Pathogens L6-10
🇬🇧
In English
In English
Practice Known Questions
Stay up to date with your due questions
Complete 5 questions to enable practice
Exams
Exam: Test your skills
Test your skills in exam mode
Learn New Questions
Manual Mode [BETA]
Select your own question and answer types
Specific modes
Learn with flashcards
Complete the sentence
Listening & SpellingSpelling: Type what you hear
multiple choiceMultiple choice mode
SpeakingAnswer with voice
Speaking & ListeningPractice pronunciation
TypingTyping only mode
Pathogens L6-10 - Leaderboard
Pathogens L6-10 - Details
Levels:
Questions:
46 questions
| 🇬🇧 | 🇬🇧 |
| Importance and Significance of EM | 1) EM are opportunistic pathogens: Can have a diversity of hosts, Survive outside a host and have free living habit, Particular risk to immunocompromised persons. 2) EM may interfere with BCG efficacy: a) Blocking, b) Masking |
| Cutaneous Disease: Buruli ulcer | Buruli ulcer (BU), caused by Mycobacterium ulcerans, is an indolent necrotizing disease of the skin, subcutaneous tissue, and bone. Buruli ulcer is presently the third most common mycobacterial disease of humans, after tuberculosis and leprosy, and the least understood of the three. Cutaneous ulcers caused by M. ulcerans were discovered at nearly the same time in two antipodal regions: in 1937 in Southeast Australia and in 1942 in tropical Africa. |
| Phylogenetic analysis and evolutionary scenario for Mycobacterium ulcerans | Phylogeny of related species based on conserved gene sequences; comparison of 16S rRNA and on 7 concatenated house keeping partial gene sequences. M. ulcerans has reduced genome due to 771 pseudogenes, and gene loss (4160 genes). Mycolactone is on a plasmid. |
| Mycolactone biosynthesis | M. ulcerans produces a family of toxin polyketide molecules, the mycolactones, which are required for the tissue destruction and local immunosuppression characteristic of Buruli ulcer. In vitro experiments show that the major mycolactones, a mixture of cis-trans isomers (mycolactone A and B), produce apoptosis and necrosis in many human cell types. Mycolactone enters cells by diffusion and accumulates in the cytosol. In addition, mycolactones appear to play a role in inhibiting the recruitment of inflammatory cells to the site of infection. |
| Traits of M. ulcerans as a pathogen | 1. Mycobacterium ulcerans is closely related phylogenetically to M. tuberculosis, 2. Replication and persistence of M. ulcerans in BU lesions is profoundly influenced by production of mycolactone, a macrolide cytotoxin that has immunosuppressive properties. 3. it induces apoptosis of infected host cells, inhibits production of the proinflammatory cytokine TNF-α. 4. Mycolactone also damages nerve cells. 5. can diffuse from infected skin tissue to lymphoid organs. 6. |
| Diagnosis | Clinical diagnosis. Microscopy. Culture. IS2404 PCR-based tests DNA based. Methods in development for rapid POC : ELISA/LAMP/Mycolactone |
| Treatment of Buruli ulcer | Some antimycobacterial drugs have good in-vitro activity. Surgery and hospital treatment of wounds for skin grafts. treatment schedules included two or more active compounds (MDT), because monotherapy is bound to result in selection of drugresistant strains. |
| Transmission of Buruli ulcer | 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 from swamps, has found evidence of M. ulcerans. Insects such as mosquitoes7 and waterresiding biting arthropodshave been associated with M. ulcerans. A. Difficult to isolate Mu from nvironmental samples, B. Lesions in children less indicative of specific exposure patterns C. Conflicting evidence for vector transmission i.e. lab based infection studies but experiments suggested skin trauma. |
| Transmission pathways of M. ulcerans | 1. Possums ingest M. ulcerans from the environment and/or infected by an insect vector. 2. Possums amplify and shed M. ulcerans into the environment. 3. Insect vectors become contaminated with M. ulcerans from the environment and/or from contact with infected possums. 4. M. ulcerans transmitted to humans via insect vector and/or direct contact with contaminated environment. |
| African trypanosomes | Flagellated protozoa and vector borne disease. African tryps - Trypanosoma brucei species, HAT. American tryps - Trypanosoma cruzi and Chagas disease. |
| Kinetoplastids | Flagellated forms (locomotion by flagella). Kinetoplastids distinguished by kinetoplast- a large DNA-containing structure |
| Morphological forms of hemoflagellates | Amastigote, Promastigote, Epimastigote, Trypomastigote. |
| Comparison of the two parasite species causing HAT | T brucei gambiense: Endemic in 24 countries of west and central Africa, >90% of reported cases of sleeping sickness worldwide, Chronic disease, lasts for several years, Anthroponotic transmission, “Riverine” tsetse vector, Fatal if untreated. T brucei rhodesiense: Endemic in 13 countries of eastern and southern Africa, <10% of reported cases globally, Acute disease, lasts for months, Zoonosis, “savannah” tsetse vector, Fatal if untreated. |
| Vector – Tsetse fly (Glossina spp) | 1. Bloodmeal 2. Egg develops every 7/9 days 3. Produce 8/10 larva per lifetime 4. Pupatefor 30 days 5. males live for 6weeks and females for 14 weeks |
| Steps of infection | 1. Blood meal, 2. metacyclic trypomastigotes transform in the bloodstream 3. multiply further 4. trypomastigotes in blood 5. blood meal fly 6. transform into procyclic 7. leave the midgut to trasnform into epimastigotes 8. multiply in salivary gland 9. transform to metacyclic. |
| HAT Pathology | Disease progresses through two distinct phases: 1. The early stage (haemolymphatic or stage 1) 2. The late stage (encephalitic or stage 2) ‘sleeping sickness |
| The early stage | Chancre arises at site of bite in 50% T. b. rhodesiense infections – diagnostic (rarely occurs in cases of T. b. gambiense), parasite spreads through lymphatic system and invades the bloodstream |
| The late stage | Late stage: parasite invades internal organs including the central nervous system |
| Mechanisms of HAT: VSG - the decoy antigen | VSG covers the entire parasite surface including the flagellum. 106 produced per cell. The molecule is highly immunogenic. It elicits strong antibody response from the infected host. Stage-specific. |
| VSG: the decoy antigen | The parasite is able to switch VSG expression. There are >>200 VSG genes. These are under transcriptional control |
| Diagnosis and treatment of HAT | Diagnosis - symptomatic, systematic and passive screening: – CATT for T.b. gambiense only. – Rapid serological tests. – Microscopy. – Inspection of CSF obtained by lumber puncture to define disease stage. Treatment: Chemotherapy and drugs are sub-species specific. |
| Control measures to reduce transmission | Parasites: – Resistant breeds (cattle) – Chemotherapy. Tsetse flies: – Traps – Insecticides – Sterile insect technique (e.g. Zanzibar) |
| Different approaches to control HAT | T brucei gambiense: To reduce person to person transmission, Active or passive case detection and treatment, Vector control plays little to no part of control, Large scale epidemics in 20th century controlled by 1960s by active case detection and treatment programmes. T brucei rhodesiense: To reduce transmission from zoonotic reservoirs, Vector control is central Cattle treatment becoming more common, Case screening conducted for humanitarian reasons |
| Vector control rationale | Low density (1 per 1.4 m bush). low reproductive potential (approx 8 offspring x 10d cycles). 4% sustained mortality of females per day should cause extinction. |
| Insecticide applications | Traps/targets e.g. tiny target traps.• Dips or ‘Pour-on ’ – topical treatment e.g. RAP • Ultra-low volume (ULV) spraying • Sterile Insect Technique . |
| Sterile insect technique (SIT) | • Zanzibar • 1988 tsetse population suppressed using insecticidetreated cattle & traps • Serial release of sterilized males by aircraft, 60,000 per week in 1-2km flight lines • 1994-1997 >8.5 million males released. 1995 sterile : indigenous male ratio >100:1; >70% barren females • 1996-7 Tsetse population crash; Glossina austeni eradicated |
| WHO Elimination Initiatives- progress | Scale up “tiny insecticide impregnated targets”. • New improved diagnostic tests. • Utilize new drug fexnidazole. • chemotherapy / RAP for cattle against acute disease in Uganda. |
| Stamp Out Sleeping Sickness (SOS) Initiative | Early stage disease 1st line drug: uramin efficacious against T b rhodesiense. Pentamidine efficacious against T b gambiense. Pentamidine is not effective against early stage T b rhodesiense. Late stage disease: Melarsoprol efficacious against both. Late stage treatment failures of T b gambiense increasing. An alternative is Eflornithine but is not effective against T b rhodesiense. |
| Babesiosis in cattle | Incubation 3-21 days. • High fever, anorexia, seek shade, weight loss, abortion, poor milk production. • Extensive erythrocytic lysis: 75% erythrocytes destroyed in few days. • Most survive but mortality up to >50% known; slow recovery. • Carrier status (low parasitaemia) for years. |
| Cattle Babesiosis tick vectors | Babesia pass into the ovaries/eggs – vertical transmission. • Migrate to the salivary glands to reproduce in larvae. • Larvae await on grass stalks to attach. • Babesia from salivary glands injected into the mammal's bloodstream. |
| TBD Endemic/Enzootic Stability | 1. Disease is more likely or more severe in older than younger susceptibles. 2. Following infection, the probability that subsequent infection results in disease is reduced |
| Measures to maintain endemic stability | 1. Tsetse more susceptible to pyrethroid-treated cattle than are ticks- increasing intervention interval lowers impact on ticks. 2. Tsetse preferentially feed on different sites of body, particularly legs- avoid tick attachment sites. |
| Solutions: towards sustainability by farmers | Tsetse preferentially feed on older & larger herd members- leave young cattle untreated to become exposed to ticks. Treating half the herd, applying insecticide to only the larger individuals, would be only slightly less effective than treating the entire herd but would reduce the amount of insecticide used. Selective treatment of hosts with restricted application protocol (RAP) reduce insecticide costs by 90%, compared with the current regime of treating the entire herd, and the impact on non-target organisms |
| Rationale for Gambian HAT | Current low levels of HAT is the opportunity to push for its elimination. • Case detection and treatment does not prevent infection. • Coverage is only 75%. • Low sensitivity of diagnostic tests. • Residual levels of infection remain in communities to sustain transmission. • Animal reservoirs may play a larger role than previously thought. • Traditional vector control seen as too expensive in resource-poor settings. • Availability of “tiny insecticide impregnated targets” is cost-effective. • Riverine tsetse concentrate near lakes or rivers. |
| Phase 1 and 2 summary outcomes | Pre-intervention catches of 2.7 (range: 0-114) tsetse/trap/day where 84% of riverine traps caught tsetse flies. Phase 1 intervention coverage 7km: mean catches reduced to =<1 tsetse/trap/day across. Phase 1 blocks causing reduction in tsetse density in 5km (not 7km due to reinvasion “edge effect”). Phase 2: coverage expanded to 21km: mean catches of <0.5 tsetse/trap/day across Phase 1 blocks causing >90% reduction in tsetse density with 19km |
| American trypanosome | Trypanosoma cruzi and Chagas disease. 8-10 million persons infected in Latin America. incidence of disease 500,000 new cases, per year, 10,000 deaths per year. highest burden of disability-adjusted life years (DALYs) lost among the NTDs. Most important parasitic disease in Latin America |
| Transmission cycle | Bug - Human - multiply in organs - enter blood stream . Bug - mid gut - continue to multiply - hindgut. |
| Routes of transmission | Vector-borne by “kissing bugs” (80%). Transfusion of infected blood (<4% -20%). Congenital: mother to foetus (regionally high). Accidental ingestion of infected sources. |
| Risk associated with migration (Chagas) | Chagas is long-lived infection with asymptomatic chronic carriers. Leading to unusual global distribution linked not only to transmission but migration. Subsequent (autochthonous) transmission arises from blood transfusion, congenital means and transplantation routes – not vector-borne. 68,000-123,000 infected immigrants in Europe. |
| Epidemiology and global distributions | • Historically - T. cruzi existed among wild animals but later spread to domestic animals and human beings. For decades was a strictly rural disease. BUT socio-economic changes, rural exodus, deforestation and urbanisation have transformed the epidemiological profile of the disease. Led to expansion of endemic regions at start of 20th Centaury. Now more urban / peri-urban. |
| Epidemiological risk factors | Poverty / house construction favourable triatomine bug habitats in poorly constructed houses. Deforestation and human colonisation provides abundant / stationary blood sources. Rural to urban migration blood transfusions. Congenital transmission |
| Pathology: Acute phase | Acute (symptomatic) form (4-8 weeks) – most often seen in children. Abundant parasites in the bloodstream. Mostly mild, self-limited symptoms. Can be severe acute infection. |
| Pathology: Chronic phase | Chronic phase without successful treatment is lifelong. chronic T. cruzi infection, with no symptoms of disease, are “indeterminate” forms of infection. 20-30% of people who initially have the indeterminate form progress to clinical conditions developed over decades: Cardiac disease, gastrointestinal disease. |
| Diagnosis - Parasitaemia | Acute: High parasitaemia, Microscopy detection by stain blood smear or buffy coat. Chronic: Amastigotes remain in cardiac /skeletal muscle/ macrophages. Scarce trypomastigotes in blood serological tests should be used to detect anti-T. cruzi antibodies. |
| Treatment | Only 2 effective drugs: Nifurtimox, Benznidazole. In acute T. cruzi infection, treatment with either reduces the severity of symptoms and shortens the clinical course and duration of detectable parasitaemia. WHO recommends treatment for acute, congenital, and reactivated T. cruzi infection, and for children (up to 18 years of age) with chronic infection. No drugs effective for chronic phase, not for pregnant women, serious side effects, chemotherapy access is problematic. |
| Approaches to control | No vaccine. Endemic control: Sustained vector control of intra-domiciliary vectors in Latin America. Promote engagement with vector control activities. Endemic and non-endemic control: Screening of blood transfusions and organ donation worldwide, Screening pregnant women and children to control congenital transmission worldwide, Promote health seeking behavior and awareness amongst health professionals. |