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Larry Sawchuk

Curse and Blessing of the Ghetto -Author Jared Diamond and wife are of Eastern European Jewish ancestry -Tay-Sachs – incurable disease, preprogrammed in the genes -Infant appears normal for the first few months of birth -An exaggerated ‘startle reaction’ to sounds is the first ominous sign -At about 6 months baby starts to lose control of his head, can’t roll over or sit without support, drooling, breaks out into unmotivated bouts of laughter, convulsions, head grows abnormally large, blindness, usually dies before age 4 Worldwide: 1/400,000 births, 1/3,600 births Ashkenazim (Eastern European Jews), Oriental Jews (Middle East), Sephardic Jews (Spain and Mediterranean) frequency are the same as non- Jews -European whites - cystic fibrosis -African Blacks – Sickle Cell Disease -Pacific Islanders – Diabetes -TSD can be screened / prevented -W. Tay – ophthalmologist 1881 -B. Sachs – neurologist 1887 (noted by 1896 that disease was most common among Jewish children) -By 1962 the cause was linked to an excessive accumulation in nerve cells of a fatty substance called GM 2ganglioside - GM 2reakdown is via enzyme Hexosaminidase A, TS victims lack this enzyme -Autosomal recessive, needs defective gene from both parents to get TSD -Jewish dispersal / persecutions led to the Jews of France and Germany – the Ashkenazim fled east to Poland, Lithuania and Western Russia th -Beginning of the 20 century (WWII) – fled to the US -3/4 of the 13 M Jews today are Ashkenazim Potential Causes: 1. Mutations – however mutation rate higher among Ashkenazim Jews? Why? 2. Acquired TSD from another population group (Khazar) who already had the gene at high frequency (no real supporting evidence) and death of Tay-Sachs children should have eliminated the gene by natural selection in past 1,200 years 3. Founder effect and geneticdrift that may operate in small populations. • Example of this seen in group of Pennsylvania Dutch – US and French Canadians. Interestedly, Ashkenazim Jews are affected by 3 similar disorders TSD, Gaucher’s disease and Niemann-Pick disease 4. Does fat accumulation have an advantage in the heterozygote? • Query provided a resistance against TB, death rate from TB lower for TS heterozygotes • But why more common in the Ashkenazim? Suggestion that life in crowded ghettos where TB thrived was selection factor? As Jews were confined to ghettos – Jewish population was under the strongest selection to evolve genetic resistance to TB • Statistical evidence does not reach the level of proof that statisticians require to accept an effect as real rather than as one that’s arisen by chance. Plus no evidence of the biochemical mechanism by which fat accumulation might confer resistance against TB (Spyropoulos counter-argument against TB hypothesis) - Jared’s response to Spyropolous counter-argument – study of Toronto Ashkenazim Jews only examined grandparents of heterozygotes and not homozygotes -Myriathopoulos and Aronson – study indicated that correlation between TSD and TB resistance too small The Burden of Malaria in Africa -Rollback malaria target to reduce malaria by half by 2010 compared to levels in 2000 -90% of all malaria deaths worldwide occur in Africa south of the Sahara -Causes: 1. Plasmodium falciparum – most dangerous of the 4 human malaria parasites 2. Anopheles gambiae – most effective malaria vector worldwide /difficult to control -1 million people in Africa die from malaria each year, most children under 5 years old -Malaria is endemic– infection is common and some level of immunity develops -A smaller proportion of people live in areas where malaria is more seasonal and less predictable, because of either altitude or rainfall pattern– more vulnerable to highly seasonal transmission to malaria epidemics -In areas of stable malaria transmission, very young children and pregnant women are the population groups at highest risk for malaria morbidity and mortality -Most children experience their first malarian infections during the first year or two of life -90% of all malaria deaths in Africa occur in young children -Adult women in areas of stable transmission have a high level of immunity, but this is impaired, especially in first pregnancy -Malaria well controlled in northernmost African countries: Algeria, Egypt, Libyan Arab Jamahiriya, Morocco and Tunisia – disease caused by Plasmodium Vivax and transmitted by mosquitoes easier to control Malaria kills children in 3 different ways: 1. Infection in pregnancy – LBW, preterm delivery 2. Acute febrile illness – cerebral malaria, respiratory distress, hypoglycemia 3. Chronic repeated infection- severe anemia, increase susceptible to other common childhood illnesses, such as diarrhoea and respiratory infections Malaria is the cause of ~20% deaths of all children under 5 years old Children who survive malaria suffer from: 1. Repeated episodes of fever and illness 2. Reduce appetite 3. Restricted social interaction /play/educational opportunities, poor development 4. ~2% suffer from hearing impairments due to brain damage from cerebral malaria as well as epilepsy and spasticity Burden of health System: -~30% of outpatient clinic visits due to malaria (most diagnosis are made clinically) -20-50% of all hospital admissions due to malaria -High case fatalities due to late presentation, inadequate management, lack of drugs -Also a major contributor to deaths among hospital inpatients -Misdiagnosis – due to lack of laboratory facilities -High proportion of public health expenditure on curative treatment Burden on the poor: -Poor people at increased risk -Poor families live in dwellings that offer little protection against mosquitoes -Less able to afford insecticide-treated nets -Less able to pay for treatment and transportation to health facility -Malaria care 34% of the income of poor households Recent trends: -Monitoring of trends has severe limitations -Most diagnosis based on clinical symptoms vs laboratory confirmation -Malaria parasitemia common among clinic attendees so positive laboratory diagnosis does not mean patient is ill with malaria -Main clinical symptoms – fever and generous weakness are nonspecific and common for other infections -Poor data collection – limited comparison values -At present, the most reliable data available on trends in malaria deaths in children under 5 years is obtained from Demographic Surveillance Systems (DSS), number of sites increasing, 24 sites in 13 African countries, mostly in eastern and southern Africa -Increase in child mortality could be related to the spread of chloroquine-resistant malaria Factors contributing to an increase in malaria: -Drug-resistance -More frequent exposure of non-immune populations -Emergence of HIV/AIDS -Climate and environmental change -Breakdown of control programs Challenges faced by Roll Back Malaria Program: -2-3 years delay in National-level data -Low coverage of insecticide treated nets -Significant reductions in child mortality not yet observed -Lack of info on promptness and dosage and varying levels of drug effectiveness -60% coverage required before full effect of ITNs and effective treatment on child health will become apparent Rethinking the Impact of the 1918 Influenza Pandemic on Sex Differentials in Mortality -Study assesses the general impact of the 1919 influenza on overall mortality and its impact on mortality attributable to pulmonary TB in a small-scale population (Gibraltar) -Study used life table to identify: -Pre-epidemic period (1904-17) -Epidemic (1918) – health in both sexes fell significantly with a drop in life expectancy at birth -Post-epidemic (1919-27) - health rebounded, women has an increase in life expectancy -With respect to respiratory TB deaths, the immediate impact of influenza was restricted to only a significant increase in the rate among women (aged 15-54) -In the post-epidemic period TB mortality rates returned to the pre-epidemic state in both sexes -Findings from Gibraltar stand in contrast opposition to results reported for experience in the US during the 1918 flu -The 1918 influenza pandemic – most deadly influenza virus -Globally 20-40 million died -Infected 20-50% of the world’s population -Was unique in that mortality rate was greatest in young people aged 15-45 years -Was highest in males aged 21-40 -Death from influenza was from lung infection/pneumonia -Mortality was highest in towns and cities than in rural areas -Large cities and towns,however had lower mortality compared to small cites/towns probably due to better medical facilities Noymer and Garenne (2000) speculate that Mycobacterium TB and influenza interacted in the 1918 US pandemic, specifically that mortality occurred among those infected with TB through a selection effect such that death from influenza will reduce the incidence of deaths due to TB in subsequent years (example of harvesting effect, as discussed in Prof. Sawchuk lecture) Noymer and Garenne (2000) posited: 1. The flu epidemic had a strong and fairly long lasting effect on differential mortality by sex, diminishing the female advantage 2. Mechanism of change was a selection effect– those with TB in 1918 more likely to die of flu 3. Outcome affect males more than femalesbecause TB morbidity was disproportionally male 4. The reduction of the pool of male TB cases lowered the male TB death rate in the years following 1918 5. Male life expectancy moved closer to the longer female life expectancy -Gibraltar a British colony, naval base, a coaling station, a commercial centre, a garrison town and a port city -Flow of individuals for Spanish hinterland ad more distant locations -Info well documented, e.g. have a well established death registration process since 1869 -First epidemic wave was in May 1918 (8 deaths, 600-800 cases) -Second epidemic wave was from Sept. to November 1918 (36 deaths, 3000-6000 cases) -Health issues were: lack of precautionary measures/warnings, poor sanitation, lack of medical staff -In Gibraltar little was done to combat the high incidence of pulmonary TB (Great blot on the sanitary history of Gibraltar) -Highly overcrowded and unsanitary conditions -Communal patio lifestyle -Multi-family dwelling unit -Crowding and poor ventilation -Poor industrial hygiene, long hours, exposure to contaminants and dust -Local customs: -Visiting the sick -Spitting in living spaces and in the streets -Dry sweeping of the rooms of the sick -Feeding children from spoons and plates of sick relatives -Kissing of friends and relatives was a form of greeting -Selling of bedding and clothes of the sick -Ignorance regarding how TB spread -Aid was limited to TB victims -Sanitariums were not introduced until 1939 -Social stigma of the disease led to underreporting Results: Consequences of the 1918 Flu Epidemic Life expectancy at birth: 45.66 males and 52.4 females – pre-epidemic 39.60 males and 48.41 females – 1918 epidemic 46.86 males and 55.19 females – post-epidemic -Compared to men, women during the year 1918 showed a smaller decline in life expectancy at birth (4.13) -Impact of the epidemic onpulmonary TB – while respiratory TB rates among males did increase from 2.40 to 3.13 per 1,000 among men between the ages 15-54 during the epidemic period the rise was not statistically significant -After the epidemic there was in fact a slight rise in TB -The impact of influenza on pulmonary TB among women were at best temporary Reasons for contrasting results: 1. Interpopulation variation 2. Differences in methodology and/or the quality of registration 3. Variation due to local ecology, the bio-cultural properties of the community, local conditions that play a role in the spread and dispersal of the pathogen 4. State of immunity of the host population Epidemiologic Transition -Reflecting on the past can guide the future -Theory is based on systematic application of epidemiologic inference to: (1) Changing health (2) Mortality (3) Survival (4) Fertility Over time this is due to: (1) Socio-economic (2) Environmental (3) Demographic (4) Health care (5) Technological determinants -Epidemiology is the study of the health and disease patterns and their determinants and consequences in population groups -Incorporates the scientific capacity to analyze social, economic, demographic,health care, technological and environmental changes as they relate to health outcomes -Health is a dependent variable of epidemiology Proposition 1: The relative role of mortality and fertility in the epidemiologic transition: Stage 1: Pestilence and famine Stage 2: Receding pandemics Stage 3: Degenerative, stress and man-made diseases Stage 4: Declining CVD mortality, aging and emerging diseases Stage 5: Aspired quality of life with persistent inequities -Mortality rate is the measure of the number of deaths (in general, or due to a specific case) in a population, scaled to the size of that population, per unit of time (deaths/1000 individuals per year) -Documentation on mortality and fertility was lacking / poor in pre-modern times and in pre- industrial countries -Scantly evidence suggest– frequent / violent fluctuations in mortality patterns -Mortality was probably extremely high due to epidemics, famine and wars -Chronic malnutrition, endemic infectious diseases, high prenatal and maternal mortality, and life expectancy at birth short (18-35 years) -Short life expectancy and concomitant high birth rates led to a young population, growth patterns were cyclic, yielding small, if any, net increments of growth over long periods -Mortality is the most likely explanation of the slow rate of world population growth during pre- modern and pre-industrial times th -In modern period that followed (from the mid 17 century onward), the growth curve of world population slowly departed from the cyclic pattern and assumed a pattern of exponential growth -In modern times it was predominantly the declining mortathty morethhan  fertility that caused the West’s growth phase in Western Europe in the 18 and 19 centuries -Rise in population in Sweden was associated with  in mortality th th - in mortality in the Western societies in the 18 to 19 century was more socially than medically determined -Medical or health care development were too limited to have a significant impact at the time, few decisive therapies exist and surgery practiced by barbers at that time was not an accepted profession -More influential were personal lifestyle, social and environmental factors such as: (1) Improve nutrition led to decline in infectious diseases (was the largest factor in overall mortality decline at that time) by  resistance to infections (2) Early improvements in personal cleanliness, especially the use of soap, use of washable cotton underwear and bedding encouraged more frequent change of clothing and protection from disease-carrying body lice and fleas (3) Ecological recession of certain diseases which occur in waves, e.g. Scarlet fever or lost of an important link in transmission (e.g. disappearance of the black rat from Europe and the
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