Tuesday 19 January 2021

Food Science Articles in OAJBGSR

 Food Science Articles in OAJBGSR

A Critical Review on Presence of Polyphenols in Commercial Varieties of Apple Peel, their Extraction and Health Benefits by Muhammad Modassar Ali Nawaz Ranjha in Open Access Journal of Biogeneric Science and Research_OAJBGSR

Abstract

Apple peel is considered as a waste product in many fruit industries but it is a significant source of various phytochemicals, majorly polyphenols. Polyphenolic compounds are included among the phytochemicals and possess great antioxidant potential. These are the valuable natural compounds possessing a range of biological and chemical properties. Apple peel contains anti-oxidative, anti-proliferative, anti-carcinogenic properties and also have anti-inflammatory properties. Polyphenols are also of great value as they possess free radical scavenging activities. Major phenolics available in apple peel are epicatechin, oligomer, trimer, glycosides quercetin, chlorogenic acid, phloridzin3-hydroxy and procyanidin etc. Polyphenolics are extracted by using different techniques and methods like ultrasound assisted extraction and microwave extraction etc. They also perform a versatile role in disease management like cancer, cardiovascular diseases, diabetes, inflammatory bowel disease, arthritis and many others.

Keywords: Apple peel, Phenolic compounds, Extraction techniques, Phytochemistry, Antioxidant activity, health benefits 

Introduction

From centuries, products from natural sources are being used [1,2]. Apple scientifically called as Malus domestica is consumed worldwide. Apple is consumed and easily available around the world and this fruit contains many phenolic compounds [3]. According to Food and Agriculture Organization report in 2011, world apple production was calculated to be approximately 75 million tons. It is of great importance as it possess high level polyphenols and various other phytochemicals.

 

The polyphenolic compounds have five major groups which are detected in numerous varieties of apple. These include dihydrochalcones, hydroxycinnamic acids, anthocyanins, flavan-3-ols/ procyanidins, and flavanols include catechin, procyanidins or epicatechin [3]. Phytochemicals and flavonoids are also included in these. Flavonoids are of great importance because of their antioxidants properties as they possess high redox potential [4].

 

Polyphenols present in apple peel are found to be beneficial for human health and is helpful in disease management as it possesses free radical scavenging activities because of their antioxidant property [5]. In many apple varieties, the concentration of polyphenolic compounds along with their antioxidant capacity show variations due to various reasons like environmental conditions, soil content, harvesting time period, and different storage conditions etc. Their concentration in apple does not remain constant [6]. 

 

The nature of phytochemicals, its distribution varies between apple peel and its flesh. Apple flesh have catechins, Phloretin glycosides, caffeic acid, procyanidins, chlorogenic acid and phloridzin, however, in apple peel all these phytochemicals are found and additionally it holds flavonoids like quercetin glycosides and also cyanidin glycosides [7].  Their peels are treated as waste product in canned apple industries and apple sauce manufacturing industries due to their hidden potential and health benefits, their utilization should be enhanced [8].

 

 

In the United States, major cause of death is due to cardiovascular and cancer related diseases. An apple contains many advantages and is considered good for treating cardiovascular and other diseases [9]. Due to variety of antioxidant properties they reduce the risks of cardiovascular diseases and degeneration processes as these are related to oxidative stress, particularly due to free radicals and specific oxygen species which are reactive in nature [5]. However, apples not only helps to lower the risk of coronary heart disease, but it also lower the risks of diabetes [10].

Extraction of Phenolic Compounds

There are many analytical procedures which has been developed so that we can study the polyphenolic compounds and their specific behavior so that we can know their importance for undertaking the analysis. The design of every specific analytical procedure depends upon the usage and specific analysis [11,12] (Table 1).

Ultrasonic Assisted Extraction (UAE) is novel extraction technology when compared with other conventional methods as it is easy to handle and require moderate concentration of solvent and hence it is economical [13,14]. Major advantage of this technique is that it requires less processing time, produces high yields and it is also environmentally friendly [15]. Microwave assisted extraction (MAE) technique is also widely used as it gives rapid results, is becoming famous and frequently used by analytical chemist for extraction purpose. It is becoming alternative technique as compare to other conventional techniques. It has many benefits as it require less solvent and, in this extraction,, time is also minimum and we can do processing of large number of samples at the same time [16].

 

Apple peel mainly possesses diverse biological properties and is acceptable as a functional ingredient and is a byproduct obtained after apple processing [8]. Tsao et al., 2003 and Raudone et al., [17] reported that polyphenolic compounds in apple peel are hydroxycinnamates, flavanols, anthocyanins and dihydrochalcones these contributes in antihypertensive activity and in anti-inflammatory activities, , it  also possess antioxidant activity [18,19]. These compounds used in fish oil to prevent the oxidation [20].

 

Table 1: Extraction of polyphenols through various techniques.

Properties of Polyphenolic Compounds

       Phytochemicals in Apple

It is observed that cardiovascular problems and risk of cancer diseases are reduced by high intake of fruits and vegetables. Apples are more notable as they contain phytochemical which have their role in reducing oxidation and decreases the chronic diseases. The phytochemical present in apple are phloridzin, quercetin, chlorogenic acid and catechin. The apples are a good source of antioxidants because they contain phytochemicals [21]. Flavonoids are favorably in large concentration found in apple and the concentration of other phytochemical is also present and their concentration depends on several factors like processing of apple cultivation and on harvesting conditions. Procyanidins, epicatechin, catechin, chlorogenic acid and conjugates of quercetin are mostly present in apple peel. Amount of quercetin is also greater in peel than in flesh. So it means that antioxidant property of apple will be greater in peel and lower in flesh [22].

 

 

Apple peel is helpful in the inhibition of colon cancer as compared to apple flesh [23]. Epicatechin, catechin and procyanidins have function in reducing LDL and they also have a good antioxidants activity [24]. Similarly, chlorogenic acid contains a strong alkyl peroxyl radical scavenging activity. As alkyl peroxyl radical can promotes tumor and carcinogenesis so chlorogenic acid has its role in the protection against cancer [25]. A strong antioxidant ‘quercetin’ is helpful against heart diseases and cancer. It also has its role in the inhibition of tyrosine kinase and reduce the mutant expression in breast cancer cell. It also reduces the heat shock proteins [26]. Every polyphenolic compound has their own specific health benefit described under (Table 2) [27-39].

 

 

Table 2: Phytochemistry of polyphenolic compounds available in apple peel.

Utilization of Apple Peel

1.1. Antihypertensive Properties Of Apple Peel         

Apples have sufficient supply of flavonoids containing practicable benefits to health. In North America about 22% of dietary phenolics like flavonoids and phenolic acid are obtained from eating apples [40]. Hypertension is a major problem regarding to health and is increasing day by day in different parts of world. In regard of controlling high blood pressure Angiotensin converting enzyme (ACE) is considered as a major therapeutic target. Latest work shows that apple peel extract rich in flavonoids and its constituents are competitive inhibitors of ACE [41] (Table 3).

 

Compounds found in apple peel contain anthocyanins and quercetin are useful and advantageous for reducing blood pressure level and have antihypertensive effects [42]. Quercetin component and different kind of flavonoids found in high concentration of an apple peel, lower blood pressure due to its effects like antioxidants, angiotensin-converting enzyme inhibition and improved endothelium function [43].  Pro-anthocyanidins is another component in apple peel that has been studied for its antihypertensive effect. It is beneficial in prevention of oxidation of LDL cholesterol, blood pressure reduction and fat metabolism improvement [44]. Apple now has been identified in several mechanism like lowering of blood cholesterol particularly LDL, weight loss, antioxidant action and prevention of atherosclerosis [41].

 

It is reported that apple have ability to lower the cholesterol predominately because of presence of phytochemicals like epicatechin, β-carotene, proanthocyanidin-B1 and catechin [45]. Rupasinghe et al. [46] reported that medicinal (pharmaceutical and nutraceutical) methods using apple peel extracts have been derived for treating cardiovascular disease, that lessens cholesterol levels and inhibit low density lipoprotein (LDL) oxidation. Atanassova & Bagdassarian [47] reported that rutin lowers the degree at which mitochondrial damage will occur and improves functions and structure of cardiac mitochondria.

 

1.2. Antioxidative Properties of Apple Peel Extract

Apple flesh extracts has lower antioxidant actions than apple peel extract [40]. Lipid oxidation, notably oxidation of polyunsaturated fatty acids is prominent issue in the food industry influencing quality of food and health of consumers. Apple peel is considered a natural supply of antioxidant that all components of apple such as quercetin, chlorogenic acid, catechin, and phloridzin are powerful antioxidants. Flavonoids decreases the possibility of cardiovascular disease by increasing the release of endothelial nitric oxide inducing vasodilatation [48].

 

 Anthocyanidins have high antioxidant activity that protects LDL cholesterol oxidation by their action. Peeled and unpeeled apples have high antioxidant activity and suppresses the growth of cancer and helpful in chronic disease prevention. A component pro-anthocyanidins has antioxidant property. It combines with the phospholipids and limits the entrance of oxidants on surface of membrane and restricts the oxidants movement within the membrane [49]. Apple peel has high antioxidant activity compared to the flesh. The peels from an average sized apple have an antioxidant action equal to 820g of vitamin C. Concentration of the phenolics extract is responsible for total antioxidant activity [50].

 

1.3. Antiproliferative Property

Apple have antiproliferative activity. It is reported that a combination of phytochemical in apple are powerful in blockage of the expansion of tumor cell. Apple has high antiproliferative activity when compared with other fruit [51]. Apple without peel is less effective against Hep G2 cell proliferation than apple with peel. So, it is noted that peel of apple has more antiproliferative activity. Wolfe et.al suggested that peel of apple has higher rate in reduction of Hep G2 cell proliferation as compared to whole apple [52].  It is also seen that the antioxidants of apple is not directly associated in the inhibition of cell proliferation of tumor but they indirectly reduces the cell proliferation [53].

 

1.4. Anti-Inflammatory Properties

Martín, M. A. & Ramos [54] reported that flavonols such as epicatechin have anti-inflammatory and antioxidant properties and they shows biological effect on target and are chief constituent of human diet. Quercetin have antioxidant property which leads to anti-inflammatory activity and its inhibitory action on enzymes to stop inflammation process with successive inhibition of inflammation mediators like leukotrienes and prostaglandins describe that flavonoid (quercetin) found in apples, red grapes and blueberries have anti-inflammatory properties shown in chronic inflammatory diseases and joint health [54].

 

1.5. Antidiabetic Property

Apple not only reduces the probability of asthma, diseases related to heart and cancer but it is also noted that eating apple is also related with the low risk of diabetes. It is noted that around 10,000 people who eats apple have lower risk of type II diabetes. As mentioned, quercetin is present in apple in rich amount and its intake help in the reduction of type II diabetes. Apple consumption is also related with increased function of lung and weight loss. Weight loss is noted in middle age Brazilian women by consuming apple [52].

 

1.6. Ant Carcinogenic Properties Of Apple Peel

Abundance of phytochemicals like catechin, quercetin, chlorogenic acid, and phloridzin are present in apple peel and these considerably act as antioxidants [55]. Triterpenoids isolated from apple peels have strong anti-proliferative activity and might be partly responsible for the apple’s anticancer activity [56]. Rutin is effective against prevention of some cancers and have antioxidant activity like other polyphenols [57]. Biological activity of flavonoids has protective effect in hepatic tumor cells [58,59]. 

 

Apples possesses antiproliferative activity against tumor cell growth as well as antioxidant activity that prevents oxidative damage in cellular components [60]. Apple peel instead of apple is used for antioxidant and antiproliferative activity because of high level of quercetin glycosides [38].

 

Abraham ., et al., Cher et al, and Hall et al., [61-63] describes the  antiproliferative effects of apple peel extract increases the maspin expression which inhibits the growth of cancer cells in breast [61–63]. Phytochemicals in fruits and vegetables have synergistic and additive effect that manages their anticancer and antioxidant actions [64]. Interaction of anthocyanins and Proanthocyanidins increases the potency of flavonoid-rich fruits against cancer, metabolic syndrome and cardiovascular diseases [65].

 

 Apple peel constitutes greater quantity of flavonoids, anthocyanins and phenolics and these compounds possess antiproliferative activities [66]. Apple peel have shown strong antioxidant and anti-proliferative activity than apple flesh, specifying that apple peel contains more bioactive phytochemicals. This also gives the idea that presence of high phenolic content, high antioxidant activity and high proliferative activity in apple peel shows that these give health benefits upon consuming and proved to be a valuable source of antioxidants and bioactive compounds [38].

 

Apple contain larger quantity of biologically active compounds but phenolic distribution in apple peel and apple flesh is different. Both contains chlorogenic acid, Phloretin glycosides, phloridzin but peel have additional flavonoids that are not present in flesh. By evaluating nutritional quality of apple peel contents of phenol, flavonoids and antioxidant activity along with tumor cell growth is higher in peel flesh, regardless of cultivar [67]. Apple extracts from skin and flesh have a dosage-dependent activity which inhibits the proliferation of colon carcinoma and the inhibitory effect was significant in extracts of apple peel [49].

 

 

Table 3: Presence and absence of polyphenolic compounds in different Commercial varieties of apple peel and flesh.

Conclusion

Polyphenolic compounds in apple and their specific properties shows great potential in preventing various diseases like cardiovascular, colon cancer, obesity, diabetes and other chronic diseases. They also reduce the risk of carcinogenesis and indicate various mechanisms through which these polyphenols have great beneficial effects on human’s welfare. We can extract them by using many techniques. They also show many valuable effects which includes antiproliferative, anti-carcinogenic and anti-oxidative effects. Thus, a valuable food ingredient can be introduced in the market by using the apple peels if we convert them into dried powder form without losing the polyphenols and phytochemicals and as a result, we can utilize this wastage, can also form many products like pectin etc. and can get many benefits.


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Wednesday 6 January 2021

Veterinary Medicine Articles in JBGSR

Review on Q Fever: Epidemiology, Public Health Importance and Preventive Measures by Gizaw Mekonnen* in Open Access Journal of Biogeneric Science and Research (JBGSR)

Summary

Q fever is worldwide zoonotic disease which is caused by obligate intracellular gram-negative bacteria, called Coxiella burnetii. Q fever is air born disease and thus inhalation is considered as primary mode of transmission in both animal and human, sometimes through ingestion they may be infected and ticks play essential role in transmission. The agent is spread a long distance through the wind. The geographical distribution of Q fever is worldwide except New Zealand. The main reservoirs for human infections are cattle, goat, sheep, and pets and ticks are the natural primary reservoir for animal. Coxiella burnetii in ruminant cause reproductive problems like miscarriage, infertility and reduced milk production. The organism can be found in the milk, urine, feces placenta and birth fluids of animals. The airborne transmission of C. burnetii associated with its highly resistance to environments and the ability to easily produce huge quantities of C. burnetii in the after birth of aborted ewes or goats have led to classify C. burnetii as a Category-B, biological terrorism agent. The incubation period of Q fever is depending on the size of infectious. The recommended treatment for ruminant administering two injection of Oxytetracycline during the last month of gestation, also Doxycycline is the best drug. C. burnetii can be reduced in the farm environment by regular cleaning and disinfection of animal facilities. Q fever is global health problem and it is an OIE notifiable disease. Q fever is one of infectious disease which is considered as being having economic and public health importance in Ethiopia. Therefore, awareness creation and, application of prevention and control method has paramount importance in reduce the hazardous effect of this disease.

 

Abbreviations: SCV: Small cell variant; LCV: Large cell variant; CFSPH: Central food security public Heath; PCR: Polymerase chain reaction; LPS: Lipopolysaccharide; IFA: Indirect fluorescent antibody; OIE: Office international des Epizooties

Introduction

Q fever is a serious zoonotic disease caused by an obligate intracellular bacterium Coxiella burnetii and it is presumed to be one of the most widespread zoonosis in the world. The disease has known since the 1930s and has a worldwide distribution, with the exception of the Antarctica and possibly New Zealand [1]. The disease first identified in Queensland, Australia, in 1935, after an outbreak of febrile illness among slaughterhouse workers [2]. Some authors suggested that the Q stood of Queensland, the state in which the disease was first founds [3], but after testing all those who were affected and could not arrive at a diagnosis from the patients’ history, physical examination, and a few investigations, Derrick termed the illness “Q” for Query fever, because its etiopathogenesis was not known at the time [4]. It also known by several synonyms such as Abattoir fever, Australian Q fever, Balkan influenza, Coxiellosis, Nine-mile fever, and Pneumorickettsiosis [5].

 

Domestic animals such as cattle, sheep and goats are considered as the mainreservoir for the pathogen which can infect a large variety of animals, humans, birds, and arthropods [5]. Q fever is a mainly airborne zoonosis; infection is most acquired by breathing infectious aerosols or contaminated dust [6]. Infection can occur also in individuals not having direct contact with animals, such as persons living along a road used by farm vehicles or those handling contaminated clothing. The infection result from inhalation of endospores and from contact with the milk, urine, feces, vaginal mucus or semen of infected animals [7]. The pathogen is highly resistant to adverse physical conditions and chemical agents, so it can survive for months and even years in the environment which create conducive condition for infection [8].

 

Q fever is frequently asymptomatic, in sheep and goats it causes abortion, stillbirth, premature delivery, and delivery of weak offspring and in cattle and camel may develop infertility, metritis, and mastitis [9]. The majority of human coxiella burnetii infections are asymptomatic, especially among high-risk groups such as veterinary and slaughterhouse workers, other livestock handlers, and laboratory workers [10]. In more recent dates Q fever is classified as a “Category “B” critical biological agent” by the Centre for Diseases Control and Prevention (CDC) and is considered a potential weapon for bioterrorism [11]. The disease so is considered has having public health concern throughout the worldalongside with its economic importance. On top this, although Qfever is an OIE notifiable disease, it remains poorly reported and its surveillance is frequently severely neglected [12]. Review of the disease epidemiologic status, public health significance is lacking in different countries, including Ethiopia.

Therefore, the objectives of this seminar paper are:
i. 
To overview Q Fevers Epidemiology, Public health importance, and preventive measures
ii. 
To highlight current status of Q fever in Ethiopia

History of Q Fever

Q fever was first described in 1935 by Edward Holbrook Derrick [2] in abattoir workers in Brisbane, Queensland, Australia. The “Q” stands for “query” and was applied at a time when the causative agent was unknown; it was chosen over suggestions of “abattoir fever” and “Queensland rickettsial fever,” to avoid directing negative connotations at either the cattle industry or the state of Queensland [13]. Derrick inoculated guinea pigs with blood or urine from the "Q" fever patients. The guinea pigs became febrile. Derrick was unable to isolate the agent responsible for the fever so he sent a saline emulsion of infected guinea pig liver to Macfarlane Burnet in Melbourne. Burnet was able to isolate organisms, which "appeared to be of rickettsia nature" [7]. 

In 1936, Herald Rea Cox joined Davis at the Rocky Mountain Laboratory to additional characterize the “Nine Mile agent.” Burnet and Freeman, as well as Davis and Cox, demonstrated that the etiological agent was filterable and displayed properties of both viruses and rickettsiae. A major advance obtained in 1938, when Cox succeeded in propagating the infectious agent in embryonated eggs. Cox termed the Nine Mile Agent Rickettsia diaporica (diaporica means having the ability to pass through) a reference to the filterable property of the agent. In intervening time in Australia, Derrick suggested the name of Rickettsia burnetii for the Q fever agent. In 1948, Cornelius B. Philip proposed that R. burnetii considered as the single species of a distinct genus since it was now apparent that this organism was unique among the rickettsiae. He proposed the name Coxiella. The Q fever agent is known as Coxiella burnetii. C. burnetii, a namewhichhonors bothCox and Burnet who had identified the Q fever agent as a new rickettsial species [14].

Etiology and Taxonomy

Coxiella burnetii, the causative agent of Q fever, is a small (3–5mm) polymorphic obligate intracellular gram-negative bacteria belonging to the genus Coxiella, family Coxiellaceae, order Legionellales, class Gammaproteobacteria, and phylum Proteobacteria [15]. C. burnetii display two antigenic phases based on changes that occur in the organism during in vitro culture, such as phase I and phase II [16]. They are liable to the Lipopolysaccharide (LPS) of the membrane. Phase-I Coxiella burnetii antigenare more highly infectious and are corresponds to the smooth phase of Gram-negative bacteriaand phase-II antigen is corresponding to the granular (Rough) phase which has a lower virulence [17]. C. burnetii has a biphasic life cycle, alternating between a large cell variant (LCV), which is the replicating form within a cell, and a small cell variant (SCV), the non-replicating, infectious form. The SCV has an unusual spore-like structure with highly condensed chromatin, and it is highly resistant to environmental conditions [18].

 

Since, Coxiella burnetii thought the only species member of genus Coxella but recently several Candidatespecies have been recognized in reptiles, birds, and humans like C. cheraxi, C. avium and C. massiliensis. Coxiella-like bacteria are also common in ticks, and one of these organisms was recently found in horses. The newly-recognized relatives of C. burnetii have the potential to alter some aspects of its epidemiology for instance, C. burnetii is often said to occur in more than 40 species of ticks; however, the current PCR tests can also amplify Coxiella-like bacteria, and whether all of these ticks were truly infected with C. burnetii is now in doubt [19].

 

Genomic group contains reference Coxiella burnetii strain that were isolated from infected human end/or animals. Strain in genomic group 1, 2 and 3 have been isolated from tick, human blood (acute Q fever), from milk of persistently infected dairy cattle, and/or aborted fetal tissue. Strains in genomic group 4 and 5 have been isolated from the heart of humans with chronic Q fever and/ or aborted tissue of animals. Strains in genomic group 6 have been isolated only from rodents; these strains are of unknown virulent for humans and animals [20].

Epidemiology

1.1. Reservoirs of Q Fever

The reservoir includes many wild and domestic mammals, birds, and arthropods such as tick [21] Over 40 species of ticks are naturally infected. The organisms multiply in the cell of the midgut and stomach of the ticks. After multiplying ticks excrete bacteria in the faces and saliva [12]. Throughout the world the most commonly identified reservoirs of human infections are farm animals such as cattle, goats, and sheep, Pets, including cats, rabbits, and dogs, have also been demonstrated to be potential sources of urban outbreaks of disease [22].

 

1.2. Geographical Distribution

Q fever disease outbreak occurs primarily in Queensland, Australia, in 1935 in slaughterhouse workers [2]. Q fever has described worldwide except New Zealand [23]. Two characteristics of the organism are important in the epidemiologic distribution of the disease. These are its ability to withstand harsh environmental conditions, probably as a result of spore formation and its extraordinary virulence for man. C. burnetii has been a very successful pathogen because of this a single organism can cause disease in man. In 1955, Q fever had been reported from 51 countries on five continents. From 1999 to 2004, there were 18 reported outbreaks of Q fever from 12 different countries [24].

 

1.3. Transmission and Source of infection

The organism can be found in the milk, urine and feces of the animals as well as the placenta and birth fluids. Humans are most commonly infected through inhalation of contaminated dust or aerosols generated by livestock operations involving these animals [25]. Accordingly, Q fever is an occupational hazard for veterinarians, abattoir workers, dairy farmers and anyone with regular contact with livestock or their products [7]. Urban outbreaks of Q fever are also associated with contact with infected domestic cats [26]. Inhalation is the primary mode of transmission in both human and animal. Under experimental conditions, inhalation of a single C. burnetii can produce infection and clinical disease in humans. Coxiella burnetii also spreads by wind causing infections at adistance from the initial source of bacteria. In domestic ruminants, milk is the most regular route of pathogen shedding and thus recently, OIE advises not to drink raw milk originating from the infected livestock farms [27].

 

Tick may play important role in transmission of C. burnetii among the wild vertebrates, especially in rodents, lagomorphs, wild birds. Dog can also be infected by tick bites. Although experimental transmission of C. burnetii from infected to uninfected guinea pigs via tick bites has been performed with Ixodes holocyclus, Haemaphysalis bispinosa, Rhipicephales sanguineus,ticks are not important in natural cycle of C. burnetii infection in livestock. Tick expels C. burnetii with their faces in the skin of animal host at the time of feeding [28]. Human-to-human transmission does not usually occur [12].

 

1.4.  Risk Factors

Agent Factors: The severity of the infection depends on the strains of the infecting bacteria. Phase I type bacteria are more virulent than the phase II type. Acute infection in humans is caused by Coxiella burnetii genomic type IIII, whereas type IV and V are responsible for chronic infection. The virulence of type VI is unknown [29,30].

 

Host Factors: Age and gender are the two risk factors which are shown to influence the occurrence of Q fever in humans. Old people are the most vulnerable and the clinical disease is mostly prevalent in men [31]. An interaction of Coxiella burnetii infection with age and sex was also found in animals, particularly in cattle. The prevalence of Coxiella burnetii infection increases with age or with the number of parity in cattle and sheep. Prevalence is higher in dairy cows than in beef cattle. Veterinarians, animal farm workers, abattoir workers, laboratory personnel, and immunosuppressed people are at a higher risk of being infected or seropositive than others; and highly prevalent [32].

 

Environmental Factors: Seasonal variation is observed in the occurrence of human Q fever. This variation, however, varies according to geographical region. But most cases of Q fever have been reported in the spring or early summer. Human Q fever has been shown to have a relationship with rainfall rather than season [31,33].

A high prevalence of Q fever was observed among people living in close proximity to infected animals or in areas with a high livestock density. Several management factors such as housing systems, isolation of a newly introduced animal may also contribute to the seroprevalence of Coxiella burnetii infection in animals [32].

Pathogenesis

The pathogenesis of Coxiella burnetii infectionin humans and animals is not clearly understood. But, it is believed that bacterial LPS play an important role in the pathogenesis of Q fever in both humans and animals. The organism probably follows the oropharyngeal route as its port of entry into the lungs and intestine of both humans and animals. The disease is highly infectious, and a very low dose is enough to initiate infection. Primary multiplication takes place in the regional lymph nodes after the initial entry, and a transient bacteremia develops which persists for five to seven days [17].

 

The SCVs are shed by infected animals. After infection the organism attaches to the cell membrane of phagocytic cells. After phagocytosis, the phagosome containing the SCV fuses with the lysosome. The SCVs can undergo vegetative growth to form LCVs. The LCVs and the activated SVCs can both divide by binary fission and the LCV can also undergo sporogenic differentiation. The spores that are produced can undergo further  development  to become metabolically inactive SCVs and both spores and SCVs can then be released from the infected host cell by either cell lysis or exocytosis. The entire development cycle of metabolically active C. burnetii takes place in acidic phagolysosomes; C. burnetii are resistant to microbicidal activities in the host macrophages. The acidic environment  also protects C. burnetii from the effects of antibiotics. The SCV and spore forms are more difficult to denature than LCVs [34].

Clinical Sign

In animals, during the acute phase, C. burnetii can be found in the blood, lungs, spleen, and liver whereas during the chronic phase it is presented as a persistent shedding of C. burnetii in feces and urine. Most animals remain totally asymptomatic, including a lack of fever. However, low birth weight animals can occur. Clinical symptom of Q fever in sheep and goats are pneumonia, abortion, stillbirth, premature delivery, and delivery of weak offspring or reproductive failure. In cattle, Q fever is frequently asymptomatic. Clinically infected cows develop infertility, metritis, and mastitis. In addition, C. burnetiid was found to be significantly associated with placentitis. Placental necrosis and fetal bronchopneumonia were also significantly associated with the presence of Coxiella burnetii in the trophoblasts. In most abortive cases, the aborted foetus appears normal but discolored exudates and intracotyledonary fibrous thickening may be observed in an infected placenta. Severe myometrial inflammation and metritis are the frequently observed clinical manifestations in goats and cows, soabortion rate is comparatively higher in ewes and goats than in cows. Abortion is usually observed in late pregnancy in ewes, goats, and cattle [1].Infection in most domestic animals remains unrecognized. Coxiellosis is considered a cause of abortion and reproductive disorders in domestic animals.

 

Temperature is an important factor related to abortion rates in herds, since fewer abortions take place between months of November and December, the occurrence of abortion rate increases gradually from January to February, decreasing again in March [1]. In Humans Coxiella burnetiid infection can cause either an asymptomatic, acute, or chronic disease. Clinical manifestations of Q fever in human are Prolonged fever, Pneumonia, Hepatitis, Endocarditis, Osteomyelitis, Neurological manifestations, Skin rash and Myocarditis. A prolonged fever, which may reach 39-40oC, usually stays for 2-4 days and then gradually decreases to a normal level through the following 5-14 days. The fever is usually accompanied by severe headaches. However, in untreated patients, fever may last from 5 to 57 days. Pneumonia is mild in most cases being characterized by a dry cough, fever, and minimal respiratory distress.

 

Almost all patients suffering from acute Q fever pneumonia present with a fever usually associated with fatigue, chills, headaches, myalgia, and sweats. Myocarditis is a rare but life-threatening clinical manifestation of acute Q fever and it isfound in 2% of patients with the acute illness and it may be associated with pericarditis, and a pericardial effusion may be observed on chest radiographs. Clinical manifestations of Q fever pericarditis are not specific and most often correspond to a fever with thoracic pain [35]. Q fever hepatitis is usually only revealed by an increase in hepatic enzyme levels. Q fever hepatitis is usually accompanied clinically by fever and less frequently by abdominal pain (especially in the right hypochondrium), anorexia, nausea, vomiting, and diarrhea. Progressive jaundice and palpation of a mass in the right hypochondrium have also been reported. Extensive destruction of liver tissue leading to hepatic coma and death has occasionally been reported. Skin rashes and neurologic disorders such as meningoencephalitis or encephalitis, lymphocytic meningitis and peripheral neuropathy have also been observed in acute Q fever. Skin lesions have been found in 5–21% of Q fever patients in different series. The Q fever rash is nonspecific and may correspond to pink macular lesions or purpuric red papules of the trunk. There are 3 major neurological entities associated with Q fever: (1) meningoencephalitis or encephalitis; (2) lymphocytic meningitis and (3) peripheral neuropathy.

 

Spontaneous abortion, intrauterine fetal death, premature delivery or retarded intrauterine growth may occur in women that become infected during pregnancy. When a woman is infected by C. burnetii during pregnancy, the bacteria settle in the uterus and in the mammary glands [36]. Q fever endocarditis is the most frequent clinical presentation of chronic Q fever. It occurs almost exclusively in patients with a previous cardiac defect or in immune compromised patients. Unspecific signs like intermittent fever, cardiac failure, weakness, fatigue, weight loss or anorexia may be present. Other manifestations are osteomyelitis, osteoarthritis, chronic hepatitis, hepatomegaly, splenomegaly, digital clubbing, purpuric rash and an arterial embolism. The incubation period is depending on the size of the infectious doses, usually 2 to 3 weeks. Chronic Q fever can develop years after an initial infection [37].

Diagnosis, Differential Diagnosis and Treatment

1.1. Diagnosis

The clinical signs of Q fever are nonspecific both in human and animal because of this laboratory evidence of infection is needed for diagnosis. Four categories of diagnostic tests are available: isolation of the organism, which must be conducted in a biosafety-level 3 laboratory using tissue-culture; laboratory animals, or embryonated eggs; serologic tests, including indirect fluorescent antibody (IFA), enzyme immunoassay, and complement fixation test; antigen detection assays, including immunohistochemical staining (IHC); and nucleic acid detection assays, including polymerase chain reaction (PCR)assays [5]. Routine diagnosis of Q fever in animals is usually established by examination of fixed impressions or smears prepared from the placenta stained by the Stamp, Gimenez or Machiavello methods, associated with serological tests [38].

 

1.2. Differential diagnosis

There is some disease that we appreciate the same sign with Q fever such as Salmonellosis, Brucellosis, Leptospirosis, Campylobacteriosis, Listeriosis, Elective Abortion, Influenza, and Rickettsial Infection. At initial stages, i.e., before pulmonary symptoms are present, influenza may be suspected. Listeriosis is called circling disease, affected animal circle in one direction only and show swallowing, fever, blindness and head pressings. There is necrosis of placenta which leads to abortion and the fetus may be macerated or delivered weak and moribund, paralysis and death follow in 2 to 3 weeks later. Listerial abortion occurs in late gestation. Brucella is life longer infection it causes in female animal abortion around seventh month of pregnancy and retention of placenta and metritis are common and in male it causes orchitis, epididymitis, synovitis and sterility. Salmonellosis has sign like fever, dehydration and foul-smelling diarrhea and cause abortion in the last two months of gestation. Leptospirosis is show sign like excessive salivation, muscular rigidity, conjunctivitis, hemoglobinuria, pallor of mucosa and jaundice. Leptospiral abortion occurs with or without placental degeneration and encephalitis, Abortion usually occurs 3-4 weeks later. Most affected animals are found dead, apparently from septicemia [32].

 

1.3. Treatment

Antibiotics can shorten the course of acute Q fever, and may reduce its severity. The recommended administrations for human acute Q fever are Doxycycline (100 mg daily for 14 days), Fluoroquinolones (200mg three times a day or Pefloxacin (400mg) for 14-21 days), Rifampin (1200mg per day for 21 day). For pregnant patient we use drug like Trimethoprim (320mg) and Sulfamethoxazole (1600mg) for >5 weeks. Doxycycline (100mg per day for 10-14 days) is suitable. Fluoroquinolones are considered to be a reliable alternative and have been supported for patients with Q fever meningoencephalitis, because they penetrate the cerebrospinal fluid. Cotrimoxazole and rifampin can be used in case of allergy to tetracyclines or contraindication). Erythromycin and other new macrolides such as clarithromycin and roxithromycin, could be considered a reasonable treatment for acute C. burnetii infection [39].

 

The recommended administration for human chronic Q fever is Doxycycline (100mg per day) and Hydroxychloroquine (600mg) for >18 months for adult, Trimethoprim and Sulfamethoxazole for >18 months for children. Doxycycline is the first choice of drug treatment for all adults and children in both acute and chronic case those have sever illines . Tetracyclines are recommended most often in non-pregnant patients, but other drugs are sometimes used such as Quinolones, and Trimethoprim/ sulfamethoxazole (“cotrimoxazole”). Cotrimoxazole is much employed in pregnant women to avoid side effects from other drugs. Treatment of chronic Q fever is more difficult because of this single antibiotic are not generally effective. Tetracyclines combined with hydroxychloroquine are traditionally used, typically for 18-24 months, but tetracyclines combined with quinolones have also been used successfully. The recommended treatment for ruminant(animal) is consist in administering two injection of oxytetracycline (20 mg per kg body weight) during the last month of gestation. This treatment does not completely suppress the abortions and shedding of C. burnetii at lambing.

Prevention and Control

To prevent and reduce the animal and environmental contamination, several actions can be proposed. When introducing a new animal into a Q fever free flocks, in order to avoid the spread of infection, specific care taken. An antibody investigation for Q fever should be performed in the flock of the seller and animals from seropositive flocks can only be introduced in seropositive or vaccinated flocks. C. burnetii can be reduced in the farm environment by regular cleaning and disinfection of animal facilities, with particular care of parturition areas, using 10% sodium hypochlorite. In the UK, Health Protection Agency guidelines mention the use of 2% formaldehyde, 1% Lysol, 5% hydrogen peroxide, 70% ethanol, or 5% chloroform for decontamination of surfaces. Pregnant animals must be kept in separate pens, placentas and aborted fetuses must be removed quickly and disposed under hygienic condition to avoid being ingested by dogs, cats or wildlife. Since parturition is critical for the transmission of the disease, in infected flocks, birth must take place in a specific location, which must be disinfected as well as every utensil used for delivery.

 

Appropriate tick control strategies and good hygiene practice can decrease environmental contamination. Infected fetal fluids and membranes, aborted fetuses and contaminated bedding should be incinerated or buried. In addition, manure must be treated with lime or calcium cyanide 0.4% before spreading on fields; this must be done in the absence of wind to avoid spreading of the microorganism faraway. The best methods available for prevention and control of Coxiellosis are antibiotic treatment and vaccination. In-feed addition of tetracycline or injectable oxytetracycline pre-partum has not been shown to prevent C. burnetii shedding in feces, milk and vaginal secretions [40].

 

Human-to-human transmission is extremely rare and Q fever is mainly an airborne disease, measures of prevention are aimed at avoiding the exposure of humans and particularly persons at risk, to animal and environmental contamination. At human level, prevention of exposure to animals or wearing gloves, boots, and masks during manipulation of animals. Pasteurization at 72 °C during 15 s, or sterilization of milk from infected flocks is regularly recommended even if the oral route is not the main one [41].

 

C. burnetii is able to survive for long periods in the environment and in wild animals. The only way to really prevent the disease in ruminants is to vaccinate uninfected flocks, with an efficient vaccine. Three types of vaccine have been proposed for providing human protection against Q fever: the attenuated live vaccine (produced and trialled in Russia but subsequently abandoned because of concern about its safety); chloroform–methanol residue extracted vaccine or other extracted vaccines (trialled in animals but not humans); and the whole-cell formalin-inactivated vaccine, which is considered acceptably safe for humans [40]. Vaccines can prevent abortion in animals, and it is evident that a phase I vaccine must be used to control the disease and to reduce environmental contamination and thus, the risk of transmission to humans. The widespread application of such a vaccine in cattle in Slovakia in the 1970s and 1980s significantly reduced the occurrence of Q fever in that country [42]. 

Public Health Importance of Q Fever

Q fever is a global public health concern, as is reported from more than 59 countries of the world [43]. Human infections occur after inhalation of aerosols generated from contaminated dust resulting from contaminated manure and desiccation of infected placenta.

The existence of C. burnetii in the environment allows it to be disseminated by wind far away from its original source. This indicates the appearance of Q fever cases in urban areas, where an important percentage of patients fail to report direct contact with animals [44]. Apparently without animal contact, birds can also be responsible for human cases in urban areas since they are able to transmit Q fever via their feces or their ectoparasites [45].

 

C. burnetii receivedas a Category-B, biological terrorism agent. The attention of public health personnel and medical on Q fever, which could be responsible for the apparent increase of Q fever cases and its apparent reemergence, has been focused. Less efficient route of contamination is ingestion of contaminated raw milk or raw milk products. Without clinical signs, seroconversions in human volunteers have been induced by drinking of contaminated milk, but none of them presented aggravating risk factors. Nevertheless, some studies have reported clinical disease linked to the ingestion of cheese; but these outcomes are sometimes contested since it is difficult to guarantee even for prisoners that the patients did not inhale contaminated dust or aerosols [46].

 

 

It is highly infectious for risky groups including veterinarians, laboratory workers, farmers and abattoir workers. Surveys have shown that significant numbers of livestock handlers have antibodies indicating exposure to the organism. Less than half of people infected become ill, and most infections are mild. But affected persons can develop a high fever with headache, muscle pains, sore throat nausea and vomiting, chest and stomach pains. The fever can last for one or two weeks, and lead to pneumonia or affect the liver. People with suppressed immune systems and those with pre-existing heart valve problems are at risk of this complication, which is often fatal. There is also a post Q fever syndrome of chronic fatigue. Q fever is the second most commonly reported laboratory infection with several recorded outbreaks involving 15 or more persons [47].

Status of Q Fever in Ethiopia

In Ethiopia, the existence of antibody against Coxiella burnetii was reported in goats and sheep slaughtered at Addis Ababa abattoir, and its peri-urban zone. A seroprevalence of 6.5% was also reported in Addis Ababa abattoir workers according to [48]. A seroprevalence of 31.6%, 90%, and 54.2% of C. burnetii was recorded in cattle, camels and goats respectively in South Eastern Ethiopian pastoral zones of the Somali and Oromia regional states as reported by Abebe [49]. Ticks were tested for C. burnetii in Ethiopia by quantitative real time polymerase chain reaction targeting two different genes followed by multispacer sequence typing (MST).

 

An overall prevalence of 6.4% of C. burnetii was recorded. C. burnetii was detected in 28.6% of Amblyomma gemma, 25% of Rhipicephalus pulchellus, 7.1% of Hyalomma marginatum rufipes, 3.2% of Amblyomma variegatum, 3.1% of Amblyomma cohaerens, 1.6% of Rhihipicephalus praetextatus, and 0.6% of Rhipicephalus (Boophilus) decoloratus. Significantly higher overall frequencies of C. burnetii DNA were observed in Amblyomma gemma and Rhihipicephalus pulchellusthan in other tick species as reviewed by Tagesu.

Abortion is one of the most important reproductive health problems of dairy cows in Ethiopia in terms of economic impact. Both infectious and non-infectious agents may cause abortion in cattle. Q fever is one of infectious disease which cause abortion in Ethiopia [50].

Conclusion and Recommendation

Q fever is airborne disease caused by obligate intracellular bacteria of the genus Coxella. It affects both human and animal in the worldwide except New Zealand. It is the second most commonly reported laboratory infection. It is a serious zoonotic disease which affects both human and animal. In Ethiopia it has been reported by causing abortion in dairy cattle and the existence of antibody in sheep and goat. The main source of infection is contaminated dust with birth fluid, faces, urine, and milk and tick. The reservoirs of human infections are farm animals such as cattle, goats, sheep, and Pets, including cats, rabbits, and dogs, have also been demonstrated to be potential sources of urban outbreaks of disease C. burnetii is transmitted through inhalation and sometimes also transmitted through ingestion. C. burnetii is highly resistant to physical conditions and chemical agents, so it can survive for months and even years in the environment. Q fever is diagnosed by serological test. Tetracycline is recommended drug in the treatment of Q fever. It can be controlled by controlling tick by using insecticide. The prevention of Q fever is done by burning contaminated bedding and good hygiene practice. 

Therefore, based on the above conclusion the following recommendations are forwarded:

a)       Public awareness should be created in consumption of dairy products

b)      Public awareness should be created in proper handling and disposing of aborted birth products.

c)       Government should wide and the availability and accessibility of effective diagnostic techniques.

d)      Government should vaccinate animals were found in endemic area.

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