Neglected Tropical Diseases Flashcards
What are Neglected Tropical Diseases?
- Disparate group of diseases, both communicable and non-communicable
- Parasitic bacterial, viral and fungal infections (defined by WHO)
- Diseases of poverty found ‘at the end of the road’ with major health impacts but neglected by lack of research and public health prioritisation
- Many are parasitic with complex life-cycles and/or intermediate hosts
- Guinea worm (copepod)
- Schistosomiasis (snails)
- Some are zoonotic
- Rabies
- Transmitted through canine bite/ bats
- Snake bite
- Some are vector borne diseases
- Chagas disease (triatomine bug)
- Dengue (mosquito)
- A few non infectious
- Snake bite
What are the reasons that NTDs exist?
- Poor marginalised population diseases
- Limited research into them
- Control stratergies are unavailable and non-implemented
What are the most 7 most common NTDs?
- Ascariasis: 1 billion people worldwide
- Trichuriasis: 800 mill
- Hookworm 700 mill
- Schistosomiasis over 200 mill
- Lymphatic filariasis 120 mill
- Trachoma 41 mill
- Onchocerciasis 26 mill
Where is the global overlap of the 6 most common NTDs?
•The concentration of NTDs and conc of NTDs and the people affected are in SS Africa + yemen with over 5 NTDs being present here!
What contributes to contracting an NTD?
- Infections of poverty
- Poor Education
- Poor hygiene
- Poor access to clean water
- Poor sanitation
- Poor housing
- All contribute to risk of contracting NTDs
What are NTDs mitigated by?
NTDs are mitigated through development
What are the 3 main species of Schistosomiasis?
- Schistosoma mansoni
- Found in Latin America
- Parts of Africa
- Middle East
- Infects intestinal tract and the liver
- S. haematobium
- Infects bladder and urine tract
- S. japonicum
- Infects intestinal tract and liver
State the life cycle of S.haematobium
- Compex life cycle with snail intermediate host
- People in contaminated water which are infested with worms
- They pass through skin + peripheral circulation + lungs
- Migrates into liver where they develop into schistosoma and adults
- In hepatic venous system or system in bladder, they develop into adults
- They coupulate and females release thousands of eggs into bladder
- Egg is excreted through urine
- Develops into mirisidium which infectes snail
•Contaminates water
Name the life cycles of both S.japonicum and S.mansoni
- The eggs are found in the hepatic venous system
- •Eggs are washed into capillaries around intestinal tract
- Pushed through intestinal tract via inflammatory response
- Excreted through faeces
- In bladder, they embolise in capillaries + pass though bladder mucosa into urine + excreted through urine
How can reinfection occur in Schistosomiasis
Reinfection can occur through urinating or defacating in water where people swim
What is the pathology of shistosomiasis
Causes blood in the urine (occurs around puberty in endemic areas)
Secondary splenomegaly
Granulomas, fibrosis and cihrrosis of the liver
What is the treatment and control of Schistosomiasis?
- Treatment
- Praziquantel
- Given annualy to infected communities to prevent reinfection
- Control
- Mass-treatment with praziquantel
- Control of snail populations by spraying chemical insecticides
- Safe disposal of faeces
What is the mechanism of –Praziquantel
Praziquantel (PZQ) is the drug of choice for treating infection with worms from the genus Schistosoma.
The drug is effective, cheap and has few side effects.
However, despite its use in millions of patients for over 40 years its molecular mechanism of action remains elusive.
Early studies demonstrated that PZQ disrupts calcium ion homeostasis in the worm and the current consensus is that it antagonises voltage-gated calcium channels.
It is hypothesised that disruption of these channels results in uncontrolled calcium ion influx leading to uncontrolled muscle contraction and paralysis.
What is Trachoma caused by?
- Caused by Chlamydia trachomatis (same bacteria as the bacteria that causes chlamydia)
- Flies are important ‘mechanical’ vectors
- Flies get the tears and excretions from the eyes and transmit from one child
To another
•Recurrent chronic, progressive disease causing blindness (~5.5 million. But due to
Control programs has reduced this blindness occurrence)
Endemic in Africa and Asia
Aborigional children in Australia
Describe the global elimination of Trachoma
What is the SAFE acronym with regards to trachoma?
S urgery
A ntibiotic
F ace washing (part of water sanitation stratergy)
E nvironmental control
What are the symptoms of trachoma?
Mild itching and irritation of the eyes
Discharge with mucus/pus
Eyelid swelling
Light sensitivity
Eye pain
What are the stages of trachoma?
•Inflammation – follicular
–5 or more follicles
•Inflammation – intense
–Infectious with thickening of eyelid
- Eyelid scarring
- Ingrown eyelashes (trichiasis)
–Eyelashes rub on cornea
–Causes inflammation
•Corneal clouding
Opacification caused by repeated inflammation
What is the control of trachoma?
- •Surgery
–Entropion/trichiasis
•Antibiotics
–azithromycin
•Facial hygiene
–washing
•Environmental improvements
–Rubbish cleaning
–Sanitation
–Clean water
What is Lymphatic filariasis
- Worm parasite
- Causes elephantitis
- Three parasites
–Wuchereria bancrofti
–Brugia malayi
•Found in Asia
–Brugia pahangi
•Found in Asia
•
Confined to tropics, SE Asia, SS Africa
What is the life cycle of lymphatic filariasis?
- •When mosquito bites someone, transfers L3 larvae into skin
- Migrates into lymphatics
- Adults live in lymphatics
- Females release thousands of larvae called microfilariae
- If you take blood film, you see parasite in blood
- Adults die in lymphatics->inflammation-> acute filarial lymphangitis (filarial fever) -> lymphedema
What can lymphoedema turn into?
Elephantiatis
- Often unilateral
- Accumilation of fluids causes repeat infections-> further damage of tissue
What are the different symptoms/presentations of lymphatic filariasis?
- Acute filarial lymphangitis (filarial fever)
- Elephantitis (often unilateral)
- Acute dermatolymphangioadenitis
- inflammation of skin +lymphatic tracts/lymph nodes
- Hydrocele (elephantitis of the scrotum)
- Elephantitis of the breast
How would you prevent a secondary infection in lymphatic filariasis?
Infection prevention is regular washing of the infected region with soap and water to prevent secondary infection
What is a secondary syndrome related to lymphatic filariases?
Tropical pulmonary eosinophilia
- •Syndrome related to Lymphatic filariasis where people become Hypersensitised to the presence of microfilariae
- Cannot find microfilariae in the blood during the day -> find at night. They are sequestered in the lungs
- People with hypersensitised microfilariae causes severe pulmonary eosinophilia
- Leads to fibrosis of lungs
- This is a hypersensitivity reaction in the lungs
- You see granuloma in the lungs
Is there a cure for lymphatic filariasis (LF)?
- No cure for LF
- Key is prevention (prevention of mosquito bites)
- Oral drugs
- Health education is needed
What is the diagnosis of Lymphatic filariasis?
- Thick smears using capillary blood at night for W. bancrofti (10 pm to 2 am)
- Microfilariae are sequestered during the day
- Knotts technique using 1 mL blood
- More blood= more chance of finding parasite
- Rapid tests to detect circulating antigen
- Anti-filarial IgG antibodies
- PCR to detect parasite DNA in blood
What are the treatment options of lymphatic filariasis?
IDA treatment.
Triple Drug Therapy or IDA is a combination of three drugs: Ivermectin, DEC and Albendazole
- Ivermectin + Albendazole
- DEC + Albendazole
What are the benefits of IDA treatment in treating lymphatic filariasis?
More effective in clearing microfilaria faster than two drug regime
Continues to keep microfilaria clearance low even after two years with a single dose
Potential to accelerate LF elimination programs and help countries reach elimination targets faster
What are the potential drawbacks of treating with IDA in reference to treating lymphatic filariasis?
- Some drugs have adverse reactions to populations which are treating other parasite infections
- Must be treated repeatedly
What is the distribution of chagas disease?
- Currently 10 mill infected in endemic areas
- 365 000 cases in the USA
- 100 000 cases in Europe (87% in Spain)
- Distribution confined to latin America
- Central + S America
- Some cases in NA and Europe but these are due to migration (migrant populations)
What is the causal agent of Chagas disease?
Caused by the parasite Trypanosoma cruzi, which is transmitted to animals and people by insect vectors and is found only in the Americas (mainly, in rural areas of Latin America where poverty is widespread).
What is the life cycle of T.cruzi? The organism responsible for causing chagas disease?
- Triatomine Bug takes a blood meal
- Parasite (Trypansoma cruzi) = transmitted through faeces
- When you scratch bite, you scratch faeces through the skin
- If you bite around the eye, you get direct contact via mucous membranes
- Transmits Metacyclic trypomastigotes which invades cells (ie muscle + neurons)
- They develop into sacs of amastigotes
- Amastigotes multiply by binary fission in cells of infected tissues
- Cells burst releasing amastigotes which infect other cells
- When bug takes another blood meal, it transfers parasite
What is the difference between a sylvatic lufe-cycle and a peridomestic lifecycle?
In context, they are related to Chagas disease
Sylvatic=-> SYLVATIC SPECIES maintains lifecycle in marcupial host. People get infected by going too close to palm trees
Peridomestic lifecycle:
- Wild animals cause transmission
- Dogs are a reservoir of infection
What are the various modes of transmission of chagas disease?
Whole or blood derivatives but not lypholised blood has a 10-20% risk of aquiring chagas disease
Organ transplants= 20-30% transmission risk
Oral infections-> high infections. High mortality rates (1/3 people die after taking a chagas infected juice)
Transmission could occur vertically through pregnancy (1-10% passing on infection)
How can orally-transmitted chagas disease come about?
Outbreaks of disease in new areas
High proportion of sylvatic animals and domestic dogs infected
Sylvatic bugs enter houses
Bugs or bug faeces in food, fruit juices.
Higher infectious dose and greater morbidity and mortality (8-35%)
Regivia bugs in sugar cane! Spreads chagas disease
What is the pathogenesis of Chagas disease?
- Tissue damage caused by parasite replication and host inflammatory response
- Host immune response kills the cells but it causes inflammation & damage
- Acute illness resolves with effective immune response and parasite sequestration in tissues
- Host immune response develops effective immune response
- Parasites are killed and numbers are controlled
- Protective mediated by Th1 cytokines (eg IFN-g) and NO
- Progressive low-intensity destruction of:
- Nerves – autonomic nervous system
- Purkinje fibres in heart
- Autonomic ganglia in intestine
- Muscle cells - myocytes and intestinal smooth muscle
- Nerves – autonomic nervous system
What are the phases of chagas disease?
- Acute
- Incubation 1-2 weeks after bite
- Up to months after transfusion
- Infection transfusion
- Trypanosomes in blood
- Chronic ‘indeterminate’
- Lifelong infection
- No cure for chagas
- Generally trypanosomes not detectable but often positive for parasite DNA
- Seropositive
- 60-70% of infected
- Normal ECG and X rays
- Lifelong infection
- ‘Determinate’ Chronic Disease
- Seropositive
- 30-40% of infected 10-30 years after infection
- 5-10% develop chrnic chagas immediately after acute disease
What is Acute Chagas disease?
- Occurs within 3 weeks
- Generally mild or asymptomatic
- Local swelling
- Nodule or chagoma
- Fever Anorexia
- Lymphadenopathy
- 1-2% diagnosed
- Symptoms last 8 to 10 weeks
- rarely (young and IS)
- Hepatosplenomegaly
- Acute myocarditis
- Meningeoencephalitis
- Fatality (less than 5% of symptomatic)
How does cardiac disease occur in chagas?
- Develops in 20-30% of chronic infections
- Abnormalities in conduction system
- Right bundle branch block
- Left anterior fascicular block
- Ventricular premature beats
- ST-T changes
- Q waves
- Heart failure
- Right ventricular failure->left ventrivular failure
- Mural thrombi
- Thromboembolism
- Sudden death
- Cause of death (2/3rds)
- VT/VF, complete AV block, or SN dysfunction
- Abnormalities in conduction system
How does chagas disease affect the digestive system?
Develops in 10-15% of patients with chronic infections
Esophagus, rectum, and sigmoid colon most affected
How does chagas disease affect the megacolon?
- Presentation
- Constipation
- Complications
- Faecaloma
- Obstruction
- Sigmoid volvulus
- Intestine tweisting
- Ulceration
- Perforation
How would you diagnose chagas disease?
- Thick and thin film (Giemsa)
- Acute disease/re-activation
- Xenodiagnosis
- The problem with this method is that uou need lab strains
- Need to wait several weeks
- Serology
- Indirect fluorescent antibody (IFA) test
- Indirect haemagglutination
- ELISA with specific antigens
- PCR for T.cruzi DNA
- Use peripheral blood
What are the treatment options for Chagas disease?
- Benznidazole is the treatment of choice
- Nitroimaidazole derivative
- Children
- 5-10mg/kg/day orally for 60 days
- Adults
- 5mg/kg/d orally for 60 days
- AEs
- Mild to moderate dermatitis in 30%
- Neuropathy
- Bone marrow suppression
- Causes people to not complete the drug
The second drug is Nifurtimox
- 5-nitrofluran derivative
- Children
- 15 mg/kg/d orally for 60-90d
- Adults
- 8-10 mg/kg/d orally for 60-90d
- ~only 50% complete Rx in one study
- Main AEs
- Gastrointestinal (30-70%)
- Irritability, isomnia
- Mood changes
- Peripheral neuropathy
What are teh control mechanisms against chagas disease?
- Vector control
- Household spraying with residual pyrethroid insecticides for domestic and peri-domestic vectors
- But sylvatic vectors?
- The problem is that most vectors in the amazon rainforest still live in the forest canopy -> come through the house-> very difficult to control
- Improved housing
- Getting walls and windows that close
- Community education
- Screening blood donors in endemic countries
- Emerging problem in non-endemic areas
- Screen blood and organ donors from endemic areas
