EPIDEMIOLOGICAL PATTERN OF PRESENTATION OF PARAGONIMUS INFECTION IN THE HUMAN HOST IN SOUTH EAST NIGERIA AND THEIR CORRELATIVE SONOGRAPHIC FINDINGS IN SOME ORGANS

CHAPTER ONE

INTRODUCTION

BACKGROUND OF THE STUDY: Paragonimiasis also known as lung fluke disease is a parasitic disease in humans and other mammals caused by infection with paragonimus species (Nkouama et al, 2009; Procop 2009; Sohn et al, 2009). Paragonimus species are widely distributed globally and have a broad diversity of domestic and wild animal hosts (Diaz, 2013). There are over forty species in the paragonimus genus. Over ten of these infect humans (Nguyen, 2004). It was first discovered from two Bengal tigers that died in zoos in Europe in 1878 (Muller,1996; Procop,2009). Paragonimus species are highly evolved parasites with a complex life cycle that involves at least three different hosts ie snails, crustaceans and mammals. Manson proposed the snail as an intermediate host and various Japanese workers detailed the whole life cycle in the snail between 1916 and 1922(Groove, 1990). The first case described in humans was at autopsy in Taiwan in 1897, when adult flukes were found in the lung (Liu et al, 2008). Eggs in the sputum were discovered independently by Manson and Erwin Von Baelz in 1880 (Muller, 1996; Manson, 1881). The parasite is easily spread. Human infection is acquired by the consumption of raw or improperly cooked crustaceans including crayfishes and crabs. It often occurs by ingestion of infectious metacercariae in freshwater crab or crayfish (Sugiyama et al, 2009). There are cases where patients diagnosed with paragonimiasis reported that they had never eaten freshwater crabs or crayfish. It is also possible that they ate food contaminated with metacercariae from the fingers or cooking utensils of people who recently handled these crustaceans (Nakamura et al, 2002). Consumption of animals which feed on crustaceans can also transmit the parasite for cases have been cited in Japan where raw boar meat was the source of human infection (Markell and Voges, 2006). Pickling and salting which are food preparation techniques do not eliminate the causative agent. Development of eggs first occur in water after being expelled by coughing or being passed in human faeces. Paragonimus ova passed in the sputum or faeces hatch into miracidiae which then infect certain snails in which they develop into radiae and cercariae. The primary source of infection is the lung but other organs may also be involved. Paragonimus infection has a gradual onset and is characterised by low grade fever, productive cough and occasionally dry cough, night sweats, excruciating chest pain, diarrhoea, and blood stained, rust brown sputum (Cheesbrough, 2005). Infection with paragonimus can either be acute or chronic. The acute phase of the infection is said to be the stage of parasite invasion and migration. This phase lasts for several weeks and the symptoms include; abdominal pain, diarrhoea and urticaria. These initial symptoms are then followed a few days later by fever, dyspnoea, chest pain, malaise, sweats, hepatosplenomegaly, and eosinophilia. The chronic phase manifestations may be pulmonary or extra-pulmonary. Chronic pulmonary manifestations consist of dry cough followed by a cough productive of persistence and rusty or golden sputum. This phase is also characterised by haemoptysis, chest pain and radiographic abnormalities that can persist even several years after treatment (Moyou-Somo and Tagni, 2003). Pulmonary symptoms begin approximately 6 months after infection and are often mistaken for symptoms of tuberculosis. The American college of chest physicians has established clinical practice guidelines for TB and other infections (Rosen, 2006). Extra-pulmonary paragonimiasis can be divided into cerebral, abdominal, subcutaneous, and miscellaneous forms of the disease. It can occur either from the migration of young or mature flukes to various organs or from eggs that enter the circulation and are carried to any of the following sites; liver, spleen, kidney, brain, intestinal wall, peritoneum, mesenteric lymph nodes, muscle, testis/ovary, subcutaneous tissues, and spinal cord. Cerebral paragonimiasis is the most common extra-pulmonary site of infection and is responsible for 50% of all extra-pulmonary disease (Liu et al, 2008). Moreover it is seen in as many as 25% of patients requiring hospitalization. About 20% of patients with paragonimiasis are asymptomatic (Uchiyama et al, 1999).

During the journey from the intestine to the lungs, where juvenile worms mature, the juvenile worms often cause damage to the liver capsule and parenchyma (Yakogawa, 1965; Hu et al, 1982; Li et al, 2012). The parasites excyst in the small intestine penetrate the intestinal wall and enter the peritoneal cavity. They then proceed to the diaphragm, pleural cavity and the lung (Noble and Noble, 1982). The juvenile worms enter into the abdominal muscles and stay there for 5 -7days and come back into the abdominal cavity. They finally reach the lung where they become mature adult worms. Sometimes infection usually resolves without treatment and persons with light infections may have no symptoms. Lesions within the abdomen are probably common but are rarely recognised because they do not show symptoms and may not be shown without computed tomography (CT) or ultrasound. No age is immune to this infection but the disease is particularly prevalent in the 10 to 14 year age group (Nwokolo, 1972a).

Paragonimus species are extremely successful parasites and are widely geographically distributed. They are found in tropical, subtropical and temperate climates (Procop, 2009). Infection with paragonimus is more common in Southeast Asia because of their life styles. Raw seafood is a popular deilicay in these countries. In Taiwan for instance, crab hunters string raw crabs together and bring them for sale in the markets thereby making it more accessible to those who consume them. In Africa paragonimiasis is geographically clustered around the intertropical zone (Aka et al, 2008) as 80% of the ten countries in the continent where paragonimiasis has been reported are in this zone. Two species of paragonimus are described on this continent (Voelker and Vogel, 1965) and other two species were suspected (Cabaret et al, 1999). Paragonimus africanus and paragonimus uterobilateralis are known as the main pathogens of human paragonimiasis in Africa.

 

In Nigeria the first case of paragonimiasis was diagnosed in 1939 and since then several cases have been detected. There was an outbreak of paragonimiasis in Southeastern Nigeria during the Biafran war that took place from 1967 to 1970. During this period there was a lot of food scarcity and because of this many people changed their eating habit, particularly by consuming crabs. Most patients were children and originated from the region of Okigwe. Paragonimus utrobilateralis was recognized as the responsible species (Nwokolo, 1964; Nwokolo, 1972; Nwokolo, 1973; Voelker, 1975). Since 1974, several papers demonstrated that the neighbouring districts of Okigwe and Umuahia in the eastern part of Nigeria were endemic zones for paragonimiasis. According to (Sachs and Voelker, 1975), the two factors favouring parasitosis extension were local habits to eat crustaceans and lack of hygiene of these populations. Crabs are still eaten in many communities where they are found in large numbers and mainly by children of school age. These children catch the crabs either in burrows or the streams without the knowledge of their parents or guardians, prepare them and eat them. Preparation is usually by cooking or roasting and may not be properly done. Crab collectors string raw crabs together and bring them to markets and other strategic locations for sale. Eating of crabs in these communities is seen as a source of protein. Some adults also eat these crabs for one reason or the other. There is an unestablished claim that crabs are used to cure cough in the communities where they are consumed. This they do by boiling the crabs and the water remaining after cooking is then given to the patient in a quantity as may be determined by the care giver. Pregnant women are also encouraged to eat crabs in these communities because according to them this helps to keep the foetus vibrant and also to develop strong bones. They are also local delicacies in these communities. Many species of crabs constitute an important part of the local food chain in sub- saharan Africa (Bell-Osuji et al, 2006).

There is a need for accurate and sensitive diagnosis of paragonimiasis both at individual and community levels. A diagnostic procedure can be used for a number of applications, ranging from clinical diagnosis of an individual case to the evaluation of control measures. The most reliable means of diagnosis of pulmonary paragonimiasis is finding of parasite eggs in sputum, faeces, pleural effusion and bronchoscopic washing or biopsy specimens (Toscano et al, 1995). However sputum examination for detection of eggs is less sensitive method for diagnosis of paragonimiasis and up to seven sputum examinations are recommended in suspected patients (Toscano et al, 1995). The parasite eggs are not detected during the dormant period of infection or in extra-pulmonary paragonimiasis and the eggs are not present until 2 to 3 months after infection. Occasionally however, eggs are also seen in effusion fluid or biopsy material. Several efforts have been made in the past to develop immune-diagnostic methods for detection of paragonimiasis. One of the earliest tests used for diagnosis is intradermal test (ID test) (Blair et al, 1999). However, its major disadvantage is the cross reactions with other trematodes (Blair et al, 1999) and allergic reactions caused in some patients after their skin test (Chen, 1985). Subsequently enzyme linked immmunosorbent assay (ELISA) for detection of antibodies against lung flukes became popular because of suitability for mass screening (Pariyanonda et al, 1990; Maleewong   et al, 1990). Many workers have used ELISA for detection of antibodies against host sera. However, most of these workers used crude somatic antigens with the result cross- reactivity with sera of persons suffering from schistosomiasis clnorchiasis and other trematodes were reported. Another important limitation of using somatic antigen is cross reactions with sera of persons having schistome cercarial dermatitis (Narian et al, 2005). Attempts have been made to reduce cross-reactions by either using partially purified antigens or subjecting test sera to adsorption with heterogenous antigens prior to ELISA (Choi et al, 1992). Superiority of excretory/secretory antigens for increasing the specificity of the ELISA has been demonstrated by several workers (Maleewong et al, 1990). Antibody detection is useful in light infections and in the diagnosis of extra-pulmonary paragonimiasis. In the United States, detection of antibodies to paragonimus westermani has helped physicians differentiate paragonimiasis from tuberculosis in Indochinese immigrants. Radiological methods can be used to x-ray the chest and look for damages caused by the parasite. This method is easily misdiagnosed because pulmonary infections look like tuberculosis, pneumonia, or spirochaetosis. Radiological images show nodular infiltration, sometimes pleural fluid and/or cavities. Olympic ring pictures seen on chest radiographs are pathognomic of paragonimiasis (Aka et al, 2008). In order of frequency the common shadows seen on radiographs are either well defined patches of cavitation, ill defined cotton wool lesions, streaky shadows or bubble cavities (Ogakwu and Nwokolo 1973). The midzones are most commonly affected but any part of the lung may be marked. The shadows are generally of low density and may be difficult to differentiate from the early lesions of pulmonary tuberculosis. Imaging studies may increase the confidence of clinical diagnosis and demonstrate the extent of involvement.

There is resurgence of tuberculosis in human immune virus/acquired immunedeficiencysyndrome (HIV/AIDS) patients and also an increase in the incidence of neglected tropical diseases including paragonimiasis. This further complicates the diagnosis of paragonimiasis. There is therefore the need to develop other imaging technique with high specificity for paragonimiasis in order to improve management.

Ultrasonography is increasingly being used as the investigation of first choice in soft tissue imaging, in obstetrics and gynaecology and in the evaluation of upper abdominal abnormalities. The mobility of the equipment and ease of use together with the fact that it is non-invasive and causes no harm to the patients make ultrasound the ideal technique for investigating possible soft tissue changes associated with paragonimiasis. It can be used as a valuable tool for localisation of abnormalities and detecting different types of disease conditions. Ultrasonography is relatively safe and serves as a means of imaging internal anatomy. It does not involve the use of ionizing radiation and it is relatively cheap and affordable. Changes demonstrated in ultrasonography include change in organ size, shape, echogenicity and echopattern. This limited number of parameters may be affected by a wide range of disease processes and thus it is not surprising that many sonographic features are very non specific. The ultrasonographer must be able to demonstrate as many sonographic abnormalities as possible and also interpret these abnormalities in the light of any clinical information given and the results of other investigation.

​​​​​​​STATEMENT OF PROBLEM

1. Public health significance of paragonimiasis is not quite recognized because this disease is frequently misdiagnosed as pulmonary tuberculosis. In countries where both diseases co exist, there is usually a public health problem in identifying the particular disease due to similarities in their clinical and radiological presentations thereby increasing the chances of diagnostic errors. Some cases of pulmonary paragonimiasis have been diagnosed as smear negative tuberculosis and were subsequently treated with anti-tuberculosis drugs. The implication of this blind therapy is considerable, because the patient gets anti-tuberculosis treatment for a non-tubercular condition. Normally communities in remote areas perceive treatment success or failure with the disappearance of symptoms (haemoptysis and chronic cough) in this situation (Mahajan, 2005).
2. In spite of some reports of this parasitosis in Africa, the total number of patients affected by this disease cannot be accurately quantified because of the following reasons (Aka et al, 2008);
   • Tuberculosis offends paragonimiasis in their flagrant clinico-radiological similarities thus often causing their differentiation only after a long series of investigations.
   • Paragonimiasis is not listed in the official registers of illness kept by different African ministers of public health yet it poses great threat to human health in areas endemic with the parasite.
   • Owing to the lack of awareness of local health professionals to paragonimiasis, this disease is little evoked in the face of chronic cough simulating pulmonary tuberculosis so that probably several cases of paragonimiasis are long undetectable.
3. Paragonimiasis is a neglected tropical disease and with the resurgence of tuberculosis in HIV/AIDS patients, the diagnosis is further complicated.
4. The correct diagnosis of smear negative tuberculosis in areas where paragonimiasis and tuberculosis coexist cannot be sufficiently made using x-ray and clinical history alone.
5. The need to assess the potentials of soft tissue imaging and isolation of feature specific for paragonimus for ease of identification.

AIMS AND OBJECTIVES

General Objective

To assess the sonographic features of paragonimus infestation of some abdominal organs in confirmed infected subjects.

Specific Objectives

1. To determine the load of paragonimus in crabs from Lokpanta, Amagunze and Oduma. 2 . To determine the load of paragonimus in the infected subjects.
2. To characterize the echotexture of the liver, spleen and kidneys in persons infected with paragonimiasis.
3. To assess the size of the liver, spleen and kidneys in infected individuals.
4. To compare the echotexture and size of the organs in infected persons and normal (control) subjects.
5. To correlate sonographic changes with the degree of infestation.

SIGNIFICANCE OF STUDY

1. This will help in making early and appropriate diagnosis for this disease condition.
2. It will help to eliminate the confusion that occurs between paragonimiasis and tuberculosis because of the similarities that exist in their clinical features.
3. The number of cases that will advance to the pulmonary stage will be reduced or eliminated.

SCOPE OF STUDY

This study was carried out in Lokpanta, Oduma, Amagunze and University of Nigeria Teaching Hospital Enugu from January 2010 to September 2014. It involved children and adults.

​​​​​​​OPERATIONAL DEFINITION OF TERMS

1. EPIDEMIOLOGY: This means the scientific study of the distribution of diseases.
2. PARAGONIMIASIS: Paragonimiasis also known as lung fluke is a parasitic disease in humans and other mammals caused by the infection with paragonimus species (Nkouama, 2009).
3. PARASITE: An organism that leaves on or in an organism of another specie known as the host from the body of which it obtains nutrient. Parasites can cause disease in humans. Some parasitic diseases are easily treated and some are not. The burden of these diseases often rests in communities in the tropics and subtropics, but parasitic infections also affect people in developed countries.
4. ORGAN: A part of the body composed of more than one tissue that forms a structural unit responsible for a particular function(s). Examples are heart, lungs, liver, kidneys etc.
5. INFESTATION: This means the presence of animal parasites either on the skin or inside the body.
6. INFECTION: Infection is the invasion of the body by harmful organisms (pathogens), such as bacteria, fungi, protozoa, ricketsiae, or viruses. The infecting organism may be transmitted by a patient or carrier in air borne droplets expelled during coughing and sneezing or by direct contact such as kissing or sexual intercourse, by animal or insect vectors, by ingestion of contaminated food or drink and organisms from animal intermediate hosts.
7. ZOONOSIS: An infectious disease of animals that can be transmitted to man.
8. ENDEMIC: Occurring frequently in a particular region or population.
9. HEPATOMEGALY: Enlargement of the liver to such an extent that it can be felt below the rib margin. This may be due to congestion (as in heart failure), inflammation, infiltration and tumour.
10. SPLENOMEGALY: Enlargement of the spleen. It most commonly occurs in malaria, schistosomiasis and other disorders caused by parasites; in some infections, in blood disorders including some forms of anaemia or lack of platelets.
11. CYST: An abnormal sac or closed cavity with epithelium and filled with liquid or semisolid matter. There are many varieties of cyst occurring in different parts of the body.
12. PREVALENCE: In epidemiology it is the proportion of a population found to have a condition (typically of a disease or a risk factor such as smoking). It is arrived at by comparing the number of people found to have the condition with the total number of people studied, and it is usually as a fraction or percentage or as the number of cases per 10,000 or 100,000 people.
13. ULTRASONOSGRAPHY: The visualisation of deep structures of the body by recording the reflections of the echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies from 1.6 to 10 MHZ.
14. FREEZE FRAME: Control that stops a moving real time image for photography or prolonged evaluation (WHO, 1995).
15. TIME GAIN COMPENSATION (TGC): This control compensates for the loss (attenuation) of the sound beam as it passes through tissue.
16. PLEURAL EFFUSION: Is the excess fluid that accumulates in the pleural cavity, the fluid space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by mass effect, limiting the expansion of the lungs during ventilation. Various kinds of pleural effusion depending on what caused its entry into the pleural space are, hydrothorax (serous fluid), haemothorax (blood), chylothorax (chyle) or pyothorax (pus). Pneumothorax is the accumulation of air in the pleural space.