Module 1 Flashcards

Question

Specifications for a sanitation system

Answer 1

No contact by humans with waste materials within the system No access to the waste materials for insects and animals No offensive odours or insect nuisance No unacceptable contamination of groundwater that may pollute springs or wells No unacceptable contamination of surface water No unacceptable contamination of surface soil Simple and inexpensive construction, use, and maintenance Modesty needs and personal cleansing practices of users are catered for

Answer 2

What is the soil like How many people will use it, distance between dwellings, interval of emptying Sanitation ladder - not too technological too soon Is there water regularly available to flush with? How will they maintain the system?

Answer 3

Increased difficulty in control of infectious diseases Reduced effectiveness of treatment -> longer period of infectiousness -> increased risk of transmission Growth of global trade and travel allows rapid spread to distant countries Increased healthcare costs More expensive therapies required when first line treatments no longer work Longer duration of illness and treatment Increased mortality Failure to respond to standard treatment leads to prolonged illness and greater risk of death

Answer 4

Vaccinate Local/national/international surveillance projects Campaigns promoting judicious use of antimicrobials Start smart and focus (UK) Get smart (US) WHO R&D of novel therapeutics

Answer 5

Effective vaccine No natural non-human reservoir Coverage of vaccination improving Political will

Answer 6

Cheaper Easier to administer Secondarily immunises household contacts Mucosal immunity Lower rate of seroconversion in developing countries - interference by other infections and diarrhoeal disease Vaccine Associated Paralytic Poliomylitis (rarely) as OPV is similar to the wild type poliovirus

Answer 7

Older Injected Induces good humoral immunity against paralysis Much more limited impact on mucosal immunity against infection

Answer 8

Effectiveness of OPV Reaching the communities who need the vaccine Public and political support for vaccination

Answer 9

Aquatic snail releases cercaria Enters via unbroken human skin Circulates to the liver; pairs up, migrates, lays eggs in blood vessels Egg rotates in capillaries and bursts open via its spine Escapes to the bladder or the intestine If the person defecates in water, the eggs will hatch and the larva will find a snail If it does, it takes over the snail as an intermediate host And then multiple through the larval stages A month later, produces a free swimming larva (cercaria) Whole lifecycle takes over 2 months

Answer 10

Not all eggs get out of the body - some get washed to the liver, get stuck there, and die. Then the body recognises them, attacks them, and a scar is formed. Eventually the liver gets entirely blocked and fibrotic, and as much as 20-25 years later there is death, usually due to oesophageal varices and haematemesis

Answer 11

Anaemia -> poor birth outcomes | Female genital schistosomiasis: lesions on cervix which increase the HIV/AIDS risk

Answer 12

2nd most prevalent infectious disease behind malaria 200,000 deaths/year in SSA Affects 74 tropical countries in Africa, Caribbean, South America, East Asia, and the Middle East 62% of the burden occurs in 10 countries in Africa Worldwide 700 million people at risk 207 million people infected

Answer 13

Mass drug administration to school children and others considered at risk Health education and behaviour change Snail control Improve water and sanitation

Answer 14

Spraying water bodies with molluscicides Effective on small water bodies However, unless carried out intensely and in conjunction with MDA, only a short term solution as rapid re-colonisation can occur

Answer 15

Reduces the numbers, or in some cases wipes out snail populations Thomas and Tait (1984): altering light, water chemistry, water flow, sediment type, seasonal drying, aquatic and sub-aquatic plants, introducing other snail species and management of irrigation schemes Unless there is long-term commitment from rural communities, the rapid reintroduction of the species is inevitable

Answer 16

Introduce pathogens, parasites, predators, competitors, genetic manipulation Ideas still in early stages and can be complicated to implement Due to overfishing of mollusc eating fish, some areas of Lake Malawi have seen an increase in schisto cases Small community owned projects have implemented fishing boundaries to try and re-establish the fish population to reduce schisto

Answer 17

77% reduction in severity and intensity of schistosomiasis can be gained with improved water and sanitation facilities - but just because they are introduced, doesn’t mean they will be maintained Accessible urinals close by river/pond Safe laundry area near river/pond

Answer 18

Assesses impact - has the program been successful Provides feedback to: Affected communities to increase ownership and compliance Donors to show progress towards objectives and justify continued funding Enable programme adaptation Generate scientific data on the factors influencing treatment programme success Assess whether financial resources are being used appropriately Advocate for future funding and programme support

Answer 19

Competitors and predators Improved drainage Waterflow Water level fluctuations

Answer 20

Brown and DeVries (1985) - fish predators can dramatically alter the population dynamics of a single snail species

Answer 21

R Slootweg and R Keyzer - reducing schistosomiasis infection risks through improved drainage Reconstruction of the depression zone along the village diminished risk of schistosomiasis transmission considerably However, a potential transmission site with low numbers of snails remains present near the dam at a far distance from the village

Answer 22

Snails are not found where the water flow velocity exceeds 0.3 m/s except when aquatic vegetation provides them with refuge from the current High water flow velocities are well tolerated in cement-lined canals Periodically flush canal sections between the check structures High water velocity not only removes snails by washing them away or leaving them stranded high on the canal banks, it also scours silt deposits

Answer 23

Important in small canals Periodic removal of aquatic plants from canals also reduces friction to the water flow, which increases conveyance efficiencies in the irrigation system In Egypt and Sudan, control of aquatic plants in canals has been applied as an effective method of snail control

Answer 24

Inform, motivate, train and encourage communities and their leaders to play a major role in improving their own health Studies reveal many think it is an STI In some countries, it is seen as a coming of age when a boy’s urine is red

Answer 25

Control of transmission through changes in water contact behaviour Improved environmental sanitation through the control of urinary and faecal contamination of snail habitats Compliance in chemotherapy Assistance and cooperation with snail control programs The promotion of health-promoting behaviour and community motivation to sustain these programs, together with increasing self reliance in health activities

Answer 26

The dam in senegal - OMVS

Answer 27

Increasing populations in resource poor setting and demand of food leads to construction of dams and irrigation schemes This can cause transmission intensification or the introduction of diseases into previous non-endemic areas, as in Senegal 1970s - governments of Senegal, Mali an dMauritania established the OMVS to develop and use the resources of the Senegal river Integrated development scheme was designed leading to the construction of two dams and a barrage at Diama 1976 - USAID and OMVS signed an agreement for a multidisciplinary assessment of the environment to see what the impact would be of the project

Answer 28

S haematobium in the delta was at a very low level S mansoni did not occur Highest schisto prevalences were found in the nomadic tribes disseminating the disease throughout the region Explanations given: Low density human population of the delta Little contact of the population with snail infested waters Possibility that the strain of the snail in the delta is an inefficient intermediate host for the strain of S. haematobium in the Senegal River Basin Waters are harmful to schistosome larvae (miracidia) because the river water is acidic with a pH of 6 or below

Answer 29

Completed in 1985 - in 1988 S mansoni was reported in stool examinations 130km from the dam In 1989, 49% of stool samples were positive Children were reporting blood in their urine 90% of the Wolof ethnic group were positive for S haematobium and 87% of another 382 sampled By 1990, 60% were positive By 1994, there was splenomegaly, and hepatomegaly in 36% of the population

Answer 30

Physical and chemical changes in the water and environment leading to an increase in snail hosts Stopped sea water reaching areas further up the river Increase in Biomphalaria prefer and Bulinus globules Reduced adverse effects of salinity on the parasite Increase in the irrigated areas Stability of water levels

Answer 31

Treatment with PZY but only 18% of those treated were cured Rapid reinfection Presence of immature worms Low levels of antischistosome immunity Resistance/tolerance ot PZQ Larger average biomass of parasite, therefore less likely to work Further intervention - prawns Treatment with a double dose of PZQ, spaced 3 weeks apart 6 weeks earlier, released prawns into the water point and they consumed a huge number of snails The disease did not build up and build back very quickly AT the 6 month point he average parasite egg burden of 31 eggs at baseline had fallen to less than 1 At 12 months, the difference in egg burden was not as dramatic

Answer 32

The study examined schistosomiasis in hilly and marshland regions, which both have populations of humans, but the marshland has more cattle (kept by the humans) and the hilly regions have a large rodent population Rodents were by far the most common host for schistosomiasis in the hilly regions, but were very rarely hosts in the marshland regions Opposite was true of cattle Additionally, there was a difference in the timing of cercarial release (when schistosomes would be aiming to infect a host) In the marshland, cercarial release was in the early morning, before the heat of the day, when people would take their cattle to water In the hilly regions, it was in the evening. Therefore, it was clear that schistosomiasis was behaving in different ways in the two regions. They study then examined the phylogenetic tree of schistosomiasis and found that those in the hilly and in the marshland regions formed two distinct families Overall, the study showed that schistosomes exhibited variability in their genotype and phenotype which maximised their opportunities for infection and transmission in changing environments.

Answer 33

Resistance to all veterinary antihelminthics Can select for PZQ resistance in animal models Isolation of parasites with reduced sensitivity in Egypt Parasite evolution over short time periods Non-random mating amongst schistosomes Current/recent MDA programmes are highly successful - strong selective pressures Currently reliant on a single drug Monitoring is difficult - no (informative or non-informative) molecular markers available, lack of mechanistic knowledge of PZQ action Could rare resistance conferring alleles be already present in untreated populations? Are rare resistance-conferring alleles the only parasite strategy involved in apparent ‘PZQ treatment failures’?

Answer 34

``` No evidence from China Probably no drug resistance in Senegal No increase 10 years later in Egypt Predicted large refugia Long generation time in human host ```

Answer 35

No molecular markers for PZQ yet Significant genetic ‘bottleneck’ was produced by MDA on schistosome population genetics Hence, the ‘effective reservoir’ may be smaller than previously thought Continued significant reductions in diversity may reduce the schistosomes’ ability to adapt and survive any future novel environmental selective pressures to which they might be exposed Or, there may be increased success of a small number of potentially resistant alleles

Answer 36

If you treated everyone in the world with PZQ at the same time you wouldn’t eradicate schistosomiasis Some would be in the other life cycle stages, not in humans, and the juvenile worms are tolerant to PZQ There would still be a degree of refugia Schoolchildren get treated because they are infected with the greatest intensity, but this still leaves infections in older people

Answer 37

Also known as river blindness Very common 60 years ago, with about 50% of people over the age of 40 blind in some areas Today, virtually no blindness due to onchocerciasis but there are still many people infected especially in Western Central Africa and they have to be treated once a year to prevent the blindness

Answer 38

Parasite Host is the blackfly, which breeds in fast moving water This is why it’s common next to rivers (river blindness……….) The adult worm lives in the human body and gives birth to live larvae These circulate in the skin waiting to be picked up by a biting blackly They develop in the blackfly, which infects a human when it bites them The larvae circulate around the skin and cause intense itching They also circulate across the retina, and if they do this over a period of time they damage the retina and people go blind

Answer 39

Flies carrying the microorganism land on children’s eyes, to feed on discharge Women who take care of children also get the infection Flies that breed in human faeces spread the disease to others Dirty hands or face cloths also spread the disease Bacterium produces a characteristic roughening of the inner surface of the eyelids Incubation period is 5-12 days Patients experience symptoms of conjunctivitis or irritation, like pink eye

Answer 40

Usually seen in children, especially pre-school Characterised by white lumps in the under surface of the upper eyelid (conjunctival follicles or lymphoid germinal centres) Non-specific inflammation and thickening often associated with papillae Follicles may also appear at the junction of the cornea and the sclera (limbal follicles) Active trachoma will often be irritating and have a watery discharge Bacterial secondary infection may occur and cause a purulent discharge

Answer 41

Later structural changes - Includes scarring in the eyelid (tarsal conjunctive) which leads to distortion of the eyelid with buckling of the lid (tarsus) so that the lashes rub on the eye (trichiasis) These lashes will lead to corneal opacities and scarring and then to blindness

Answer 42

Children are the most susceptible to infection, but the blinding and more serious symptoms tend to be in adulthood Serious public health problem Affects the poorest populations in 46 endemic countries 146 million active cases, mainly among children and women Almost 6 million people are blind or visually disabled due to trachoma WHO estimates an annual productivity loss of $2.9 billion in 1995, adjusted to $3.5 billion in 2003 Not just Africa - also seen in indigenous populations of Australia

Answer 43

Person to person via dirty hands and clothing, but also flies Direct contact with eye, nose, and throat secretions from affected individuals or contact with fomites Mechanical transmission (flies) Environmental risk factors

Answer 44

``` Lack of water Absence of latrines or toilets Poverty in general Flies Close proximity to cattle Crowding And more ```

Answer 45

Annual mass treatment for at least 3 years with 80% population coverage target Based on expert opinion - no data at the time May eliminate infection in mesoendemic communities, but the same efforts in hyperendemic communities seem to only cause a decline in active trachoma - not a reduction to 0% - even after multiple years of treatment

Answer 46

Partnership for the Rapid Elimination of Trachoma - Gambia Found that 1 round of treatment reduces TF below the elimination threshold, and further rounds were redundant Would be better to do one high coverage (>90%) round of treatment to reduce prevalence However, this isn’t always attainable therefore other measures may be taken

Answer 47

``` Trachoma strategy: Surgery for trichiasis Antibiotics Facial cleanliness Environmental improvement ```

Answer 48

Reduces risk of progressive corneal opacification Needs training of surgeons and other staff to carry it out - not enough capacity at present RCT in Gambia found uptake was 45% higher when the surgery was village based and no difference in success of treatment, cost to patient was lower Uptake is low - lack of knowledge, cost, fear, inaccessibility Trichiasis recurrence 20% at one year and 62% at three years New strategies needed due to high rates of reinfection

Answer 49

Lower the relative risk but not much effect on the individual case Control programs use them because: Treat individual infections and reduce risk of developing scarring Limit transmission to others Mass treatment with topical tetracycline not feasible - twice a day for many weeks Single dose azithromycin received better and based on studies, safe MDA strategies were developed Pfizer donated This is a good method but resources are lost treating those not infected, therefore rapid diagnostic tests being developed

Answer 50

To prevent transmission rather than treat trichiasis or infection Gambia study - households who put a higher proportion of water towards hygiene had a reduced risk of trachoma RCT of hygiene promotion narrowly failed by WHO said it was compelling enough to warrant inclusion in the strategy

Answer 51

Not included in SAFE as no evidence that investment would have an impact on transmission Identifies putative vector Musca sorbens A large RCT which tested fly control, insecticide and provision of household latrines to reduce breeding materials significantly reduced contact between flies and eyes

Answer 52

No studies looking directly at water and trachoma Several studies show families living further from water are at a greater risk Trachoma has also been found to disappear where water has become available even in the absence of an antibiotic based programme

Answer 53

Strategy clear and understandable Measurable progress Regular meetings between actors to share achievements and ideas Delivery of services is performed effectively and inexpensively by non-specialists Success of each part encourages communities to buy into the rest of it Mass treatment (single dose azithromycin) is effective, feasible, and popular Azithromycin is well tolerated, relatively free from side effects and has additional benefits - effective against malaria as well as resp and skin infections No resistance yet Donated and shipped to endemic countries by Pfizer Advocacy by NGOs and WHO has led to governmental commitment in some countries Strong NGO involvement Intersectoral programmes - improving water supplies and sanitation while providing eye care

Answer 54

parasite that infects humans through water. The intermediate host is the water flea. People are infected when they drink unfiltered water from a pond or stream. Once in the stomach, the larvae come out and grow. After a year, they are 1m in length and the worm then travels around the body. When the female worm is ready to give birth, she forms a blister around the foot. When the worm begins to the protrude from the body the blister becomes painful and burns. The person will then go to a pond to relieve the sensation, and the larvae will come out to infect water fleas again.

Answer 55

30 years ago, there were approximately 2 million sufferers - in 2014 there are only about 150 cases globally and most are limited to Southern Sudan.

Answer 56

only humans can have guinea worm (there is no animal reservoir) and the water fleas can only transmit it to humans by mistake - i.e. if we can get people to stop drinking unfiltered/unclean water then we can stop transmission. The reductions so far have been made due to water and sanitation improvements, filtering water, health education, and case management so obviously this are effective and just need to be spread into the final few communities with guinea worm. There are multiple organisations pushing for eradication including the WHO, Bill & Melinda Gates Foundation and the Carter Centre.

Answer 57

Asymptomatic or undifferentiated fever Virus incubates for 2-7 days then fever Headache, muscle and joint pain, self limiting, 1 week

Answer 58

``` 4 grades (1-4) Capillary leakage, thrombocytopenia, altered haemostasis, liver damage, bleeding ```

Answer 59

Massive fluid loss (pleural effusion) can result in shock Ascites Bleeding Hepatomegaly

Answer 60

390 million dengue infected individuals per year of which 96 million showed symptoms 2.5 billion (2/5 of the world’s population) are at risk

Answer 61

E is a major target of neutralising and protective antibodies NS1 is a target of protective antibodies NS1-specific antibodies lead to ADCC and complement mediated cytotoxicity NS3 is a major target of T cells (CD4 and CD8) The IFN response is important Neutralising antibodies are long-lived Cross-reactive neutralising antibodies decline rapidly after infection Protection is thought to be life-long for homotypic virus, but last only a few months for heterotypic virus Serotype-specific and cross-reactive T cells are detected after infection

Answer 62

Observations that viral load is higher in DHF than DF and that there is leakage of cytokines/chemokines/mediators and/or damage of endothelial cells in DHF The hypothesis is that increased viral load leads to antibody dependent enhancement (ADE) and cross-reactive T cells

Answer 63

Shown in monkeys Sequential infections of different serotypes compared to the primary serotype Some showed increased (10-fold) viraemia Animals given dengue immune serum and then when challenged had higher viraemia than those given non-immune serum Good animal model is lacking More cytokine production and less degranulation in DHF compared to DF

Answer 64

Endothelial cells were readily infected by dengue virus in vitro However, only viral antigen found on endothelial cells in vivo Cytokines/chemokines/mediator effect is preferable because patients quickly recover from the disease without any sequel TNFalpha, lots of interleukins, complement fragments/complexes were al higher in DHF than DF

Answer 65

Equal protective responses against all 4 serotypes Need ‘all or nothing’ One strong dose for immediate effect Boosting needs to ensure that Ab levels do not drop and also that they all decline at equal rates

Answer 66

``` Sanofi Pasteur’s Chimerivax Unequally elicit antibody titres against the 4 serotypes Surrogate marker(s) for the protection efficacy neutralising antibody titres was not god enough ```

Answer 67

Vector control: Control mosquito spread No stagnant water Upside down buckets, tyres need to be removed/righted Careful transport of travellers ‘Vaccinating’ mosquitoes by infecting them with wolbachia bacteria Global warming needs to be considered as it is leading to mosquito spread

Answer 68

Viral disease Causes estimated 55,000 deaths per year in Asia and Africa Once symptoms develop the death rate is 100%

Answer 69

Canine vaccination Humane management of dogs Vaccination of people immediately after exposure Elimination target is 2015 in Latin America and 2020 in China and Japan

Answer 70

Buruli ulcer is a chronic skin condition caused by Mycobacterium ulcers infection Endemic in 33 countries, but is most common in Ghana, Gabon, and Australia. About 5000 cases per year are reported between all these countries, but poor knowledge and reporting may mean that the true prevalence is higher. Buruli ulcer can be contained, but it isn’t always - some people suffer very greatly and are killed by it.

Answer 71

Training health workers (which is vital because there are so few cases) Early case detection and treatment with antibiotics to prevent complications Generally better case management with surgery if necessary.

Answer 72

Leprosy is quite unique in that only 1 in 20 people are actually susceptible to it Caused by a bacterial infection with Mycobacterium leprae Leads to a chronic disease - the incubation period is very long (about 5 years) and so symptoms take some time to show Primarily leads to numbnesss and paralysis in the extremities, which can eventually cause permanent disability especially as patients may not notice injuries, which can become infected as a result. Additionally, it can cause blindness due to damage to the eyelid muscles, which means there is inadequate blinking and the eye itself is damaged.

Answer 73

There were 220,000 cases in 2005, down from 5.2 million in 1985 as a result of political will and commitment towards elimination. However, the real rates may be higher as patients suffer the stigma of a diagnosis which may discourage them from seeking care. Due to the disability and the (incorrect) perception of leprosy’s infectiousness, patients can be case out from their communities and suffer a large burden of discrimination leaving them unable to work or marry.

Answer 74

Implementing a strategy of early detection and treatment with MDT before the person becomes disabled. Capacity building will be needed to sustain control Community education programmes can be used to reduce stigma and discrimination. Intensified research may provide us new strategies for diagnosis, treatment and control.

Answer 75

There is an effective multi-drug therapy (MDT that has been recommended by the WHO since 1981 to kill the pathogen and cure the patient. This is now being donated by Novartis.

Answer 76

South American form of sleeping sickness Trypanosoma cruzi 10 million people infection, can cause major heart problems in up to 30% of these (Cardiomegaly; also megacolon, megaoesophagus) Transmitted by bed bugs, therefore confined to people with poor quality housing Recently spread into Europe via immigrants who sell blood

Answer 77

Louisiana and Texas Treatment costs up to $1000 per year and diagnosis/access to care are major constraints Vector control is crucial for breaking transmission

Answer 78

found in West and Central Africa Represents more than 90% of reported cases of sleeping sickness Chronic infection Person can be infected for years without symptoms; when the symptoms do emerge they are often already in an advanced disease stage where the CNS is affected Transmitted by the Tsetse fly

Answer 79

Represents less than 10% of reported cases Acute infection First signs and symptoms after a few months or weeks Disease develops rapidly and invades the CNS Transmitted by Tsetse fly (which has a very limited distribution)

Answer 80

Early diagnosis (less than 10,000 cases diagnosed in 2010) Therapy to infected persons (drugs donated by Sanofi and Bayer) Tsetse control New therapy using systemic insecticides in cattle so that when the fly bites the cattle, it dies

Answer 81

a filarial worm distributed around West and Central Africa | Transmitted by Tabanids (horseflies).

Answer 82

There is no pathology in loa loa in itself - you will not know that you have it, although some patients can develop lymphoedema. Important because albendazole and ivermectin (used in the mass treatment of lymphatic filariasis and onchocerciasis) can cause serious side effects in people infected with Loa Loa. Especially true of people with high Loa Loa microfilarial densities.

Answer 83

The idea is that killing large numbers of microfilaria, some of which may be near the ocular and brain regions, can lead to encephalopathy.

Answer 84

the development of more specific diagnostic tests for Loa Loa to identify high risk areas prior to mass treatment.

Answer 85

Cysticercosis is caused by the Taenia solium worm which can be contracted by eating uncooked pork.

Answer 86

It is the eggs which are ingested. The eggs form a cyst in the human host, which tends to be in the brain. The cyst then causes seizures - it is the cause of 10% of seizures presenting to emergency departments in Los Angeles. Most common cause of seizures in Hispanic Americans. 41,400-169,000 cases. The eggs of the worm will then be excreted in the stool (the adult worm lives in the human gut)

Answer 87

Poor hygiene is generally the cause of humans consuming eggs and therefore the cause of epilepsy - so better hygiene is ultimately the best control measure for cysticercosis. The adult worm in humans is susceptible to praziquantel which also kills the cyst in the brain. This can change the cyst from asymptomatic to symptomatic, and hence should be considered when treating schistosomiasis. Pigs can also be treated, but hygiene is still a better intervention.

Answer 88

Cutaneous | Visceral

Answer 89

Most common form of leishmaniasis affecting humans Skin infection caused by a single celled parasite, transmitted by phlebotomine sandfly; there are about 20 species of Leishmania that can cause cutaneous leishmaniasis Nasty, suppurating wound at the site of the bite which heals in about 6 months Can ulcerate and become secondarily infected Can become a ‘mucocutaneous’ form causing gross mutilation by destroying soft tissues in the nose, mouth, and throat

Answer 90

Most severe form Leads to fever, weight loss, and an enlarged spleen and liver Patients will have a low RBC (anaemia), low WBC, and low platelets If untreated, very fatal

Answer 91

Transmitted by sandflies, which are small enough to go through a mosquito net and produce a pinprick bite

Answer 92

90% of causes of cutaneous leishmaniasis occur in parts of Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, and Syria, and in Brazil and Peru Over 90% cause of visceral leishmaniasis occur in India, Bangladesh, Nepal, Sudan, and Brazil

Answer 93

Early diagnosis and effective case management Vector control e.g. insecticide spray, personal protection Effective disease surveillance Control of reservoir hosts (dogs and other animals) Social mobilisation and strengthening partnerships with the community, with effective behavioural change interventions

Answer 94

Diarrhoeal disease makes up a large part of infant mortality Associated mostly with poverty and poor infrastructure. Cause of 8.8 million deaths of children under the age of 5 in 2008, and a large proportion of mortality in under 5s is due to infectious diseases (68%) The main globally important diarrhoeal diseases are Shigellosis, viral diarrhoeal diseases (such as rotavirus) and cholera.

Answer 95

major cause of dysenteric, or severe, diarrhoea, causing 1.1 million deaths per annum, 61% of which were in those under the age of 5 (Kotloff et all 1999). Dysenteric diarrhoea responds less well to Oral Rehydration Therapy (ORT) and so the risk of death is about 2-7 times that of just having watery diarrhoea.

Answer 96

such as rotavirus are another common cause of diarrhoea worldwide and some are even vaccine preventable. Rotavirus is the commonest viral gastroenteritis in children and (although also common in the developed world) is a common cause of mortality in the developing world. About 40% of hospitalisations with diarrhoea in sub-Saharan Africa are due to rotavirus. Even in the developed world, although rarely fatal it is so common that it can place a significant burden on health systems.

Answer 97

trend towards reduction in child mortality due to diarrhoeal disease, most significantly in the countries with the greatest burden, but a large global burden still remains. This is especially important as tackling diarrhoeal disease will be a vital part of achieving Millennium Development Goal 4 of reducing childhood mortality.

Answer 98

``` broad but are mostly associated with poverty and a lack of healthcare provision. They include: Not exclusively breastfeeding Being underweight Stunting Wasting Vitamin A deficiency Zinc deficiency Measles. ```

Answer 99

Better nutrition Avoidance of contaminated water Contains protective factors. Oligosaccharides may block pathogen attachment to the mucosa IgA may help to fight off the pathogens, and lactoferrin increases lymphocyte activity, antimicrobial and anti-inflammatory activity. A systematic review has found that there was a benefit to breastfeeding on mortality from diarrhoeal disease.

Answer 100

Measles vaccine Possible rotavirus vaccine Cholera vaccine may be available soon

Answer 101

(Zaman et al 2010).

Answer 102

Low osmolality ORS is now recommended, which has been found to produce a 20% reduction in stool output, 30% reduction in vomiting, and a 40% eduction in the need for unscheduled IV treatment (Santosham et al 2010).

Answer 103

This may be due to less specific funding, or changes to the definition of an acceptable fluid schedule. In order to increase uptake, ORS could be produced with better flavours (as there is no longer a concern that children might OD since the newer formulations were released), more convenient packaging or dosing, or bundling with zinc, and better distribution, for example through schools or community workers.

Answer 104

been found to reduce duration of episodes of both acute and chronic diarrhoea, and the risk of recurrence in the next 2-3 months (Bhutta et al 2013). When introduced to community programmes, it also increased the uptake of ORS Overall, Bhutta et al (2013) found a 46% reduction in all cause mortality and a 23% reduction in hospitalisation. Bundling zinc and ORS may be helpful, as well as task shifting their distribution to community healthcare workers or schools.

Answer 105

Zeng-sui et al (1989) found that deep well tap water provision in rural China significantly reduced rates of some diarrhoeal diseases. Quick et al studied point of use sterilisation with hypochlorite, durable plastic storage bottles, and community education interventions in Zambia - they found that intervention families had fewer episodes of diarrhoea.

Answer 106

of Water Related Infections can be used to organise water related health problems into four distinct categories: water-washed (or water scarce), water based, water related insect vector, and water borne.

Answer 107

those which undergo person to person transmission due to inadequate personal and domestic hygiene. This is a water availability, rather than a water quality, issue. An example would be trachoma, where recurrent chlamydia infections of the eye are caused by inadequate face washing and flies buzzing around the face. The recurrent conjunctivitis causes scarring of the eyelid and the eyelid starts to turn inwards. As a result, the lashes scratch the cornea leading to blindness.

Answer 108

those where transmission of infections is via an obligatory aquatic host, such as a snail. An example would be schistosomiasis (bilharzia), a parasitic disease caused by a fluke which has the snail as its host in the water It causes damage to internal organs, including the liver, and can compare growth and cognitive development in children. There is a clear relationship between water sanitation and the incidence of schistosomiasis.

Answer 109

those where transmission is by insects which breed in (or bite near) water. An example would be malaria, a disease caused by Plasmodium species parasites and transmitted by female Anopheles mosquitoes.

Answer 110

those which are contracted when a person drinks or eats contaminated food or water. An example would be Ascaris and other intestinal infections. About 1/3 of the world’s population are infected with intestinal worms, mostly children. These can cause malnutrition, anaemia, malabsorption syndrome, intestinal obstruction, and mental and physical growth retardation or massive dysentery. Safer water, sanitation, and improved hygiene can reduce the morbidity from Ascaris by 29%.

Answer 111

It is difficult to know the true impact of hand hygiene due to a lack of data in many countries, both outside and inside healthcare facilities. This could be due to incomplete reporting of cases, or also that in some areas the largest proportion of care is delivered outside a hospital setting. However, hand hygiene is the most common vehicle to transmit healthcare associated pathogens. It is definitely capable of transmitting diarrhoeal disease, which represents a large proportion of the burden of disease in developing countries. Diarrhoeal disease can cause more serious illnesses (or increase the severity of baseline illnesses), prolong stays in healthcare, cause long term disability and excess deaths,a s well as having a high additional financial burden and high personal costs on patients and their families. In 2011, 2.5 billion people still lacked access to improved sanitation facilities.

Answer 112

promoting hand washing can reduce diarrhoea episodes by about 1/3 This is comparable to the effect of clean water provision in a low-income area, which is arguably more expensive and more difficult to do. One paper found that using soap for hand washing had more of an impact on diarrhoeal disease than refuse disposal, or the mother’s education.

Answer 113

System change - access to safe, continuous water supply as well as to soap and towels, readily accessible alcohol hand rub at the point of care Training/education - providing regular training to al health care workers Evaluation and feedback Reminders in the workplace Create an institutional safety environment

Answer 114

direct observation, and this has been found to be fundamental to confronting health care workers with their actual behaviour and to call for accountability with regard to patient safety (Allegranzi et al 2013) but this is expensive and logistically difficult in resource poor settings. It also can modify behaviour by itself.

Answer 115

Hepatitis C is widespread and there are areas of high infection, for example in Egypt and Italy. Its consequences are similar to hepatitis B, with patients progressing to liver cirrhosis or liver cancer. Many people die from Hep C related disease - there are 130-150 million people with chronic hepatitis C infection and 350,000 to 500,000 deaths annually from hepatitis C related liver disease.

Answer 116

gestational diabetes and preterm delivery. | However, these are difficult to separate from social and behavioural factors (the reasons the person has hepatitis C).

Answer 117

Compared to hepatitis B, there is not much mother to child transmission. It is difficult to get true transmission figures as those we have vary enormously, but the figure generally used is 3-5%. This happens either in utero, or peripartum. Having said this, it is still important to reduce mother to child transmission as much as possible regardless given the outcomes of chronic hepatitis C infection.

Answer 118

prolonged rupture of membranes (over 6 hours), exposure to maternal blood during vaginal delivery (consequent to vaginal and/or perineal lacerations), and invasive monitoring of the foetus with scalp electrodes or intrauterine pressure catheter placement. Much more research has been done on mother to child transmission of HIV, and the risk factors seem to be the same.

Answer 119

There are interventions which have proved to be successful in HIV, but so far these have not been shown to be of much benefit in Hepatitis C. They include: Using Caesarean section as the mode of delivery Formula feeding (there are very low levels of hepatitis C in breast milk) It is thought that anti-hepatitis C therapies in pregnancy would help but these will not be prescribed in pregnancy at present. Clearly, more research will be needed to find interventions that work.

Answer 120

‘sustained virological response’, or SVR. In the UK, this is done using three interventions: pegylated interferon (once weekly subcutaneous, provides immune activation), ribavirin (an oral antiviral), and additional drugs for G1 genotype (boceprevir or telaprevir).

Answer 121

many side effects including depression and flu-like symptoms, and the additional drugs for the G1 phase have added side effects. There is up to a year of therapy so it should be carefully planned around work commitments etc. Patients should be regularly monitored for side effects including liver biochemistry and blood count.

Answer 122

Cure rates are 50-60% at best, lower (30-40%) if they have HIV coinfection. Outcomes appear to be similar in low income countries - a study found that cure rates were actually slightly higher in low income countries but this may not be completely accurate.

Answer 123

The new Direct Acting Antiviral (DAA) drugs for hepatitis C have been shown to produce SVR in over 90% of treated people, and SVR reduces the risks of all cause mortality in hepatitis C As well as specific outcomes including hepatocellular carcinoma, liver transplant, and liver related death. However, the results have not been consistently seen in all studies and there is always a risk of reinfection.

Answer 124

costs, cure rates, and complexity.

Answer 125

Costs are an issue everywhere, as pricing is based on what the health system will pay. Therefore, there is variation in the cost depending on the location. The current estimates for the cost of early access to Sofosbuvir are £35k for 12 weeks. Drug spending is expected to increase by about 200% between 2015 and 2016, which is far more than for other conditions. To add to this problem, there are no specific global funding mechanisms for HCV.

Answer 126

Firstly, Gilead is taking forward the model of reducing costs in line with their HIV programme. Tiered prices are being used, and they have recently signed a contract with generics manufacturers. The manufacturers are developing capacity to produce, for example, daclatasvir. Additionally, it is hoped that shortened treatment durations may be an option for the future as these seem to work quite well.

Answer 127

At the moment, patients can hope for a 50-60% cure rate at best. The rate is lower if they have HIV coinfection - about 30-40%. Newer Direct Acting Antiviral drugs (DAAs) have been reported as inducing SVR in 90% of patients but this has not been consistently shown in all studies. Further research is needed into the DAAs to see if they will actually provide a higher cure rate of hepatitis C.

Answer 128

also due to under-diagnosis. About 80% of HCV cases are undiagnosed, and so there may be some role for screening to ensure all cases are identified, especially amongst the HIV positive population.

Answer 129

HCV treatment is highly toxic and can therefore be complicated, as it can cause secondary issues such as anaemia and depression. There is potential for simplified monitoring tests during treatment, which would hopefully allow us to extend treatment programmes to lower-resource settings where it is currently difficult to monitor the treatment. Additionally, in the future it is hoped that there will be options for treatment depending on genotype, as the genotypes vary globally. Treatment could hopefully also be shortened - currently can take a year

Answer 130

there can hopefully some improvements made to health systems to allow for task shifting and integration with other services (for example HIV). Patient and community engagement will be needed to encourage people to come forward for testing.

Answer 131

An HCV vaccine would probably be the most cost effective and best strategy to control HCV. However, it is difficult to produce a vaccine as the genotypes vary according to geographical region. We cannot use an attenuated vaccine as natural immunity is not complete or fully understood, although there is evidence that reinfection is associated with lower viraemia and a shorter duration of viraemia.

Answer 132

Alphavirus, spread by A. aegypti mosquitoes Prevalent in the Indian Ocean region - Reunion, Maldives, Sri Lanka, India Distribution is different from Dengue - focused on South East Asia and less in South America and other places where dengue is prevalent Emerging mosquito borne virus Usually causes a short lived illness with high fever, rash,and arthritis especially of the small joints Some suggestion it could lead to chronic problems May have the ability to cause a lot of morbidity and mortality

Answer 133

High prevalence globally - both contribute to sustained global morbidity and mortality from chronic liver disease, cirrhosis, and hepatocellular carcinoma HBV vaccination is widely implemented but for HCV there is no effective vaccine on the horizon Hepatitis B 350 million chronically infected More than 1 million deaths per year Prevalence is high in Africa, especially West Africa Infection up to 10-15% in some areas Hepatitis C 130-150 million people with chronic hepatitis C infection 350,000 to 500,000 deaths annually from hepatitis C related liver disease.

Answer 134

``` Global health agenda Requirement for complex diagnostics Drug cost and availability Skills and education Lack of political will Financing issues ```

Answer 135

Not an NTD even though 2 billion people have been infected and there are 350-400 million with chronic HBV, 25-40% of which will die of cirrhosis or liver cancer HBV is 50-100 times more common than HIV

Answer 136

Complex due to the presence of different stages and the need for LFTs as well as hepatitis B tests Need to decide who should be treated, and the benefits of treatment depend on the severity of liver disease and the probability of treatment response Hopefully newer drugs will be more effective and with fewer adverse effects so you can just treat more people

Answer 137

``` Haematology Biochemistry Viral serology Viral load testing Liver biopsy and histology These require lots of specific equipment and training ```

Answer 138

guidelines are being adapted for low resource settings and new innovative tools: Low cost point of care tests Dried blood spot testing Non invasive markers of liver fibrosis

Answer 139

Costs are high generally However, drug prices in general have decreased e.g. tenofovir Generic prices seem to be static One consequence of this is drug resistance - because lamivudine was cheaper and has been available longer, many people in SSA and SE Asia have been treated with it and are now resistant (there are now different guidelines)

Answer 140

``` Need local capacity building and training e.g.: Screening teams Treatment work up including labs Monitoring during treatment Side effects of treatment Treatment failure ?End points of therapy HIV uses similar drugs in similar places, so integration with HIV services may have a benefit: Trained staff Lab facilities Drug supply Management of coinfection ```

Answer 141

No specific global funding mechanisms for HCV or HBV Access to treatment is likely to be limited in European countries Global Fund is limited to TB, HIV and malaria UNITAID is hopefully going to help: Improving market for drugs and diagnostics Moving into HIV/HCV coinfection French government are strong advocates of expanded remit UK government resistance has waned

Answer 142

A safe and effective hepatitis B vaccine has been available since 1982 WHO recommends universal infant vaccination since 1992 Reduces risk of chronic HBV infection and HCC Many examples of successful vaccination programmes worldwide, but not all countries vaccinate

Answer 143

Gambia has been vaccinating since 1986, RCT randomised half the country to vaccine and half to no vaccine Found 67% efficacy against infection and 96.6% efficacy against chronic infection at 15 years Vaccination in Taiwan, since 1984, has been very systematic Age specific incidence has greatly decreased following vaccination There were some very young liver cancers in Taiwan, but rates have now decreased

Answer 144

Reduces risk of chronic HBV infection and HCC | Infant vaccination is very cheap and effective

Answer 145

coverage is suboptimal and is most suboptimal in places where the prevalence is high Secondly, infant vaccination reduces childhood transmission but doesn’t eliminate risk of perinatal transmission And perinatal transmission has the highest risk of becoming a chronic carrier

Answer 146

Most of the ill health effects of hepatitis B are due to chronic infection 25% of people with chronic HBV develop cirrhosis or liver cancer About 600,000 (up to 1 million) die annually of HBV related disease The risk of chronic carriage depends on the method of transmission of HBV: Perinatally - 90% Childhood - 30-50% Adult - 5% Therefore, perinatal transmission is hugely important in causing the morbidity and mortality of HBV Perinatal transmission accounts for most transmission in SE Asia, whereas childhood transmission is the main route of transmission in SSA This creates a vicious cycle as you are more likely to chronically carry in the areas where HBV is already very common

Answer 147

Birth dose vaccine Birth dose immunoglobulin Treatment of highly infectious mothers

Answer 148

Infant vaccination Cheap and effective Reduces incidence and childhood transmission However doesn’t eliminate risk of perinatal transmission and coverage isn’t great, especially in areas where HBV is high

Answer 149

Passive immunisation with IVIG Reduces transmission from the mother However, storage and delivery of IVIG is a problem

Answer 150

Treat highly infectious mothers Usually in the 3rd trimester Reduces transmission Not routinely practiced: Need to know if a mother is positive or negative (therefore needing good antenatal care) Also need facilities to check viral load and e antigen Then you also need access to treatment

Answer 151

Good antenatal care system Viral load and HBeAg testing Logistics and access to rural areas Finances

Answer 152

The pool of chronic HBV carriers are the ones at risk of developing cirrhosis of HCC If vaccination coverage is suboptimal, they will also be able to contribute to ongoing transmission

Answer 153

we may need to consider screening to find those who are chronically infected Also need to expand access to antiviral therapy in resource poor settings

Answer 154

Hill et al 2014:

Answer 155

gonorrhoea, chlamydia, HSV 1/2, HPV and syphilis

Answer 156

Whilst these diseases do not contribute much mortality, they do cause a significant burden of disability, particularly in the form of female infertility. There are only an estimated 0.1 million deaths annually from STIs other than HIV. However, there were an estimated 5.1 million years old due to disability in women in 2002, and 1.9 million in men. One of the issues with the global burden of curable STIs is that many of the infections are asymptomatic, and so the true prevalence rates may be much higher than the numbers diagnosed in STI clinics.

Answer 157

“Any sexual act, attempt to obtain a sexual act, unwanted sexual comments of advances, or acts to traffic, or otherwise directed, against a person’s sexuality using coercion, by any person regardless of their relationship to the victim, in any setting, including but not limited to home and work”

Answer 158

“Sexual violence is any sexual act that is perpetrated against someone’s will. SV encompasses a range of offences, including a completed non-consensual sex act (i.e. rape) an attempted non-consensual sex act, abusive sexual contact (i.e. unwanted touching) and non-contact sexual abuse (e.g. threatened sexual violence, exhibitionism, verbal sexual harassment). All types involve victims who do not consent, or who are unable to consent, or refuse to allow the act”

Answer 159

Type of violence: physical force/psychological violence Type of act: anal, vaginal, oral Type of perpetrator: stranger/intimate Number of perpetrators: one/several (gang rape/streamlining in South Africa) Frequency Intensity/severity

Answer 160

Men and women can be victims of sexual violence although the vast majority of sexually violent acts are committed by men against women and children It is a gendered phenomenon: its nature and extent are a reflection of pre existing social, cultural, end economic disparities between men and women Rape is an act through which men communicate their power to their victim Sexual violence has been linked to a cluster of male behaviours which include: sexual and physical violence, having many sexual partners, transactional sex, and alcohol abuse Can be an act of punishment and an expression of holding power over someone, and it can be an act through which the perpetrators affirm to themselves a sense of power which they may not feel in other aspects o their lives Male privilege and control was identified as one of the three top factors predicting the perpetration of violence against women

Answer 161

Reducing alcohol abuse Behaviour change communication strategies Programs targeting gender attitudes and norms Structural interventions: Public awareness Economic empowerment of women Strengthening laws and policies Health services: Access to emergency reproductive health services Prevention Health services integration

Answer 162

High levels of underreporting Fear of revenge Fear of stigmatisation Inefficient and corrupt justice systems When taking surveys, need to be aware that ‘sex’ can be interpreted in different ways, and some ways of asking questions will obtain more accurate results than others Direct questions about their experience of specific acts of violence over a defined period of time results in higher disclosure than generic questions about whether the respondent has been ‘abused’ or has experienced ‘domestic violence’, ‘rape’ or ‘sexual abuse’

Answer 163

Global prevalence of physical and/or sexual intimate partner violence among all ever-partnered women was 30% Global lifetime prevalence of non sexual violence is 7.2% Indicates that the perpetrators of sexual violence are most often an intimate partner or family member Globally, 35.6% of women have ever experienced either non-partner sexual violence or physical or sexual violence by an intimate partner, or both Up to 1/3 of girls report that their first sexual experience was forced Between 250,000 and 500,000 women were raped in Rwanda during the 1994 genocide Highest worldwide prevalences were in the Mediterranean region, then South East Asia then West Africa

Answer 164

HIV prevalence among young women in SSA is several folds higher than in young men of the same age - could be due to: Age differentials in mixing patterns (sugar daddies) Transactional sex Higher susceptibility of genital tract at a young age Sexual violence Young women often have sexual relationships with older men for money, survival, goods e.g. mobile phones

Answer 165

PTSD, social exclusion and rejection, pelvic fistulae, and many more - HIV is just one

Answer 166

Of 5 studies on incident HIV and STI, 3 large studies (from SSA and India) found an increased risk of HIV/STI among those reporting partner violence The 4th study among women attending substance misuse clinics in the USA used self reported data on HIV and STI diagnosis and found some evidence of lower risk of HIV among those reporting intimate partner violence The best estimate is an odds ratio of 1.52 (CI 1.03-2.23)

Answer 167

Genito anal injury Age related anatomic/physiological characteristics Pregnancy - much more evidence coming out that women who are pregnant have a higher risk of acquiring HIV when exposed to it due to hormonal changes Heterosexual anal sex Risk behaviour of the perpetrator (which increases his risk of being infected)

Answer 168

Have multiple partners Have sex more often Practice transactional sex Practice anal sex Report symptoms of or have sexually transmitted infections Also, there is lower condom use due to an inability to negotiate with a violent partner Proposing the use of the condom may increase women’s risk of violence There is often more frequent sexual activity as the woman is not able to refuse It has been proposed that women who have experienced sexual violence may have a weakened immune system but this is not fully understood Additionally, fear of partner violence and rape impede women’s access to HIV/AIDS information, HIV testing, treatment, and counselling

Answer 169

Widows Female sex workers Women in conflict settings Prisoners

Answer 170

Estimated 34 million people living with HIV 5% adults in sub-Saharan Africa (much higher in some population groups) 0.8% of the global population Incidence was 2.7 million new cases in 2010 Mortality 1.8 million in 2010 1-1.5 million patients started on ART each year - so more new infections than we are treating Basically for every person put on treatment 2 are infected 260,000 children die of AIDS every year 30 million AIDS-related deaths to date Increasing potential treatment costs of $35 billion per year

Answer 171

Simplicity of treatment has improved Single pill therapy 17% better adherence Patient preference Reduced risk of stock outs More realistic for the developing world Simpler guidelines also mean no more problems with migration and patients having to switch treatments More effective therapy with options for those failing treatment Medication is less toxic and pill burden reduced Better management of complications Atripla now costs about £5000-£6000 per year in the UK but can be manufactured and sold for <$99/year in poorer areas

Answer 172

First drug was licensed in 1987 Primarily due to repurposing of AZT Very high doses, so very toxic Activity of AZT against HIV was shown in 1985, 25 months before licensing Extended life, but at the cost of high toxicity Mid-90s - addition of 3rd agents to the earlier combinations of 2 treatments transformed outcomes The era of Highly Active Anti Retroviral Therapy (HAART) began Drop in mortality in the UK, which encouraged more people to be tested and treated

Answer 173

``` Primary prevention Change sexual behaviour, including condom promotion Clean blood supply Prevent mother to child transmission Safe drug use Vaccines, microbicides, and PrEP Secondary prevention Testing and intervention to those infected Treatment with ARVs ```

Answer 174

Difficult for women to negotiate condom use with partners due to issues of trust, gender inequality, etc Also, in areas with high importance fertility, they may not be adopted

Answer 175

Are associated with the infectiousness of somebody who has HIV - they are more likely to shed the virus in genital secretions Make someone more susceptible to contracting HIV if exposed - due to breakdown of mucosal surfaces, higher levels of inflammation so more target cells

Answer 176

Good in the developed world Methods: C section birth Put on ARVs Don’t breastfeed In the developing world, ARVs can be made available but C-sections are not so easy to provide The issues surrounding breastfeeding are also more complicated as there are important benefits to breastfeeding in the developing world; may be more of a risk than from HIV

Answer 177

>57% reduction Doesn’t prevent transmission from men to women but does reduce men’s susceptibility to infection from when More complicated with MSM couples Thought that the surface exposed to the virus is decreased Also debate about whether the glans epithelium becomes keratinised Comparative advantage of being a one-time intervention that doesn’t require long-term behaviour change Meta analysis of data from the one RCT and 6 longitudinal studies showed little evidence that male circumcision directly affects the risk of transmitting HIV to women (Lancet 2009)

Answer 178

People basically become less infectious with treatment as the viral load is lower Whenever you encourage people to come forward for testing, starting education programs with availability of ARVs reduces the incidence

Answer 179

Not so far

Answer 180

Injectable contraception is population in the developing world so the technologies could be rolled out together Ability to be more spontaneous compared to PrEP or topical microbicides

Answer 181

US study PrEP had an efficacy of about 44% Up to 92% in those who took the drugs every day

Answer 182

topical PrEP (microbicides) Women applying microbicide 12 hours before and 12 hours after sex Most effective in the middle of the study - some people stopped using it towards the end About 54% effective in ‘high adherers’ (>80% adherence)

Answer 183

Safety and effectiveness of 1% tenofovir gel applied 12 hours before sex, and as soon as possible within 12 hours after sex Probability of HIV infection was significantly lower in the tenofovir group than the placebo group Have to bear in mind that a trial reduces incidence in itself just because people are more aware

Answer 184

Prevention of HIV infection with early antiretroviral therapy 96% reduction in transmission within discordant heterosexual couples when treatment of the infected partner was started earlier rather than based on the standard of a CD4 count of <350 cells/mm3

Answer 185

Thai trial Prime boost vaccine Protective efficacy a little over 31% No effect on viral load or CD4 count in subjects infected with HIV Lessons: Protection from infection is possible Low levels of primary neutralising antibody Limited CD8 T cell immunity Other immune effectors likely to play a role Highest protection in first 6-12 months Antibody titres appear to wane in line with protection Follow up studies to determine if boosting can prolong protection

Answer 186

Vaginal and Oral Interventions to Control the Epidemic Multisite PrEP trial in young women in South Africa, Zimbabwe and Uganda Daily application of 1% tenofovir gel and daily oral tenofovir and tenofovir emtricitabine (Truvada) No effectiveness Widespread product non-use (plasma levels taken) despite high end of study retention rates and high self reported product use

Answer 187

reasons given for non use: HIV stigma Fear of being mistakenly labelled as having HIV Ambivalence about the research process Confusion about the use of antiretrovirals to prevent infection The need to balance trial participation with other priorities and social relationships

Answer 188

Who will pay for them? Who will be eligible? IS it safe to give ARV drugs to HIV negative subjects for prolonged periods? Will people adhere to daily PrEP for prolonged periods (risk perception) Will PREP change risk behaviour? Can PrEP be equally effective if used in an intermittent fashion? If people get infected while taking PrEP, will it impact on subsequent treatment (resistance?)

Answer 189

Immune control is possible Majority of HIV infected individuals initially suppress the viral load Populations resistant to HIV infection exist Highly exposed, uninfected Children of infected mothers Long term non-progressors - control infection for many years Vaccine candidates in experimental models Live attenuated SIV Can’t make a live attenuated HIV but may be able to add HIV to other viruses Broadly neutralising antibodies Recent data: CMV vector First proof of concept in people RV144 Thai trial: modest level of protection against HIV infection

Answer 190

Classic vaccines mimic natural immunity against infection - no one has recovered from HIV infection Most vaccines protect against disease, not against infection - HIV infection may remain latent for long periods before causing disease (provirus) Protection against HIV infection may require sterilising immunity y(preventing entry); no current vaccine is known to do this Many vaccines use attenuated pathogens, this approach would not be appropriate due to safety concerns HIV has multiple mechanisms of immune evasion Lack of relevant animal models Clinical trials are long and costly A long term effort requires long term, high level global commitment and incentives for industry

Answer 191

High levels of mutation Viral latency and infection of immuno-privileged sites Absence of neutralising antibodies due to high levels of glycosylation, epitope masking by hypervariable loops, and shedding of monomeric p120 Promotion of Th1 to Th2 switch (misdirection) Destruction of immune response (CD4 cells role in coordinating immunity) HIV has relatively few spike glycoproteins on the surface compared to e.g. flu Only in the right combination for a short time until they break down Then the internal components are much more immunogenic and not seen on the surface which almost acts like a decoy Spike envelope is covered in sugar The sugars are mobile - there is a glycol coat on the envelope Antibodies don’t like binding to sugar - so we have to try to find ways around the sugar HIV exists in multiple subtypes (clades) with different geographical distribution More viral diversity in a single HIV patient than in influenza across the world

Answer 192

Long lived broadly neutralising antibodies High levels of central and effector memory T cells Present at the time of exposure Rapidly boosted by mucosal infection Augmented by innate responses Able to rapidly eliminate infection before immune escape

Answer 193

Block HIV from coming into contact with target cells and tissues Reduce the number of susceptible cells Control the spread of HIV from infected cells Eliminate any infected cels that occur within the vaccinated host or enter the host as part of the innoculum

Answer 194

First trials were unsuccessful Merck Ad5 (vectored vaccine) provided no protection Draws attention to the potential danger of pre-existing immunity Magnitude and quality of the bacon induced T cell responses (especially CD8) were not optimal T cell vaccines are still an important component of the overall vaccine strategy They provide the critical priming component in combination regimens with env proteins May substantially impact the magnitude, quality and durability of the antibody response induced by env protein vaccines Are likely to augment partially protective antibody responses May control viraemia if breadth and magnitude can be maintained In non human studies there has been robust control of SIV (simian virus) They became infected but could eliminate the virus Don’t understand why the other 50% became infected

Answer 195

Up to 25% of infected subjects have broadly neutralising antibodies a year or more after infection 1% (elite controllers) have potent activity against a majority of strains Cross reactive antibodies arise over years - maturation of response (? implications for vaccines) Maturation likely to focus on less immunogenic, more conserved regions of env Induction of responses to such regions could provide potent protection

Answer 196

``` The HIV envelope trimer Highly variable Unstable Immune evasion Gp140 mimics ≠ the native structure ```

Answer 197

``` Money Drug supply chains Trained staff Capacity within failing health care systems Stigma Gender based violence Human rights/coercion Acceptability at a population level ```

Answer 198

``` HR Decentralisation Diagnosis Earlier initiation Single preferred regimen and improved viral load monitoring Service integration ```

Answer 199

``` Structural barriers Livelihood insecurity Low awareness about services Weak public health infrastructure Financial constraints on access Poor overlap Social barriers Gender differences in health seeking behaviour Problems of disclosure Stigma about HIV, even amongst staff at treatment centres Behavioural barriers Individual level constraints on behaviour Neglecting health and symptoms Fulfilling social expectations HIV stigma ```

Module 1 Flashcards

(223 cards)