Microbial pathogens 2 Flashcards
Cryptosporidium parvum and hominis
-in humans and animals
-only reproduce in humans
-dirty nappies
-waterbourne pathogens
-cause cryptosporidiosis
-diarrhoea a d flu-like symptoms
Cryptosporidiosis intro
-quite serious and potentially threatening in immunodeficient patients (AIDs)
-characterised hy a profuse watery diarrhoea
-second leading cause of diarrhoea in young children and a major contributor for diarrheal deaths in LMICs
-community outbreaks can occur
cryptosporidium life cycle
-one host required
-for c hominis host is human
-for c parvum it is human or animal (cattle)
transmission routes
-swallowing water or beverages contaminated by stool from infected humans or animals
-swallowing recretional water contaminated
-eating contaminated uncooked food
-touching mouth with contaminated hands
risk factors of Cryptosporidiosis
-small size oocysts
-wide range of host specificity
-monoxenous development (only 1 host)
-close associations between human and animal hosts
-large number of oocysts excreted
-low infective dose
-robust oocysts which are resistant to chlorine
-complex protective barrier consisting of a double layer of a protein- lipid carbohydrate matrix
occupationally acquired Cryptosporidiosis
-workers in sewage and waste water
-workers in outdoor leisure industries in contact with water
-farmers
-abbattoir workers, meta processing plant workers and butchers
-vet surgeons
-healthcare and care workers
-construction/demolition/building renovation workers
Cryptosporidiosis disease presentatiob
-symptoms start 2-10 days after infection
-some are asymptomatic
-in immuno-competent people the main symptom watery diarrhoea for 1-2 weeks
-stomach cramps or pain
-nausea and vomiting
-weight loss, dehydration and fever
Cryptosporidiosis children under 5
especially where malnoruished
-even a single episode of cryptosporidiosis can result in growth deficits lomg term
Cryptosporidiosis case study immunosuppressed patient
-65 year old man with 6 month diarrhoea syndrome co-infected with HIv
-mucosa of colon and rectum presented wth hyperplasia in clusters
-biopsies showed intestinal crytosporidiosis
-can cause severe chronic and cholera-like diarrhoea
-long periods of time
hyperplasia
increased cell production
cause of disease symptoms
-exact mechanism still unclear
-invasion of parasites in gut epithelial trigger disease and malaborption of nutrients
cryptosporidiosis diagnosis
-microscopic examination of stool samples for presence of oocysts
-immunoassay
-molecular methods PCR, real time PCR
Cryptosporidiosis treatment
-since it is a self-limiting illness in immuno-comprimised ->supportive care is only treatment
-oral or intravenous rehydration and replacement of electrolytes may be necessary for particularly voluminous watery diarrhoea
-nitoxazonide is partially effective in immuno-competent patients but works no better than a placebo in immuno-suppressed patients
-patients with HIV/AIDs are advised to take anti retrovirals to improve immune response
control of cryptosporidiosis
-remove contaminatin at source water suppky, swimming pool
-monitoring
-hygiene measures as for prevetion of all faecal-oral diseases
-especially for at risk professions (nursery/agriculture)
cryptosporidiosis vaccines
-no vaccine on horizon
-knowledge in anti-malarial is beneficial
cryptosporidiosis case study
-Outbreak in Milwaukee during the spring of 1993 A o f
in which an estimated 400,000 people-developed Population
symptomatic cryptosporidiosis with 50 deaths
93% had HIV
Future directions of Cryptosporidiosis
Developmentofaneffectivedrug
– Children
– Immunosuppressed people
- Cryptosporidium Conclusions
- Cryptosporidium parvum and Cryptosporidium hominis are waterborne pathogens that causes cryptosporidiosis, a flu-like intestinal disorder
- Disease in immunocompetent people is normally self-limiting but can be chronic and severe in immunocompromised people especially with AIDS
- There can be outbreaks, mainly from contaminated water sources or swimming pools
Toxoplasmosis intro
-T.gondii causes chronic infections in up to one-third of the human population and in animals
-in healthy individuals a primary infection with toxoplasma causes relatively mild symptoms whereas in the immunocompromised patient or in the
developing foetus, it can cause life-threatening infections with severe
neurological and ocular manifestations
-felines are the only definitive host
-toxoplasma has a complex life cycle consisting of intestinal and tissue phases
Toxoplasmosis intestinal phase
of the infection occurs only in felines and exhibits a typical intestinal life cycle consisting of merogony and gametogony.
Toxoplasmosis sexual cycle
produces oocysts which are excreted in faeces
Toxoplasmosis transmission routes
-ingestiob of material contaminated with sporoulated oocysts cat faeces
-ingestion of undercooked meat containing tissue cysts or tachyzoites
-infection rates of 50% r higher in domestic chickens, geese, cattle goats, pigs and sheep
-38% meat samples in UK positive
Toxoplasmosis congentical transmission
-can only occur during an acute infection acquired during pregnancy
-mothers with a chronic infection acquired before pregnancy are not at risk for transmitting toxoplasma
-2 in 1000 women catch toxoplasmosis
-in only 30-40% of women teh infection passes onto foetus
-Risk is greatest in the third trimester at 70%, whereas in early pregnancy only 15% of infants will become infected.
Toxoplasmosis
acute disease
In immuno competent individuals – Does not normally cause symptoms – Can cause flu-like symptoms
– Typically self-resolving within 6 week
toxoplasmosis acute disease those most at risk
- Pregnant women and their unborn children
- Those with weakened immune systems
- Toxoplasmosis infection may lead to miscarriage, stillbirth or survival with growth problems, blindness, water on the brain (hydrocephalus), brain damage, epilepsy, or deafness. This often develops after birth, so even normally born infants of women with known infection should be kept under observation for some time.
toxoplasmosis chronic disease
-effects of congentical toxoplasmosis can be life long
-coular disease
-reactivation of dormant tissue cysts can occur
-neuroloical effects
toxoplasmosis dormant or resting stage
*As the host develops immunity the replication rate will slow and the infected host cells will become encapsulated (ie, tissue cysts).
– These slowly replicating forms are called bradyzoites (brady means slow) and represent a dormant or resting stage.
* Bradyzoites secrete chitin and other components to form a cyst wall
toxoplasmosis reactivation
-associated with waning immunity (malignancies, transplantation and AIDs)
-results from release of encysted organisms and the intitiation of te tachzoite stage of infection followed by tissue damage and inflammation
Ocular toxoplasmosis
-occurs from activation of cysts deposited in or near the retina
Reports of clinical toxoplasmosis in immunocompetent people- case study
-late 1994 and early 1995 outbreak of toxoplasmosis occured in a canadian community
-serological evidence consistent with acute toxoplasmosis was demonstrated in 100 people
-epidemiologic evidence implicated contamination of the city water supply withh oocysts
toxoplasmosis diagnosis
- Serologic testing IgG or IgM
- Molecular testing eg PCR
- Can detect parasite in biopsies
- Ocular disease by case history and serologic testing
toxoplasmosis treatment
- The recommended treatment is the synergistic combination of pyrimethamine plus sulfadiazine.
- Spiramycin for prophylactic use during pregnancy
toxoplasmosis control
-cooking meat to safe temps
-wash fruit and veg
-avoid drinking untreated water
-wear gloves for gardening and wash hands afterwards
-clean cat litter trays immedietly avoid if pregnant
toxoplasmosis vaccine development and validation
-Toxovax® is intended for the prevention of toxoplasmosis abortion in ewes
(may revert to pathogenic strain so not suitable for humans)
-another type of vaccine that would be of grrat importance would be one administered to cats that could prevent or reduce the shedding of oocysts
-oral vaccine was developed and validated for cats
chromic effects of latent toxoplasmosis
rodent
– Host behavioural changes could benefit parasite
– infected rodents are more likely to investigate novel stimuli and appear less cautious when presented with signs of cats.
– hypothesised to increase the susceptibility of infected rodents to predation by cats, and therefore to increase the odds of completing the T. gondii life cycle.
chronic efffects of latent toxoplasmosis
human
– No adaptive benefit to parasite
– Case-control studies show interesting correlations with human behaviours, mental health disorders and toxoplasma seropositivity
* Schizophrenia, autism, risk-taking eg risk of traffic accident
toxoplasmosis conclusions
- Felines are the definitive host for Toxoplasma gondii
- Toxoplasma gondii causes chronic infections in up to one-third of the human population and in animals
- In the immunocompromised patient or in the developing foetus, it can cause life-threatening infections with severe neurological and ocular manifestations
- T. gondii observed to alter rodent psychology and studies suggest association with human behaviour
Introduction to slow-growing Mycobacteria
- The doubling time of slow-growing mycobacteria is no less than 16 hrs
- Most are harmless environmental bacteria
- A few have evolved as major human pathogens
- M. tuberculosis * M. leprae
- M. ulcerans
3 chronic diseases slow growing mycobacteria
- Mycobacteria tuberculosis causes tuberculosis
- World’s deadliest infectious disease
- Mycobacteria leprae causes leprosy
- Affects skin, nerves, eyes and respiratory tract * Documented in ancient literature
- Mycobacteria ulcerans causes Buruli ulcer
- Affects the skin and sometimes bone
- can lead to permanent disfigurement and long-term disability
mycobacteria
what makes them pathogenic
- Low infectious dose (1 cell)
- Intracellular pathogens – in macrophage
- Resistant cell wall
- Subvert the human immune system
- Mycobacterial cell surface components stop phagosome killing
- Form characteristic granulomatous lesions
- Immune cell cluster limiting mycobacterial invasion which mycobacteria
can survive within * Slow-growing
mycobacteria granuloma
-host immune cells fight infection by clustering into granuloma
-mycobacteria are inside of macrophages in centre of granuloma
-contained but surviving
-suppressing phagosome killing
-balance between host and pathogen varies
Mycobacterial cell wall
- Acid fast staining
- NB neither Gram positive nor Gram negative
- thick, waxy, hydrophobic cell envelope
mycobacteria challenges to treatment/vaccination
- Resilient to most antibiotics
- Drugs are available that treat mycobacterial infections
- Resistance develops through mutation
- Long term treatment with antibiotic mixtures necessary
- The vaccine BCG offers partial protection, particularly to children
- Vaccines work poorly due to immune evasion strategies of mycobacteria
Slow growing mycobacteria summary
- Some slow growing mycobacteria are intracellular pathogens
- Unique features
- Cell wall structure
- Slow doubling time * Immune subversion
- Major disease causing agents * Human tuberculosis
- Leprosy
- Buruli ulcer
- Treatable but resistance to drugs a problem * Vaccine available- poor efficacy
Leprosy or hansens disease intro
a chronic infectious disease of the skin and nerves.
* The main causal agent is Mycobacterium leprae
* Symptoms are:
* loss of sensation in hands and feet * leading to disability through injury * blindness.
* Curable with multidrug treatment regimes
leprosy
-one of the oldest and most stigmatised diseases
-the stigma can result in rejection and exclusion (linked to widespread misunderstanding)
-not highly contagious
-typically caught via close contact over an extended period and is mainly spread through droplets from the nose and mouth by coughing
-can be cured
global distribution of leprosy
remains endemic in central africa, southeast asia and south america
-with more than 200000 new cases per year globally
leprosy statistics (WHO 2019 data)
-15,000 children were diagnosed
-an estimated 2 to 3 million people with leprosy
-countries with highest number of new diagnosis is india, brazil and indonesia
-over half of new cases are in india
-hoem to third of world’s poor a group disporoportiannally affected by the disease
leprosy nine banded armadillos
-in the USA they have been shown to transmit M.leprae to humans
-strains are shared
-respresents zoonotic resevoir
leprosy red squirrells in UK
-possible zoonotic resevoir
-only recently detected 2008
-non known squirrel-human transmission case
Leprosy disease presentation
-affects skin and nerves
symptoms are skin lesions, loss of sensation in hands and feet, disability through injury, blindness and nasal septum damage
M. leprae is intraceullar parasite of
-keratinocytes
-nerve cells
-dendritic cells
-macrophages
leprosy pathology
-chronic granulomatous disease effecting teh skin and peripheral nerves
-understanding of its pathogenesis and interaction with the human host is limited inability to culture the bacterium in vitro (some animal model organisms)
leprosy disease progression
-95% of people show no symptoms (heritable)
-within the 5% there are a range of symptoms
-classified in spectrum from Tb to leprosy
lepramatous leprosy
-extensive sensory loss over a longer period
-more severe disease and larger numbers of bacteria
-facial deformaties and paralysis
-involvement of eyes, bones and other tissues
spectrum from tuberculoid to lepromatous
cell-mediated immunity
-macrophage activation
humoral immunity
-macrophage suppression and b cell stimulation
Lepromatous leprosy is characterized by a Th2 T-cell immune response
- antibody complex formation
- the absence of granulomas
- failure to restrain M. leprae growth.
- robust antibody formation occurs but is not protective
- cell-mediated immunity is conspicuously absent (eg activation of macrophages)
tuberculoid leprosy
eatures Th1 T-cell cytokine response
* vigorous T-cell responses to M. leprae antigen
* containment of the infection in well-formed granulomas
leprosy nerve cell interactions
M. leprae is an obligate intracellular pathogen with a distinct preference for Schwann cells of the peripheral nervous system and for macrophages
ischemia
resticted blood flow
apoptosis
programmed cell death
demyelination
loss of myelin sheath
Co-evolution of humans and M. leprae
- an obligate intracellular parasite whose primary host is humans
- likely that the leprosy bacilli started parasitic evolution in humans or early hominids millions of years ago
- makes leprosy the oldest human-specific infection
M. leprae evolution
-intraceullar therefore small genome through reductive evolution
-evolved to incresingly parasitic lifestyle resulting in only being able to grow within host cells
* It contained around 1,600 pseudogenes with loss of ~50% of the ancestral genes
* Pseudogenes are considered as molecular fossils
human co-evolution with M. leprae
- Susceptibility to leprosy varies, with protection heritable
- Multiple single nucleotide polymorphisms (SNPs) involving many genes have been found to be associated with increased or decreased protection
- Region specific prevalences
- Example:
- Tol-like receptor 1 (TLR1) mutation from isoleucine to serine at AA 602 * Homozygous individuals protected against leprosy
- Suggests TLR1 part of pathogenesis mechanism for leprosy * Involved in immune response/signalling in macrophage
leprosy diagnosis
at least one of:
1. definitelossofsensationinapale(hypopigmented)or reddish skin patch
2. thickenedorenlargedperipheralnerve,withlossof sensation and/or weakness of the muscles supplied by that nerve
3. microscopicdetectionofbacilliinaslit-skinsmear
leprosy Classification of disease severity
- Paucibacillary (PB) :
- a case of leprosy with 1 to 5 skin lesions, without demonstrated
presence of bacilli in a skin smear. - Multibacillary (MB) :
- a case of leprosy with more than five skin lesions;
Image from Open University - or with nerve involvement (pure neuritis, or any number of skin lesions and neuritis);
- or with the demonstrated presence of bacilli in a slit-skin smear, irrespective of the number of skin lesions.
leprosy Treatment is dependent on PB or MB
- In 1981, the World Health Organization (WHO), recommended the use of multidrug therapy comprising of:
- dapsone
- clofazimine * rifampin
- 6 months treatment for PB
- 12 months treatment for MB
- Early diagnosis and prompt treatment can help to prevent disabilities
- WHO provide the multi drug therapy free of cost- donated through an agreement with Novartis
leprosy Treatment is dependent on PB or MB problems!!
- Problems of resistance emerging to all three drugs * Dapsone has been used since 1945
- most resistance to this drug
- Some cases relapse several years after therapy completed * Second line drugs are available if resistance to MDT arises
Dapsone
- A sulfone antibiotic
- inhibitor in the folate synthesizing enzyme system
- Folic acid is necessary for bacteria and humans alike
- Bacteriostatic
- Resistance can arise through point mutations on gene (folP1) for target enzyme
Rifampicin
- Ansamycin class of antibiotics
- Semisynthetic as it is modified from the natural product rifamycin * Action is as an RNA polymerase inhibitor
- Blocks bacterial transcription
- Side effects common
- Resistance occurs through mutations at binding site of rifampicin on RNA pol
Clofazimine
- Synthesised for 70 years
- Molecular mode of action against mycobacteria unclear!
- anti-inflammatory
- Resistance can occur through over expression of transporters
leprosy prevention
- Community awareness is key
- Case detection and treatment with MDT
- WHO recommends tracing household contacts along with neighbourhood and social contacts of each patient
- administration of a single dose of rifampicin as preventive chemotherapy to close contacts
- BCG vaccination given primarily for TB may offer some protection against leprosy
Problems with stigma associated with leprosy
- Many people living with leprosy are unable to work due to disability caused by the disease or may face stigma that prevents them from working
- In some countries, the law allows a person to legally divorce a spouse because they are affected by the disease
- The stigma of leprosy affects the physical, psychological, social, and economic well-being of those with leprosy, contributing to the cycle of poverty in the affected regions
leprosy Eradication of disease
- As a curable disease there is an aim to eradicate it within the human population through interruption of transmission
The Global Leprosy Strategy 2021–2030 “Towards zero leprosy”
1. implement integrated, country-owned zero leprosy road maps in all endemic countries
2. scale up leprosy prevention alongside integrated active case detection
3. manage leprosy and its complications and prevent new disability
4. combat stigma and ensure human rights are respected
Tuberculosis (TB)
-infectious air bourne disease
-main causal agent is Mtb)
-immune response can contain Mtb as latent form of disease
-active form is cotagious and causes disease symptoms
-primarily a pulmonary disease (lungs)
-can cause disease in most parts of body
-2021 second leaing infectious cause of death
-many low and middle income countries TB is a major cause of morbidity
TB summarised intro
- Curable with prolonged multidrug treatment regimes
- Increasing problems with drug resistance
- BCG vaccine offers some protection
- Other mycobacteria can also cause tuberculosis from the Mycobacterium tuberculosis complex (MTBC) including M. bovis
TB global distribution
sub saharan africa and asia
co infection with HIV
estimated HIV prevalence in new and relapse TB cases
TB transmission
-primarily airborne disease
-not highly infectious (3-10 people)
-long period of infectiousness without treatment 1yr<
Disease progression of TB
-eliminated
or
-latent = strong cell mediated response
or
-active = weak cell mediated response
Tb disease symptomss
- Pulmonary presentation
- a bad cough that lasts 3 weeks or longer
- pain in the chest
- coughing up blood or sputum (phlegm from deep inside the lungs)
- Other symptoms of TB disease are: * weakness or fatigue
- weight loss
- no appetite
- chills
- fever
- sweating at night
- TB in other parts of the body symptoms depend on part affected
diagnosis of Tb
- Physiology- night sweats, temperature, persistent cough, weight loss, fatigue
- Smear test- microscopic visualization of acid-fast bacilli in the sputum
- X-ray of the chest to detect patches on the lungs
- Cultivation sputum using highly growth sensitive systems such as the MGIT
Tb Diagnosis contnued
- Tuberculin skin test (Mantoux test) for hypersensitivity to antigens of Mtb.
- IFN-gamma release assay
- T-SPOT.TB assay for activated TB-specific effector T
cells (TB ELISpot) - Detection of Mtb specific antigens in the blood
- Detection of specific genes using qPCR GeneXpert targets Mtb using rpoB, also will detect rifampicin resistance
TB drog resistance
- MDR-TB is resistant to at least isoniazid and rifampicin, the two most important first-line drugs used in the treatment of TB.
- This may result from either primary infection with drug-resistant bacteria or
- May develop in the course of a patient’s treatment when non-optimal
treatment durations or regimens are used. - Cure rates for MDR-TB are lower, typically ranging from 50% to 70%.
- XDR-TB is resistant to isoniazid and rifampicin as well as
any
Drug resistance (XDR-TB)
- XDR-TB is resistant to isoniazid and rifampicin as well as any fluoroquinolone and any of the second-line anti-TB injectable drugs (amikacin, kanamycinor capreomycin).
- It has very high mortality rates.
TB Latency and drug resistance
- Latent TB is asymptomatic and not infectious; it arises upon immune restriction of the growth of M. tuberculosis in hosts.
- Hypoxia (one of several environmental stresses encountered by the Mtb in host cells), has been shown to induce non-replicative bacterial phenotypes, leading to tolerance towards certain drugs like cell-wall inhibitors such as isoniazid
- lack of potent drug activity on these bacterial phenotypes may be responsible for prolonging the TB treatment duration
TB prevention
Diagnosis and treatment of active TB cases
* Identify and test close contacts
- Identifying high risk latent TB cases and giving preventive treatment
- Manage environment: * Good ventilation
- Natural light (UV kills bacteria) * Good hygiene
- Improve conditions- healthy immune system
- BCG vaccination
TB future directions
- New drugs
- Alter existing drugs * Phage therapy
Current clinical pipeline for TB
Each drug candidate is shown with its current clinical phase of
development along with the
target family.
TMC207 is in phase IIb trials for MDR-TB and in phase Iia trials for DS-TB.
The structure of AZD-5847 has not been disclosed.
NDA, new drug application (for regulatory approval)
pathogenic mycobacterial characterstics
-low infectious dose (1 cell)
-intracellular pathogens - in macrophage
-resistant cell wall
-subvert the human immune system (enable macrophage survival)
-mycobacteria form characteristic granulomatous lesions - immune cell cluster limiting mycobacterial invasion which mycobacteria can survive within
-slow growing
environmental or non-tuberculous mycobacteria (NTM)
-typically not pathogenic environment
-cause disease infrequently - opportunistic pathogen
-in immunocomprised and immunocompetent
-no person-person transmission
-pulmonary disease is most common especially with those who have pre-esisting lung disease
-often MISDIAGNOSED as tb
combined host, environmental and organisms risk factors of NTM disease
-increased prevalence in north america, europe and asia over the last few decades
disseminated =
spread through body
environmental mycobacteria
-cervical lymohadenitis
-swimming pool granuloma
-buruli ulcer (m. ulcerans)
mycobacteria
treatment complications and economic burden of NTM
-prolonged multi-drug therapy for pulmonary NTM (12-24 months)
-high rates of re-infection (rather than recurrence)
-frequent adverse drug reactions
-20-40% of MAC-lung disease patients initially fail to respond
-dug resistant
-co-morbidity
Buruli ulcer- mycobacteria ulcerans
-indolentnecrotsising disease of the skin, subcutaneus tissue and bone
-the third most common mycobacterial disease (least understood)
-cutaneous ulcers caused by M. ulcerans were discovered at nearly the same time in two regions of southern hemisphere
indolent=
causing little or no pain
necrotising
death of tissues
Buruli ulcer (BU)
-painless necrotic skin lesions
-mycobacterium ulcerans is closely related phylogenetically to tuberculosis
-replication and persistance of M. ulcerans in BU lesions is profoundly influenced by production of mycolactone (other bacteria dont tend to have cytotoxins)
-a cytotoxin that has immunosuppressive properties
reported cases of buruli ulcer disease in 2009 by WHO
where?
across africa and australia
buruli ulcer transmission routes of
-there is little evidence of human to human transmission
-infected by envronment or vectors
-in endemic regions the disease is highly focal and usually associated with wetlands or coastal regions
-PCR testing of environmental samples such as water aquatic plants soil and detritus has found evidence of the bacteria
-insects such as mosquitos and water-residing btiing arthropods have been associated with M. ulcerans epidemiologically and via PCR testing therefore proposed as vectors for transmission
-possibly native possums
detection of m. ulcerans DNA in insect tissues from an endemic area
-insect samples were pooled by type
-monthly collection
-testing in pools of insects by type
-some types of insect more positive than others seasonal effect
KEY= non-endemic area had no PCR positive insect pools
epidemiology of Buruli ulcer
-key difference between endemic and non
-despite their closephysical proximity the non areas were unaffected by human actvity but in endemic the bank of the nyong river had been deforested
A major role for mammals in the ecology of mycobacterium ulcerans
-possum excrement from ground
found ulcers with same geome in possums as humans
-not peer reviewed
buruli ulcer
study testing mosqutos in south melbourne
-66,000 mosquitos captured and tested
-5/1000 were positive for M. ulcerans (PCR)
-Key= genome sequencing showed teh m ulcerans in people possum and humans was identical
-mouse model showed mosquitos can transmit m ulcerans
proposed transmission pathways of M. ulcerans between the environment mosquitos possums and humans
-possums ingest m ulcerans from the environment and/or infected by an insect vector
-they applify and shed the bacteria into the environment
-insect vectors become contaminated with m ulcerans from environment and/or from contact with infected possums
-m ulcerans transmitted to humans via insect vector and/or direct contact with contaminated environment
-rare cases of direct transmission from possum to human after bite
M.ulcerans progression of the disease
-resistance to M.ulcerans has been associated with the development of the Th1 type response
-granuloma observed during progression to healing
-Progression of disease due primarily to mycolactone - an exotoxin
M. ulcerans Location of skin ulcers
-lower leg lesions
-despite the use of appropriate antibiotics oedematous lesions usually ulcerate
-often well into antibiotic treatment and require debridement +/2 skin grafting
Features of M ulcerans that promote pathogenesis of BU:
-low optimal temperatures of growth (29-33°C) that makes the skin its preferntial target
-M. ulcerans behaves as an intracellular pathogen triggering inflammatory cell responses and cell mediated immunity
-unusual toxin production, mycolactone associated high cytotoxcity that contrasys with the intraceullar traits of its mycobacterial nature
-in advanced BU lesions, extraceullar clusters of M ulcerans reside in necotic subcutaneous tissue and are protected from infiltrating leukocytes by the cytotoxic activity of secreted mycolactone
-it also has immunosuppressive properties
Mycolactone- a polyketide cytotocin that has immunosuppressive properties
-precise cellular targets of mycolactone remain mysterious
-induces apoptosis of infected cells
-inhibits production of the proinflammatory cytokine TNF-alpha by macrophages
-suppresses dendritic priming of t cells
Granuloma formation
-in centre mycolactone is cytotoxic and has burtsts
-early immune response may be capacble of clearing an intial M.ulcerans inoculum
-spontaneous healing of BU lesions and serological evidence of exposure of healthy individuals to M.ulcerans indicate the host immune system can contain teh infectious pathogen although mechanisms conferring protection are not clear
-progression of lesions is highly diverse and not at all non-ulcerative lesions ulcerate
-high concentrations og mycolactone in the lesion core cause apoptosis of both resident skin cells and infiltrating leukocytes
-chronic necrotic lesions develop with destruction of subcutaneous tissue
disease progression pf buruli ulcer infection caused by mycobacterium ulcerans
-progressuib from the pre-ulcerative to the ulcerative and healing stages of buruli ulcer disease is shown the width of the green, red and yellow shapes denotes the extent of the progression for bacyerial load necrosis and inflammatory responses
M. ulcerans Diagnosis
-clinical diagnosis
-microscopy- smear
-culture
-PCR-based tests DNA based
treatment
-multidrug therapy to reduce selection of drug-resistant strains
-combo of rifampicin and clarithomycin in now the WHO recommended treatment
-surgery and hospital treatment of wounds for skin grafts
-in well developed lesions with ongoing necrosis due to teh effects of high mycolactone toxin load then the removal of this tissue is necessary
-physiotherpay and rehabilitation
wound managmenyt
-vital but often goes neglected
-healing time can be months or years to heal even after antibiotic treatment
-improved wound dressings emerging from other ulcer disease eg diabetes
M.ulcerans Identification of high risk zones
-active surveillance
-case management
-treatment
-case study is republic of congo
-identification of this zone as a high risk area for buruli ulcer disease helped the ministry
early detection, biological confirmation and treatment programs
M. ulcerans Vaccines
-some protection seen with BCG but inconsistent
-vaccines specific to m ulcerans targeting a mycolyl transferase of the bacteria being tested
avoid risky behaviours in endemic areas
-swimming
-fishing
-agricultural works
-mosquito nets may help if insect borne (australia)
-good pre-existing wound care
-protective clothing to prevent wounds
diagnostics for NTM
-Research priorities recommended in the US and the UK include rapid diagnostic tools fast identification of infecting species
-methods (ELISA, LAMP and mycolactone specific tests)
-simple and cheap screening tool to identify patients
-faster initiation of appropriate treatment and ultimately superior care
Buruli ulcer future directions
-efforts to shorten the duration of treatment are in progress involving two studies
-Telacebec is a new anti-tuburculsis drug developed by korean company quirent
-clinical trial comparing the standard treatment of the combination of rifampicin and clarithromycin for 8 weeks and amoxicillin/clavulanate for 4 weeks
Mycology
-the study of fungi (including yeats,moulds and fleshy fungi)
Fungi facts
-eukaryotic
-rigid cell wall consisting of layers of polysaccahrides which forms a rigid matrix
-chemoheterotrophs (require organic compounds for both carbon and energy sources)
-obtains nutrients as saprophytes (live off decaying matter) or as parasites (living matter)
-can stimulate plant roots to proliferate
-lichens are composed of fungi and a photosynthetci component either a eukaryotic alga or a cyanobacterium
-disease causing fungi mostly infects skin, hair and nails can hydrolyse keratin
Asperigillus species fungi
-produce a toxic compounds called aflatoxin which causes liver cancer
Ergot
-hallucinogenic drug LSD produced by fungi
of the 100,000 species of fungi only 100 are
-pathogenic for animals
-play a major role in the recycling of nutrients by their ability to cause decay and are used by industry
-however they also lead to undesireable economic effects such as destrucyion of fruits, grains wood and leather products
The Archaebacteria and the Eubacteria
are prokaryotes.
Eukaryotes encompass the other five Kingdoms:
Protista (now often called Protozoa), Chromista, Plantae, Animalia and Eumycota.
Fungi fit into two kingdoms
-since fungi have several distinguishing features eukaryotic, heterotrophic (cant make own food) and osmotrophic (absorb food)
they develop a rather diffuse branched and tubular body (radiating hyphae making up mycelia or colonies and reproduce by means of spores
__ species of fungi cause human disease
50
Fungi cause disease through three major mechanisms:
i) by causing immune responses that result in allergic (hypersensitivity) reactions following exposure to specific fungal antigens
ii) by producing toxins a large diverse group of fungal exotoxins produces aflatoxins which induce tumours in birds
iii) by infection the growth of a fungus on or in the body is MYCOSIS
Dermatophytes
-a few fungi have evolved a rather specific ability to attack the outer surface of human beings
thermal dimorphic saprobes
-A few other fungi which cause disease in people are normally soil organisms,
-but have also adapted to life in the unusual and rather hostile environment of the human body, often responding to this environment by developing a different morphology
opportunistic saprobes
-fungi that can attack us when defences are down
-when our immune systems themselves are diseased or deficient or when we artificially suppress them
Three main types of human fungal infections (mycoses)
1)Cutaneous
(superficial mycoses)
involved the outer layers of the skin and cause an allergic orinflammatory responses
Three main types of human fungal infections (mycoses)
2)Subcutaneous mycoses
usually involving fungi of low inherent virulence which have been introduced to the tissues through a wound of some kind and which remain localized or spread only by direct mycelial growth
Three main types of human fungal infections (mycoses)
3)systemic mycoses
-caused by true pathogenic fungi or by opportunistic saprobic fungi
-could not infect a healthy host but can attack individuals whose immune system is not working or is comprimised
-may become widley disseminated in host
usually pulmonary infections can enter the
bloodstream
Tinea
= the medical name for a group of related skin infections, including athlete’s foot, jock itch, & ringworm
systemic infections
-inhalation of spores leads to fungi in bloodstream can lead to brain damage
Histoplasma capsulatum, cause of
histoplasmosis
Cutaneous (superficial) mycoses
[These also include superficial cosmetic fungal infections of the skin or hair shaft where no living tissue is invaded and there is no cellular response from the host. Essentially no pathological changes are elicited
Dermatophytes have the ability to
utilise keratin as a nutrient source: they invade keratin via enzymatic digestion and mechanical pressure
Tinea pedis
-caused by T. rubrum. Sub-clinical infection causes mild maceration of toe
-usually caused by the shedding of skin scales containing viable infectious hyphal elements [arthroconidia] of the fungus.
Treatment and prevention of tinea infections
-topical therapy (creams) but oral antifungals are used for extensive skin infections or those for nail and scalp
-prophylactic use of antifungal foot powder elps reduce spread of infection for swimmers
fluconazole
-widely used bis-triazole antifungal agent
-as with other triazoles it has a membered ring structures containing three nitrogen atoms
mechanism of action of fluconazole
-by inhibition of cytochrome P450 14a-demethylase an enzyme in teh sterol biosynthesis pathway that leads from lanosterol to ergosterol an essential component of the fungal cytoplasmic membrane
Yeasts (can cause superficial & systemic
infections)
yeast morphology
-unicellular fungi which usually appear as oval cells
-typical eukaryotic structures
-facultative anaerobes get their energy through aerobic respiration as well as fermentation
yeast how the body protectes itself
-The body does this by recognizing molecules unique to micro-organisms that are not associated with human cells
-These unique molecules are called pathogen-associated molecular patterns.
-Components of the yeast cell wall bind to pattern- recognition receptors on a variety of defense cells of the body and triggers
innate immune defenses such as inflammation, fever, and phagocytosis.
-Yeast cell wall components also activate the alternative complement pathway and the lectin pathway, defense pathways that play a variety of roles in body defense.
Yeast Candida albicans
-in addition to its usual oval budding form, is also able to produce pseudohyphae.
-Buds elongate forming a tube-like structure called a germ tube. The elongated buds remain attached to one another and eventually produce a filament called a pseudohypha because it resembles the hypha (a long filament of cells) of a mould.
-The pseudohyphae help the yeast to invade deeper tissues after it colonizes the epithelium. Since Candida is able to grow as a yeast as well as in a pseudohyphal form it is said to be dimorphic i.e. it has two growth forms yeast-like and mould-like.
Pseudohyphae =
Branching filaments of attached, elongated yeast cells resembling the hyphae of moulds
Blastospores =
asexual reproductive spores
Chlamydospores =
thick- walled survival spores
yeast infections - Candida albicans
found as normal flora on the mucous membranes and in the gastrointestinal tract; usually held in check by:
1) normal flora bacteria; and
2) normal body defenses.
Candida can cause a variety of opportunistic infections in people who are debilitated, immunosuppressed, or have received prolonged antibacterial therapy. Women who are diabetic, pregnant, taking oral contraceptives, or having menopause are also more prone to vaginitis.
Reproduction of yeasts
Yeasts reproduce asexually by a process called budding
-Yeasts reproduce asexually by a process called budding allowing for genetic recomibination
vaginitis
These conditions alter the sugar concentration and pH of the vagina making it more favourable for the growth of Candida. People who are immunosuppressed frequently develop thrush, vaginitis, and sometimes disseminated infections.
Any Candida infection is called
candidiasis
Candida most commonly causes vaginitis (inflammation of the mucous membranes of the vagina),
thrush (infection of the mucous membranes of the mouth),
balantitis (Candida lesions on the penis from a female with vaginitis), and cutaneous infections (Infections of moist skin or the nail beds)
Less commonly, Candida can infect the lungs, blood, heart, and meninges
Oropharyngeal candidiasis: includes thrush
Clinically, white plaques that resemble milk curd form on the buccal mucosa and less commonly on the tongue, gums, the palate or the pharynx. Symptoms may be absent or include burning or dryness of the mouth, loss of taste, and pain on swallowing.
Cutaneous candidiasis: includes “Nappy rash” candidiasis
can occur between the fingers or toes, or in the groin
”Nappy rash” candidiasis is common in infants under unhygienic conditions of chronic moisture and local skin maceration associated with irritation due to irregularly changed unclean nappies
Vaginal candidiasis
a common condition in women
often associated with the use of broad-spectrum antibiotics, the
third trimester of pregnancy, low vaginal pH and diabetes mellitus
Sexual activity and oral contraception may also be contributing factors and infections may extend to include the vulva and the cervix.
Symptoms include intense itching, burning or soreness and production of a creamy white, curd-like discharge.
Chronic refractory vaginal candidiasis, associated with oral candidiasis, may also be a presentation of HIV infection or AIDS
Candidiasis (summary)
a primary or secondary mycotic infection caused by members of the genus Candida
clinical manifestations may be acute, subacute or chronic to episodic.
Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract, or become systemic as in septicaemia and meningitis.
In healthy individuals, Candida infections are usually due to impaired epithelial barrier functions and occur in all age groups, but are most common in the newborn and the elderly. They usually remain superficial and respond readily to treatment.
Systemic candidiasis is usually seen in patients with cell-mediated immune deficiency, and those receiving aggressive cancer treatment, immunosuppression, or transplantation therapy.
Diagnosis of Candida infections
1)collect samples from skin
2)direct microscopy =Examine specimens for the presence of small, round to oval, thin-walled clusters of budding yeast cells (blastoconidia) and branching pseudohyphae
Subcutaneous mycoses I chromoblastomycosis
-a chronic localised disease of the skin and subcutaneous tissues causative organisms are Cladophialophora sp. Fonsecaea sp., Phialophora sp.
-infections are caused by the tramuatic implantation of fungal elements into the skin and are chronic slowly progressive and localised
-characterised by crusted, warty lesions usually involving the limbs world-wide distribution but more common in bare footed populations living in tropical regions
I Chromoblastomycosis (cont.)
Diagnosis
-presence in skin scrapings and/or biopsy tissue of brown
pigmented, planate-dividing, rounded sclerotic bodies from a patient with
supporting clinical symptoms
I Chromoblastomycosis (cont.)
Treatment
-can involve surgical removal of tissue (through requires removal of a margin of uninfected tissue to prevent local dissmination
-flurocytosine (a pyrimidine analog) and the azoles thiabendazole and itraconazole
II Sporotrichosis
Primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and adjacent lymphatics
Characterized by nodular lesions which may ulcerate.
Infections are caused by the traumatic implantation of the fungus into
the skin, or very rarely, by inhalation into the lungs.
Secondary spread to joints, bone and muscle is not infrequent, and the infection may also occasionally involve the central nervous system, lungs or genitourinary tract.
Pulmonary sporotrichosis
is rare; usually caused by the inhalation of conidia. Symptoms are non-specific and include cough, sputum production, fever, weight loss and upper-lobe lesion. Haemoptysis (coughing up blood) may occur and it can be massive and fatal. The natural course of the lung lesion is gradual progression to death.
sporotrichosis diagnosis
-Tissue biopsy will contain very low numbers of narrow base budding yeast cells (2-5um)
sporotrichosis treatment
Cutaneous lesions respond well to saturated potassium iodide itraconazole & terbinafine have also proved to be effective
Terbinafine
an allylamine - a synthetic antifungal agent
it is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues
Terbinafine mechanism of action
As with the other allylamines, terbinafine inhibits ergosterol biosynthesis via inhibition of squalene epoxidase. This enzyme is part of the fungal sterol synthesis pathway that creates the sterols needed for the fungal cell membrane
II Pneumocystis carinii
-although pneumocytis carinii based on its appearence and sensitivity to antiprotozoan drugs thought to be protozoan it is more closely related to fungi
-thought to be transmitted from person to person by the respiratory route and is almost always asymptomatic.
-However, in persons with highly depressed immune responses, P. carinii can cause an often lethal pneumonia called PCP (Pneumocystis carinii pneumonia).
III Blastomycosis
-Disease caused by the dimorphic fungus Blastomyces dermatitidis (dimorphic = having two distinct forms, as in some fungal pathogens of humans, which are yeast-like in the host, but mycelial in culture)
-Endemic in the southeastern and south central states of North America
-associated with occupational or recreational activities around streams or rivers with high content of moist soil enriched with organic debris and/or rotting wood.
-Infection is acquired via inhalation of the conidia, which transform into the yeast form once in the lungs.
After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur.
However, at least 50% of primary infections are asymptomatic.
IV Histoplasmosis
-Condition caused by infection with the dimorphic endemic fungus Histoplasma capsulatum
-most common cause of fungal respiratory infections in the world
-majority of acute cases of infection with this fungus follow a sub-clinical and benign course in normal hosts
-However, a disseminated and potentially fatal picture is seen among immunosuppressed individuals, children <2 years old, the elderly and people exposed to a very large inoculum.
Histoplasmosis disseminated in HIV patient
-skin lesion and can become disseminated to internal organs
Histoplasmosis ->The mold or mycelial form exists in the soil, where it
-absorbs nutrients from dead organic matter and produces infectious spores
-when inhaled they encounter the warm moist envrionment of the lungs and undergo a transformation to the yeast or parasitic form
V Aspergillosis one of the most prevelant
-refers to the broad range of disease states whose etiological agents are members of the genus Aspergillus
-Aspergillus spp. are ubiquitous organsims progressievly associated witha growing spectrum of infections in immunocomprimised hosts
-aspergillus fumigatus is responsible for over 90% of cases of invasive asperigillosis
Allergic bronchopulmonary Aspergillosis
-produces an allergy to the spores of aspergillus molds
-common in asthmatics (up to 20% of asthamtics may develop this at some point)
-also common in CF patients as they reach adolescence and adulthood
-symptoms are similar to those of asthma: intermittent episodes of feeling unwell, coughing and wheezing some pateints cough up brown coloured plugs of mucus
diagosis: X rays
Aspergilloma
-disease where aspergillus grows within a cavity of the lung (previously damaged by disease like TB)
-any disease that causes cavities in lung can lead to an individual developing an aspergilloma
-the spores penetrate the cavity and germinate forming a fungal ball within the cavity
-illness is caused by secretion of toxins/other products
Aspergilloma symptoms
-brain fog (STM lost)
-weight changes
-chronic cough
-feeling rundown
-coughing of blood (hemotypsis can occur in up to 50-80% of affected people
-diagnosis is made by x rays scans of lungs and blood tests
Invasive Aspergillosis
-often fatal -no good diagnostic test
-often treatment must be started when suspected infection has occured
-RISK-as bone marrow transplant, low white cells after cancer treatment, AIDS or major burns.->chronic granulomatous disease which puts affected people at moderate risk
-people with invasive aspergillosis usually have a fever and symptooms from the lungs (cough chest pain or discomfort which do not respond to standard antibiotics x rays and scans are usually abnormal and help to localize the disease
-bronchoscopy (inspection of the inside of the lung with a small tube inserted via the nose) is often used to help to confirm the diagnosis
Treatment and Control of Systemic Pathogenic Fungi
-effective chemo against systemic fungal infections is very difficult
-one of the most effective antibiotics is amphotericin B (punches holes in membranes) a polyene
-side effects on kidney toxicity
-exposure to fungi can rarely be eliminated except using air filtration in restricted local environments
Azyls
inhibit biosynthesis of membranes
Trypanosoma cruzi and chagas disease
-6-7 million infected in latin america (endemic)
-incidence of diseases 500000 new cases per year 10000 deaths per year
-high mortality sometimes without knowledge of infection
-highest burden of disability-adjusted life years (DALYs) lost amoung the NTDs
Trapanosoma cruzi
-41% of 283 andean mummies dated 9,000 yrs old positive for T. cruzi DNa
-40% of mummies have t crucei
-humans are a very recent host
-T cruzi is > 150 million years old
1909 carlos chagas
-brazillian doctor first described the disease and life cycle
Trypanosoma cruzi the vectors
-reduviid or triatominae bugs
-not effcient at transmitting parasite
-able to surive for months without bloodmeal therefore control is more difficul
-8-10 times more bloodmeal than bodyweight therefore large number of parasites
5 stages until develop wings one bloodmeal is required for each stage
Trypanosoma cruzi the routes of transmission
Vector-borne by “kissing bugs” (80%)
* Transfusion of infected blood (<4% -20%)
* Congenital: mother to foetus (regionally high) COMMON FORM OF TRANSMISSION
* Accidental ingestion of infected sources
Chagas disease epidemiology and global distributions
-8 million people are infected
-10,000 deaths per year
-remains one of the biggest public health problems in 21 latin countries
-urbanisation migration increased transmission
Chagas risk associated with migration
-Chagas is long-lived infection with asymptomatic chronic carriers.
-leads to unusual global distribution (lots of cases in europe dependent on arrangements made with south american countries
-subsequent (autochthonous) transmission is NOT vector-borne rather mainy congenital also blood transfusions and infected organ transplants
Chagas epidemiological risk factors
-poverty/house construction
-favourable triatomine bug habitats in poorly constructed houses
-deforestation and human colonization of triatomine habitats
-provides abundant/stationary blood sources
-rural to urban migration
-blood transfusions
congenital transmission
Chagas pathology-acute phase
-Acute (symptomatic) form (4-8 weeks) – most often seen in children
-ever, swelling lymph glands, liver and spleen enlargement, local injammation of inoculation site e.g. “Romaña’s sign” (photo).
Abundant parasites in the bloodstream
-fatality rate 0.25-0.5%
-myocarditis meningoencephalitis both life threatening
Chagas pathology-Chronic phase
-cardiomyopathy in 20-30% of chronically infected individuals
-develop digestive damage (megaviscera
-peripheral nervous involvement
Pathology: Chronic phase continued
-chronic without successful treatment is life long
-indeterminate forms of infection = no symptoms
-20-30% of people who initially have the inteterminate form progress to clinical conditions developed over three decades
-cardiac disease (more common) and plethora of complications leading to sudden death
-gastrointestinal diseases (less common) of the oespohagus/ colon with advancement to megaesophagus/megacolon predominant in southern cone
-social consequences of infection too
Chagas diagnosis
-high parasitaemia
-microscopy of stained blood smear PCR
chagas diagnosis chronic
-amastigotes remian in cardiac/skeletal muscle/ macrophages
-scarce trypomatigotes in blood
-two serological IgG antibody tests due to low sensitivity
-no satisfactory test to define parasitological cure (low PCR sensitivity)
-hit or miss success
Chagas treatment
drugs = Nifurtimox, Benznidazole
-effective against acute and chronic
-serious/frequent side-effects (40%) more common with increasing age
-in acute treatment reduces and shortens clinical severity and duration of detectable parasitemia
-60-85% cure in acute phase
Chagas WHO
recommends treatment for acute, congenital, and reactivated T. cruzi infection, and for children (up to 18 years of age) with chronic infection.
Chagas treatment
-No drugs effective for chronic phase
-debate over usefulness in adults with long standing infection
Chagas treatment remians problematic
-serious side effects
-access: less than 1% of patients have access ro benznidazole
-only recomeded in areas with vector control
-due to re-infection and risks associated with treatment
-disease is poorly understood by health professionals in non-endemic areas - making detection in acute phase difficult
-desperately need new drugs and to improve parasitological detection
Chagas approach to control in endemic and non-endemic regions
-screen blood transfusions and organ donation
-screen pregenat women and children to control congenital transmission
-promote health seeking behaviour and awareness amoungst health professionals
Chagas approach to control
-no vaccine
-sustained vector control of intra-domicillary vectors in latin america
-prevent vector borne transmission
-promote engagement with vector control activities
Flagellated protozoa: American trypanosomes
CHAGAS
focus of control
-no vaccine
-chemo cannot be relied on to prevent spread of infection only useful in acute/early chronic
-not widely available
-vector infestation leads to high levels of re-infection
-need to focus on prevention
Chagas prevention methods
- controlling intra-domiciliary vectors in Latin America - screening bloodbanks for transfusions
- screening organs for transplantation
- screening for congenital infection
indoor residual spraying (IRS)
-Through Na channels impacts CNS
contact insecticides - vector has to land on insecticide
insecticide and other control options
-insecticide impregnated nets (ITNs)
-house improvements (environmental management) Plastering of walls (earth, cow dung, lime or cement mixes) to seal gaps
-social interventions
-school teachers meetings and house vists
-sustainability is a key parameter
-good practises may be required but abandoned if regarded low priority
southern cone intitaive
-focused on reducing vector density
-launched in 1991
-serological screening of blood
-housing improvements
Triatoma infestans
-highly domesticated vector
-Genome has reduced in size therefore less adaptable
-not huge fluctuations in climate in south america
Triatoma infestans issue with salvatic/domestic
populations have gene flow between them therefire can infect on seasonal basis
Southern Cone Initiative, 1983-1999
common age infected
was young so hard to detect
Chagas challenges in Gran Chaco region
Argentina, Bolivia, Paraguay
* 1.3 million km2
* Indigenous communities
* Highest transmission
* House infestation 82–100%
* T. infestans infection with
T.cruzi, 50%
MARGINALISED COMMINITY therefore dont have voice
CHAGAS
issues with survelance
-poor recapture success
chagas Community treatment hinges on surveillance and vector control
Household infesta/on threshold to trigger vector control by IRS
IRS “aaack phase” conducted typically un?l reduced to <5% of houses infested;
Infesta?on indicated by Timed Manual Capture (TMC): 0.5 person hours search for vectors in household buildings
chagas Successful vector control is required to trigger human treatment:
Treatment of childhood infec?on recommended only if area is under ecec?ve
vector control commonly dedned as:
House infesta?on Index: <3% houses* in community infested, and absence of infestation in case households
sustaible house construction improvement to
reduce crevices and increase surface adhesion of IRS insecticides
Post-interven?on vector control following house improvements
chagas
-house improvement + IRS
-Assisted IRs
Wild T. infestans popula?ons associated with wild guinea- pigs in a sylva?c cycle
-higher T. infestans genetic diversity in blivian andes suggests
* Region of origin and
geographic dispersal
* Andean and non-Andean T.
infestans populations are
essentially digerent
* Still limited gene how
between sylvatic and
domestic populations
Chagas
t.cruzei species
-Rhodnius prolixus
-Triatoma dimidiata
Triatomine resistance to insecticides is patchy* DDT is not ecec?ve against Triatomids
- Organophosphates (Dieldrin); Organochlorines
(benzene hexachloride (BHC)); Carbamates
(propoxur) - Synthe?c pyrethroids (cypermethrin, cyWuthrin,
deltamethrin, permethrin, lambdacyhalothrin)
Chagas control- good progress in Latin America so far
Latin America
* Incidence declined from 700,000 to 40,000 cases per year in 25 years
* Mortality decline: 45,000 to 12,500 deaths
* But still annual cost of US$8 billion
* Elimination of T.infestans in
majority of region
Who/Paho goals for endemic and non-endemic countries
1) Elimina?on as a public health problem (in 20 endemic countries + 75% access to treatment);
2) Interrup?on of intradomiciliary (vectorial) transmission (0% Infesta?on Index and 0% T. cruzi
human infec?on incidence;
3) Elimina?on of blood transfusion & ?ssue transplant transmission (100% of target countries);
4) Interrup?on of congenital transmission: 90% screening coverage and treatment of women,
and when infected, screening of their new-borns and siblings.
