infected children makes them susceptible to

53
opportunistic infections Dakul et al., 2015. To summarize, co-infection elicits immune and other

molecular responses, thus treatment or preventive strategies need to be developed.

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 CHAPTER THREE

MATERIALS AND METHOD

3.1 Study Area

Adoka is a village under Otukpo local government area in domiciled in Benue state, North-

central geopolitical zone of Nigeria and has its headquarters in the town of Otukpo, lies on the

geographical coordinates of 6° 49' 0" N, 8° 40' 0" E. The LGA is bordered by the Apa, Ohimini,

Ado, and Olamaboro LGAs with the LGA made up of several towns and villages such as Allen,

Adoka-icho, AdokaEhaji, Entekpa, Icho, Adoka, Ogboju, and Otobi. The estimated population of

Otukpo LGA is put at 199,009 inhabitants with the area mostly inhabited by the Idoma people.

The Idoma language is commonly spoken in the LGA while the religion of Christianity is widely

practiced in the area. Otukpo LGA is widely renowned for its rich agricultural heritage as the

people are predominantly farmers with crops such as yam, maize, cassava, beniseed, soybeans,

and millet grown in large quantities within the area. Otukpo has a tropical savanna climate. It is

warm every month with both a wet and dry season. The average annual temperature for Otukpo

is 64° degrees and there is about 244 inch of rain in a year. It is dry for 169 days a year with an

average humidity of 61% and an UV-index of 7. The climate is tropical in Otukpo. The average

annual temperature in Otukpo is 27.2 °C. In the month of August, the average temperature is

25.5 °C. It is the lowest average temperature of the whole year.

55
Figure 8: Map of Otukpo Local Government Area Showing Settlements

Source: Ministry of Lands and Survey Makurdi.

56
3.2 Sample size Determination

The sample size (n) was estimated using Chocran formula (n = Z² (1-p)/L²) (Chocran, 1963)

N = Z² (1−p) 2L²

Where:

n = is the sample size required.

Z = The normal distribution at 95% confidence interval.

P = Proportion of infected individuals on a scale of 1.

q = Proportion of infection free individuals on a scale of 1.

L = Precision level or allowable error on a scale of 1.

3.3 Ethical Approval

Before the commencement of the study, ethical approval will be obtained from Benue State

Ministry of Health.

3.4 Study Period

The study will be conducted for a period of three (3) months, from April to June, 2023.

3.5 Study Design

Random sampling technique will be used in selecting participants from house to house, schools

and in/out patients of hospitals across Adoka. Nigeria. Villages under Adoka to be sampled

include Opa-Adoka, Okpeje-Adoka, Aune-Adoka, Onipi-Adoka, Obena-Adoka, Aukpa-Adoka,

Odaubi-Adoka, Adoka Central, Ogodumu-Adoka, and Ojinebe-Adoka.

57
3.6 Data Collection and Questionnaire Administration

The data will be gathered from the respondents using a structured questionnaire. Socio-

demographic data such as age, sex, occupation water source, water contact activities, method of

water treatment, housing distance from water body, outdoor activities, mode of defecation and

other variables will be asked. With my understanding and fluency in Idoma language these

questions will be asked. Also, community health workers and laboratory technicians in Christian

Maternity Hospital Adoka will help me in data collection and administration of questionnaires.

3.7 Sample Collection and Laboratory analysis of samples

Five hundred samples (50 from each village) in blood, urine and stool will be collected from

individuals. The samples will be collected in clean, wide mouth; screws capped and dry

transparent containers for stool and sterile urine sampling bottles for urine (Cheesbrough, 2006).

Blood samples will be collected by pricking of thumb or index finger using a lancet and

immediately transfer to a rapid diagnostic test strip for malaria for result. Sample collection will

done between the hours of 7am and 10am. Samples will be transported to the laboratory in

Christian Maternity Hospital, Adoka for analysis according to the method of Cheesbrough

(2005).

3.8 Analysis of Urine Samples for Schistosomiasis detection

For haematuria examination, chemical reagent strip methods as described by (Cheesbrough,

2002; WHO, 2011) will be employed. Reagent strip combi-9 andcombi-10 (Medi-Test

Macherey-Nagel, Germany) will be dipped into each urine sample and the color was matched

with the standard color by the side of the container as recommended by the manufacturer to

58
determine the presence of blood in urine. Urine samples will be examined to detect the presence

of eggs using sedimentation technique. Each urine sample will be thoroughly shaken and

10mldecanted into a test-tube and centrifuged at 3,000 rpm for 5 minutes in haematocrit

centrifuge machine and the supernatant will be discarded leaving the sediments. A drop of the

sediment will be placed on a clean microscope slide and stained using Lugol’s iodine and left for

15seconds for the stain to penetrate the eggs and viewed under microscope at low power (× 10)

and then × 40 objective lens(Cheesbrough, 2002; WHO, 2011). The number of S. haematobium

eggs per 10ml of urine was counted for each positive sample and the result will be calculated by

multiplying the crude egg numbers per slide with the number of ml of the respective urine

sample and dividing by 10 to represent the intensity. Heavy intensity of infection is defined as

>50 S. haematobium eggs per10ml.

Schistosoma mansoni eggs are large (114 to 180 µm long by 45-70 µm wide) and have a

characteristic shape, with a prominent lateral spine near the posterior end. The anterior end is

tapered and slightly curved. When the eggs are excreted in stool, they contain a mature

miracidium.

Plate 1: Schistosoma mansoni egg under a microscope

59
The eggs of Schistosoma haematobium are large (110-170 µm long by 40-70 µm wide) and bear

a conspicuous terminal spine. Eggs contain a mature miracidium when shed in urine (WHO,

1991 and WHO, 2011).

Plate 2: Schistosoma haematobiumegg under a microscope

3.9 Analyses of Blood Samples for Malaria Detection using Rapid Diagnostic Test Kit

Malaria is detected faster in endemic areas with mass population to be tested using a Rapid

Diagnostic Test Kit (RDT). The strip gives an accurate result without telling the species of

Plasmodium and the level of intensity of the parasite. The blood sample is collected using a

lancet to prick the thumb or index finger. The pricked blood on the index finger is collected

using a capillary tube and placed on a hole labelled “A” on the strip. A few drops of buffer

solution are dropped on a hole labelled “B” before the blood sample on the strip, wait for

15minutes and read the result. The strip has a two-line indicator “C” and “T”. if the indicator line

C and T appears it means the result is POSITIVE. If the indicator line C appears bold and T

appears faint it is still POSITIVE. If the indicator line T appears only it is NEGATIVE. If no

indicator line appears then the result is INVALID.

60
3.10 Data Analysis

Descriptive statistics will be used to determine the frequency of distribution and percentage

prevalence of Plasmodium and Schistosoma species. Chi-Square will be used to test the

relationship of Plasmodium and Schistosoma species with demographic and socio-economic

factors and prevalence of infection. Differences in the mean variables of the Plasmodium and

Schistosoma species will be analyzed using t-test and one-way ANOVA. Values will also be

considered to be significant at P < 0.05.

61