Malaria – Prevalence of Asymptomatic Plasmodium Falciparium Parasitaemia Among Students
Malaria - Asymptomatic Plasmodium falciparium parasitaema, the presence of parasitaemia in the absence of fever or malaria-related symptoms, is also an extremely common and chronic condition among (semi) immune person in malaria areas with prevalence rates exceeding 50% in some area (Camargo et al, 1999). Malaria is caused by unicellular, protozoan parasites belonging to the genus Plasmodium. Over 100 distinct Plasmodium species have been identified that are capable of infecting mammals, birds and reptiles. ***************************************************************************** To Place Order For The Complete Project Material, Pay N4000 To: Bank Name: Guaranty Trust Bank (GTB) Account Name: Chibuzor Tochi Onyemenam Account Number: 0044056891 Or Bank Name: First Bank Plc Account Name: Chibuzor Tochi Onyemenam Account Number: 3066880122 For Inquiries Call – 07033378184 ******************************************************************************Until recently four Plasmodium species were considered infectious to humans; P. falciparum P. ovale. P. malaria and P.vivax. However, Plasmodium knowlesi the natural host of which are the long and the pig-tailed macaque monkeys, has now been suggested as the fifth human malaria parasite (White, 2008). In 2008, malaria caused nearly one million deaths; mostly among African children. Malaria is preventable and curable but can decrease gross domestic product by as much as 1.3% in countries with high disease rates (WHO, 2001). Human malaria is transmitted exclusively by female mosquitoes of the genus Anopheles. In sub-Saharan Africa, the predominant vectors belong to the Anopheles gambiae complex that includes some of the most efficient transmitters of human malaria. Of the five plasmodium species that can cause disease in human, most cases of severe malaria are attributable to P. falciparium. The other species cause rather mild infections with low parasite loads. Nonetheless, exceptions have been reported, in particular for P.vivax (Coxsingh et al., 2008). Malaria infection are asymptomatic during the liver stage and clinical symptoms do not develop until rupture of the infected erythrocytes. Early symptoms are often rather non-specific such as fever, headache, weakness, muscle/joints and abdominal pains, diarrhea and vomiting. The mechanisms associated with P falciparum pathogenesis are still largely unknown/. However the parasite’s ability to sequester in the deep vascular system along with the high multiplication rate are though to be key features. The outcome and severity of disease depends on age, genetic disposition, immune status and general health of the person. Besides infants and children, pregnant women represent another risk group for malaria disease. Despite repeated infections during childhood and adolescence, resulting in acquired malaria immunity; women become susceptible to disease during pregnancy. Pregnancy associated malaria is characterized by placental malaria sequestration of parasites in the placenta. The infection might be asymptomatic however, adverse consequence of maternal infection include anaemia and low birth weight of the infant (Shulman et al., 1996; Aribodor et al, 2009). Malaria symptoms can be categorized as uncomplicated i.e Symptoms as described above, without signs of severe malaria. Provided that efficient treatment is given, the case fatality rate is low for uncomplicated falciparium malaria (1/1000). However without prompt treatment the disease can progress to life-threatening severe malaria within hours. The clinical manifestations of severe malaria includes cerebral malaria (unrousable coma), severe anaemia (haemoglobin concentration (Hb) ≤5.0gldl), respiratory distress, acidosis and hypoglycemia (WHO, 2008).
Aims and Objectives
This study aimed at:
- Investigating the prevalence of asymptomatic Plasmodium falciparium parasitaemia among students of Ebonyi State University.
- To determine the age and sex distribution of P.falciparium among the student.
The life cycle of Plasmodium falciparum
The life cycle of the malaria parasite is very complex and comprises morphological and antigenically distinct stages both in the Anopheles mosquito and in the human host. When an infected female Anopheles mosquito Penetrates the human skin for a blood meal. Sporozoite are injected along with anticoagulant saliva. The sporozoite readily migrate through the bloodstream to the liver where they invade the hepatocytes. Within the liver, the sporozoite can either undergo initial growth followed by asexual replication (liver schizogony) into a mature liver schizont containing up to 30,000 merozoite, or as for P. vivax and P. ovale, the sporozoite can enter a dormant stage (hypnozoite) that can cause clinical relapses, weeks, months or years after the primary infection. The liver schizogony takes 5-16 days depending on species (5-7 days for P falciparum) and is asymptomatic. As the mature liver schizonts rupture, merozoites are released. Most are ingested by live macrophage i.e Kupffer cells, however, the merozoite that do escape rapidly invade the erythrocytes (red blood cells). Once inside the erythrocytes, the merozoite re-differentiate to an immature trophozoite (ring form), then to a mature trophozoite, followed by asexual replication to a mature schizont containing 10 to 20 merozoites. The merozoites are released upon erythrocyte rupture and rapidly infect new erythrocytes. The duration of the erythrocytic cycle differs between species; 24 hours for P. Knowles, 48 hours for P. falciparum P. vivax and P. ovale; while 72 hours for P. malariae. A characteristic of P. falciparum is sequestration i.e. binding of infected erythrocytes to endothelium in the deep vascular system during the second half of the erythrocytic cycle. Therefore only ring forms and early trophozoites are detectable in peripheral blood. As the erythrocytes rupture, parasite debris are released. This induces host responses e.g fever and cytokines and the symptomatic phase of the infection starts. The clinical manifestations vary from asymptomatic infections to severe-life threatening conditions. Some merozoites do not undergo the asexual replication; instead they develop into male and female gametocytes. Erythrocytes containing gametocytes do not rupture; instead they circulate waiting to be extracted from the human host by blood feeding mosquitoes. Within the mosquito’s gut the gametocytes, triggered by the presence of specific mosquito factors and the drop in temperature, form male and female gametes (Anne, 2012).
Transmission of Malaria
Malaria is transmitted exclusively through the bites of female Anopheles mosquitoes. The intensity of transmission, the factors are related to the parasite vector, the human host and the environment. Some of the vector species bite at night. They breed in shallow collections of freshwater like puddles, rice fields and hoof prints. Transmission also depends on the climatic conditions that may affect abundance and survival of mosquitoes, such as rainfall pattern, temperature and humidity. In many places transmission is seasonal, with the peak during and just after rainy season. Malaria epidemics can occur when climate and other conditions suddenly favour transmission in areas where people with little or low immunity to malaria live. They can also occur when people with low immunity move into area with intense malaria transmission. (WHO, 2001).
Symptoms of Malaria
Malaria is an acute febrile illness. Symptoms appear several days or more casually 10-15 days, after the infective mosquito bite. The first symptoms fever, headache, chills and vomiting may be mild and difficult to recognize as malaria. If not treated within 24 hours P. falciparum can progress to severe illness leading to death. Children in endemic areas with severe disease frequently develop one or more syndromic presentations; severe anemia, respiratory distress in relation to metabolic acidosis, or cerebral malaria. In adult, multi-organ involvement is also frequent. For both P. vivax and P. ovale, clinical relapses may occur months after the first infection, even when the patient has left the malarious area. The new episodes arise from dormant liver forms (absent in P. falciparum and P. malariae) and special treatment targeted at the liver stages is mandatory for a complete cure (WHO, 2001).
The infection commences with the intravenous inoculation of the sporozoites by the infected mosquito. These invade hepatocytes and undergo multiplication for about a week before thousands of merozoites rupture these cells to invade erythrocytes and commence erythrocytic cycle. Probably only tens to hundreds of hepatocytes are targeted by sporozoites at this stage. That is not responsible for any disease. The pathologic process occurs only during trhe erythrocytic cycle. During this stage there is a huge, periodic amplification of the size of parasite populations that enhance probability of differentiation of gametocytes, the stage infectious to mosquitoes. A peculiarity of P. falciparum is its ability to adhere to venular endothelium (cytoadherence) of erythrocytes infected with maturing parasites. The parasitized erythrocytes remain attached until merozoites are formed that are released to invade other erythrocytes. Thus the predominant form seen in peripheral circulation is the ring infected erythrocytes, the young form of the parasite. Two aspects of invasion have a profound effect on pathogenesis: invasion of all erythrocytes, or only a sub-population (for example, reticulocytes), and the redundancy in invasion pathways P. vivax invades only reticulocytes, and P. faciparum invades erythrocytes of all ages (Miller, 1994).
Malaria is primarily a disease of the tropics and subtropics and is widespread in the hot humid regions of Africa, Asia and Central America. The disease was also common in the temperate areas including the USA, Europe and northern Eurasia and Asia, but has been eradicated. Most infections are common in endemic areas. P. vivax and P. falciparum are the most commonly encountered species with P vivax being the most widely spread geographically (Mueller et al., 2007). Malaria is commonly associated with poverty, but is also a cause of poverty and is more common in rural areas than in cities (van et al., 2005).
By contrast in Africa malaria is present in both rural and urban areas through the risk is lower in larger cities (Keiser et al., 2004). Malaria has been found to cause cognitive impairments been especially in children.
It causes widespread anemia during the period of brain development and also direct brain damage results from cerebral malaria to which children are more vunerable (Boivin, 2002).
Malaria Control in Africa.
The malaria parasite has persisted through decades of global eradication efforts, development of efficient drugs and over 30years of vaccine research. In 1955 the Global malaria Eradication Program was launched by WHO. Although successful in some countries e.g USA and parts of Europe, transmission could not be interrupted in many high endemic countries and the program was abandoned in 1972. Malaria resurged in many areas alongside the emergence of parasite resistance to chloroquine and sulphadoxine- pyrimethamine (Sp) and insect resistance to DDT. Subsequently the efforts were reoriented from eradication to malaria control. WHO defines malaria control as; reducing the burden of disease to a level at which it is no longer a public health problem (WHO, 2008). The main tools for malaria control are; effective antimalarial drugs, including artemisinin-based combination therapy (ACT) insecticides treated nets (ITN), indoor residual spraying (IRS) and intermittent preventive treatment (IPT).
Diagnosis and treatment of malaria
Malaria is a curable disease provided that prompt diagnosis and effective treatment is available. Fever or history of fever within the past 24h and/or pronounced anemia is often the basis for a clinical diagnosis in remote areas. However, due to overlapping clinical presentation of malaria with other diseases, e.g influenza and pneumonia (O’ Dempsey et al., 1993); English et al., 1996), a confirmed malaria diagnosis is desirable to reduce unnecessary treatment with anti-malarial. Light microscopy of stained thick and thin blood smears remains the conventional method for malaria diagnosis. The technique is relatively cheap and is fairly sensitive with detection down to 50-100 parasites/ml blood under filed conditions (Wongsrichanala et al., 2007). Moreover, slide examination allows for species identification and quantification of the parasite load. However, the method requires skilled personnel with sufficient time for reading each slide, functional microscopes and electricity. Rapid diagnostic test (RDT) for malaria is a more simple method that does not require skilled personnel for interpretation or electricity. The test detects malaria antigens e.g histidine-rich protein 2 (HRP-2) for P. falciparum in small blood volumes (5-15ml) in 5-20min. Available RDTs can defect P. falciparum alone or can distinguish between P. falciparum and other human malaria species, although with varying sensitivities (Wongsrichanala et al., 2007). They can however not quantify the parasite load and P. falciparum, might be hard to detect at low densities. Although more expensive than microscopy, RDTs might be valuable in the diagnosis of febrile illnesses in remote areas where microscopy is not available. The recommended first line drug for uncomplicated malaria is a combination of antimalarials i.e artemisinin-based combination therapy (ACT) given for a minimum of three days (WHO, 2010). Severe malaria is treated with intravenous quinine or with certain artemisinin derivatives e.g artemether and artesunate.
Genetic Diversity of P. falciparum
The P. Falciparum genome is 23 megabases long, consist of 14 chromosomes and encodes for approximately 5300 genes (Gardner et al, 2007). A large number of genes exhibit extensive polymorphism. In particular, the loci encoding proteins displayed on the surface of the sporozoite (circumsporozite protein (CSP) and the merozoite surface protein (e.g MSP1, MSP2,) and thus accessible to the host immune components, are highly polymorphic (Escalante et al., 1998). In this genes conserved and semi-conserved regions are interspersed with variable regions containing repetitive units that differ in sequence, length and copy number. The diversity is preserved through a high number of non-synonymous nucleotide substitutions (Escalante et al., 1998) as well as duplications and /or deletions of restive units (Felger et al., 1997; Rich et al., 2000). Sequential expression of alternate forms of an antigen is an additional mechanism for genetic variation in P falicparum erythrocyte membrane protein 1 (PFEMP1). The var genes form a multi-gene family, comprising approximately 60 genes disposed over several chromosomes (Gardner et al., 2002). During early stages of the parasite’s intra-erythrocytic development, multiple var genes may be transcribed, however during the late stages, one transcript dominates and only a single variant of PFEMP1 is expressed on the surface of the infected erythrocyte (Chen et al., 1998). The switching in var gene expression result in the transcription of a new dormant var gene and the expression of a different PFEMP1 variant. PFEMP1 is known to mediate cytoadhesion of infected RBCS to endothelial cells (Smith et al., 1995) and binding to uninfected erythrocytes i.e resetting (Chen et al., 1998), mechanisms believed to be associated with immune evasion and pathogenesis. Other characterized P. falciparum proteins that exhibits great diversity are the PIFINS and STEVORS which are encoded by one of the around 200 rif genes (Kyes et al., 1999) an d 30-40 stevor genes (Blythe et al., 2004) respectively. Moreover, genetic polymorphisms in s number of genes (e.g Pfmdrl, Pfcrt and dhfr) has been associated with parasite resistance to antimalarials (e.g chloroquine, amodiaquine and Sulphadoxine-pyrimethamine) and treatment failure (Picot et al., 2009).
Immunity to Malaria
Immunity to malaria develops after repeated infection by P. falciparum parasites. The acquisition of immunity is largely dependent on the level of malaria transmission. In an age dependent manner where children under few years of age are at Highest risk of disease and clinical manifestations among adults are rare: while in areas of low/ unstable transmission, immunity is not acquired and therefore all age groups are at risk (Anne, 2010).
The development of a malaria vaccine has been difficult. Nonetheless, great investments and research developments have resulted in a large number of potential vaccine candidates that are now in preclinical development or in clinical trials (Anne, 2010). The primary objective of a pre-erythrocytic vaccine is to prevent blood stage infection and thus protect against any clinical malaria. Trials are ongoing evaluation synthetic sub-unit vaccines based on the Thrombospondin-related adhesive protein (TRAP) and the circumsporozoite proteins of the sporozite (Targett and Greenwood 2008), with the latter being the major constituent t of the RTS, S vaccine. Immunization with RTS, S resulted in almost a 50% protection against clinical malaria and 30% protection against clinical malaria in children (Alonso et al., 2005). Recent studies have confirmed the efficacy of RTS, S in infant and children (Abdulla et al., 2008; bejon et al., 2008). A blood-stage vaccine will not prevent infection but might protect against clinical symptoms. The extensive polymorphism in many of the P faciparum blood-stage proteins has complicated the task of developing a blood stage vaccine. There are however certain promising vaccine candidates including MSP3 (Druihe et al., 2005) and MSP/MSP2 and RESA (Genton et al 2002) and more recently the recombinant AMA-1 (Spring et al., 2009). Immunity induced by polymorphic vaccine antigens is largely allele specific and the allelic types of the antigens included in a vaccine are likely to affect the outcome. In a trial of the vaccine combination B (Genton et al., 2002) comprising the 3D7 allele of MSP2 there was an increased incidence of malaria morbidity attributable to the FC27 allele of MSP2 there was an increased incidence of malaria morbidity attributable to the FC27 allele of MSP2 among vaccine recipients suggesting that vaccination induced selection of parasite expressing the alternative allele. Thus, vaccine formulations should include components covering all important allelic types and for conserved antigens (Anne, 2010).
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This article was extracted from a Project Research Work/Material Topic “PREVALENCE OF ASYMPTOMATIC PLASMODIUM FALCIPARIUM PARASITAEMIA AMONG STUDENTS OF EBONYI STATE UNIVERSITY.”
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