The devastating effects of infectious diseases on the world’s population are a source of concern. Pathogenic microorganisms such as viruses, bacteria, fungi or parasites are implicated in the establishment of infectious diseases which can be spread directly or indirectly, from one person to another. Despite a century of seemingly successful prevention and control efforts, infectious diseases remain an important global problem in public health, causing over 13 million deaths each year (Cohen, 2000). Changes in society, technology, and the microorganisms themselves are contributing to the emergence of new diseases, the re-emergence of diseases once controlled, and to the development of antimicrobial resistance (Cohen, 2000). Yellow fever and Malaria are two infectious diseases that were studied in this research.
Yellow fever (YF) is caused by the yellow fever virus and it is considered a vector-borne disease because it can be transmitted from person to person via mosquito bites. Several species of mosquitoes belonging to the genus Aedes are capable of transmitting yellow fever, although Aedes aegypti is mostly associated with transmission of the virus (Mutebi and Barrett, 2002). About seven (7) yellow fever virus (YFV) genotypes have been described, including five (5) in Africa and two (2) in South America (de Sauza et al., 2010; von Lindern et al., 2006).
YFV is endemic in tropical areas of Africa and South-Central America, with approximately 90% of cases originating from Africa (WHO, 2013). Although underreporting is a concern, myriad of outbreaks have been reported in Africa. About 170,000 cases of severe yellow fever disease and 29,000 – 60,000 related deaths are estimated to occur annually in Africa (WHO, 2013). Furthermore, the number of children in Nigeria at risk of yellow fever is estimated at 23 million, for those children in urban areas only (WHO, 2015). Fortunately, there is an effective vaccine against yellow fever disease.
Malaria is considered the most prevalent infectious disease in the tropical and subtropical regions of the world in addition to being the major cause of morbidity in the tropics (Mishra et al., 2003). Like yellow fever, Malaria is also a vector-borne disease – it is transmitted from person to person via mosquito bites. This infectious disease affects humans and other animals, and it is caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the genus Plasmodium (WHO, 2016). Five species of Plasmodium can infect and be spread by humans. Apart from P. malariae that causes a milder form of malaria, most deaths are caused by P. falciparum, P. ovale, and P. vivax (Caraballo, 2014). Plasmodium knowlesi rarely causes disease in humans.
Records have shown that about 50% of the Nigerian population suffer from at least one episode of malaria annually with over 45% of all out-patient visits being associated with malaria. Approximately 0.25 million deaths of Nigerian children under the age of 5 have been associated with malaria yearly (UNICEF, 2009).
Morbidity and mortality as a result of malaria infection vary among countries. A 2010 estimate by the World Health Organization shows that there were 219 million cases of malaria which resulted in 660,000 deaths (Nadjm and Behrens, 2012; WHO, 2012). About 125 million pregnant women are at risk of infection each year. Maternal malaria in Sub-Saharan Africa accounts for about 200,000 estimated infant deaths yearly (Hartman et al., 2010).
In spite of the dreadful nature of malaria and yellow fever mono-infections, there are few instances where ill patients suffer from both diseases at the same time. In such situations infected patients struggle for recuperation from two pathogens. A study conducted in South-eastern Senegal revealed a co-infection of yellow fever and malaria in only seven (7) out of 13,845 patients enrolled for the study (Sow et al., 2016). In Nigeria however, a study which enrolled 310 febrile, clinically suspected malaria/typhoid patients, did not record any yellow fever and malaria co-infection (Baba et al., 2013).
This study therefore investigated the rate of malaria and yellow fever co-infection among febrile patients in Ilorin. It also assessed the distribution of mosquito vectors which are responsible for transmitting the diseases, and then went further to determine the immunity of the enrolled patients against yellow fever infection with the view to predicting the possibility of an outbreak.
1.1 YELLOW FEVER
Yellow fever (YF) is a mosquito-borne disease caused by yellow fever virus (YFV). It was the first illness demonstrated by Walter Reed around 1900 to be transmissible by filtered human serum and transmitted by mosquitoes (Staples and Monath, 2008). Yellow fever is an old disease that has accounted for widespread epidemics during the 17th, 18th, 19th, and early 20th centuries (Soper, 1944; Monath, 1988). It is regarded an emerging disease and remains an important public health problem especially in Africa (Gardner, 2010). Bleeding problem is probable in the course of the disease. The ‘yellow’ in the name of the illness denotes the jaundice that affects some patients. Illness ranges in severity from a self-limited febrile illness to bleeding, eventual shock, and failure of multiple organs (CDC, 2015).
1.1.2 YELLOW FEVER VIRUS
Yellow fever virus is a 40- to 50-nm wide enveloped RNA virus which belongs to the family, Flaviviridae (Lindenbach et al., 2007). The genus Flavivirus is composed of approximately 70 viruses, of which almost half are pathogens of humans and/or animals, and can be considered zoonotic viruses. The positive-sense, single-stranded RNA is about 11kb long and has a single open reading frame encoding a polyprotein. This polyprotein is cut by host proteases into three structural (C, prM, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration tallies with the arrangement of the protein coding genes in the genome (Sampath and Padmanabhan, 2009). Between the NS4A and NS4B genes lies a 2K non-structural gene. The prototype strain of YF virus is Asibi, which was isolated in Ghana in 1927 (Mutebi and Barrett, 2002).
Figure 1.1: Genome organization of yellow fever virus (Mutebi and Barrett, 2002).
Up to seven (7) yellow fever virus genotypes have been described, including five (5) in Africa and 2 in South America. The African genotypes include: West African genotype I (Gabon, Cameroon, and Nigeria), West African genotype II (Ghana, Ivory Coast, Guinea, and Senegal), East and Central African genotype (Democratic Republic of Congo, Central African Republic, Ethiopia and Sudan), East African genotype (Kenya), and Angola genotype (Angola) (de Sauza et al., 2010; von Lindern et al., 2006).
Nucleotide variability among the different genotypes ranges from 25 to 30%, meanwhile sequence homology within one genotype can be very high even if isolations were done decades apart, suggesting a very slow evolution rate and a genetic stability of the virus (Mutebi et al., 2001).
Yellow fever virus likely originated in Central Africa and subsequently spread to West and East Africa, and was introduced into the Americas following slave trade between 16th and 19th centuries (Mutebi and Barrett, 2002; Barrett and Monath, 2003).
1.1.3 REPLICATION OF YELLOW FEVER VIRUS
The virus infect amongst others, macrophages, monocytes, and dendritic cells. It attaches to the cell surface via specific receptors and is taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. The capsid enters the cytosol, decays, and releases the genome. Receptor binding, as well as membrane fusion, are catalysed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers (Sampath and Padmanabhan, 2009).
Following a successful entry into the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form and is therefore denoted as prM (precursor M) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host’s protein – furin, which cleaves prM to M. This releases E from the complex which can now take its place in the mature, infectious virion (Sampath and Padmanabhan, 2009).
Figure 1.2: Replication pattern of a Flavivirus (NIAID, 2012).
1.1.4 TRANSMISSION OF YELLOW FEVER VIRUS
Yellow fever virus is principally transmitted through the bite of the yellow fever mosquito Aedes aegypti. However, other mosquitoes such as Aedes albopictus often referred to as the tiger mosquito, can also serve as a vector for this virus. Like other Arboviruses that are transmitted by mosquitoes, the yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or other primates. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and then get to the salivary glands. When next the mosquito sucks blood, it inadvertently transfers its saliva into the wound, and the virus reaches the bloodstream of the bitten person. The transmission of the yellow fever virus from a female Ae. aegypti mosquito to her eggs and then larvae (transovarial and transstadial transmission), has been shown. This infection of vectors without a previous blood meal appears to play a role in single, sudden breakouts of the disease (Fontenille et al., 1997).
Three epidemiologically different infectious cycles (urban, sylvatic, and savannah) occur, in which the virus is transmitted from mosquitoes to humans or other primates. In the “urban cycle”, only the yellow fever mosquito Ae. aegypti is involved. It is well adapted to urban areas and also capable of transmitting other diseases, including dengue fever and chikungunya. Major outbreaks of yellow fever that occur in Africa are a result of the urban cycle. Apart from the 1999 outbreak in Bolivia, this urban cycle no longer exists in South America (Barrett and Higgs, 2007).
Besides the urban cycle, both in Africa and South America, a sylvatic cycle (also called jungle cycle or forest cycle) exists, where Ae. africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors. In the jungle, the mosquitoes infect mainly non-human primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can infect each other, which explains the low incidence of yellow fever cases on the continent. People who become infected in the jungle can carry the virus to urban areas, where Ae. aegypti acts as a vector. Because of this sylvatic cycle, it is difficult to eradicate yellow fever (Barrett and Higgs, 2007).
In Africa, a third infectious cycle known as savannah cycle or intermediate cycle, occurs between the jungle and urban cycles. Different mosquitoes of the genus Aedes are involved. They include Aedes luteocephalus, Aedes furcifer, Aedes metallicus, Aedes opok, Aedes taylori, Aedes vittatus and members of the Aedes simpsoni complex (Mutebi and Barrett, 2002).
Figure 1.3: Transmission of yellow fever virus (CDC, 2015a).
1.1.5 PATHOGENESIS OF YELLOW FEVER VIRUS
Following inoculation of the skin by the bite of a blood feeding mosquito or through syringe/needle inoculation, virus replication occurs in draining lymph nodes, and then, with the ensuing viremia, in other tissues (Monath, 2008). Immature and mature dendritic cells (DCs) are highly susceptible to yellow fever virus infection, and unlike dengue, this is not dependent on DC-SIGN receptors (Barba-Spaeth et al., 2005). The biodistribution of YF 17D virus in monkeys revealed the predominant replication in lymphoid tissues that extended beyond the appearance of neutralizing antibodies. Lymphoid tissues undergo profound changes in yellow fever infection, characterized by appearance of large mononuclear or histiocytic cells, distension of the follicles, and necrosis of B cell germinal centers. It is presumed that the activation of cells in these tissues contributes to the systemic terminal features of YF, characterized by release of pro-inflammatory cytokines (Monath, 2008). The liver is the most important organ affected in YF. Pathological changes observed in moribund animals and fatal human cases include eosinophilic degeneration of hepatocytes and Kupffer cells, and microvesicular fatty change. These changes are most prominent in the midzonal region and are due to apoptosis. An overlooked feature of YF is the marked granulocytic leukocytosis observed in the terminal stage of disease. Given the elevated serum levels of IL-8 and TNF-α, it is likely that these granulocytes are activated, with consequent release of platelet activating factor (PAF), elastase and other proteases, and leukotrienes, which may modify endothelial integrity, particularly in the presence of pro-inflammatory cytokines, causing capillary leak. The syndrome in YF thus resembles many elements seen in overwhelming sepsis (Monath, 2008).
1.1.6 SIGNS AND SYMPTOMS OF YELLOW FEVER VIRUS INFECTION
Most yellow fever virus infections in humans are asymptomatic. Clinical disease varies from a mild, undifferentiated febrile illness to severe disease with jaundice or hemorrhagic manifestations (Monath et al., 2012).
Yellow fever begins after an incubation period of three to six (3-6) days. Most cases only cause a mild infection with fever, headache, chills, back pain, fatigue, muscle pain, general body ache, nausea, and vomiting (CDC, 2015). In these cases, the infection lasts only three to four days, in which case the patient is viremic. Many patients have an uneventful recovery.
In approximately15 percent of cases, however, people enter a second, toxic phase of the disease with recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain within 48 hours following viremic period. Bleeding in the mouth, the eyes, and the gastrointestinal tract will cause vomit containing blood, hence the Spanish name for yellow fever, vomito negro (“black vomit”) (Chastel, 2003). Viremia is generally absent during this phase of symptom recrudescence (Staples et al., 2010). The toxic phase is fatal in about 20% of cases, making the overall fatality rate for the disease 3% (Monath, 2008). In severe epidemics, the mortality may exceed 50% (Tomori, 2004). Surviving the infection provides lifelong immunity, and usually there is no permanent damage to organs (Rogers et al., 2006).
1.1.7 DIAGNOSIS OF YELLOW FEVER VIRUS INFECTION
Laboratory diagnosis of yellow fever virus infection is generally accomplished by testing serum to detect virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by serologic assays. Serologic cross-reactions occur with other flaviviruses (e.g., dengue and West Nile viruses), therefore positive results should be confirmed with more specific test (e.g. plaque reduction neutralization test (Staples et al., 2010).
During 3-4 days of infection, yellow fever virus or yellow fever viral RNA can often be detected in the serum by nucleic acid amplification testing (e.g., reverse transcription polymerase chain reaction [RT-PCR]). However, once the overt symptoms become manifested, the virus or the viral RNA is often undetectable (Staples et al., 2010).
Histology and immunochemistry can also be done. After isolation, the virus can be confirmed in the cell culture supernatant by RT-PCR, neutralization or ELISA tests using appropriate polyclonal or monoclonal antibodies, or in the virus-infected cells by indirect immunofluorescence or RT-PCR (WHO, 2004).
1.1.8 EPIDEMIOLOGY OF YELLOW FEVER
YFV is endemic in tropical areas of Africa and South-Central America, with approximately 90% of cases originating from Africa (WHO, 2013). In Africa, about 170,000 cases of severe yellow fever disease and 29,000 – 60,000 related deaths are estimated to occur annually (WHO, 2013). Yellow fever is conspicuously absent from Asia, despite multiple opportunities for introduction. The reason for this is unclear (Rogers et al., 2006).
Underreporting is a concern – the true number of cases is estimated to be 10 to 250 times what is now being reported. Series of outbreaks have been reported in Africa. In Nigeria, the last reported outbreak of YF was in 2010 (WHO, 2015). Further, the number of children in Nigeria at risk for YF is estimated at 23 million, for those children in urban areas only (WHO, 2015).
Figure 1.4: A map of Africa showing the YF endemic region (shaded in green and red) and the recognized distribution of YF genotypes (colored ellipses). Highlighted in red are countries that have reported YF outbreaks from 1984 to 2001 (data from the WHO) ((Mutebi and Barrett, 2002).
1.1.9 TREATMENT, PREVENTION, AND CONTROL OF YELLOW FEVER
Treatment and management of yellow fever:
Despite the fact that multiple drugs have been evaluated or empirically used to treat yellow fever disease, to date, specific benefits have not been derived from the usage of such drugs. Management is essentially supportive and based on symptoms and organ systems involved. Patients with multisystem organ involvement will likely require critical-care support with possible mechanical ventilation or haemodialysis (Staples et al., 2010). To reduce milder symptoms of fever and myalgias, rest, fluids, and nonsteroidal anti-inflammatory drugs or acetaminophen can be used. Aspirin should be avoided because of the risk for haemorrhagic complications. Infected persons should be protected from further mosquito exposure (staying indoors and/or under a mosquito net) during the first few days of illness so they do not contribute to the transmission cycle (Staples et al., 2010).
Prevention and control of yellow fever:
Prevention and control of yellow fever can be achieved through immunization of people, as well as control of the yellow fever vector, Ae. aegypti.
There is an effective vaccine against yellow fever developed by Max Theiler in 1937 (Barrett and Teuwen, 2009). The attenuated live vaccine stem 17D is capable of conferring immunity for at least 10 years. In 95% of people, protection normally begins by the 10th day after vaccine administration. Vaccination is highly recommended for those traveling to affected areas, because non-native people tend to suffer more severe illness when infected (Barrett and Teuwen, 2009). The World Health Organization (WHO) recommends routine vaccinations for people living in affected areas between the 9th and 12th month after birth. However, up to one in four people experience fever, aches, and local soreness and redness at the site of injection (CDC, 2011). Prompt detection of yellow fever and rapid response through emergency vaccination campaigns are essential for controlling outbreaks.
Control of Ae. aegypti, the yellow fever mosquito, is important because it also transmits other arboviruses such as dengue virus and chikungunya virus. Like Anopheles, the malaria vector, Ae. aegypti breeds in water. The use of larvicides in the mosquitoes’ breeding areas can significantly interfere with their breeding. Also, population of adult mosquitoes can be checked with the use of insecticides. The use of insecticide-treated mosquito nets is equally effective (Tolle, 2009).
Mosquitoes are probably the most successful member of the arthropod family as they express good ability to adapt to different environmental conditions; unfortunately they play a significant role in the transmission of diseases such as malaria, filariasis, yellow fever, dengue, West Nile, and chikungunya (Ramathialaga et al., 2012). They are distributed almost worldwide, except in some few islands and Antarctica (Leopoldo, 2008).
Mosquitoes breed in aquatic bodies such as fresh water, marshes, mangrove, stagnant water, river banks and temporary rain pools during the appropriate season (Afolabi et al., 2013). The breeding of mosquito in tropical and sub-Saharan regions is influenced by climatic conditions and vegetation (Leopoldo, 2008). The breeding patterns of mosquitoes differ with species; many species prefer vegetative habitats while some breed in open pools.
Several studies have been conducted on the distribution of mosquitoes in Nigeria (Eni et al., 2014; Afolabi et al., 2013; Lamidi, 2009). Over one hundred species of mosquitoes are capable of disease transmission to man and other animals (Leopoldo, 2008). Some of these mosquitoes include Anopheles sp., Aedes sp., Mansonia sp., Culex sp., and Coquelletidia sp. Malaria for instance is transmitted by a species of mosquito – Anopheles. Over 80% of all malaria mortality occurs in the tropical and Sub-Saharan Africa (WHO, 2011). Nigeria has high prevalence of malaria disease, as it remains the major cause of maternal mortality and morbidity (Aribodor et al., 2007). At least 50% of Nigeria’s population suffers at least one episode of malaria each year. Malaria infection is mostly seasonal with its major incidence occurring during the rainy season (FMH, 2005).
Aedes species, a common vector of most Arboviruses, can easily adapt and proliferate in new areas, resulting to the wide spread of Aedes borne diseases. West Nile virus for instance, has been spread from its origin in Africa to America, Europe, and the rest of Asia by travellers (Leopoldo, 2008).
Unhygienic practices such as littering of the environment with domestic and industrial wastes is not uncommon in Ilorin. This practice, as well as the use of open drainage system, encourage the breeding of mosquitoes and consequently increase the morbidity from mosquito borne diseases to which there are mostly no vaccine available for prophylaxis.
To effectively control mosquitoes, there is need for a good knowledge on breeding ecology, the type and nature of habitat that enables the adaptation and survival of the mosquitoes (Olayemi et al., 2010: Afolabi et al., 2013). Different strategies have been used to reduce mosquito-borne diseases (Lee et al., 2010). This includes among others, non-hazardous biological control method such as the larvicidal activity of some bacteria against mosquito larva (Ramathialaga et al., 2012). Mosquito control technique using pesticides may be perilous. Some pesticides may be toxic to birds, fish, wild life, aquatic invertebrates and honeybees (Rose, 2001).
Malaria is the most prevalent infectious disease in the tropical and subtropical regions of the world in addition to being the major cause of morbidity in the tropics (Mishra et al., 2003). Like yellow fever, malaria is a mosquito-borne disease. It affects humans and other animals, and it is caused by parasitic protozoans (a group of single-celled microorganism) belonging to the genus Plasmodium (WHO, 2016). Five species of Plasmodium can infect and be spread by humans. Apart from P. malariae that causes a milder form of malaria, most deaths are caused by P. falciparum, P. ovale, and P. vivax (Caraballo, 2014). The species P. knowlesi rarely causes disease in humans. Malaria is commonly associated with poverty and has a major significant effect on economic development (Worrall et al., 2005).In Africa it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and effects on tourism (Greenwood et al., 2005). Records have shown that about 50% of the Nigerian population suffer from at least one episode of malaria annually with over 45% of all out-patient visits being associated with malaria. Approximately 0.25 million deaths of Nigerian children under the age of 5 have been associated with malaria yearly (UNICEF, 2009).
Depending on severity of disease, organ or tissue affected, transmission pattern and symptom, malaria has been described with different names: cerebral malaria, congenital malaria, algid malaria, bilious malaria, pernicious malaria and transfusion malaria.
1.3.1 TRANSMISSION OF MALARIA PARASITE (PLASMODIUM)
The principal means by which malaria parasite is transmitted is through mosquito bite. Generally, male mosquitoes feed on plant nectar and do not transmit disease while only female mosquitoes feed on blood and consequently transmit disease. The female mosquitoes of the genus Anopheles are responsible for transmitting malaria parasite and they feed mostly at night. They normally start searching for meal at dusk, and will continue throughout the night until taking a meal (Schlagenhauf-Lawlor, 2008).
1.3.2 LIFE CYCLE OF PLASMODIUM
A definitive host (female Anopheles mosquito) can be said to initiate the life cycle of Plasmodium and it acts as a transmission vector. It transmits a motile infective form known as sporozoite to vertebrate host such as human (the secondary host). A sporozoite travels through the blood vessels to liver cells (hepatocytes). At the liver, the sporozoite undergo asexual reproduction (tissue schizogony) to produce thousands of merozoites which then infect new red blood cells and initiate a series of asexual multiplication cycles (blood schizogony) that produce 8 to 24 new infective merozoites. At this point the cells burst and give rise to a new infective cycle (Schlagenhauf-Lawlor, 2008).
Other merozoites develop into immature gametocytes, which are the precursors of male and female gametes. When an infected person is bitten by a fertilized mosquito, gametocytes are taken up with the blood and mature in the gut of the mosquito. The male and female gametocytes fuse and form an ookinete (a fertilized, motile zygote). Ookenetes develop into new sporozoites that migrate to the insect’s salivary glands, ready to infect a new vertebrate host. When the mosquito takes a subsequent blood meal, it injects the sporozoites into the skin of the vertebrate host.
1.3.3 PATHOGENESIS OF MALARIA
The development of malaria infection is in two phases: one that involves the erythrocytes or red blood cell (erythrocytic phase) and one that involves the liver (exoerythrocytic phase). In an attempt to take blood meal, infected mosquitoes inject sporozoites from their saliva into the skin of a vertebrate host. The sporozoites enter the blood stream and migrate to the liver where within 8-30 days they multiply asexually and asymptomatically (Bledsoe, 2005).
At the liver, the sporozoites differentiate into thousands of merozoites which rupture and infect red blood cells, thereby initiating the erythrocytic stage of the life cycle (Bledsoe, 2005). The parasite escapes from the liver by covering itself in the cell membrane of the infected host liver cell (Vaughan et al., 2008).
Within the red blood cells, the parasites further multiply asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur, giving rise to waves of fever from simultaneous waves of merozoites escaping and infecting red blood cells (Bledsoe, 2005).
Notably, some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (about 7–10 months) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections (White, 2011), although their existence in P. ovale is uncertain (Richter et al., 2010).
Plasmodium appears to evade attack by the host immune system because in a large part of its human life cycle it is denizen within the blood cells and liver, making it relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid being destroyed, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen (Tilley et al., 2011). Sequestered red blood cells can breach the blood-brain barrier and cause cerebral malaria (Rénia et al., 2012).
People with liver condition such as viral hepatitis or chronic liver disease may suffer liver dysfunction in an event of malaria infection, although it is an uncommon occurrence. Liver compromise in people with malaria correlates with a greater likelihood of complications and mortality (Bhalla et al., 2006).
1.3.4 SIGNS AND SYMPTOMS OF MALARIA INFECTION
The signs and symptoms of malaria typically begin 8–25 days following infection (Fairhurst and Wellems, 2010); however, symptoms may occur later in those who have taken antimalarial medications as prevention (Nadjm and Behrens, 2012). Flu-like symptoms characterize the initial manifestations of the disease common to all malaria species and can resemble other conditions such as gastroenteritis, sepsis, and viral diseases (Nadjm and Behrens, 2012). The presentation may include fever, headache, shivering, vomiting, joint pain, jaundice, haemolytic anaemia, convulsion, haemoglobin in the urine, and retinal damage.
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection (Bartoloni and Zammarchi, 2012). Individuals with cerebral malaria frequently exhibit neurological symptoms, including nystagmus, abnormal posturing, conjugate gaze palsy (failure of the eyes to turn together in the same direction), coma, seizures, or opisthotonus (Bartoloni and Zammarchi, 2012).
1.3.5 LABORATORY DIAGNOSIS OF MALARIA INFECTION
Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Microscopy is perhaps the commonest method employed in the diagnosis of malaria. Methods that use the polymerase chain reaction to detect the parasite’s DNA have been developed, but are not widely used in areas where malaria is common due to their cost and complexity (Nadjm and Behrens, 2012).
Malaria is classified into either “severe” or “uncomplicated” by the World Health Organization (WHO) (Nadjm and Behrens, 2012). It is considered severe for P. falciparum malaria when any of the following criteria are present, otherwise it is considered uncomplicated: Decreased consciousness, significant weakness such that the person is unable to walk, inability to feed, two or more convulsions, low blood pressure (less than 70 mmHg in adults and 50 mmHg in children), circulatory shock, breathing problems, kidney failure or haemoglobin in the urine, bleeding problems or haemoglobin less than 50 g/L (5 g/dL), pulmonary oedema, blood glucose less than 2.2 mmol/L (40 mg/dL), acidosis or lactate levels of greater than 5 mmol/L, and a parasite level in the blood of greater than 100,000 per microliter (µL) in low-intensity transmission areas, or 250,000 per µL in high-intensity transmission areas (WHO, 2010).
1.3.6 EPIDEMIOLOGY OF MALARIA
Morbidity and mortality as a result of malaria infection vary among countries. A 2010 estimate by the WHO shows that there were 219 million cases of malaria which resulted in 660,000 deaths (Nadjm and Behrens, 2012; WHO, 2012). About 125 million pregnant women are at risk of infection each year. Maternal malaria in Sub-Saharan Africa accounts for about 200,000 estimated infant deaths yearly (Hartman et al., 2010).
While there are about 10,000 malaria cases per year in Western Europe, there is only about 1300–1500 in the United States (Taylor et al., 2012). About 900 people died from the disease in Europe between 1993 and 2003 (Kajfasz, 2009). Both the global incidence of disease and resulting mortality has declined in recent years. According to the WHO and UNICEF, deaths attributable to malaria in 2015 were reduced by 60% (WHO and UNICEF, 2015) from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies (Howitt et al., 2012). According to the most recent WHO estimates released in December 2015, there were 214 million cases of malaria in 2015 and 438,000 deaths (WHO, 2016). Presently, malaria is endemic in regions around the equator, in area of the Americas, many parts of Asia, and much of Africa. 85-90% of malaria fatalities occur in Sub-Saharan Africa. With the help of the Malaria Atlas Project it was shown that as of 2010, about 100 countries have endemic malaria (WHO, 2012; Feachem et al., 2010).
Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters in which mosquito larvae readily proliferate, providing them with the environment they need for continuous breeding (Jamieson et al., 2006). Malaria is more common in rural areas than in cities. For example, several cities in the Greater Mekong sub-region of Southeast Asia are essentially malaria-free, but the disease is prevalent in many rural regions, including along international borders and forest fringes (Cui et al., 2012). In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities (Machault et al., 2011).
1.3.7 PREVENTION AND CONTROL OF MALARIA
There is currently no vaccine for malaria although effort towards getting one is underway. Preventive measures against malaria therefore include medications, prevention of mosquito bites and elimination of mosquitoes. For malaria to be present in an environment there would be combination of factors such as Anopheles mosquito population density, human population density and high rate of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these factors is sufficiently checked, the parasite will eventually disappear from such environment, as observed in Europe, North America and parts of the Middle East. Re-establishment of the parasite is however possible if combination of the highlighted factors become favourable for the parasites reproduction. Sadly, the cost per person of eliminating Anopheles mosquitoes increases with decreasing population density, making it economically unfeasible in some environment (WHO, 1958).
In environments where malaria is common, children under five years old often have anaemia which is sometimes due to malaria. Giving children with anaemia in these environments preventive antimalarial medication slightly improves red blood cell levels but did not affect the risk of death or need for hospitalization (Athuman et al., 2015). Intermittent preventive therapy is another intervention that has been successfully used to control malaria in infants and pregnant women (Bardají et al., 2012), and in preschool children where transmission is seasonal (Meremikwu et al., 2012). Transmission can also be reduced if confirmed cases are quickly treated with artemisinin-based combination therapies (ACTs).
Mosquito control helps decrease malaria by reducing the levels of transmission by mosquitoes. The use of mosquito nets, insect repellents, or mosquito-control measures such as draining of standing water and spraying of insecticides can effectively reduce the risk of contracting malaria (Caraballo, 2014). Indoor residual spraying (IRS) and the use of Insecticide-treated mosquito net (ITNs) have been shown to be highly efficient in preventing malaria among children in areas where malaria is widespread (Lengeler, 2004; Pluess et al., 2010).
Indoor residual spraying refers to the spraying of insecticides on the walls inside a home. Usually, many mosquitoes rest on a nearby surface after feeding in order to digest blood meal. Thus, houses whose walls are coated with insecticides will kill resting mosquitoes before they can bite another person and transfer the malaria parasite (Enayati and Hemingway, 2010). Several insecticides have been in use in IRS operations, including DDT and the pyrethoids cyfluthrin and deltamethrin (WHO, 2006). However, insecticide resistance is one major problem with all forms of indoor residual spraying; indoor mosquitoes affected by irritation from indoor sprays tend to rest and live outdoors and are thus less likely to be affected (Pates and Curtis, 2005).
Mosquito nets help prevent people from direct contact with mosquitoes thereby reducing infection rates as well as the transmission of malaria parasites. Mosquito nets are usually treated with insecticides designed to kill mosquitoes before they make way pass the net. Although insecticide-treated mosquito nets (ITNs) are not perfect barriers, they are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared to conditions where nets are not used (Raghavendra et al., 2011).
In order to reduce mosquito bites, developing mosquito larvae can also be checked. This can be achieved by decreasing the availability of open water in which they develop or by adding inhibitory substances that are capable of impairing their development (Tusting et al., 2013).
Health education and community participation strategies aimed at promoting awareness of malaria and the importance of control measures have been successfully used to lessen the incidence of malaria in some parts of the developing world (Lalloo et al., 2006). Proper health education help inform people of the need to cover stagnant waters including those in tanks that serve as ideal breeding grounds for mosquito larvae.
Treatment of Malaria
The kind of antimalarial medication taken depends on the type and severity of the disease. Oral medications may be used to treat simple and uncomplicated malaria. Despite a need, no effective vaccine against malaria exists, although efforts to develop one are on-going (WHO, 2016). The recommended treatment for malaria is a combination of antimalarial medications that includes an artemisinin (Caraballo, 2014). The second medication may be mefloquine, lumefantrine, or sulfadoxine/pyrimethamine. Quinine along with doxycycline may be used if an artemisinin is not available (WHO, 2010). Occasional doses of the medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. It is recommended that in areas where the disease is common, malaria is confirmed if possible before treatment is started due to concerns of increasing drug resistance. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistance P. falciparum has spread to most malaria areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia (WHO, 2016).
1.4 YELLOW FEVER AND MALARIA CO-INFECTION
Myriad of researches have been conducted on yellow fever and malaria mono-infections, but co-infection studies are grossly scarce in scientific literatures probably due to under-reporting or indifference to the co-infection studies by researchers. However, sizeable research on co-infection of yellow fever and other Arboviruses abound.
A study conducted in South-eastern Senegal revealed a co-infection of yellow fever and malaria in only seven (7) out of 13,845 patients enrolled for the study (Sow et al., 2016). In Nigeria however, a study which enrolled 310 febrile, clinically suspected malaria/typhoid patients, did not record any yellow fever and malaria co-infection (Baba et al., 2013).
1.5 STATEMENT OF PROBLEM
Yellow fever and malaria constitute diseases of public health importance. On yearly basis, numerous deaths are recorded from malaria and effort to contain the disease is only with staggering results. Although there is a potent vaccine against yellow fever virus infection, but vaccination coverage seems grossly inadequate; most people interviewed in Ilorin, Kwara State, did not know their vaccination status either due to lack of awareness about the infection or because they never received a yellow fever vaccination certificate. A low level of immunity among the population may lead to an outbreak of yellow fever in an event of massive viral transmission from person to person via infected mosquitoes especially in view of the recent outbreaks in neighbouring African countries.
Yellow fever and malaria are transmitted by mosquitoes of different species. The widespread of mosquitoes as a result of practices that promote their breeding can contribute largely to yellow fever and malaria co-infection in Kwara State and beyond.
Yellow fever and malaria co-infection is highly probable among sick patients diagnosed with only malaria infection because both diseases have similar early symptoms. Most healthcare centres do not go the extra mile to determine the yellow fever serostatus of sick patients, which may lead to a missed or incomplete diagnosis.
Haemorrhagic fever, a late complication of yellow fever is very fatal and therefore early diagnosis is paramount. The World Health Organization’s (WHO) recent estimate of children at risk of yellow fever placed 23 million Nigerian children below the age of 14 at risk of yellow fever infection.
Yellow fever virus is endemic in West Africa and the risk of epidemics is very possible. Nigeria has recorded some outbreaks with the last one occurring in Kano State. Owing to intercity travels, evasion of immunization among some citizens, and the pervasiveness of the vector, the tendency of an outbreak cannot be ruled out in Kwara State.
To the best of our knowledge, this study is the first of its kind in this study area. It will provide baseline data on yellow fever and malaria co-infection and the risk of yellow fever outbreak in Kwara State.
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