Yeapp it is quite annoying but like the say you got ta stay tough, Best wishes

Wow, after a long tiring attemp, finally succeeded. Someone dropped me the hint that I should apply by around 4:00pm, Good luck y'all

It would surprise you to know that my application has been refusing to submit: Whenever I attempt the message

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What does this mean, is everyone having this problem?

NAFDAC has just posted new positions of vacancies to be filled, follow the link for more information

http://www.nakachiconsulting.net/index.php/component/content/article/101

best wishes,

Without any political intensions to campaign for a candidate I wish to state an objective case for the Nigerian youth with regards the political system and the opportunities it provides for intersectional change. Though it is merely two days from the deciding moment it is important to state this case than stay mute and be weighed down by the ‘Nigerians are known more for their eloquence than accomplishments’, (not that there are none notable). A lot has been said about the desire for a dynamic economy that can be open with options for all members of the society, equal opportunities and a lot more. The recent electoral processes starting way back as 14 months from date has illustrated the presence of the anticipated atmosphere that would drive the national philosophy of citizenship and leadership through a decisive vantage point engineered by the youths. This element though bred on societal misnomer of youth violence and menace has gradually provided an opportunity for a formidable action essential for coexistence and growth from a literal and legal perspective.

This opinion is drawn from several tempting assumptions that the current national conundrum is a deliberate attempt to relegate the average young Nigerian from participation in national building and intelligent contribution to the economic growth of the nation so as to create opportunities for gratification to non performance in several sectors headed by ‘youths’. It is no doubt that the age group range of Nigerians who constitute the vibrant labor force of the society are the youths, consequently it is expected that their input on national growth through manual labor, intellectual property, business management and other spheres of human activity is largest; yet they are considered as the leaders of tomorrow [leaders only after the current leaders are entirely gone]. It would be sinister to think that the young Nigerians would anticipate such an opportunity to exercise their strengths which can be contestably argued to be better than what is currently obtainable evident from how young jobless individuals invent jobs and engage others. Several other likelihoods can be raised but to maintain focus, let us elaborate on the activities at the April 2011 polls, and how it promises a transformation of the international envy, Nigeria.

At the polls, the hope of the ideal voter identifies escalating utility expenditures resulting from insufficient social amenities and infrastructure to promote productivity and the consequence of better available alternatives. These include on the list a stable power supply, access to affordable quality healthcare and education, better job opportunities, provision of adequate agricultural input and the list goes on including other things like the desire for transparency and reassurance in willingness to provide humane security and protection of lives and property. Disappointingly in the realistic case, loss of confidence in the system lures the strong element of decision towards ethnic lines, religion, self interests, regionalization and other uncertain indices.

This current electoral process provides a unique opportunity and distinct candidate to create a rapid evolution of Nigerian politics using salient pointers, stated with no bias; Currently, Nigerians battle with the fact that a certain age must be attained to contest the seat of leadership, this is flawed by several circumstances one of which is, a condition where there is no competent candidate available; or rather option-worthy candidate. In such a situation the available becomes the desirable and thus results to what is obtained in many electoral positions in Nigeria. The Polls has created an opportunity to allow any young Nigerian with an average background and desire to deliver a change to make a consequential contest, which could be fair. This success would invariable reorder the ‘leader of tomorrow ideology’ and better stratify the national system for effectiveness. The craving for a visionary to direct the cause of national greatness is at peak, this also has been demonstrated by previous and recent dog-headed ambitions of an aspirant at the polls. Indeed it is no doubt that to regain the ‘giants status’ there is a need for a resolute captain to navigate the compass and break through storms. Two candidates clearly elaborate these tendencies, one meets the first criteria stated were as the second is however limited by the fading sands in time factor. Also if a synergy of both players is considered it would catalyze the national ambition subscribed by both. At the polls, elites look at a dynamic global arena which progressively requires initiation and pro-activeness born out of innovation and general action to the benefit of all, on this, one candidate demonstrates this aptitude. There is no questioning that Nigeria is and international player in policy formulation and global governance, yet this ability is threatened by local rivalry in politics and national administration.

Finally, it still remains a valid fact that leadership is a gradual process that is established with time, but the April 16 polls presents a golden opportunity which should not be lost on trivial issues. And it is time to re-establish the correct notion that “children are the leaders of tomorrow”; consequently, youths are the leaders of today, and elders were the leaders of yesterday. It is vital that ignorance be left aside as we stop running in circles.

The writer is a consultant working with Community Based Organizations in Northern Nigeria towards raising awareness of youths and promoting quality practices.

Ha, who is taking about being proud about a country, wake up, and watch what you are praising and who is taking which glory, the future of the youths is being insured and you think the older folks would bank it for you? guy wake up and do, before your time is over

I woke up with my pen in my hand and it’s Nigeria @ 50. What a celebration?,  I do not mean to sound pessimistic but rather objective. I tried to raise my spirits of jubilation but alas my grief is greater. How can I celebrate the fact that yesterday at the bus park I was rushed by over 20 agile young men who sat in wait for their future as they helplessly watched it pass like luxurious cars on speed lanes in an express highway. The sights of me and my backpack reunited them with their hope to earn the next kobo that might lead to their future billions. A hope I felt in the firmness of their grip and the strengths of their push. A hope that I in a confused state and also searching for mine dashed away in search for the closest Mama-put. What touched my heart the most was the perseverance I saw in the eyes of one of them; I would rather refer to as my uncle. So patient yet coaxingly still asking “If you intend to travel would you kindly not forget that I’m the guy sitting beside the white marcopolo?” Then came my last words, “No Bros, I just dey look for place where I go bend down”. He showed me a spot and turned back to join his other colleagues in the wait.

Sitting with my friend across the table we placed our orders. Madam served Garri and Orrah; another restless looking guy brought us water. He occasionally threw glances and smiles at us as we munched our way down the delicacy garnished with huge goat meats. At the end of our treat my friend asked “My guy wetin be our money?” Quickly stealing a glance over his shoulder to make sure Madam’s attention was fully engrossed in her mirror and powder pad, he picked up a drinking glass and moved closer trying to whisper. Madam was immediately distracted and she asked “Na wetin?” “Dem wan know how much be their money”. She quickly stood up told us our bill and stretched out for the pay. On receiving our change we still sat a little longer to wrap up our gist then came the guy “So oga how far now?” my friend was surprised, “I go come your place come chop and then you go tax me again?” I quickly remembered the last money I had in my pocket was just N10 and pulled it and stretched it towards the guy and added a “shey you understand ba?”. The guy smiled and collected it expressing his gratitude. My friend still in the shock and confusion asked me “But what was he expecting me to do? Afterall Madam would pay him?”; that I wasn’t sure of.

Then I imagined that a whooping sum of N10 billion Naira would be spent just on the jubilation of 50 years of steady decline in national economy, unstable power supply, joblessness of the vibrant labor force and you name it. It would startle you to know that even this writer who as a young scientist is currently a jobless youth (in the Nigerian context) so why should I join the old buffoons in celebrating my doom. I choose to disagree and morn my current state so that I would not be satisfied and seek away out where posterity would thrive. I mourn that I would never be like the politicians who only seek to celebrate in a bid to catch the next millions that would satisfy the vanity of their children alone whilst others are roaming dangerous roads with dishes and are being knocked down by flashy cars. I morn Nigeria @ 50 not because I am as old as 50.

I woke up with my pen in my hand and it’s Nigeria @ 50. What a celebration?,  I do not mean to sound pessimistic but rather objective. I tried to raise my spirits of jubilation but alas my grief is greater. How can I celebrate the fact that yesterday at the bus park I was rushed by over 20 agile young men who sat in wait for their future as they helplessly watched it pass like luxurious cars on speed lanes in an express highway. The sights of me and my backpack reunited them with their hope to earn the next kobo that might lead to their future billions. A hope I felt in the firmness of their grip and the strengths of their push. A hope that I in a confused state and also searching for mine dashed away in search for the closest Mama-put. What touched my heart the most was the perseverance I saw in the eyes of one of them; I would rather refer to as my uncle. So patient yet coarsingly still asking “If you intend to travel would you kindly not forget that I’m the guy sitting beside the white marcopolo?” Then came my last words, “No Bros, I just dey look for place where I go bend down”. He showed me a spot and turned back to join his other colleagues in the wait.

Sitting with my friend across the table we placed our orders. Madam served Garri and Orrah; another restless looking guy brought us water. He occasionally threw glances and smiles at us as we munched our way down the delicacy garnished with huge goat meats. At the end of our treat my friend asked “My guy wetin be our money?” Quickly stealing a glance over his shoulder to make sure Madam’s attention was fully engrossed in her mirror and powder pad, he picked up a drinking glass and moved closer trying to whisper. Madam was immediately distracted and she asked “Na wetin?” “Dem wan know how much be their money”. She quickly stood up told us our bill and stretched out for the pay. On receiving our change we still sat a little longer to wrap up our gist then came the guy “So oga how far now?” my friend was surprised, “I go come your place come chop and then you go tax me again?” I quickly remembered the last money I had in my pocket was just N10 and pulled it and stretched it towards the guy and added a “shey you understand ba?”. The guy smiled and collected it expressing his gratitude. My friend still in the shock and confusion asked me “But what was he expecting me to do? Afterall Madam would pay him?”; that I wasn’t sure of.

Then I imagined that a whooping sum of N10 billion Naira would be spent just on the jubilation of 50 years of steady decline in national economy, unstable power supply, joblessness of the vibrant labor force and you name it. It would startle you to know that even this writer who as a young scientist is currently jobless youth (in the Nigerian context) so why should I join the old buffoons in celebrating my doom. I choose to disagree and morn my current state so that I would not be satisfied and seek away out where posterity would thrive. I mourn that I would never be like the politicians who only seek to celebrate in a bid to catch the next millions that would satisfy the vanity of their children alone whilst others are roaming dangerous roads with dishes and are being knocked down by flashy cars. I morn Nigeria @ 50 not because I am as old as 50.

THE STRUCTURE OF FUNGI

They are eukaryotic, comprising of both unicellular and multicellular. Yeasts are the unicellular fungi, while moulds are the multicellular fungi.
Fig 1.
Multicellular fungi are most common where many cells become coordinate to exist in a hyphal form. The coordination yields two varieties of structures. In some of the fungi, the cell continues to divide along the horizantal layer so that either of the tip will divides to form multi-hyphae.
Fig 2.
Some may have cross wall, or it may dissolve and sometimes become absent.
Fig 3.

The hyphae or mycelium is a membraneous structure consisting of mass of cytoplasm with many nuclei.Growth takes place at the tip of the mycelium and this is obtain by outgrowth (or germinates) of a single reproductive cell or spore, to form elongated hyphal strand comprising of many cells.
Fig4.
They continue to distribute mycelium until all the surrounding is inhibited.
They can be as small as 3um (yeast), as well as hyphae up to 10-50um.
Uninucleate or multinucleate spore form at tip confers asexual reproduction ability.
Fig 5.
Fig 6.

CATEGORIES OF FUNGI BASED ON STRUCTURE AND PHYSIOLOGY.
1. Phycomycetes: Aseptate including the slime moulds. They live in water and soil. The terristerial phycomycetes (soil) are charesteristically different from water phycomycetes because of the absence of a flagellated zoospore (Reproductive spore). This character is the line of evolution between the water and terristerial fungi. Members of the group of rhizophus are typical example of terristrial phycomycetes.
2. Ascomycetes: Coenocytic, producing ascus spores.
3. Basidiomycetes:

The above three groups possess both asexual and sexual stages.

4. Deutromycetes: Called fungi imperfecti because of the absence of asexual stage.

MYCOBIOTA AS AN AGENT RELATED TO DISEASES PRODUCTION.

Based on Robert Koch’s postulates, a diseases agent must conform to certain criteria as follows:
1. The organism must be present at certain stage of the disease process. The distribution of the organism in every aspect of the disease must conform with the observed lesion due to that particular disease

(However, this was criticized because it may not at all the time the causative agent be present. Organism may be present, but disease or symptoms may not appear. E.g in salmonelloisis, where by a seemingly healthy individual will harbor the organism as a carrier without showing any sign or symptoms).

2. The organism must be isolated and maintained in a pure culture, and be maintained for several generations.

(This was also critisized because it may be difficult in certain organisms. Viruses were used as typical example).

3. The organism must produce the disease in suitable experimental animal.

(However, some are only perculiar to human and very difficult to confirm in animals. E.g Candida albicans).

4. The organism should be recoverable from experimental animal.

If the above rules were established, then the organism can be confirmed as the causative agent of a particular disease under investigation.

DEFINATION OF INFECTION
Based on the above postulates, infection can be defined as the regular production of a typical lession or symptoms in the main host or experimental animals, resulting in the generation of Immunofluroscencin materials, which can lead to the production of specific protective antibodies, due to the response of the host to the antigens carries by the pathogenic organism ( as a result of being virulent,invasivness), and response of the infective individual to specific chemotheraphy, as well as serological reactions.

SOURCE OF INFECTION (FUNGAL INFECTION)
1. From infected individual in the community, or a reservour host when shedding their contaminated body fluids from lessions, or by contact, or by inhalation, or by urogenital tract, or by GIT (feaco-orally).
2. From infected animal.
3. From food items, soil, contaminated water, contaminated spropagules.

MODE OF TRANSMISSION OF INFECTION.
The modes of transmission of infection are dependant on source of infection. Mode of transmission can be achieved by:
1. Direct Transmission: This can be achieved between two individuals, the infected and the susceptable host (non-infected). It can be physical or through, contact such as hand shaking, kissing, sexual intercourse, exchange of cloths, etc.
2. Indirect Transmission: By air, soil, water, foods/beverages, insects, etc.

STATES OF INFECTION
Three states of infections exist as follows:
1. Fatal Infection
2. Clinical Infection ;( Usually present with signs and symptoms).
3. Sub-Clinical/Latest Infection; The aetiological agent established itself, the host tolerates and may not present with life threatening symptoms.

FACTORS THAT DETERMINES HOST PARASITE INTERACTION
1. VIRULENCE: Virulance or disease producing power is defined as the ability of the organism to cause harm to, and or injure the body of the host. The virulance of an organism can range from low to high and can be termed as either LC (Lethal Concentration), or LD (Lethal Dose). The known contributing factors to organism’s virulance could be:
• Toxin production; which injure or even kill the tissue cells, paralysing the body defence. Two kinds of toxin are exotoxin, which diffuses out of intact organism’s cell and endotoxin, which do not diffuse but act from within the organism’s cell.
• Formation of capsules; which appear to functioned as organism’s defence against phagocytic activity of PMN cells of WBC, and also in organism’s resistance against anti- microbial agents.
2. INFECTIOUSNESS: Defending on its virulance and condition of the host, an organism can be infective or not.
3. INVASIVENESS: This is the ability of the organism to enter or invade the host body, established, multiply and damage the tissue cells. An organism can infect, but may not cause disease if it is not invasive. Invasiveness could alter the physiological mechanism of the host body system due to intracellular replication of the organism and the excretion of extracellular metabolites such as:
• Keratinase formation: Enzyme capable of digesting keratin. Example in Trycopathon species.
• Leukocidin formation: These are leukocytes digesting metabolites.
• Coagulase formation: Enzyme causing coagulation.
• Hyaluronidase formation: Enzyme capable of digesting hyaluronic acid.

4. PATHOGENICITY: This is the ability of an organism to induce pathogenic presentation as a result of interaction with the host.
Pathogenicity of an organism could be due to the following:
• Toxin production; such as the exotoxins, endotoxins and microtoxins.
• Anti-phagocytic activities,
• Competative Metabolism; I.e competition between the host and the parasite on nutrients of the host, and consequently outcompete the host in terms of utilisation of nutrients.
• Generating of Cellulicidal Materials; I.e, cell killing materials such as leukocidins, etc.
• Ability to induce allergic damage; I.e damage to the tissues, induction of tissue aggregation, fibrosis, tissue inflamation, necrosis, cavitation, exudates/caseation formation, high tissue fragility leading to trauma and heamorrhage.
• Production of Autoimmune Diseases; Such as the production of allergic immunoglobulins such as IgD and IgE. Autoimmune disease is an immunologic reaction between the immune complex of the host and its own self. E.g rhumatoid arthritis.
• Glomerulonepharitis,
• Cardiac lession,
• Antigen/Antibody reaction,
• Destruction of immune-response (Immuno-compromisation).

FUNGI AS PARASITES
A parasite is an organism completely or partially dependant on a suitable susceptable host for nutrients and shelter. Three types of parasites are:
1. Symbiotic: Living together both the parasite and the host benefits. (search for fungi which live in symbiotic r/ship with man).
2. Commensal; Living together, the parasite is benefiting, while the host neither benefits nor harmed.
3. Pathogenic; The parasite is benefited while the host is harmed.Many fungal pathogens of man are Di-Morphic (having two morphological features), i.e, convertible into either mouldy structure (mycelia clump together), or yeast-like (exist as yeast cells). The mouldy ones exist as normal saprophytic culture, but when they are inside a living tissue (370c), they become a yeast-like.

CHARACTERISTICS OF PARASITIC FUNGI
Before an organism will be regarded as a parasite, it must posses the following characteristics:
1. It must be capable of finding a suitable portal of entry into the host.
2. It must adapt easily with the new environment (host organs, tissues or cells).
3. It must multiply on or within the host.
4. It must leave the host through a suitable portal of exit.
5. It must survive in an immune subject/host.
6. It must be communicable; i.e must have the ability of surviving outside the host until it reaches a new susceptable host.

GROUPS OF FUNGI ASSOCIATED WITH MAN AND ANIMALS.
1. PHYCOMYCETES GROUP: These group of fungi include the:
a) Coelomycetaceae: Associated with insects.
b) Cateraniaceae: Associated with worms (Nematodes, Flat helminths).
c) Lagenidraceae: Associated with Crustaceans (Cyclops, Artenia spps, Dapnia).
d) Saprolegniaceae: Associated with fishes.
e) Mucoraceae: Associated with man and animals.
f) Entomucoraceae: Associated with insects, humans and horses.
g) Zoophagaceae: Associated with protozoan, nematenia.
h) Eccrinaceae: Associated with Arthropods.
2. ASCOMYCETES GROUP: These group of fungi include:
a) Hypocreales: Associated with insects.
b) Labouboniles: Associated with insects.
c) Aspergillates: Associated with man and animals.
d) Saccromycetes: Associated with man and insects.
3. BASIDIOMYCETES: This group of fungi produces mycotoxins which affect birds and insects.
4. DEUTROMYCETES: These groups of fungi are associated with man. They caused diseases such as mycetoma, chromiomycoses, cladosporosis, phaesprotricoses, etc.
5. ACTINOMYCETES: These are very limited in distribution.

SPORULATION AS A SURVIVAL STRATEGY IN FUNGI.
Sporulation can be defined as a process of producing spores in microorganisms.
Deviation from the optimal level of the physico-chemical factors that affect the physiological well being of the organism may induce adverse environmental condition to the organism.
Thus, a spore is a specialized structure with enhanced survival value that enables the organism to endure adverse environmental conditions, and with features that promote dispersion.
1. The nature of spores among fungi is an essential tool in their classification.
2. The growth medium (environmental condition) influences the type of spore produced.
3. A medium deficient in sugar content, low nitrogen, low protein content (peptone) are experimentally found to be more ideal for sporulation.
4. Specific organism posses specific signal factor that encourages them to sporulate, e.g, Streptomyces spp’s response to deficiency in biotin (a co-enzyme).
5. Some depend on either the presence or absence of light to sporulate.


Sporulation helps fungi in mantainance of the following:
a) Temperature: Normal optimal temperature for fungi is 250c, but if incerased further due to adverse env condition, fungal spore may tolerate it up to 450c and above.
b) Water Activity: (Also refer to humidity and hydrostatic activity). The usual tolerable limit by fungi is between 0.65 to 0.99 Aw.
c) Redox Potential: Fungi are capable of surviving under any condition due to their redox potential.
d) Change in Ph: Fungal spores are capable of surviving in more acidic Ph.

Some fungi produce spores that are haploid (sexual) in nature, while other produced spores that are diploid (asexual) in nature, (Both are produced at chromosomal stage).
Two forms in which spores can exit are available:
1. Microscopic spores (Microconidia); which are in the limit of 3-5um in size. They are at the nucleus level (haploid).
2. Macroscopic spores (Macroconidia); which are more than 6.0um in size.They are at the cellular level, and can break into pieces to generate cylindrical spores.
Fig: 7.

Some fungi produces circular or sac-like spores in nature.E.g the
Ascus in Ascomycetes.
Some are produced at a branchial structure, giving rise to new younger spores.
Fig:8.
Some can produce intercallary spores.
Fig: 9.
Some can produce terminal spores.
Fig: 10.
Some produced it in large quantities, as in rhizopus.
Fig: 11.

It should however be noted that another name for spore is conidium.
The term conidium is commonly applicable to asexual kind of spore as well as sporongiophore.
The sexual spores are formed by blastogamy i.e. when two cells meet, the result is blastogamy.
Fig: 12.

Some fungi (and yeast) produce sexual spores by either,
1. Karyogamy,
2. Syngamy, or
3. Meosis.
These may lead to the formation of varieties of spores with features or outlook. E.g,
1. Ascospores, as in Ascomycetes, (Aspergillus).
2. Basidiospores as in Basidiomycetes, (Mushrooms).
3. Zygospore; which posses thick wall.

TYPES OF ASEXUAL SPORES IN FUNGI.
1. Arthrospores (Arthroconidia); This is formed by hyphal septation, and is observed in the following organism;
• Observed as geotrachum in the organism Geotrichum (found in ithe soil, and is cylindrical).
• Observed as trachosporum in the organism Coccidioides immitis (spherical spores).
2. Phialospores(Phialoconidia); This is observed in the following fungal organisms:
• Aspergillus spps (Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus) Fig 13.
• Penicillum spps (Penicillum notatum, Penicillum chrisogenium) Fig 14.
3. (Aleorioconidia); Spores or conidia are borned on lateral or terminal conidiospore. They are attached by the conidiospore at a broad base which approached the diameter of the conidium itself, and the conidium is not released immediately. Eventual release of the conidium is by the sterigma (opening) and the cell wall rapture. However, the conidia retains it characteristics ragged peripheral structure.(Fig 15).
4. Chlamydospores (Chlamydoconidia); these are produced either on top or within the strand of the hyphae (on top as terminal spore, within the strand as intercallary spore) (Fig 16). This is usually common among Cladosphora. The chlamydospore borned either terminal or intercallary, containing a large reserved of glycogen and other stored materials.
5. Sporongiospore (Sporongioconidia); these are spore carried by a sporongiophore. They are formed by progressive cleavage of sporogenous cells within the sporongium. These spores are common among Phycomycetes.
6. Endospores (Endoconidia); these are usually spores formed inside or within the tabular end of a hyphae. They are separated by septum formation. (Fig 17).
7. Blastospores ; these are formed by conjugating blastoconidia.(Fig 18).

PRE-DISPOSING FACTORS TO MYCOTIC DISEASES.
1. Immunosuppression.
2. Poor personal hygiene
3. Debilitating and Diabetic conditions
4. Concurrent diseases such as Leukemia, HIV, TB, etc.
5. Hyper susceptibility due to prolonged treatment with corticosteroids (Hydrocortisone), antibiotics or immunosuppressive agents.
6. Repeated exposure of body parts to prickling agents (tongs, pins, etc.), which lacerates or break the skin. Exposure of body parts like feet especially in the tropics can pre-dispose to fungal infections.
7. Abression/Breaking/Wounding of blood vessels or immunologically silent tissues (synovial area, brain area sole of feet, cornea of eye, etc) can also pre-dispose to fungal infections.

a. Fungi based on their ability to establish in the body of man as disease causing agent can be divided into three groups as follows:

1. Biotrophs: This group obtains parts of their nutrients from living host to complete their life cycle. They are further sub-divided into two:
• Halobiotrophs; which cannot be cultured on artificial medium. They only thrive and produce sexual spores in the host.
• Metabiotrophs; which can be cultured on artificial medim, and can exist as saprophytes when outside a host.
2. Hemi-biotrophs: This group like the biotrophs started within a living host. They invade, infect and metabolised after an incubation period. The invaded host tissue becomes necrotic, and they would then revert to being saprophytic and hence will sporulate. During this process, they compete or associate with other saprophytes/parasites at this level.
3. Pathotrophs: These groups are fungi which act within the host cell. They kill the host cell in advance of invasion, before obtaining nutrients from freshly killed host tissue.

b. Based on the body part affected, fungal diseases can be classified into two groups as follows:

1. Dermatophytosis; ( or superficial Mycoses),which affects the external body parts, such as the skin, hair and nails.
2. Mycoses; which are fungal diseases that affects the internal tissues and organs of the body.They are further divided as:
• Cutaneous Mycoses,
• Subcutaneous Mycoses
• Systemic Mycoses.

(Practice Question)
Enumerates the characteristics of spores of several pathogenic fungi and how they can be identified.

DERMATOPHYTOSES.

• These are generally called ring worm diseases. They are also called superficial mycoses.
• They occur on the skin, hair and mucuos membranes.

Aetiology: Caused by fungal organisms called Dermatophytes, comprising of the genera; Trichophyton, Microsporum and Epidermophyton species. The causative agents are sometimes present in the tissues without producing symptoms, and they rarely if ever cause fatal infections.

Epidemiology: The diseases are wide spread and cosmopolitan (anywhere in the world), affecting any races, i.e, the Negroes, the Caucassians and the Mangloids. The disease is more troublesome in the whites, probably due to less quantity of skin melanin. The disease is also among animals as well.

Transmission: Transmission is by direct contact with infected individual, animal, or both. Transmission can also be through a formite (article/object), contaminated by the mycelia or spore of the fungi.

Pathology: Anatomical changes due to the diseases are observed,as a result of abnormal presentation of the body parts affected, which will appear different from the normal body parts.

Signs and Symptoms: The clinical presentation of these infections is somewhat silent, sub-clinical or sub-acute at initial stage, and may progress gradually to chronic stage. The diseases are however more annoying.

Example of the Diseases Caused:
1. Onchomycosis (Disease of Nails); due to the fungal organism, Trichophyton rubrum, Trichophyton magninii.
2. Tinea capitis (Disease of the scalp, eyebrows and eyelashes); a ringworm disease due to the fungal organisms, Microsporum canis (cats, dogs, horses), Microsporum gypseum (humans), Microsporum audounii (children).
3. Tinea Barbea (Diseases of the beard and moustache), caused by the zoophilc fungi; T. verrucosum and T. mentagrophytes.
4. Tinea Corporis ( Face and trunks).
5. Tinea Cruris ( Groin, perineal and perineal areas).
6. Ring worm of glabrous skin (where there is no hair); due to Trichophyton violaceum and T. scheneli.
7. Ring worm of cattle; due to Trichophyton verrucosum.
8. Ring worm of birds; due to Trichophyton gallinae.

Control and Treatment:
Due to the facts that fungal organisms are eukaryotic, mimicking higher cells in activities, such diseases are very difficult to control, even with the most powerful anti-fungal agents.
Promising anti-fungal agents include; AmphotericinB, Nystatin, Clotrimazole, Griseofluvin and Fluconazole. Other useful anti-fungal drugs are Ketaconazole, Hydrogen peroxide, Zinc, Sulphur and Benzoate topicals.
Treatment requires long time of exposure of the affected body parts to these agents; otherwise short time exposure will only be successful in removing the surface organisms.


Table of some common Dermatophytes.

Fungal Grp. Example. Occurrence & Disease Type
Epidermophyton. E. floccosum Skin, Nails on fingers & toes
Microsporum. M. audounii.
M. canis.
M. gypseum Ringworm of scalp in childn
Cats, dogs &other animals
Saphyt in soil, para of lw ani.
Trichophyton Gypseum Subgrp.
T. mentagrophytes
T. rubrum
T. tonsurans

Faviform Subgrp
T. scheonleni
T. violaveum
T. ferrugineum
T. concentricum
T. verrucossum

Rosaceum Subgrp.

T. magnini
T. gallinae
Parasite of the hair
Hair,scalp & many body prts
Infects hair & scalp


All cause ringworm of skin
scalp and glabrous skin in
humans




Ringworm of human scalp.
Ringworm of birds (chicken)


Miscellanoeus: Piedraiahorti


Trichosporon beigeli

Norcadia minutissima


Melassezia furfur




Norcadia spps Hair & scalp xterzed by hard
black concretions(blk piedra)

Same as above, white conc

Causes erythrasma; a chron
ic infectn of axillae & genital

Caused tinae vasicolor; a Generalized fungus infection Of the skin covering trunk And other body parts.

Caused disease of pubic & Auxillary hairs called Trichomycosis axillaris.

Aspergillus, Penicillum, Mucor & Rhizopus spps These common saprophytes
May cause Otomycosis(ear
Infections) & produced lesions in other body parts.
Aspergillus fumigatus Know to produce a neurotoxin called aflatoxin.



SKIN CHANGES DUE TO FUNGAL DISEASES.

1. Alopecia: Loss of hair.
2. Depigmentation: Loss of melanin.
3. Echymoses: Extravasation of blood
4. Erythema: Reddish spots of skin site from vasodialation, usually blanched by pressure.
5. Haemosidirosis: Deposition of haemosiderin (yellowish-brown mucous like) at the site of infection.
6. Hypopigmentation: Low/diminishes in melanin pigmentation.
7. In filtration: Palpable and thickened skin by absorption of fluid materials from the skin.
8. Melanosis: Darkening of skin due to increased melanocyte activity.
9. Oedema: Thickening, swelling and palour (pale) especially at the palm, face, feet, etc, mostly due to extracellular fluid retention at the infected area.
10. Purpura: Extravasation of blood into the skin. Similar to erythema, but is extensive rather than localized, i.e., it does not blanch.
11. Telangicetasis: Persistent vasodialation, not blanch by pressing.

SHAPES OF LESIONS USEFUL IN DIAGNOSIS OF FUNGAL INFECTIONS

1. Arcuate Annular Lesions: Psoriasis, Lichens planus, tuberculoid leprosy, in 2nd and 3rd degree thickness.
2. Concentric Rings: Such as in erythema multiformis.
3. Horse-shoe shape: Infiltrate patches, such as in all fungiodes.



MYCOSES.

Aspergillosis:
This is a name given to wide varieties of pulmonary diseases, caused by less common fungal pathogens of the genus Aspergillus, causing disseminated diseases in terminally ill patients and immunocompromised individuals. The common menifestations are a range of respiratory diseases, such as allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, and invasive aspergillosis; the nature of which is determined by the immune response of the host.

Aetiology: Aspergillus niger, A.fumigatus, A. flavus, A. nichilans, A. terreus and A. carneus.
Transmission: Transmission is chiefly by air, where most humans inhale Aspergillus spores constantly.
Symptoms: A fungus ball in the lung may cause no symptoms and may be discovered only with chest x-ray.
Or it may cause repeated coughing of blood and occasionally severe, even fatal bleeding.
A rapidly invasive aspegillosis in the lungs often cause cough, fever, chest pain and difficulty breathing.
Aspergillosis affecting deeper tissues can make a person very ill. Syptoms include fever, chills, shock, delirium and blood clots. The patient may develop kidney failure, liver failure (causing jaundice), and breathing difficulties. Death can occur quickly.
Aspergillosis of the ear canal cause itching and occasionally pain. Fluid draining overnight from the ear may leave a stain on the pillow.
Aspergillosis of the sinuses causes a felling of congestion and sometimes pain or discharged.
Diagnosis: On chest x-ray and computerized tomography, pulmonary aspergillosis menifests as an air cresent sign.
In hematologic patient with invasive aspergillosis, the galactomann test can make the diagnosis in non-invasive way.
Treatment: The drugs; amphotericin B, caspofungin, flucytosine, itraconazole, vericonazole are used to treat this fungal infection.
For severe cases of invasive aspergillosis, a combination therapy of vericonazole and caspofungin is suggested as a first line treatment.
Inflammation can also be resolved by the use of nasal sprays containing corticosteroids, eg, beclomethasone, budesonide, etc.

Blastomycosis.
This is primarily a pulmonary disease, also known as ‘North American’ blastomycosis, ‘Blastomycetic dermatitis’, ‘Gilchrist’s disease’(discovered by Thomas Casper Gilchrist in 1894),or Chicago disease.

Aetiology: It is a fungal infection caused by the organism Blastomyces dermatitidis.
Epidemiology/ Occurance: The disease is endemic to eastern and portions of northern USA. These include Mississippi river and Ohio River basins and around the Great lakes. The case is also greater in northern states such as Wisconsin.
In Canada, most cases occur in Northwestern Ontario, particularly in the moist acidic soil around the Kenora area.
Blastomycosis is distributed world wide; where cases are sometimes reported from Africa.
Transmission: Infection can occur by inhalation of the fungus from its natural soil habitat, usually from dust. The incubation period is between 30 to 100 days, although infection can be asymptomatic.
Pathology: Once inhaled in the lungs, the organism multiply and may dessiminate through the blood and lymphatics to other organs, including the skin, bone, genitourinary tract and brain.
Clinical Menifestations/Sign and Symptoms: Infection starts as asymptomatic, and may present in one of the following ways:
• A flu-like illness with fever, chills, myalgia, headache and nonproductive cough, which may resolve spontaneously within days.
• An acute illness resembling bacterial pneumonia, with symptoms of high fever, chills, a productive cough, and pleuritic chest pain.
• A chronic illness that mimics tuberculosis or lung cancer, with symptoms of low grade fever, productive cough, night sweat and weight lost.
• A fast progressive and severe disease that menifest as ARDS, with fever, shortness of breath, tachypnea, hypoxemia and diffuse pulmonary infiltrates.
• Skin lesions, usually asymptomatic, appear as ulcerated lesions with small pastules at the margins.
• Bone lytic lesions can cause bone or joint pain.
• Prostatitis, which may be asymptomatic, or may cause pain on urinating.
• Laryngeal involvement, which can cause hoarseness.
Diagnosis: Once suspected, diagnosis can be confirmed by demonstration of the characteristic broad based budding organisms in sputum or tissues by potassium hydroxide (KOH) preparation, cytology or histology.
Tissue biopsy of skin or other organs may be required in order to diagnose extra pulmonary disease.
Commercially available urine antigen testing appears to be quite sensitive in suggesting the diagnosis in case where the organism is not readily detected.
While culture remains the definative diagnostic standard, the low growing nature of the organism can lead to delays in treatmentof up to several weeks.
However, sometimes blood and sputum cultures may not detect the organism, lung biopsy is another option, and result will be shown promptly.
Treatment: Itraconazole when given orally is the treatment of choice for most forms of the disease. Ketaconazole may also be used. Cure rates are high, and the treatment over a period of months is usually well tolerated.
Although amphotericin B is another mainstay of theraphy, it is considerably toxic, and is usually reserved for immunocompromised patients who are critically ill.
Imidazoles have also been used successfully.

Candidiasis
This is commonly a yeast infection, also called; “thrush”, “candidosis”, “moniliasis”, or “Oidiomycosis”.
History and Taxonomic classification.
The genus Candida and specie C. albicans was described by Christine Marie Berkhout in her doctoral thesis at the University of Utrecht, the Netherlands in 1923. Over the years, the classification of the genera and species has evolved.
Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans.
The current classification is Nomen conservandum, which means the name, is authorized for use by the International Botanical Congress (IBC).
The genus Candida includes about 150 different species, however, only a few are known to cause human infections: Candida albicans is the most significant pathogenic specie. Other Candida species pathogenic in humans include C. tropicalis, C.glabrata, C. krusei, C. parapsilosis, C. dubliniensis and C. lusitaniae.

Aetiology:
• It is a fungal infection (mycosis) due to any Candida specie, of which Candida albicans is the most common. Even though Candida albicans is a common commensal of oral and vaginal mucosae, it causes infections that range from superficial, such as, skin, oral thrush and vaginitis, to systemic and potentially life-threatening diseases, which are refer to as candidemia and are usually confined to severely immunocompromised patients, such as AIDS, cancer and transplant patients.
• Candidiasis describes a number of different disease syndromes that often differ in their cause and outcomes. Unlike dermatophytes, it invades living tissues, leading to serious systemic infections.
• Candida yeasts are commonly present in humans, and their growth is normally suppressed by the immune system and by other microorganisms, such as bacteria occupying the same locations (niche) in the human body.
Predisposing Factors to Candida Infections.
• Weakened or undeveloped immune system or metabolic illnesses such as diabetes are significant predisposing factors to Candida infections. Diseases or conditions linked to candidiasis include HIV/AIDS, mononucleosis, cancer treatment, TB, steroids, stress and nutrients deficiency. About 15 percent of people with weakened immune systems develop a systemic illness cause by Candida species. In extreme cases, these superficial infections of the skin or mucous membranes may enter into the blood stream and cause systemic Candida infections.
• Patients receiving broad spectrum antibiotics, which distort the local microbial ecology and intravenous drug abusers, are also prone to disseminated candida infections.
• External use of detergents or internal disturbances (hormonal or physiological) can perturb the normal vaginal flora, consisting of lactic acid bacteria such as Lactobacilli and result in an overgrowth of Candida causing symptoms of infection such as local inflammation.
• Pregnancy and the use of contraceptives have been reported as risk factors.

• Hormone replacement therapy and infertility treatments may also be predisposing factors.
•

Table of some factors facilitating Candida infections.

Local. General.
1. Maceration of skin. Debility
2. Topical steroids Extreme of ages.
3. Dentures Immunosuppression by drugs or HIV
4. Poor oral hygiene Broad spectrum antibiotics
5. High oral candidiasis corticosteroids


Epidemiology: The disease has a world wide distribution.
Types:
Candidiasis may be divided into the following types:
• Oral candidiasis (thrush)
• Perleche
• Candidal vulvovaginitis
• Candidal intertrigo
• Diaper candidiasis
• Congenital cutaneous candidiasis
• Perianal candidiasis
• Candidal paronychia
• Erosio interdigitalis blastomycetica
• Chronic muco cutaneous candidiasis
• Systemic candidiasis
• Candida
• Antibiotic candidiasis.
Clinical Manifestations:
• Most Candidal infections are treatable and results in minimal complications such as redness, itching and discomfort, though complications may be severe or fatal if left untreated.
• In immunocompetent persons, candidiasis is usually a very limited localized infection of the skin or mucosal membranes, including the oral cavity (thrush), the pharynx or esophagus, the gastrointestinal tract, the urinary bladder, or the Instruments (vagina, penis).
• At the other, it can cause pneumonia; endocarditis and septicemia. The disease is a very common cause of vaginal irritation, or vaginitis and can occur on the male genitals. In immunocompromised patients, Candida infections can affect the esophagus with the potential of becoming systemic, causing a much more serious condition; a fungemia called candidemia.
• Children, mostly between the ages of three and nine years can also be affected by chronic mouth yeast infections, normally seen around the mouth as white patches.


Table of Some of the Clinical patterns of Candida infections.

Type. Pattern of infection. Features.
A. Oral
• Thrush: White patches: Can be scraped off to reveal inflamed
Mucus membrane.
• Atrophic Painful red atrophic Common with antibiotic treatment.
Candidiasis: mucus membrane:
• Chronic Thickened white Needs differentiating from
Hyperplastic adherent plaque. Leukoplakia
• Candidiasia
• Angular Soreness & Occurs in folds usually due to ill fitting
Stomatitis fissuring @ angles. Dentures.
B. Skin
• Intertrigo (danya); Sore, red, marginated skin: Due to maceration.
C. Ano-genital
• Vulvovaginitis: Itchy, sore with curd like dischrg: Common in pregnancy.
• Balanitis: Tiny red papules on penis: Usually from sex partner
D. Nails
• Paroncyhia: Painful swlln nail wit loss of adhesion: Maceration/poor circle.
• Onychia: Thickened discolor nails: uncommon, immune def.
There are several clinical types:
Group 1: Swiss type, a gamma-globulinamiea, with well defined major primary immune defect.
Group 2: Are those cases without primary immune defect, even though may do have abnormalities on investigation.
Sub-Groups:
1. Candida endocrinopathy syndrome; with hyperparathyroidism and Addison’s disease, being the commonest associated organ-specific autoimmune diseases.
2. Autosomal recessive.
3. Autosomal dominant.
4. Diffuse (severe) mucocutaneous candidiasis
5. Late onset candidiasis in which HIV infection should be considered.
Symptoms.
• Symptoms of candidiasis may vary depending on the area affected.
• Infection of the vagina or vulva may cause severe itching, burning, soreness and irritation, and a whitish or whitish grey discharge, often with a curd like appearance. These symptoms are also more common in bacterial vaginosis.
• Symptoms of infection of the male Instruments include red patchy sores near the head of the penis or on the foreskin, severe itching, or a burning sensation. Candidiasis of the penis may also have a white discharge, although uncommon. However, having no symptoms at all is common, and a more severe form of the symptoms may emerge later.
• In immunosuppresed patients, the infection becomes wide spread and refractory to treatment. Skin lesions often resemble ringworm and nails tend to be affected.

Diagnosis.
1. Light Microscopy: A scraping or swab of the affected area is placed on a microscopic slide; a single drop of 10 percent KOH is then added to the specimen. The KOH dissolves the skin cells, but leave the Candida cells intact, permitting visualization of hyphae and yeast cells typical of many Candida species.
2. Culture: A sterile swab is rub on the infected skin surface; the swab is then streak on sabroud agar medium. The culture is incubated at 370 C for several days, to allow development of yeast. The characteristics, such as morphology and colour of the colonies may allow initial diagnosis.
3. Chest X-ray: This may reveal pulmonary infiltrates, with Candida in bronchial washing.
4. Ultrasound Guided Biopsy: This may detect small abscess elsewhere such as in the liver.
5. Post mortem: This detects Candida septicemia, and is often a terminal event.
6. Clinical Signs: This is usually minimal, but there may be endophthalmitis (of the eye) with fluffy yellow/white retinal spots, resembling cotton-wool spots.
Treatment.
• Prior to treatment, removal of any remediable predisposing factor is recommended.
• Since Candida species are frequently part of the human body normal flora as well as intestinal flora, treatment with antibiotics should be done with caution so as not to eliminate the yeast’s natural competitors which may increase the severity of the condition.
• In clinical settings, the infection is commonly treated with antimycotic- the antifungal drugs, such as; topical clotrimazole, topical Nystatin, fluconazole and topical ketoconazole. For example, a one time dose of fluconazole (as Diflucan 150-mg tablet taken orally) has been reported as being 90 percent effective in treating vaginal Candidiasis. However, this dose is effective only for vaginal yeast infection; other candidiasis may require different treatment.
• In severe infections (generally in hospitalized patients), amphotericin B, caspofungin, or vericonazole may be used. However, the intravenous administration of amphotericin B should be done with caution, in view of its possible acute toxicity. It can cause hypotension and collapse.
• Gentian violet can be used for breast feeding thrush. However, pediatricians recommend its use sparingly, since in large quantities it can lead to mouth and throat ulceration in nursing babies.
• The use of oral ketoconazole for chronic mucocutaneous candidiasis in HIV patients is recommended.

However, it should be noted that treating Candidiasis solely with medications may not yield desired results, and other underlying conditions may be the cause. Oral Candidiasis may be the signs of more serious conditions, such as HIV infection or other immunodeficiency diseases.
It should also be noted that as with other pathogens, Candida albicans can also develop resistance to antimycotic drugs. As such the use of anti fungal agents should be done with caution.

Both cell mediated and humoral immunity participates in the control of Candida, since specific inherited deficiency of T-cell function causes severe but localized disease, whereas in mixed inherited deficiency of T- cell, the infection become disseminated.

CRYPTOCOCCOSIS.
This is a serious and potentially fatal fungal disease; also refer to as Torulopsis, caused by yeast-like fungi of Cryptococcus neoformans species complex.
Aetiology: Caused by yeast like fungi; of members of the Cryptococcus neoformans species complex, comprising the two species, C. neoformans and C. gattii, with C. neoformans further divided into two varieties: var. neoformans and var. grubii.
C. neoformans v. grubii, and v. neoformans causes clinically evident infections in immunocompromised persons, such as AIDS patients, who are especially susceptible to disseminated cryptococcosis, while C. gattii causes infections in immunocompetent persons.
Transmission: The organism is contracted from inhalation of soil infective propagules from the environment, contaminated with bird’s droppings, especially those of pigeons.
Epidemiology: The distribution is world wide. The prevalence of cryptococcosis has been increasing over the past 20 years, for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.
Clinical manifestations:
Cryptococcosis is a defining opportunistic infection for AIDS. In humans, C. neoformans causes three types of infections:
1. Wound or cutaneous cryptococcosis
2. Pulmonary cryptococcosis
3. Cryptococcal meningitis (Infection of the meninges, the tissues surrounding the brain and spinal cord) causes chronic meningitis with low grade symptoms at presentation, and it is believed to result from dissemination of the fungus from pulmonary infection.
Symptoms: These include chest pain, dry cough, swelling of abdomen, headache, blurred vision and confusion.
Diagnosis:
• Culture; using CSF, sputum and urine. However, little abnormality is found, apart from few cells, mainly lymphocytes, mildly reduces glucose compared to the blood and slightly reduced protein. However, blood culture may be positive in heavy infections.
• Direct Microscopic Examination; The organism may be observed under the microscope after staining with Indian ink.
• Serology; to detect Cryptococcal antigen (capsular materials) in CSF and blood.
Treatment:
• The standard regimen of treatment in non-AIDS patients is amphotericin B with oral flucytosine.
• AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole can be used.


COCCIDIOIDOMYCOSIS.
Etiology:
Coccidioidomycosis is an airborne infection; a systemic mycoses caused by inhaling the microscopic spores of the dimorphic fungus, Coccidioides immitis.

Epidemiology:
The organism is distributed in the arid regions of western hemispheres, such as the southwestern United States, northwestern Mexico, Argentina and other areas of Central and South America.

Mode of Transmission: Transmission is by air, after inhaling the microscopic spores of the fungus.

Clinical menifestations :
The clinical menifestations of this infection have been divided into three types:
1. Initial pulmonary infection, which is usually self-limiting,
2. Pulmonary complications, and
3. Extra pulmonary diseases.

Pathology:
After inhalation of the fungal spores, granulomatous response occur around the fungal spherules, while superative lesions with leukocytes characterize the tissue response to endospores.
The outcome of the disease depends on the host response to the organism.
Dissemination of infection from initial site of pulmonary disease may occur. Pregnant females shows increases incidence of dissemination.
All tissues and organs of the body may be affected.
Meningitis is one of the most severe manifestations of disseminated infection.

Symptoms.
Few patients may present with respiratory symptoms such as;
• Cough,
• Pneumonitis,
• Chest pain with fever and malaise. [CPC]
In some patients, pulmonary infiltrates, sometimes with cavitation persists.
Other symptoms include;
• Muscles pain,
• Night sweats and chills,
• Macular erythematous rashes (erythema nodosum and erythema multiforme.
• Hilar adenopathy and pleural effusion (as demonstrated by radiography).
Asymptomatic infection may also occur in approximately 3/5 of patients in such cases infection is detected through skin testing.

Diagnosis.
Even though there is a considerable risk of laboratory infection with this organism, the following are laboratory methods for diagnosis of infection caused by this dimorphic fungus:
1. Direct Microscopic Examination: By wet mount preparation using KOH or Calcofluor white to demonstrate the organism in body fluids, exudates, sputum and biopsy tissues. Spherules are thick walled, usually 20 to 60 um in diameter. Endospores can be observed in intact or recently disrupted spherules.
2. Culture: This involves inoculating the specimen in slants using conventional media, such as SDA at 25 to 30 degrees C, usually within 1 week. C. immitis colony appear as floccose compose of hyaline, septate hyphae with arthroconidia.
3. PCR: With specific nucleotide primers, C. immitis DNA can be amplified by Polymerase Chain Reaction.
4. Molecular Probe: This technique hybridizes with C .immitis RNA.
5. Serological Test: Indirect demonstration of the infection can be achieved by serological analysis to detect fungal antigen or host antibody produced against the fungus.

Treatment.
IV Amphotericin B, or PO fluconazole are recommended in progressive or disseminated disease, or in which patients are immunocompromised.
Alternatively, Itraconazole or Ketoconazole may be used.

PARACOCCIDIOIDOMYCOSIS.
Etiology.
This is also systemic mycoses caused by the dimorphic fungus of the genus Paracoccidioides brasiliensis.

Epidemiology.
The disease is usually restricted to South America; in the area between Mexico and Argentina, as such it is often refer to as “South American Blastomycosis”.

Transmission.
The natural environment of the organism is uncertain, so as its mode of acquisition by humans, though inhalation is the most likely mode of transmission.

Clinical Manifestations.
The disease frequently involves the mucous membranes, lymph nodes, spleen, liver GIT, adrenal glands, bones and lungs. Unlike other systemic mycoses, the infection can also affect immunocompetent persons, although Immunosupression increases the severity of the fungus.

Symptoms.
Adults may present with the following symptoms:
• Progressive respiratory symptoms, sometimes accompanied by ulcers in the mouth and nose.
• Dysphagia
• Voice changes,
• Skin lesions,
• Cervical lymphadenopathy.

Diagnosis.
This can be achieved by culture or histology.

Treatment.
1. Sulfonamides; such as sulpadimethoxime, sufadiazine and co-trimoxazole.
2. Amphotericin B.
3. Imidazoles; such as itraconazole, ketoconazole, etc.


HISTOPLASMOSIS
Etiology.
This is caused by the dimorphic fungus Histoplasma capsulatum classical, and Histoplasma capsulatum var, duboisii (found in central Africa).

Epidemiology.
The disease is cosmopolitan, and can be found throughout the world.

Transmission.
Histoplasmosis is an air-borne infection due to inhalation of the fungal spores, usually in bats and poultry droppings, and in dust. The fungus is thermally dimorphic in the environment, where it grows as brownish mycelium, but in humans (at body tempt of 37 degrees), it morphs into a yeast to initiate infection.

Clinical manifestations.
Majority of infected individuals are asymptomatic, but still the disease may be divided into the following:
1. Primary Pulmonary Histoplasmosis
2. Progressive Disseminated Histoplasmosis
3. Primary Cutaneous Histoplasmosis
4. African Histoplasmosis.
Severe infections can cause hepatosplenomegaly, lymphadenopathy and adrenal glands enlargement. Lesions have a tendency to calcify as they heal.

Pathogenesis.
As a dimorphic fungus, the inoculum is represented principally as microconidia that once inhaled into the alveolar spaces, germinates and transform into a budding yeast cells.
The organism infects tissue macrophages, resembling tuberculosis in its pathogenesis.

Symptoms.
If occur, symptoms starts within 3-17 days after exposure. Most infected individuals have clinically silent manifestation with no afferent ill effects.
The acute phase is characterized by flu-like symptoms, often with cough.
Chronic form resembles tuberculosis, and the disseminated form can affect multiple organs and systems in the body.

Diagnosis.
1. By Culture; using specimens such as sputum, blood, or tissue biopsy.
2. By Serological Test; such as ELISA and PCR to detect antigens in blood and urine, and also the detection of antibodies in blood.

COLLECTION, STORAGE AND TRANSPORTATION OF SPECIMENS
Advisable to collect as much materials as possible for an extended period as fungal isolates are less common than those of bacteria;

1. Skin, Hair and Nail samples
I. Skin Scrapings: - collected near the zone of fresh growth using curved disposable scalpel across the inflamed margin of the lesion into apparently healthy tissue. The skin should first be cleaned with 70% ethanol.
II. Skin stippings: - apply cello-tape or waterproof transparent vinyl adhesive ( 3m type 681) firmly to the affected area and feel it off. The tape now being a thin layer of skin is the applied to a sterile glass microscope alide for transport to the laboratory. Dermatophytes and ueast can be identified by culture (Milne and Barneston, 1974). However these stippings are unsuitable for microscopic examination except in cases of Pityriasis versicolour.
III. Nail samples; - are obtained by removing the friable materials under the nail.
- Clippings may be taken form the distal border with scissors of nail clippers.
- In cases of Paronychia; i.e. where a yeast infection is suspected – exudates are expressed from the paronychial folds by probing with a flat excavator and collecting on a swab previously moistened with sterile saline.
IV. Hair specimen: - hairs at the infected site should be removed by PLUCKING using epilating forceps and not cutting that cannot show the base of the hair around the hair follicle containing the infecting agents.
- The infected follicle fluoresces under woods lamp.
Storage and Transport
- All the keratinous materials should be allowed to dry to prevent overgrowth of saprophyte bacteria and fungi.
- Store in black paper pockets. Ringworm fungi remain viable for weeks or months.
- Do not refrigerate specimens as the viability of some dermatopytes is reduced.
- Strippings on cello-tape stuck on microscopic slides can maintain skin fungi viable for long and so can be stored in black paper pockets as well.
2. Sputum
This should be collected for three days consecutively at every 8 hourly.
It should be refrigerated to avoid saprophytic growth of bacteria and yeast.

3. Cerebrospinal Fluid Samples
This is collected by lumbar puncture (a minimum of 5ml is recommended). This is applicable for the investigation of Cryptococcus neoformas etc.
Transport without delay to the laboratory for examination.

4. Swabs
For yeast investigation (e.g. Candida vaginalis and C. tropicalis)
The swab should be heavily charged with pressing sites where plaques/sores are available. It should be stored at 4oC or treated immediately. The survival of yeast on dry swab is inversely proportional to time and storage temperature. Use suitable transport medium e.g. Trichomonas medium (Oxoid).

5. Other specimen
Tissue biopsies, urine, blood and all materials not mentioned above should be collected, stored and transported in a manner similar to that employed for bacteriology.

Hypersensitivity
Respiratory tract is always exposed to spores and conidia of fungi in air.
- Their surface antigens elicit strong allergic reactions (Hypersensitivity) which may be with
a. Delayed presentation
b. Immediate presentation
Depending on the site of deposition of the allergies the following symptoms can be presented:
1. Rhinitis
2. Bronchial asthma
3. Alveolitis
4. Generalized pneumonitis
The offending fungi are often non infections; ascomycetes e.g. Stachybotrys, Cladosporium, Fusarium.
The range of hypersensitivity reactions (diagnosis) can be determined by; skin testing with fungal extracts.
Control/Prevention
i. Avoidance of offending allergies
ii. Treat with corticosteroids
iii. Attempt to desensitize patients (by immunocompromisation)

“Sick Building Sydrome”
Indoor air exposure to large numbers of fungal spores, moisture in construction materials, such as wood, fiberboard allows contamination molds to flourish e.g. high population of conidia in such cases leads to debilitation cases of systemic allergic or toxic reactions.
- In cases where the fungal infestation is so high, it becomes impossible to eliminate them by fungicides or filtration.
- Such buildings should be demolished.

Mycotoxins
These are poisonous substances produced by fungi which cause acute or chronic intoxication and damage.
The toxins are secondary metabolites whose effect does not depend on fungal infection or viability.
1. Mushroom of Amanita species produces a variety of such toxins of which their ingestion can result in a dose related disease called Mycetomas.
Cooking has less effect on its potency which may cause fatal/severe damage to liver and kidney
2. Aspergillus flavus produces aflatoxin in peanuts (groundnuts) corn, grains etc. they can be mutagenic, carcinogenic and extremely toxic to experimental animals.


ANTIFUNGAL CHEMOTHERAPY
At present the available standard orthodox antifungals have limited applications because of
1. Profound side effects on animals and humans being Eukaryotic like fungi especially as regards gene, protein and cellular structures and molecular processes.
2. Narrow antimycotic spectrum
3. Poor penetration of some tissues
4. Selection of resistant fungi
Despite that new, promising one are being developed and others are in clinical trials.

The classes of the available antifungals:
A. Polyenes e.g. Amphotericin B and Nystatin which bind to ergosterol in cell membrane.
B. Flucytocine an analogue to pyrimidine cytosine on important Nitrogen base for the synthesis of Nucleic acids in cell and so for cellular multiplication.
C. The Azoles e.g. Clotrimazole and ketoconazole, these are inhibitors of ergosterol synthesis
D. Echinocardins which inhibit the synthesis of cell wall beta-glucan
E. Griseofulvin which interferes with microtubule assembly disrupts cytoskeleton element formation and so preventing mitosis and meiosis in the susceptible fungus.
At present the following are under investigation;
i. Nikkomycin; inhibits cell wall synthesis better as animal cell has no cell/chitin
ii. Pradimicin: inhibits cell wall synthesis better as animal cell has no cell/chitin
iii. Sordarin: inhibits cell elongation factor 2.






Fig. of a chemical structure

Pharmacology

Amphotericin B as intravenous injection in Sodium deoxycholate dissolved in dextrose solution. Well distributed in tissues but poorly distributed in cerebrospinal fluid. Binds firmly to ergosterol in cell membrane where it alters the membrane fluidity, perforates it and causes leakages of essential ions and small molecule out of the cell causing fungicidal effect.

Mammalian cells have no ergosterol so they are relatively resistant to the cidal effect, but since it binds to cholesterol of mammalian cell membranes, it can be toxic to them.

It has an immunostimulating effect at low dosages. It is of broad spectrum and indicated in almost all systemic infections Cryptococcus, Blastomycosis, Mycetomas, Aspergillosis, and Sporotrichosis. But Pseudolescheria boydii and Aspergillus tereus are resistant.

Side effects of Amphotericin B.
Fever
Chills
Dyspnea
Hypertension
These can be alleviated by a concomitant administration of hydrocortisone or acetaminophen (analogue) although tolerance can develop during therapy.

Chronic side effects ensure maintenance of serum creatinine and ions
Nephrotoxicity
Hypocalcium
Nausea and vomiting
Azotemia (toxicity due to the high aminoacid content due to
Renal tubular acidosis
Permanent reduction of glomerular and renal tubular function

Prevention strategy
Presently the damage can be corrected with the lipid formulation of Amphotericin B i.e. abelcet, amphotec and ambisome

FLUCYTOSINE (5-Fluorocytosine)





It is orally used but in combination with AmpB in Cryptococcus or Candidiasis and in dermataceous fungal infections.
Pharmacology: Penetrates well into all tissues.
Action: the drug is transported into cells by facilitated diffusion using permease. The fungal enzyme cytosine deaminase converts it to 5-fluorouracil and incorporated into 5-fluorodeoxyuridylic acid monophosphate. Which interferes with the activity of thymidylate synthetase and DNA synthesis. Mammalian cells lack cytosine deaminase and are therefore protected from the toxic effects of the drug. However, resistant mutants emerge rapidly. This limits its utlilit; But synergistic combination with AmpB was shown to alleviate this (negative) setback.
Indications: Cryptococcus, Candidiasis, Dermatiaceous infections such as Chromoblastomycosis.

Side effects: The metabolite of the drug fluorouracil is highly toxic to mammals. Fluorocytosine by itself has little toxicity. Prolonged action leads to the
- The metabolites producing bone marrow suppression, hair loss, abnormal liver function.
- The conversion of flucytosine to fluorouracil by enteric bacteria may cause colitis.
- AIDS patients are more susceptible
Reversal: Monitoring of serum level to the bearest minimum level advised. Stop treatment immediately incase of adverse reactions.

AZOLES
They are mainly oral antifungals for local and systemic infections.
i. Imidazoles: Ketoconazole (Miconazole, Clotrimazole are topical
ii. Tiazoles: Fluconazole, Vericonazole and Itraconazole. They are fungistatic drugs.
Action: Interferes with ergosterol synthesis. They block the cytochrome P450 – dependent 1,4 alpha – demethylation of Lanosterol a precursor of ergosterol in fungi and cholesterol in mammalian cells. The fungal cytochrome P450 are 100 – 1000 times more sensitive to azol

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@all,
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Computer Details
Dell Inspiron 1300, Celeron M, RAM 256; 80 gig.

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